Publications by authors named "Jun Liang"

839 Publications

Social support status and associated factors among people living with HIV/AIDS in Kunming city, China.

BMC Public Health 2021 Jul 17;21(1):1413. Epub 2021 Jul 17.

Department of AIDS and Sexually Transmitted Disease Control and Prevention, Kunming Center for Disease Control and Prevention, 1.4# Zi Yun Road, Dian Chi Lv You Du Jia District, Kunming, Yunnan Province, China.

Background: People living with HIV/AIDS not only require effective treatment for the alleviation of physical discomfort but also require social support to help them address difficulties in life and relieve their psychological anxiety and uneasiness. The social support network is of tremendous importance in helping people living with HIV/AIDS maintain good physical and mental health. This study aims to analyse the social support status among people living with HIV/AIDS in Kunming and explore associated factors.

Method: The Social Support Rating Scale (SSRS) was used, and a questionnaire survey was conducted using convenience sampling to select people living with HIV/AIDS from 14 counties of Kunming. It collected information on general demographic information and social support status. Univariate and multivariate linear regression models were used to explore the associated factors.

Results: A total of 990 valid questionnaires were completed. Data from all participants were analysed. Univariate analysis suggested that the factors associated with social support may include marital status, monthly income, and antiretroviral therapy. On the other hand, factors including monthly income and antiretroviral therapy accounted for the social support total score in the multivariate analysis.

Conclusion: Social support among people living with HIV/AIDS in Kunming was generally low. This study identified a number of factors associated with social support among people living with HIV/AIDS. Based on our findings, appropriate interventions should be introduced to provide social support for those living with HIV/AIDS.
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http://dx.doi.org/10.1186/s12889-021-11253-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285876PMC
July 2021

Image-guided, intensity-modulated radiotherapy for the treatment of diffuse-type tenosynovial giant cell tumor of the knee: Case report and review of the literature.

Medicine (Baltimore) 2021 Jul;100(28):e26659

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.

Rationale: Tenosynovial giant cell tumor (TGCT) is a neoplastic, inflammatory disease with a benign but aggressive course that often presents as localized (TGCT-L) and diffuse (TGCT-D) forms based on the growth pattern and clinical behavior. For TGCT-L, simple excision of the diseased synovial tissue is the preferred treatment option, while for TGCT-D, adequate synovectomy is usually tricky but is essential. However, approximately 44% of TGCT-D cases will relapse after surgery alone. Thus, the optimal treatment strategy in patients with TGCT-D is evolving, and standalone surgical resection can no longer be regarded as the only treatment. The previous studies have shown that postoperative adjuvant radiotherapy can reduce recurrence in TGCT, especially in patients with incomplete synovectomy.

Patient Concerns: In the first case, a 54-year-old male presented with recurrent pain and swelling of the right knee with a protracted disease course (≥10 years). The other patient is a 64-year-old male who developed swelling, pain, abnormal bending, and limited movement of the left knee without obvious inducement.

Diagnoses: Clinical and imaging examinations can provide a definitive diagnosis, and pathology is the gold standard. TGCT-D was confirmed by postoperative pathology. After the operation, the patients underwent an MRI re-examination and showed that the lesions of the knee were not completely resected.

Interventions: Arthroscopic synovectomy was performed on the patients, and postoperative pathology was confirmed as TGCT-D. Because of incomplete synovectomy, the 2 cases received image-guided, intensity-modulated radiotherapy (IG-IMRT) after the operation.

Outcomes: The follow-up time was 1 year, no evidence of disease progression was found in MRI. No obvious adverse effects associated with radiotherapy were detected during the follow-up period.

Lessons: These cases and reviews illustrate the necessity of radiotherapy for TGCT-D and that IG-IMRT is a safe and effective method for treating TGCT-D of the knee.
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http://dx.doi.org/10.1097/MD.0000000000026659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284748PMC
July 2021

GDC-9545 (Giredestrant): A Potent and Orally Bioavailable Selective Estrogen Receptor Antagonist and Degrader with an Exceptional Preclinical Profile for ER+ Breast Cancer.

J Med Chem 2021 Jul 12. Epub 2021 Jul 12.

Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, United States.

