Publications by authors named "Qin Zhou"

1,063 Publications

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Cost-effectiveness of nivolumab plus ipilimumab as first-line treatment for American patients with unresectable malignant pleural mesothelioma.

Front Public Health 2022 22;10:947375. Epub 2022 Jul 22.

Department of Oncology, Xiangya Hospital, Central South University, Changsha, China.

Background: The treatment paradigm of unresectable malignant pleural mesothelioma (MPM) has changed in recent years. Checkmate 743 demonstrate that nivolumab plus ipilimumab showed good clinical benefits compared with chemotherapy in the treatment of MPM. The study is aim to evaluate the cost-effectiveness of Nivolumab plus ipilimumab vs. platinum plus chemotherapy for the first-line treatment of unresectable MPM.

Methods: A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of nivolumab plus ipilimumab and chemotherapy over a 10-year time horizon. Clinical efficacy and safety data were extracted from the CheckMate 743 trials. Health state utilities were obtained from published literature. Costs were collected from an US payer perspective. One-way and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties on the cost-effectiveness's results.

Results: In the base case analysis, the incremental healthcare costs and QALYs for Nivolumab plus Ipilimumab vs. chemotherapy are $196,604.22 and 0.53, respectively, resulting an incremental cost-effectiveness ratio (ICER) of $372,414.28/QALYs for the model cohort of patients with locally advanced or metastatic MPM. However, Probabilistic sensitivity analysis showed that there was no probability that Nivolumab plus ipilimumab was cost-effective within the fluctuation range of other model parameters in first-line in unresectable MPM. The results of one-way sensitivity analysis showed that the cost of Nivolumab was the most sensitive parameter.

Conclusions: The ICER of Nivolumab plus ipilimumab is above the theoretical willingness-to-pay threshold in the U.S, which suggests that first-line nivolumab plus ipilimumab for unresectable MPM may be not a cost-effective choice.
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http://dx.doi.org/10.3389/fpubh.2022.947375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354521PMC
July 2022

A Signature Based on Costimulatory Molecules for the Assessment of Prognosis and Immune Characteristics in Patients With Stomach Adenocarcinoma.

Front Immunol 2022 22;13:928742. Epub 2022 Jul 22.

Department of Gastroenterology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

Although costimulatory molecules have been shown to boost antitumor immune responses, their significance in stomach adenocarcinoma (STAD) remains unknown. The purpose of this study was to examine the gene expression patterns of costimulatory molecule genes in patients with STAD and develop a predictive signature to aid in therapy selection and outcome prediction. We used 60 costimulatory family genes from prior research to conduct the first complete costimulatory molecular analysis in patients with STAD. In the two study groups, consensus clustering analysis based on these 60 genes indicated unique distribution patterns and prognostic differences. Using the least absolute shrinkage and selection operator and Cox regression analysis, we identified nine costimulatory molecular gene pairs (CMGPs) with prognostic value. With these nine CMGPs, we were able to develop a costimulatory molecule-related prognostic signature that performed well in an external dataset. For the patients with STAD, the signature was proven to be a risk factor independent of the clinical characteristics, indicating that this signature may be employed in conjunction with clinical considerations. A further connection between the signature and immunotherapy response was discovered. The patients with high mutation rates, an abundance of infiltrating immune cells, and an immunosuppressive milieu were classified as high-risk patients. It is possible that these high-risk patients have a better prognosis for immunotherapy since they have higher cytolytic activity scores and immunophenoscores of CTLA4 and PD-L1/PD-L2 blockers. Therefore, our signature may help clinicians in assessing patient prognosis and developing treatment plans.
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http://dx.doi.org/10.3389/fimmu.2022.928742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9353527PMC
July 2022

Association of Apatinib and Breast Cancer: A systematic review and meta-analysis.

Surg Oncol 2022 Jul 19;44:101818. Epub 2022 Jul 19.

AMITA Health Saint Joseph Hospital Chicago, 2900 N. Lake Shore Drive, Chicago, IL, 60657, USA. Electronic address:

Background: Breast cancer (BC) is a common malignant tumor. Apatinib in combination with other treatments has been used for BC; however, its safety and efficacy are not well-known. Therefore, this meta-analysis was performed to assess the efficacy and safety of apatinib in the treatment of BC.

Methods: Studies comparing the effects of apatinib-based therapy versus control among BC patients were included. On January 21, 2022, a systematic search was performed in 9 databases. The risk ratio (RR) with 95% confidence interval (CI) was used to estimate efficacy and safety. The I square value (I) was used to assess heterogeneity. A leave-one-out sensitivity analysis was also conducted. Publication bias was assessed by funnel plots and Egger's and Begg's tests.

Results: A total of 31 studies including 2,258 BC patients were included. The results showed that apatinib group had a significant improvement in disease control rate (DCR, RR = 1.43, 95% CI = 1.35-1.52, I = 43.8%) and objective response rate (ORR, RR = 1.79, 95% CI = 1.51-2.13, I = 61.8%) compared to the control group. Except for hemorrhage, hypertension, and hand-foot syndrome, the adverse events were similar between apatinib group and control group. Subgroup analyses found statistically significant differences in DCR in all subgroups except for apatinib combined with radiation therapy and with paclitaxel liposome plus S1. For ORR, there were statistically significant differences in all subgroups except for the radiation therapy, and apatinib monotherapy subgroups.

Conclusions: Our study shown apatinib showed good efficacy and acceptable safety in the treatment of BC patients. More high-quality randomized controlled trials from different regions and countries are needed to confirm our findings.
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http://dx.doi.org/10.1016/j.suronc.2022.101818DOI Listing
July 2022

Present situation and analysis of factors affecting perimenopausal syndrome among clinical nurses-a cross-sectional survey.

Ann Palliat Med 2022 Jul;11(7):2432-2442

Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Background: The quality of life of women is seriously affected by perimenopausal symptoms and related diseases. Clinical nurses often suffer from job burnout due to high pressure and intensity of work and life, which is easy to induce and aggravate perimenopausal syndrome. Nursing occupational environment varies greatly in different economic regions, but relevant studies are limited to northern cities, and are often confined to the second and third grade hospitals or a hospital in a certain region, lacking multi-center studies on hospitals of different grades. Therefore, it is necessary to understand the occurrence of perimenopausal syndrome in clinical nurses in Chongqing and its influencing factors, so as to provide reference for managers to take targeted intervention measures.

Methods: The investigation was conducted using the method of stratified random cluster sampling. A questionnaire survey was conducted among 933 clinical nurses aged from 40 to 55 in primary, secondary and tertiary hospitals. Kupperman's total symptom score ranged from 0 to 63, while a score of ≥7 can determine the existence of perimenopausal syndrome.

Results: Among the 933 clinical nurses surveyed, 662 (70.95%) had perimenopausal syndrome, the results of the multivariate unconditional logistic regression analysis showed that The age ranges from 51 to 55 (OR =2.035, 95% CI: 1.070-3.872), the presence of chronic diseases (OR =1.659, 95% CI: 1.095-2.512), menopause (OR =1.989, 95% CI: 1.198-3.303), moderate family function impairment (OR =1.940, 95% CI: 1.356-2.776), severe family dysfunction weekly (OR =2.309, 95% CI: 1.178-4.524), never participation in sports (OR =3.328, 95% CI: 1.657-6.684) and exercising 1-5 times per week (OR =2.689, 95% CI: 1.516-4.768) were risk factors for perimenopausal syndrome in clinical nurses, basic security (OR =0.939, 95% CI: 0.887-0.994), and sufficient manpower (OR =0.915, 95% CI: 0.855-0.979) were protective factors for perimenopausal syndrome in clinical nurses.