Breast cancer remains a leading cause of cancer death in women, representing a significant unmet medical need. Here, we disclose our discovery efforts culminating in a clinical candidate, (GDC-9545 or giredestrant). is an efficient and potent selective estrogen receptor degrader (SERD) and a full antagonist, which translates into better antiproliferation activity than known SERDs (, , , and ) across multiple cell lines. Fine-tuning the physiochemical properties enabled once daily oral dosing of in preclinical species and humans. exhibits low drug-drug interaction liability and demonstrates excellent and safety profiles. At low doses, induces tumor regressions either as a single agent or in combination with a CDK4/6 inhibitor in an ESR1 mutant PDX or a wild-type ERα tumor model. Currently, is being evaluated in Phase III clinical trials.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00847DOI Listing
July 2021

Definitive Simultaneous Integrated Boost Versus Conventional-Fractionated Intensity Modulated Radiotherapy for Patients With Advanced Esophageal Squamous Cell Carcinoma: A Propensity Score-Matched Analysis.

Front Oncol 2021 21;11:618776. Epub 2021 Jun 21.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The aim of this study was to compare the effects of simultaneous integrated boost-intensity modulated radiotherapy (SIB-IMRT) and conventional fractionated-IMRT (CF-IMRT) for patients with esophageal squamous cell carcinoma (ESCC).

Methods: The data of 1173 patients treated with either CF-IMRT or SIB-IMRT for a curative intent from 2005 to 2016 were retrospectively reviewed. Propensity score matching (PSM) was used to create a well-balanced cohort of 687 patients at 1:2 ratio (237 patients in SIB-IMRT group and 450 patients in CF-IMRT group). Overall survival (OS), progression-free survival (PFS), recurrence pattern, and toxicity profiles were evaluated and compared between the two groups after PSM.

Results: After a median follow-up time of 42.3 months (range, 3.0-153.2 months) for surviving patients, survival results were comparable in the two groups. After PSM, the 1-year, 2-year and 4-year OS rates in the SIB-IMRT and CF-IMRT groups were 70.0% 66.4%, 41.9% 41.7% and 30.2% 27.6%, respectively ( = 0.87). The 1-year, 2-year and 4-year PFS rates were 48.4% 49.1%, 31.2% 29.4%, and 26.1% 17.9%, respectively ( = 0.64). Locoregional recurrence ( = 0.32) and distant metastasis ( = 0.54) rates were also comparable between two groups. The toxicity profile was similar in the two groups. Multivariate analyses in the matched samples showed that female, concurrent chemotherapy and earlier clinical stage were independently associated with longer OS and PFS.

Conclusions: SIB-IMRT appears to be equivalent to CF-IMRT in treatment efficacy and safety, and could become an alternative option for definitive radiotherapy of ESCC.
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http://dx.doi.org/10.3389/fonc.2021.618776DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256744PMC
June 2021

Low-polymerization compositional fingerprinting for characterization of Schisandra polysaccharides by hydrophilic interaction liquid chromatography-electrospray mass spectrometry.

Int J Biol Macromol 2021 Jul 3;185:983-996. Epub 2021 Jul 3.

Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin 150040, PR China. Electronic address:

A hydrophilic interaction liquid chromatography-negative electrospray-mass spectrometry (HILIC-ESI-MS) coupled with microwave assisted mild acid (MAMA) depolymerization is proposed here for unusual discrimination and characterization of plant polysaccharides: a case study of fruit polysaccharides in Schisandra chinensis and S. sphenanthera (SCP and SSP). The optimized MAMA hydrolysis procedure was proposed for sample preparations of low-polymerization saccharides (M < 5000 Da) released in SCP and SSP. In addition, HILIC-MS/MS was employed for elucidation of isomeric glycosidic linkages in terms of O labelling. The MAMA hydrolysates showed that the amount of neutral →(Hex)→ moiety is confirmed to be more bigger than that of acidic →(HexA) → in SCP, whereas the amount of acidic →(HexA)→ moiety seems to be more bigger than that of neutral →(Hex)→ in SSP. The resulting low-polymerization compositional fingerprinting (LCF) showed the performance on rapid visualization of SCP and SSP by HILIC-MIM-MS. Principal components analysis (PCA) and hierarchical cluster analysis (HCA) further unveils several key Q-markers (e.g., m/z 503, 369, 665, 827, 989, 1151 and 735) for rapid discrimination of SCP and SSP. This practical study showed that the LCF with PCA and HCA could effectively reflect structural differences and could rapidly achieve discrimination of SCP and SSP.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.206DOI Listing
July 2021

Persulfate Oxidation of Sulfamethoxazole by Magnetic Iron-Char Composites via Nonradical Pathways: Fe(IV) Versus Surface-Mediated Electron Transfer.