Conclusions: The incidence of perimenopausal syndrome in clinical nurses at all levels of hospitals situated in Chongqing is relatively high. It is suggested that nursing managers should attach great importance to the physical and mental condition of this population and timely take targeted intervention measures to prevent or alleviate the occurrence and development of perimenopausal syndrome in clinical nurses.
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http://dx.doi.org/10.21037/apm-22-563DOI Listing
July 2022

4-tert-butylphenol triggers common carp hepatocytes ferroptosis via oxidative stress, iron overload, SLC7A11/GSH/GPX4 axis, and ATF4/HSPA5/GPX4 axis.

Ecotoxicol Environ Saf 2022 Aug 1;242:113944. Epub 2022 Aug 1.

Institute of Animal Science Chinese Academy of Agricultural Sciences, Beijing 100193, People's Republic of China. Electronic address:

4-tert-butylphenol (4-tBP) is a toxic environmental pollutant with moderate bioaccumulation, environmental persistence, and long-term toxicity. Its toxicity to aquatic organisms has become an issue of concern. However, the molecular mechanism of 4-tBP toxicity to aquatic organisms remained unclear. Liver is a target organ for environmental pollutants. Here, we established 4-tBP-exposed toxicity model in vivo and primary hepatocyte model in vitro in common carp (Cyprinus carpio L.). We found increased hepatic-somatic index (HSI) and abnormal serum biochemical indexes (ALT, AST, and LDH) after 4-tBP exposure, indicating liver damage. We further revealed that 4-tBP damaged the structural integrity of the livers with typical features of ferroptosis. Based on toxicogenomics analysis, we found ferroptosis is likely to be involved in the mechanism of 4-tBP-induced liver damage. Moreover, our in vivo and in vitro experiment provided evidences that 4-tBP-exposure led to excess oxidative stress, iron overload, decreased MMP, and abnormal expression of ferroptosis-related factors. Interestingly, ferrostatin-1 (Fer-1, a ferroptosis inhibitor) pretreatment alleviated above changes. In summary, we demonstrated that 4-tBP triggered hepatocytes ferroptosis via oxidative stress, iron overload, SLC7A11/GSH/GPX4 axis, and ATF4/HSPA5/GPX4 axis. For the first time, we discovered that Fer-1 can ameliorate the toxicity of 4-tBP, which needs more investigations. Our results provided a scientific basis of molecular mechanism of 4-tBP-induced fish poisoning.
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http://dx.doi.org/10.1016/j.ecoenv.2022.113944DOI Listing
August 2022

Continuous infusion versus intermittent infusion of vancomycin in critically ill patients undergoing continuous venovenous hemofiltration: a prospective interventional study.

BMC Infect Dis 2022 Aug 2;22(1):667. Epub 2022 Aug 2.

Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, 215002, China.

Background: A prospective interventional study comparing outcomes in critically ill patients receiving intermittent infusion (II) or continuous infusion (CI) of vancomycin during continuous venovenous hemofiltration (CVVH) is lacking. The objective of this study was to compare the pharmacokinetic/pharmacodynamics (PK/PD) target attainment, therapeutic efficacy and safety among critically ill patients who received CI or II of vancomycin in a prospective interventional trial and to explore the correlations of effluent flow rate (EFR) with PK/PD indices.

Methods: This prospective interventional study was conducted in two independent intensive care units (ICUs) from February 2021 to January 2022. Patients in one ICU were assigned to receive CI (intervention group) of vancomycin, whereas patients in the other ICU were assigned to receive II regimen (control group). The primary outcome was to compare the PK/PD target attainment, including target concentration and target area under the curve over 24 h to minimum inhibitory concentration (AUC/MIC).

Results: Overall target attainment of PK/PD indices was higher with CI compared with II, irrespective of target concentration (78.7% vs. 40.5%; P < 0.05) or AUC/MIC (53.2% vs. 28.6%; P < 0.05). There were no significant differences in clinical success (72.2% vs. 50.0%; P = 0.183) and microbiological success (83.3% vs. 75.0%, P = 0.681) between the patients treated with CI or II of vancomycin. Adverse reactions occurred at similar rates (0.0% vs. 4.4%; P = 0.462), and mortality between the two modalities was also not significant different (21.7% vs. 17.9%; P = 0.728). Correlation analysis showed a weak to moderately inverse correlation of EFR with observed concentration (r = - 0.3921, P = 0.01) and AUC/MIC (r = - 0.3811, P = 0.013) in the II group, whereas the correlation between EFR and observed concentration (r = - 0.5711, P < 0.001) or AUC/MIC (r = - 0.5458, P < 0.001) in the CI group was stronger.

Conclusion: As compared to II, CI of vancomycin in critically ill patients undergoing CVVH was associated with improved attainment of PK/PD indices. Furthermore, the inverse correlation of PK/PD indices with EFR was stronger among patients treated with CI of vancomycin. Trial registration The trial was registered in the Chinese clinical trial registration center (21/01/2021-No. ChiCTR2100042393).
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http://dx.doi.org/10.1186/s12879-022-07618-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344630PMC
August 2022

Association of urinary or blood heavy metals and mortality from all causes, cardiovascular disease, and cancer in the general population: a systematic review and meta-analysis of cohort studies.

Environ Sci Pollut Res Int 2022 Aug 2. Epub 2022 Aug 2.

AMITA Health Saint Joseph Hospital Chicago, 2900 N. Lake Shore Drive, Chicago, IL, 60657, USA.

Amounting epidemiological evidence has shown detrimental effects of heavy metals on a wide range of diseases. However, the effect of heavy metal exposure on mortality in the general population remains unclear. The primary objective of this study was to clarify the associations between heavy metals and mortality from all causes, cardiovascular disease (CVD), and cancer based on prospective studies. We comprehensively searched Pubmed, Embase, and Web of Science electronic databases to identify studies published from their inception until 1 March 2022. Investigators identified inclusion criteria, extracted study characteristics, and assessed the methodological quality of included studies according to standardized guidelines. Meta-analysis was conducted if the effect estimates of the same outcome were reported in at least three studies. Finally, 42 original studies were identified. The results of meta-analysis showed that cadmium and lead exposure was significantly associated with mortality from all causes, CVD, and cancer in the general population. Moderate evidence suggested there was a link between arsenic exposure and mortality. The adverse effects of mercury and other heavy metals on mortality were inconclusive. Epidemiological evidence for the joint effect of heavy metal exposure on mortality was still indeterminate. In summary, our study provided compelling evidence that exposure to cadmium, lead, and arsenic were associated with mortality from all causes, CVD, and cancer, while the evidence on other heavy metals, for example mercury, was insignificant or indeterminate. Nevertheless, further prospective studies are warranted to explore the joint effects of multiple metal exposure on mortality.
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http://dx.doi.org/10.1007/s11356-022-22353-wDOI Listing
August 2022

Identification and Verification of Potential Biomarkers in Gastric Cancer By Integrated Bioinformatic Analysis.

Front Genet 2022 15;13:911740. Epub 2022 Jul 15.

Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Gastric cancer (GC) is a common cancer with high mortality. This study aimed to identify its differentially expressed genes (DEGs) using bioinformatics methods. DEGs were screened from four GEO (Gene Expression Omnibus) gene expression profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. A protein-protein interaction (PPI) network was constructed. Expression and prognosis were assessed. Meta-analysis was conducted to further validate prognosis. The receiver operating characteristic curve (ROC) was analyzed to identify diagnostic markers, and a nomogram was developed. Exploration of drugs and immune cell infiltration analysis were conducted. Nine up-regulated and three down-regulated hub genes were identified, with close relations to gastric functions, extracellular activities, and structures. Overexpressed Collagen Type VIII Alpha 1 Chain (COL8A1), Collagen Type X Alpha 1 Chain (COL10A1), Collagen Triple Helix Repeat Containing 1 (CTHRC1), and Fibroblast Activation Protein (FAP) correlated with poor prognosis. The area under the curve (AUC) of ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (ADAMTS2), COL10A1, Collagen Type XI Alpha 1 Chain (COL11A1), and CTHRC1 was >0.9. A nomogram model based on CTHRC1 was developed. Infiltration of macrophages, neutrophils, and dendritic cells positively correlated with COL8A1, COL10A1, CTHRC1, and FAP. Meta-analysis confirmed poor prognosis of overexpressed CTHRC1. ADAMTS2, COL10A1, COL11A1, and CTHRC1 have diagnostic values in GC. COL8A1, COL10A1, CTHRC1, and FAP correlated with worse prognosis, showing prognostic and therapeutic values. The immune cell infiltration needs further investigations.
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http://dx.doi.org/10.3389/fgene.2022.911740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337873PMC
July 2022

CCNB2 expression correlates with worse outcomes in breast cancer patients: a pooled analysis.

Women Health 2022 Aug 26;62(7):655-663. Epub 2022 Jul 26.

Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.

Cyclin B2 (CCNB2) is upregulated in Breast Cancer (BC) and associated with worse relapse-free survival (RFS). However, its correlation with other clinical outcomes in BC was yet to be clarified. Therefore, this study aimed to explore the clinical significance of CCNB2 in BC. A comprehensive search was performed in PrognoScan and Gene Expression Omnibus (GEO) databases by searching the keywords of CCNB2 and breast cancer. Pooled hazard ratios (HRs) of overall survival (OS), relapse-free survival (RFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and disease-free survival (DFS), and their corresponding 95 percent confidence intervals (CI) were calculated. Sensitivity analysis by omitting one study at a time and publication bias assessment by Egger's test and Begg's test were conducted. The clinical outcomes were externally verified via Kaplan-Meier Plotter. All of the statistical analyses were performed through STATA 17.0, and values of less than 0.05 were taken to be statistically significant. Seven records with 1,074 participants were included for OS, with HR of 1.71 (95 percent CI = 1.24-2.35). Verification through Kaplan-Meier Plotter online tool based on 1,897 patients showed an HR of 1.75 (95 percent CI = 1.45-2.12,  < .01). For RFS, 11 records with 1,253 participants were included with the pooled HR of 1.37 (95 percent CI: 1.10-1.71). Verification based on 4,929 patients found and HR of 1.97 (95 percent CI = 1.78-2.19,  < .01). Regarding DMFS, the pooled HR of 10 records with 1,395 participants was 1.60 (95 percent CI: 1.24-2.05) and verification based on 2,765 patients revealed an HR of 1.97 (95 percent CI = 1.68-2.31,  < .01). For DSS, four records with 689 participants were included for DSS, with HR of 1.38 (95 percent CI = 0.59-3.24). The HR of DFS was 1.60 (95 percent CI: 0.46-5.51) after pooling 3 records with 379 participants. High expression of CCNB2 in BC is associated with worse OS, RFS, and DMFS, but not with DSS and DFS. More well-designed studies from different populations and different BC types are still needed.
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http://dx.doi.org/10.1080/03630242.2022.2106530DOI Listing
August 2022

Associations between circulating proteins and risk of breast cancer by intrinsic subtypes: a Mendelian randomisation analysis.

Br J Cancer 2022 Jul 26. Epub 2022 Jul 26.

Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: The aetiologic role of circulating proteins in the development of breast cancer subtypes is not clear. We aimed to examine the potential causal effects of circulating proteins on the risk of breast cancer by intrinsic-like subtypes within the Mendelian randomisation (MR) framework.

Methods: MR was performed using summary statistics from two sources: the INTERVAL protein quantitative trait loci (pQTL) Study (1890 circulating proteins and 3301 healthy individuals) and the Breast Cancer Association Consortium (BCAC; 106,278 invasive cases and 91,477 controls). The inverse-variance (IVW)-weighted method was used as the main analysis to evaluate the associations between genetically predicted proteins and the risk of five different intrinsic-like breast cancer subtypes and the weighted median MR method, the Egger regression, the MR-PRESSO, and the MRLocus method were performed as secondary analysis.

Results: We identified 98 unique proteins significantly associated with the risk of one or more subtypes (Benjamini-Hochberg false discovery rate < 0.05). Among them, 51 were potentially specific to luminal A-like subtype, 14 to luminal B/Her2-negative-like, 11 to triple negative, 3 to luminal B-like, and 2 to Her2-enriched-like breast cancer (n = 81). Associations for three proteins (ICAM1, PLA2R1 and TXNDC12) showed evident heterogeneity across the subtypes. For example, higher levels of genetically predicted ICAM1 (per unit of increase) were associated with an increased risk of luminal B/HER2-negative-like cancer (OR = 1.06, 95% CI = 1.03-1.08, BH-FDR = 2.43 × 10) while inversely associated with triple-negative breast cancer with borderline significance (OR = 0.97, 95% CI = 0.95-0.99, BH-FDR = 0.065, P < 0.005).

Conclusions: Our study found potential causal associations with the risk of subtypes of breast cancer for 98 proteins. Associations of ICAM1, PLA2R1 and TXNDC12 varied substantially across the subtypes. The identified proteins may partly explain the heterogeneity in the aetiology of distinct subtypes of breast cancer and facilitate the personalised risk assessment of the malignancy.
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http://dx.doi.org/10.1038/s41416-022-01923-2DOI Listing
July 2022

A retrospective study of estrogen in the pretreatment for medical management of early pregnancy loss and the inference from intrauterine adhesion.

Eur J Med Res 2022 Jul 25;27(1):129. Epub 2022 Jul 25.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

Background: Estrogen has been usually used in clinic for medical pretreatment of early pregnancy loss. There was little reported the effect of estrogen combined with prostaglandin analogs in the medical management of early pregnancy loss. This retrospective study aimed to evaluate the efficacy of estrogen pretreatment for medical management of early pregnancy loss and explore the confounding factor of intrauterine adhesion (IUA) on the outcome of medical management.