Environ Sci Technol 2021 Jul 2;55(14):10077-10086. Epub 2021 Jul 2.

School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.

Despite the vital roles of reactive radical species in the coupled iron-carbon composite/persulfate (PS) system for eliminating pollutants, nonradical contributions are typically overlooked. Herein, we developed two efficient magnetic iron-char composites via low-temperature (BCFe-400) and high-temperature (BCFe-700) pyrolysis. The two composites activated PS through nonradical pathways for sulfamethoxazole (SMX) degradation. In the BCFe-400/PS system, high-valent iron Fe(IV) was the dominant active species for the oxidation, evidenced by methyl phenyl sulfoxide-based probe tests, Mössbauer spectroscopy, and in situ Raman analyses with kinetic evaluation. In the BCFe-700/PS system, surface-mediated electron transfer dominated the oxidation, and the nonradical regime was probed by the electrochemical test and in situ Raman analysis. Furthermore, the BCFe-400/PS system maintained high efficiency in continuous degradation of SMX due to the feasible Fegeneration toward Fe(IV) formation. In the BCFe-700/PS system, the stability of the system was limited due to the hindered electron transfer between the surface reactive complex (i.e., BCFe-700-PS*) and SMX, and thermal treatment would help recover the reactivity. Both BCFe-400/PS and BCFe-700/PS systems exhibited high performances for SMX removal in the presence of chloride and humic acid and in real water matrixes (e.g., seawater, piggery wastewater, and landfill leachate), exhibiting the great merits of the nonradical system. Overall, the study would provide new insights into PS activation by iron-loaded catalysts to efficiently degrade pollutants via nonradical pathways.
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http://dx.doi.org/10.1021/acs.est.1c01618DOI Listing
July 2021

Upregulation of GBP1 in thyroid primordium is required for developmental thyroid morphogenesis.

Genet Med 2021 Jun 30. Epub 2021 Jun 30.

The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics & Endocrinology, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Purpose: Congenital hypothyroidism (CH) is a common congenital endocrine disorder in humans. CH-related diseases such as athyreosis, thyroid ectopy, and hypoplasia are primarily caused by dysgenic thyroid development. However, the underlying molecular mechanisms remain unknown.

Methods: To identify novel CH candidate genes, 192 CH patients were enrolled, and target sequencing of 21 known CH-related genes was performed. The remaining 98 CH patients carrying no known genes were subjected to exome sequencing (ES). The functions of the identified variants were confirmed using thyroid epithelial cells in vitro and in zebrafish model organisms in vivo.

Results: Four pathogenic GBP1 variations from three patients were identified. In zebrafish embryos, gbp1 knockdown caused defective thyroid primordium morphogenesis and hypothyroidism. The thyroid cells were stuck together and failed to dissociate from each other to form individual follicles in gbp1-deficient embryos. Furthermore, defects were restored with wild-type human GBP1 (hGBP1) messenger RNA (mRNA) except for mutated hGBP1 (p.H150Y, p.L187P) overexpression. GBP1 promoted β-catenin translocation into the cytosol and suppressed the formation of cellular adhesion complexes. Suppression of cell-cell adhesion restored the thyroid primordium growth defect observed in gbp1-deficient zebrafish embryos.

Conclusion: This study provides further understanding regarding thyroid development and shows that defective cellular remodeling could cause congenital hypothyroidism.
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http://dx.doi.org/10.1038/s41436-021-01237-3DOI Listing
June 2021

Clinical Audit on Chronic Obstructive Pulmonary Disease (COPD) Management in Primary Care: A Quality Improvement Project from Hong Kong.

Int J Chron Obstruct Pulmon Dis 2021 23;16:1901-1911. Epub 2021 Jun 23.

Department of Family Medicine and Primary Health Care, Kowloon East Cluster, Hospital Authority, Hong Kong.

Objective: To enhance the quality of COPD management in primary care via a two-phase clinical audit in Hong Kong.