Methods: A total of 226 early pregnancy loss patients who received pretreatment with estradiol valerate and/or mifepristone, followed by carboprost methylate suppositories (study groups), or carboprost methylate suppositories alone (control group) in a regional central institution from March 2020 to February 2021 were retrospectively studied. All patients were evaluated by hysteroscopy 6 h after carboprost methylate suppositories use to assess whether the gestational sac was complete expulsion and assess the morphology of uterine cavity.

Results: The complete expulsion rate was 56.94% in the mifepristone and estradiol valerate-pretreatment group, 20.69% in the estradiol valerate-pretreatment group, 62.5% in the mifepristone-pretreatment group, and 12.5% in the control group. Compared with the control group, pretreatment with estradiol valerate did not increase the complete expulsion rate significantly (P = 0.297), pretreatment with mifepristone increased the complete expulsion rate significantly (P < 0.001). Pretreatment with mifepristone combined with estradiol valerate did not increase the complete expulsion rate significantly comparing with pretreatment with mifepristone (P = 0.222). The data of IUA showed that the complete expulsion rate in patients with IUA was lower than that in those patients without IUA (P < 0.001).

Conclusions: Pretreatment with estrogen was not a sensible substitute for mifepristone in the medical management of early pregnancy loss. Mifepristone followed by carboprost methylate suppositories was likelihood of the ideal medical scheme in early pregnancy loss. IUA decreased the complete expulsion rate of medical management, it is cautious about medical management for early pregnancy loss with risk of IUA.

Trial Registration Number: ChiCTR2100046503. Date of registration (retrospectively registered): May 18, 2021. Trial registration website: http://www.chictr.org.cn/ .
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http://dx.doi.org/10.1186/s40001-022-00767-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310452PMC
July 2022

The MEMORY Study: MulticentEr study of Minimally invasive surgery versus Open Radical hYsterectomy in the management of early-stage cervical cancer: Survival outcomes.

Gynecol Oncol 2022 Jul 22. Epub 2022 Jul 22.

University of Alabama at Birmingham, Birmingham, AL, United States of America.

Objective: The Laparoscopic Approach to Cervical Cancer (LACC) trial found that minimally invasive radical hysterectomy compared to open radical hysterectomy compromised oncologic outcomes and was associated with worse progression-free survival (PFS) and overall survival (OS) in early-stage cervical carcinoma. We sought to assess oncologic outcomes at multiple centers between minimally invasive (MIS) radical hysterectomy and OPEN radical hysterectomy.

Methods: This is a multi-institutional, retrospective cohort study of patients with 2009 FIGO stage IA1 (with lymphovascular space invasion) to IB1 cervical carcinoma from 1/2007-12/2016. Patients who underwent preoperative therapy were excluded. Squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinomas were included. Appropriate statistical tests were used.

Results: We identified 1093 cases for analysis-715 MIS (558 robotic [78%]) and 378. OPEN procedures. The OPEN cohort had more patients with tumors >2 cm, residual disease in the hysterectomy specimen, and more likely to have had adjuvant therapy. Median follow-up for the MIS and OPEN cohorts were 38.5 months (range, 0.03-149.51) and 54.98 months (range, 0.03-145.20), respectively. Three-year PFS rates were 87.9% (95% CI: 84.9-90.4%) and 89% (95% CI: 84.9-92%), respectively (P = 0.6). On multivariate analysis, the adjusted HR for recurrence/death was 0.70 (95% CI: 0.47-1.03; P = 0.07). Three-year OS rates were 95.8% (95% CI: 93.6-97.2%) and 96.6% (95% CI: 93.8-98.2%), respectively (P = 0.8). On multivariate analysis, the adjusted HR for death was 0.81 (95% CI: 0.43-1.52; P = 0.5).

Conclusion: This multi-institutional analysis showed that an MIS compared to OPEN radical hysterectomy for cervical cancer did not appear to compromise oncologic outcomes, with similar PFS and OS.
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http://dx.doi.org/10.1016/j.ygyno.2022.07.002DOI Listing
July 2022

Predictive Value of the Respiratory Variation in Inferior Vena Cava Diameter for Ventilated Children With Septic Shock.

Front Pediatr 2022 7;10:895651. Epub 2022 Jul 7.

Department of Pediatrics/Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University, Chengdu, China.

Objectives: This study aimed to investigate the predictive utility of respiratory variations of inferior vena cava diameters on fluid responsiveness in children with septic shock.

Design: A prospective observational single-center study.

Setting: A pediatric intensive care unit in a tertiary hospital in China.

Participants: Patients with sepsis shock who require invasive mechanical ventilation were recruited between 1 December 2017 and 1 November 2021.

Interventions And Measurements: Volume expansion (VE) was induced by a 30-min infusion of 20 ml/kg of normal saline. Hemodynamics indexes were obtained through bedside transthoracic echocardiography (TTE) measurement and calculation.

Results: A total of 86 patients were enrolled in this study, among them, 45 patients (52.3%) were considered to be non-responders (NR), with an increase in stroke volume variation (SVV) <15% after VE. Multivariate logistic analysis showed that ΔIVC (adjusted OR = 1.615, 95% CI 1.092-2.215, = 0.012) was the significant predictor associated with the fluid responsiveness. The area under the ROC of ΔIVC was 0.922 (95% CI: 0.829-1.000, < 0.01), and the cutoff value of ΔIVC used to predict fluid responsiveness was 28.5%, with a sensitivity and specificity of 95.4 and 68.5%, respectively.

Conclusions: The ΔIVC was found to have a potential value in predicting fluid responsiveness in mechanically ventilated children with septic shock.
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http://dx.doi.org/10.3389/fped.2022.895651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301070PMC
July 2022

Moraxella occupied the largest proportion in the nasal microbiome in healthy children, which potential protect them from COVID-19.

Microb Pathog 2022 Jul 21;170:105685. Epub 2022 Jul 21.

Department of Obstetrics and Gynecology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, PR China. Electronic address:

Background: In the prevalence of COVID-19, infection symptoms are different in children and adults. In this study to investigate the differences in the upper respiratory tract microbiome profile between healthy children and adults and to explore which microbiome protect them from COVID-19.

Methods: Thirty healthy children and 24 healthy adults were enrolled between October 2020 and January 2021. Nasal and throat swabs were obtained at enrollment, and DNA was extracted. We performed 16S rDNA sequencing to compare the alpha and beta diversity of the nasal and throat microbiomes between children and adults and assessed potential microbiome biomarkers.

Results: In the nasal microbiome, there were significant differences between healthy children and adults, and Moraxella occupied the largest proportion in healthy children. Notably, there was no significant difference between healthy children and adults in the throat microbiome, and it was predominated by Firmicutes. In the function analysis, compared with adults, there was increased enrichment in pathways related to amino acid metabolism and lipid metabolism, in children.

Conclusions: In the upper respiratory tract microbiome profiles, Moraxella may be involved in protecting children from COVID-19 infections and may be involved the amino acid metabolism and lipid metabolism.
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http://dx.doi.org/10.1016/j.micpath.2022.105685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299982PMC
July 2022

ATF4 promotes brain vascular smooth muscle cells proliferation, invasion and migration by targeting miR-552-SKI axis.

PLoS One 2022 20;17(7):e0270880. Epub 2022 Jul 20.

Department of Neurology, Wuhan Brain Hospital, General Hospital of the YANGTZE River Shipping, Wuhan, China.

Background: Studies have indicated vascular smooth muscle cells (VSMCs) played a crucial role in atherosclerosis and microRNAs (miRNAs) played key roles in biological functions of VSMCs. Whereas, the potential function and mechanism of miR-552 in VSMCs remains unclear. Our aim was to explore the role of miR-552 on VSMCs and underlying mechanism.

Material/methods: MTT assay and transwell assay were used to measure the proliferation, invasion, and migration of human brain VSMCs (HBVSMCs) and mice VSMCs (mVSMCs), respectively. Bioinformatics tools and luciferase assay were adopted to verify the association between miR-552 and SKI. Rescue experiments were employed to assess the interaction of miR-552 and SKI in modulating biological functions in HBVSMCs and mVSMCs. The expression level of transcription factors (TFs)was measured via qRT-PCR assay. The effect of ATF4 on miR-552 and SKI expression was tested by qRT-PCR or western blot assay. Finally, chromatin immunoprecipitation (ChIP) assay and JASPAR databases were used to analyze the regulatory linkage between ATF4 and miR-552.

Results: We found that miR-552 was upregulated in HBVSMCs treated with PDGF-bb and miR-552 overexpression could promote proliferation, invasion, and migration of HBVSMCs and mVSMCs, whereas, miR-552 knockdown had the opposite impact. In addition, we also found that SKI was a direct target of miR-552, which reversed miR-552-mediated proliferation, invasion, and migration in HBVSMCs and mVSMCs. Furthermore, we also discovered that miR-552 overexpression promoted the effects of ATF4 elevation on proliferation, migration and invasion of HBVSMCs and mVSMCs, but, miR-552 decline had the opposite impact.

Conclusions: ATF4-miR-552-SKI axis played critical roles in the proliferation and migration of HBVSMCs and mVSMCs, which were closely involved in atherosclerosis (AS). Therefore, our findings might offer a novel therapeutic target for AS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270880PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299314PMC
July 2022

Genome sequence of the novel freshwater Microcystis cyanophage Mwe-Yong1112-1.

Arch Virol 2022 Jul 20. Epub 2022 Jul 20.

College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.

The freshwater cyanophage Mwe-Yong1112-1 was isolated using Microcystis wesenbergii as a host and found to have an icosahedral head, about 45 nm in diameter, and a flexible tail, approximately 133 nm in length and 4.5 nm in width. The complete genome of the cyanophage is 39,679 bp in length with a G+C content of 66.6%. Mwe-Yong1112-1 shared the highest pairwise average nucleotide identity (ANI) value of 67.7% (below the ≥95% boundary to define a species) and the highest nucleotide sequence similarity of 17.48% (below the >70% boundary to define a genus) with the most closely related phage. In a proteomic tree, Mwe-Yong1112-1 and three unclassified phages formed a monophyletic clade between the families Saparoviridae and Pyrstoviridae, but Mwe-Yong1112-1 occupied a separate branch from the other three phages, suggesting that it represents a new evolutionary lineage. This study enriches the available information about freshwater cyanophages.
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http://dx.doi.org/10.1007/s00705-022-05542-3DOI Listing
July 2022

Microsatellite instability-high endometrial cancers with MLH1 promoter hypermethylation have distinct molecular and clinical profiles.

Clin Cancer Res 2022 Jul 18. Epub 2022 Jul 18.

Memorial Sloan Kettering Cancer Center, New York, NY, United States.

Purpose: Microsatellite instability-high (MSI-H) endometrial carcinomas (ECs) are underpinned by distinct mechanisms of DNA mismatch repair deficiencies (MMR-D). We sought to characterize clinical and genetic features of MSI-H ECs harboring germline or somatic mutations in MMR genes or MLH1 promoter hypermethylation (MLH1ph).

Design: Of >1,100 EC patients that underwent clinical tumor-normal sequencing, 184 displayed MSI-H ECs due to somatic MMR mutations or MLH1ph, or harbored pathogenic germline MMR mutations. Clinicopathologic features, mutational landscape, and tumor infiltrating lymphocyte (TIL) scores were compared among MMR-D groups using non-parametric tests. Log-rank tests were used for categorical associations; Kaplan-Meier method and Wald-test based on Cox proportional-hazards models were employed for continuous variables and survival analyses.

Results: Compared to patients with germline (n=25) and somatic (n=39) mutations, patients with MLH1ph ECs (n=120) were older (p<0.001), more obese (p=0.001) and had more advanced disease at diagnosis (p=0.025). MLH1ph ECs were enriched for JAK1 somatic mutations as opposed to germline MMR-D ECs which showed enrichment for pathogenic ERBB2 mutations. MLH1ph ECs exhibited lower tumor mutational burden and TIL scores compared to ECs harboring germline or somatic MMR mutations (p<0.01). MLH1ph EC patients had shorter progression-free survival (PFS) on univariate analysis, but in multivariable models stage at diagnosis remained the only predictor of survival. For stage I/II EC, two-year PFS was inferior for patients with MLH1ph ECs compared to germline and somatic MMR groups (70% vs. 100%, respectively).

Conclusions: MLH1ph ECs likely constitute a distinct clinicopathologic entity compared to germline and somatic MMR-D ECs with potential treatment implications.
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http://dx.doi.org/10.1158/1078-0432.CCR-22-0713DOI Listing
July 2022

Associaton of Retinol Binding Protein 4 (RBP4) Levels With Hyperuricemia: A Cross-Sectional Study in a Chinese Population.

Front Endocrinol (Lausanne) 2022 29;13:879755. Epub 2022 Jun 29.

Department of Nephrology, South China Hospital of Shenzhen University, Shenzhen, China.

Background: There are few studies on predictive biomarkers for hyperuricemia, and the predictive value of these biomarkers tends to be poor. Additionally, no reports have described the predictive value of retinol binding protein 4 (RBP4) for hyperuricemia.

Purpose: This study was performed to evaluate the value of RBP4 for predicting the risk of hyperuricemia in a general population, determine whether RBP4 could be used alone or in combination with other factors to predict the risk of hyperuricemia in the general population, and establish an optimum predictive model.

Methods: We conducted a population-based cross-sectional survey in 2018, involving a questionnaire, physical examination, and laboratory testing. We enrolled 2303 individuals by stratified random sampling, and 2075 were included in the data analysis after applying the eligibility criteria.

Results: Serum RBP4 level had a highly significant association with hyperuricemia (<0.001). After adjusting for potential confounders, logistic regression indicated that the risk of hyperuricemia was highest in the highest RBP4 quartile (odds ratio: 7.9, 95% confidence interval [CI]: 4.18-14.84, compared to the lowest quartile). The area under the receiver operating characteristic (ROC) curve (AUC) for RBP4 was 0.749 (95% CI: 0.725-0.774, <0.001), which was higher than that for all the other predictors assessed. The optimum model for predicting hyperuricemia in the general population consisted of RBP4, sex (male), body mass index, serum creatinine, high-sensitivity C-reactive protein, fasting blood glucose, insulin, and alcohol consumption. The AUC was 0.804 (95% CI: 0.782-0.826, <0.001).