Methods: COPD patients aged 40 or above and had attended any of the 73 public primary care clinics under the Hospital Authority of Hong Kong (HAHK) for follow up (FU) during the audit period were included. Performance of six evidence-based audit criteria on COPD care was reviewed in phase 1 from 1st April 2017 to 31st March 2018. Service gaps were identified and a series of quality improvement strategies were executed in the one-year implementation phase. The outcome of the service enhancement was assessed in phase 2 from 1st April 2019 to 31st March 2020. Student's -test and the chi-square test were used to examine the statistically significant differences between the two phases.

Results: Totally 10,385 COPD cases were identified in phase 1, the majority were male (87.7%) and the mean age was 75.3±9.9 years. Among the 3102 active smokers, 1788 (57.6%) were referred to receive the smoking cessation counselling and 1578 (50.9%) actually attended it. A total of 4866 cases (46.9%) received seasonal influenza vaccine (SIV) and 4227 cases (40.7%) received pneumococcal vaccine (PCV). A total of 1983 patients (19.1%) had spirometry test done before and 1327 patients (12.8%) had history of hospital admission due to acute exacerbation of COPD (AECOPD). After the proactive implementation phase, performance on all criteria was significantly improved in phase 2, with a marked increase in the SIV and PCV uptake rate and spirometry performance rate. Most importantly, a significant reduction in AECOPD rate leading to hospital admission had been achieved (9.6%, <0.00001).

Conclusion: COPD care at all public primary care clinics of HAHK had been significantly improved for all audit criteria via the systematic team approach, which, in turn, reduced the hospital admission rate and helped relieve the burden of the health care system.
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http://dx.doi.org/10.2147/COPD.S304527DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236252PMC
June 2021

[Blood-based Biomarkers in the Immune Checkpoint Inhibitor Treatment in 
Non-small Cell Lung Cancer].

Zhongguo Fei Ai Za Zhi 2021 Jul 30;24(7):503-512. Epub 2021 Jun 30.

Department of Radiation Oncology, Peking University International Hospital, Beijing 102206, China.

Immune checkpoint inhibitors (ICI) have transformed the treatment landscape of advanced non-small cell lung cancer (NSCLC). Biomarkers are essential for guiding precision immunotherapy. Tissue-based programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB) are currently widely used biomarkers for selecting patients for immunotherapy. However, tissue specimens are often difficult to reach and couldn't overcome spatial and temporal heterogeneity. Blood biomarkers offer an alternative non-invasive solution that could provide a complete insight on patient's immune status and tumor as well, and show their potential in predicting the outcome as well as in monitoring response to immunotherapy. In this article, we summarize current knowledge on blood biomarkers in NSCLC patients treated with ICI, and we hope to provide more references for development of novel biomarkers.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.102.24DOI Listing
July 2021

Effect of Postoperative Radiotherapy for Patients With pIIIA-N2 Non-Small Cell Lung Cancer After Complete Resection and Adjuvant Chemotherapy: The Phase 3 PORT-C Randomized Clinical Trial.

JAMA Oncol 2021 Jun 24. Epub 2021 Jun 24.

Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Importance: The role of postoperative radiotherapy (PORT) has not been well defined in resected pIIIA-N2 non-small cell lung cancer (NSCLC).

Objective: To evaluate the effect of PORT using modern techniques on survival and safety in patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy.

Design, Setting, And Participants: The PORT-C randomized clinical trial was conducted in 394 patients with pIIIA-N2 NSCLC treated with complete resection and 4 cycles of platinum-based chemotherapy between January 2009 and December 2017. Data were analyzed between March 2019 and December 2020.

Interventions: Patients were randomized equally into the PORT arm (n = 202) or the observation arm (n = 192). The total dose of PORT was 50 Gy.

Main Outcomes And Measures: The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival, and toxic effects.