Conclusions: RBP4 is strongly associated with hyperuricemia, and its predictive value was higher than that of traditional predictors.
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http://dx.doi.org/10.3389/fendo.2022.879755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276999PMC
June 2022

Effect of the Chinese New Year Public Holiday on the Glycemic Control of T1DM With Intensive Insulin Therapy.

Front Endocrinol (Lausanne) 2022 28;13:915482. Epub 2022 Jun 28.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Aims: There is limited evidence that evaluates the glycemic control of type 1 diabetes mellitus (T1DM) during the Chinese New Year public holiday in China. The Chinese New Year public holiday represents various challenges to glycemic control, especially in T1DM patients, in China. We aimed to assess the effect of the Chinese New Year public holiday on several glucose metrics using flash glucose monitoring (FGM) in patients with T1DM.

Methods: Complete FGM data for 1 week before, 1 week during and 1 week after the Chinese New Year public holiday were available for 71 T1DM patients treated with multiple daily insulin injection (MDI) therapy (n = 51) or continuous subcutaneous insulin infusion (CSII) treatment (n = 20). The mean age of the study participants was 13 (9, 30) years. Of note, 59.2% of the patients (n = 42) were adults, and 40.8% of the patients (n = 29) were minors. The interval between each two adjacent periods was one week. The indicators of mean glucose, glucose variability and time in different glycemic ranges were analyzed.

Results: The Chinese New Year public holiday was associated with an increase in mean blood glucose (8.4 ± 1.7 vs. 9.2 ± 2.5; < 0.001) and time above range (TAR) (27.9% ± 16.6% vs. 35.0% ± 22.3%; < 0.001) but a decrease in time in range (TIR) (65.1% ± 15.5% vs. 58.0% ± 19.0%; < 0.001) and coefficient of variation (CV) (65.1% ± 15.5% vs. 58.0% ± 19.0%; < 0.001). There was no significant difference in time below range (TBR). The glycemic control deteriorated during the Chinese New Year public holiday in our study population regardless of age. Interestingly, in the CSII group, none of the metrics of glucose control significantly changed during the Chinese New Year public holiday.

Conclusions: These results suggested that less self-management may worsen glycemic control in the short term, indicating a need for more refined management algorithms during the Chinese New Year public holiday for T1DM patients.
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http://dx.doi.org/10.3389/fendo.2022.915482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273873PMC
June 2022

Targeting p53-MDM2 interaction by small-molecule inhibitors: learning from MDM2 inhibitors in clinical trials.

J Hematol Oncol 2022 07 13;15(1):91. Epub 2022 Jul 13.

The Affiliated Wuxi Mental Health Center of Jiangnan University, Wuxi Tongren International Rehabilitation Hospital, Wuxi, 214151, Jiangsu, China.

p53, encoded by the tumor suppressor gene TP53, is one of the most important tumor suppressor factors in vivo and can be negatively regulated by MDM2 through p53-MDM2 negative feedback loop. Abnormal p53 can be observed in almost all tumors, mainly including p53 mutation and functional inactivation. Blocking MDM2 to restore p53 function is a hotspot in the development of anticancer candidates. Till now, nine MDM2 inhibitors with different structural types have entered clinical trials. However, no MDM2 inhibitor has been approved for clinical application. This review focused on the discovery, structural modification, preclinical and clinical research of the above compounds from the perspective of medicinal chemistry. Based on this, the possible defects in MDM2 inhibitors in clinical development were analyzed to suggest that the multitarget strategy or targeted degradation strategy based on MDM2 has the potential to reduce the dose-dependent hematological toxicity of MDM2 inhibitors and improve their anti-tumor activity, providing certain guidance for the development of agents targeting the p53-MDM2 interaction.
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http://dx.doi.org/10.1186/s13045-022-01314-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277894PMC
July 2022

Demographic shifts associated with implementation of evidence-based guidelines for ovarian conservation in patients with endometrioid endometrial cancer.

Int J Gynecol Cancer 2022 Jul 13. Epub 2022 Jul 13.

Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA

Objective: In 2018, evidence-based surgical guidelines were introduced to identify appropriate patients with low-grade endometrioid endometrial cancer for ovarian conservation. We sought to identify trends and demographic shifts associated with guideline implementation.

Methods: We identified women treated for endometrioid endometrial cancer at our institution from January 2010 to June 2021. Eligibility criteria included age ≤50 years, normal-appearing ovaries on preoperative imaging, no family history of hereditary breast and ovarian cancer syndrome or Lynch syndrome, and no hormone receptor-positive malignancy. Trends in ovarian conservation were examined with the Cochran-Armitage trend test or in a logistic regression model. Associations between ovarian conservation and clinicodemographic factors before and after guideline implementation were compared using Wilcoxon rank-sum and Fisher's exact tests.

Results: Of 420 women ≤50 years of age undergoing surgery for endometrioid endometrial cancer, 355 (85%) met the criteria for ovarian conservation-267 (75%) before and 88 (25%) after guideline implementation. Median patient age was 45 years (range 25-50); 62% were non-Hispanic White, 10% Hispanic White, 8% non-Hispanic Black, 0% Hispanic Black, and 20% Asian. Patients were significantly more likely to choose ovarian conservation after (48%) compared with before guideline implementation (21%) (p<0.001). Pre-guidelines, non-Hispanic White women were less likely to elect for ovarian conservation (12%) compared with non-Hispanic Black, Asian, or Hispanic White women (28%) (p=0.002). Similarly, older women were less likely to elect for ovarian conservation compared with younger women (p<0.001). There were no differences by obesity (p=0.68), marital status (p=0.86), or insurance (p=0.89). Post-guidelines, there were no differences in ovarian conservation between non-Hispanic White women (36%) and non-Hispanic Black, Asian, or Hispanic White women (50%) (p=0.56). Older women were still less likely to elect for ovarian conservationcompared with younger women (p<0.001).

Conclusions: After guideline implementation, ovarian conservation increased and uptake disparities across demographic groups decreased.
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http://dx.doi.org/10.1136/ijgc-2022-003661DOI Listing
July 2022

Impact of RNA degradation on next-generation sequencing transcriptome data.

Genomics 2022 Jul 8;114(4):110429. Epub 2022 Jul 8.

Department of Obstetrics and Gynecology, Kunshan Hospital of Traditional Chinese Medicine, Kunshan 215300, China. Electronic address:

RNA sequencing is an innovative technology to study transcriptomes in both biological and clinical research. However, clinical specimens from patients undergoing surgical operations have a major challenge due to sample degradation. This study replicated the process of RNA degradation by maintaining cells at room temperature to achieve none, slight, middle, and high levels of RNA degradation with decreasing RNA integrity numbers (RIN) of approximately 9.8, 6.7, 4.4, and 2.5, respectively. Next, the differential expression of mRNA and long non-coding RNA (lncRNA) was analyzed in the four degradation groups along with pathway enrichment analysis. The results showed that the similarity of lncRNAs exhibited significant differences even for a slight level of RNA degradation compared with the non-degraded RNA sample. Also, the RNA degradation process was found to be universal, global, and random; the differentially expressed genes increased with an increase in degradation but the pathway enrichment phenomenon was not significantly observed.
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http://dx.doi.org/10.1016/j.ygeno.2022.110429DOI Listing
July 2022

Optimizing Nitrogen and Seed Rate Combination for Improving Grain Yield and Nitrogen Uptake Efficiency in Winter Wheat.

Plants (Basel) 2022 Jun 30;11(13). Epub 2022 Jun 30.

National Technique Innovation Centre for Regional Wheat Production, Key Laboratory of Crop and Ecophysiology in Southern China, Nanjing Agricultural University, Ministry of Agriculture, Nanjing 210095, China.

Nitrogen (N) supply and seed rate (SR) are two essential factors that affect the accumulation and partitioning of N and dry matter (DM) and, therefore, grain yield (GY) and N use efficiency (NUE). The objective of this experiment was to optimize N application and SR to regulate wheat growth and increase both GY and NU. The results revealed that net photosynthetic rate (Pn), stomatal conductance (Gs), chlorophyll content, and activities of metabolic enzymes (NR and GS) significantly increased with increasing of N levels while decreasing SR. Plant tillers, GY, DM before anthesis, and N translocation, N agronomic efficiency (NA), N recovery efficiency (NR), and N uptake efficiency (NUP) were highest in a combined treatment of N and SR. However, N levels beyond 235 kg ha significantly decreased NA, NR, and NUP. By increasing SR from 135 to 180 kg ha an increase of 12.9 % and 9.1% GY and NUPE, respectively, was observed. Based on this result, we estimate that 1 kg N ha might be replaced by an increase of approximately 0.6 kg ha SR. Our study suggested that using a combination of N and SR (N + SR) could attain maximum GY and improve NU parameters.
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http://dx.doi.org/10.3390/plants11131745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9269081PMC
June 2022

Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants.

Orphanet J Rare Dis 2022 07 8;17(1):253. Epub 2022 Jul 8.

Changzhou Maternal and Child Health Care Hospital, No.16 Ding Xiang Road, Changzhou, 213003, Jiangsu, China.

Objective: This study explores and discusses the possible factors affecting the positive predictive value (PPV) of non-invasive prenatal screening (NIPS) for the detection of fetal copy number variants (CNVs) in pregnant women.

Methods: NIPS was performed for 50,972 pregnant women and 212 cases were suspected as fetal CNVs. Post additional genetic counseling for these women, 96 underwent invasive prenatal diagnosis (amniocentesis), following which they received chromosomal microarray analysis (CMA). We analyzed the PPV of NIPS for the detection of fetal CNVs and the possible interference factors that could affect the PPV.

Results: Among the 96 pregnant women that received prenatal diagnosis by CMA, 37 cases were confirmed to be true positive for fetal CNVs with a PPV of 38.5%. There was no significant difference between the women with different NIPS indications. Five cases were reported as the false positive and false negative of fetal CNVs and the differences were mainly reflected in the inconsistency of chromosome fragments. Depending on the sizes of the CNVs, the PPVs were 48.7% for CNVs < 3 Mb, 41.4% for CNVs falling within 3 ~ 5 Mb, 42.9% for the CNVs falling within 5 ~ 10 Mb, and 14.3% for CNVs > 10 Mb. Based on the chromosomal locations of CNVs, the PPV(4.8%) of the chromosomes of group C(including chromosomes 6 ~ 12), was lower than that of the other groups (41.2% ~ 66.7%) (p = 0.021). However, there were no significant differences in the CNV characteristics, fetal fractions, unique reads, and the Z-scores between these groups.

Conclusion: NIPS with a low-coverage sequencing depth has a certain effect on detection of fetal CNVs with the PPV of 38.5%. Chromosomal locations of CNVs may be the main factor that influences its effect. This study can contribute to an increased accuracy in genetic counseling and in predicting NIPS results that are positive for fetal CNVs.
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http://dx.doi.org/10.1186/s13023-022-02406-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264683PMC
July 2022

Increased neutrophil count Is associated with the development of chronic kidney disease in patients with diabetes.

J Diabetes 2022 Jul 4;14(7):442-454. Epub 2022 Jul 4.

Department of Endocrinology, Shanghai Fifth People's Hospital, Fudan University, Shanghai, China.

Background: This study aims to investigate the potential association of peripheral inflammatory blood cell parameters with the incidence and progression of chronic kidney disease (CKD) in patients with diabetes.

Methods: The cross-sectional study included 1192 subjects with diabetes derived from one center. The cohort study included 2060 subjects with diabetes derived from another two centers followed up for 4 years. Logistic regression and Cox proportional hazards models were used to evaluate the association of peripheral inflammatory blood cell with CKD.

Results: In the cross-sectional study, neutrophil count performed best as an independent risk factor for CKD (odds ratio 2.556 [95% confidence interval 1.111, 5.879]) even after 1:1 case-control matching for age, gender, history of high blood pressure and duration of diabetes. Spline regression revealed a significant linear association of CKD incidence with continuous neutrophil count in excess of 3.6 × 10 /L. In the cohort study, subjects were grouped based on tertile of neutrophil count and neutrophil-to-lymphocyte ratio. Cox regression analysis results showed that only neutrophil count was independently associated with CKD progression (the highest group vs. the lowest group, hazard ratio 2.293 [95% confidence interval 1.260, 4.171]) after fully adjusting for potential confounders. The cumulative incidence of CKD progression in patients with diabetes gradually increased with increasing neutrophil count (53 (7.7%) subjects in the lowest group vs. 60 (8.2%) in the middle group vs. 78 (12.2%) in the highest group).

Conclusions: This study suggested that neutrophil count is an independent risk factor for progression of CKD in patients with diabetes.
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http://dx.doi.org/10.1111/1753-0407.13292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310049PMC
July 2022

Will Proton Pump Inhibitors Increase the Risk of Diabetes Mellitus? A Systemic Review and Meta-Analysis.

Turk J Gastroenterol 2022 06;33(6):497-504

Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.

Background: Proton pump inhibitor use was reported to potentially provide benefits to prevent diabetes mellitus. This study aims to investigate the association between proton pump inhibitor use and the risk of developing diabetes mellitus.

Methods: This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42021238481). A systematic literature search was conducted to identify eligible studies up to February 2021. Quality assessment was conducted according to Jadad Scoring Scale and Newcastle-Ottawa Scale. The heterogeneity among studies was tested and estimated by Q test and I2. Pooled hazard ratio with 95% CI was calculated using the random-effects or fixed-effects model depending on the heterogeneity. Subgroup analyses, sensitivity analysis, and publication bias assessment were also performed.

Results: Eight studies including 850 019 participants were included. We found that proton pump inhibitor use was associated with a statistically non-significant increased risk of diabetes mellitus (pooled hazard ratio was 1.06, 95% CI = 0.89-1.28, P = .50). In subgroup analysis, 5 studies conducted in North America confirmed the overall result; however, one study conducted in Europe demonstrated a statistically significant increased risk, while one study in Asia revealed a statistically significant decreased risk.