Results: In total, 394 patients were enrolled and 364 were eligible, with a median (range) age of 55 (25-70) years. There were 202 (55.5%) male and 162 (44.5%) female patients. The median follow-up was 46.0 (95% CI, 41.9-51.4) months, and 230 DFS events were reported. There were 184 patients in the PORT arm and 180 patients in the observation arm. The 3-year DFS rates were 40.5% with PORT vs 32.7% with observation (median, 22.1 vs 18.6 months), and the difference in DFS was not statistically significant without adjustment (hazard ratio [HR], 0.84; 95% CI, 0.65-1.09; P = .20), though it was significant with preplanned yet exploratory analysis (stratified analysis by the number of detected lymph nodes and positive lymph nodes, HR, 0.75; log-rank P = .04). The 3-year OS rates were 78.3% vs 82.8% (HR, 1.02; P = .93), and LRFS was 66.5% vs 59.7% (HR, 0.71; 95% CI, 0.51-0.97; P = .03), respectively. For 310 per-protocol patients (140 with PORT and 170 with observation), PORT significantly improved DFS (42.8% vs 30.6%; HR, 0.75; 95% CI, 0.57-1.00; P = .05) but not OS (HR, 0.83; 95% CI, 0.53-1.30; P = .41). The 3-year local recurrence only rates were 9.5% and 18.3% in the 2 arms, respectively (Fine-Gray HR, 0.55; Gray test P = .04). No radiotherapy-related grade 4 or 5 adverse event was observed.

Conclusions And Relevance: In this phase 3 randomized clinical trial of patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy, PORT did not improve DFS. Further studies exploring patients who might best benefit from PORT are needed.

Trial Registration: ClinicalTrials.gov Identifier: NCT00880971.
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http://dx.doi.org/10.1001/jamaoncol.2021.1910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227450PMC
June 2021

Capture and Separation of SO Traces in Metal-Organic Frameworks via Pre-Synthetic Pore Environment Tailoring by Methyl Groups.

Angew Chem Int Ed Engl 2021 Jun 15. Epub 2021 Jun 15.

Hoffmann Institute of Advanced Materials, Shenzhen Polytechnic, 7098 Liuxian Blvd, Nanshan District, Shenzhen, 518055, China.

Herein, we report a pre-synthetic pore environment design strategy to achieve stable methyl-functionalized metal-organic frameworks (MOFs) for preferential SO binding and thus enhanced low (partial) pressure SO adsorption and SO /CO separation. The enhanced sorption performance is for the first time attributed to an optimal pore size by increasing methyl group densities at the benzenedicarboxylate linker in [Ni (BDC-X) DABCO] (BDC-X=mono-, di-, and tetramethyl-1,4-benzenedicarboxylate/terephthalate; DABCO=1,4-diazabicyclo[2,2,2]octane). Monte Carlo simulations and first-principles density functional theory (DFT) calculations demonstrate the key role of methyl groups within the pore surface on the preferential SO affinity over the parent MOF. The SO separation potential by methyl-functionalized MOFs has been validated by gas sorption isotherms, ideal adsorbed solution theory calculations, simulated and experimental breakthrough curves, and DFT calculations.
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http://dx.doi.org/10.1002/anie.202105229DOI Listing
June 2021

Zirconium and Aluminum MOFs for Low-Pressure SO Adsorption and Potential Separation: Elucidating the Effect of Small Pores and NH Groups.

ACS Appl Mater Interfaces 2021 Jun 11;13(24):29137-29149. Epub 2021 Jun 11.

Institut für Anorganische Chemie und Strukturchemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, 40225 Düsseldorf, Germany.

Finding new adsorbents for the desulfurization of flue gases is a challenging task but is of current interest, as even low SO emissions impair the environment and health. Four Zr- and eight Al-MOFs (Zr-Fum, DUT-67(Zr), NU-1000, MOF-808, Al-Fum, MIL-53(Al), NH-MIL-53(Al), MIL-53(tdc)(Al), CAU-10-H, MIL-96(Al), MIL-100(Al), NH-MIL-101(Al)) were examined toward their SO sorption capability. Pore sizes in the range of about 4-8 Å are optimal for SO uptake in the low-pressure range (up to 0.1 bar). Pore widths that are only slightly larger than the kinetic diameter of 4.1 Å of the SO molecules allow for multi-side-dispersive interactions, which translate into high affinity at low pressure. Frameworks NH-MIL-53(Al) and NH-MIL-101(Al) with an NH-group at the linker tend to show enhanced SO affinity. Moreover, from single-gas adsorption isotherms, ideal adsorbed solution theory (IAST) selectivities toward binary SO/CO gas mixtures were determined with selectivity values between 35 and 53 at a molar fraction of 0.01 SO (10.000 ppm) and 1 bar for the frameworks Zr-Fum, MOF-808, NH-MIL-53(Al), and Al-Fum. Stability tests with exposure to dry SO during ≤10 h and humid SO during 5 h showed full retention of crystallinity and porosity for Zr-Fum and DUT-67(Zr). However, NU-1000, MOF-808, Al-Fum, MIL-53(tdc), CAU-10-H, and MIL-100(Al) exhibited ≥50-90% retained Brunauer-Emmett-Teller (BET)-surface area and pore volume; while NH-MIL-100(Al) and MIL-96(Al) demonstrated a major loss of porosity under dry SO and MIL-53(Al) and NH-MIL-53(Al) under humid SO. SO binding sites were revealed by density functional theory (DFT) simulation calculations with adsorption energies of -40 to -50 kJ·mol for Zr-Fum and Al-Fum and even above -50 kJ·mol for NH-MIL-53(Al), in agreement with the isosteric heat of adsorption near zero coverage (Δ). The predominant, highest binding energy noncovalent binding modes in both Zr-Fum and Al-Fum feature μ-OH···OSO hydrogen bonding interactions. The small pores of Al-Fum allow the interaction of two μ-OH bridges from opposite pore walls with the same SO molecule via OH···OSO···HO hydrogen bonds. For NH-MIL-53(Al), the DFT high-energy binding sites involve NH···OS together with the also present Al-μ-OH···OS hydrogen bonding interactions and C-π···SO, N···SO interactions.
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http://dx.doi.org/10.1021/acsami.1c06003DOI Listing
June 2021