Conclusion: Proton pump inhibitor use is not associated with either increased or decreased risk of diabetes mellitus. However, more well- designed studies focusing on proton pump inhibitor use and the risk of diabetes mellitus, especially among populations with different backgrounds, are still needed.
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http://dx.doi.org/10.5152/tjg.2022.21480DOI Listing
June 2022

Recent advances in C-F bond activation of trifluoromethylated carbonyl compounds and derivatives.

Org Biomol Chem 2022 07 13;20(27):5365-5376. Epub 2022 Jul 13.

College of Jiyang, Zhejiang A&F University, Zhuji 311800, China.

The selective activation of inert C-F bonds is one of the most challenging topics in modern organic chemistry. Trifluoromethylketones represent a class of versatile building blocks that are inexpensive and readily available polyfluorinated starting materials. The functionalization of C-F bond in trifluoromethylketones has recently been achieved using difluoroenolates, difluorinated acyl anions or radicals for the synthesis of difluoromethylene compounds. This strategy has also been successfully applied to their derivatives, such as trifluoromethylated esters, amides, diazo compounds and -sulfonylhydrazones, which would be of significant value for the synthesis of partially fluorinated intermediates. In this review, we mainly focus on the recent advances, challenges and perspectives of trifluoromethylated carbonyl compounds and their derivatives C-F bond activation, along with mechanistic insight.
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http://dx.doi.org/10.1039/d2ob00795aDOI Listing
July 2022

Long-term outcomes of patients with recurrent ovarian cancer treated with a polyvalent vaccine with bevacizumab combination.

Cancer Immunol Immunother 2022 Jul 2. Epub 2022 Jul 2.

Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.

Background: To characterize the safety, immunogenicity, and outcomes of patients with high-grade serous ovarian cancer (HGSOC) in second or greater remission treated with a polyvalent antigen-KLH plus OPT-821 vaccine construct and bevacizumab.

Methods: Patients with recurrent HGSOC were treated with the vaccine plus bevacizumab at our institution from 01/05/2011 to 03/20/2012. Follow-up continued until 03/2021. Blood/urine samples were collected. "Responders" had an immunogenic response to ≥ 3 antigens; "non-responders" to ≤ 2 antigens.

Results: Twenty-one patients were treated on study. One developed a dose-limiting toxicity (grade 4 fever). Two (10%) experienced bevacizumab-related grade 3 hypertension. Thirteen (68%) and 16 (84%) of 19 responded to ≥ 3 and ≥ 2 antigens, respectively (Globo-H, GM2, TF cluster Tn, MUC-1). Four of 21 patients were alive > 5 years post-treatment. Responders and non-responders had a median PFS of 4.9 months (95% CI: 2.8-8.1) and 5.0 months (95% CI: 0.7-cannot estimate), respectively; median OS was 30.7 months (95% CI: 16.9-52.0) and 34.2 months (95% CI: 12.8-cannot estimate), respectively. On two-timepoint analysis (baseline, week 17), increased IL-8 exhibited improved PFS (HR as 10-unit increase, 0.43; p = 0.04); increased PDGF exhibited worse OS (HR as 10-unit increase, 1.01; p = 0.02).

Conclusions: This is the longest follow-up of vaccine administration with bevacizumab in patients with ovarian cancer. The vaccine was well tolerated with bevacizumab. Response was not associated with improved survival. On two-timepoint analysis, increased IL-8 was associated with significant improvement in PFS; increased PDGF with significantly worse OS. For all timepoint measurements, cytokine levels were not significantly associated with survival.

Trial Registration: NCT01223235.
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http://dx.doi.org/10.1007/s00262-022-03225-1DOI Listing
July 2022

Amisulpride steady-state plasma concentration and adverse reactions in patients with schizophrenia: a study based on therapeutic drug monitoring data.

Int Clin Psychopharmacol 2022 Jun 27. Epub 2022 Jun 27.

The Affiliated Wuxi Mental Health Center of JiangNan University, Wuxi Tongren Rehabilitation Hospital, Wuxi, Jiangsu, China.

The aim of the study was to evaluate the reference range of amisulpride for Chinese patients with schizophrenia and to assess its possible influencing factors based on therapeutic drug monitoring information. The relative adverse reactions of patients induced by amisulpride were also systematically investigated. A total of 425 patients with schizophrenia were assessed, including Positive and Negative Syndrome Scales, Treatment Emergent Symptom Scale, blood routine examination, hepatorenal function, lipids, hormones, as well as myocardial enzymes at baseline, and following treatment with amisulpride for 8 weeks. The steady-state plasma concentration of amisulpride was assayed using two-dimensional liquid chromatography. At the same dose, the amisulpride plasma concentration of patients combined with clozapine was higher than that without clozapine. The therapeutic reference range of amisulpride can be defined as 230.3-527.1 ng/ml for Chinese patients with schizophrenia. The potential side effects appear to be associated with significantly increased levels of LDH, CK, creatine kinase isoenzyme (CK-MB), TC and decreased level of E2, relative to the amisulpride plasma concentration. These findings could provide individualized medication and reduce the adverse effects of amisulpride for Chinese patients with schizophrenia.
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http://dx.doi.org/10.1097/YIC.0000000000000420DOI Listing
June 2022

Optimization of the vancomycin administration regimen by clinical pharmacists based on a population pharmacokinetics model: a prospective interventional study.

J Chemother 2022 Jun 30:1-13. Epub 2022 Jun 30.

Department of Pharmacy, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Suzhou, Jiangsu, China.

In vancomycin treatment, the rates of correct blood sampling and initial trough concentrations within the target range are very low. Studies of interventions by clinical pharmacists based on population pharmacokinetics (PPK) models are limited. This study aimed to evaluate the intervention effect of clinical pharmacist-mediated optimization of the vancomycin administration regimen based on a PPK model. Retrospectively enrolled patients constituted the control group, and prospectively enrolled patients constituted the intervention group. The vancomycin administration regimen, trough concentration, pharmacokinetic parameters, and clinical outcomes of the two groups were compared. The control and intervention groups comprised 236 and 138 patients, respectively. Compared with those in the control group, the therapeutic drug monitoring (TDM) and correct TDM sampling time rates in the intervention group were significantly higher (76.92% vs. 43.59%; 63.9% vs. 39.0%, both  0.001). The rates of an initial trough concentration within 10-20 mg/L and an adjusted regimen were also significantly higher in the intervention group (55.80% vs. 30.51%, 71.95% vs. 39.18%, both  0.001). The rate of an area under the curve (AUC) within 400-650 mg·h/L was higher in the intervention group than in the control group (52.7% vs. 36.6%,  0.001). The eradication rates of Gram-positive bacteria were 91.4% in the intervention group and 81.3% in the control group ( = 0.049). Eight patients developed acute kidney injury (AKI) in the control group; however, no AKI occurred in the intervention group ( = 0.029). Intervention by clinical pharmacists can increase the rate of correct sampling time. Using the PPK model combined with Bayesian estimation, clinical pharmacists can greatly increase the trough concentration and AUCs within the target range, especially for adjusted regimens. Higher PK/PD target rates resulted in better Gram-positive bacterial eradication and reduced renal toxicity of vancomycin.
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http://dx.doi.org/10.1080/1120009X.2022.2086305DOI Listing
June 2022
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