Association of lipoproteins and thyroid hormones with cognitive dysfunction in patients with systemic lupus erythematosus.

BMC Rheumatol 2021 Jun 9;5(1):18. Epub 2021 Jun 9.

Department of Rheumatology and Immunology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, PR China.

Background: Neuropsychiatric manifestations occur in up to 75% of adult systemic lupus erythematosus (SLE) patients and are one of the major causes of death in SLE patients. Cognitive dysfunction is a typical clinical feature of neuropsychiatric SLE (NPSLE), which seriously affects the quality of life of patients. Dyslipidaemia and thyroid symptoms, which are prevalent in SLE patients, have both been related to neuropsychiatric disturbances, including significant psychiatric and cognitive disturbances. This study aimed to investigate whether cognitive dysfunction in patients with SLE was related to the expression of serum thyroid hormone and lipoprotein levels.

Methods: A total of 121 patients with SLE and 65 healthy controls (HCs) at Nanjing Drum Tower Hospital completed a cognitive function test, and 81 SLE patients were divided into a high-cognition (n = 33) group and a low-cognition group (n = 48). The clinical and laboratory characteristics of the patients were compared; moreover, correlations between serum HDL-C, LDL-C, F-T3 and F-T4 levels and cognitive function were analysed. Serum levels of APOE, APOA1, IGF-1, and IGFBP7 in 81 patients were detected by ELISA, and the correlation between these four proteins and cognition was analysed separately.

Results: The patients with SLE with abnormal cognitive function were less educated than the HCs. For low-cognition patients, the levels of albumin, F-T3 (P <  0.05) and F-T4 decreased, while D-dimer, anti-dsDNA antibody, and IgM levels increased. Serum F-T3 and F-T4 levels positively correlated with cognition. Furthermore, serum protein levels of APOE and APOA1 showed no difference between the high- and low-cognition groups. However, the serum APOE levels were negatively correlated with line orientation scores, and APOA1 levels were positively correlated with coding scores.

Conclusions: Serum F-T3 and F-T4 levels were both positively correlated with four indexes of cognition (language was the exception), while serum APOE levels were negatively correlated with line orientation scores, APOA1 levels were positively correlated with coding scores, and IGFBP7 levels were negatively correlated with figure copy scores. These results demonstrated that F-T3 and F-T4 might be clinical biomarkers of cognitive dysfunction in SLE.
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http://dx.doi.org/10.1186/s41927-021-00190-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188676PMC
June 2021

Identification and comparison of triterpene saponins in Aralia elata leaves and buds by the energy-resolved MS technique on a liquid chromatography/quadrupole time-of-flight mass spectrometry.

J Pharm Biomed Anal 2021 Sep 27;203:114176. Epub 2021 May 27.

Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin, 150040, China. Electronic address:

In this study, we identify the triterpene saponins (TSs) extracted from the leaves and buds of Aralia elata (Miq.) Seems using ultra-performance liquid chromatography and positive ionization electrospray quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF). The energy-resolved MS (erMS) technique is applied in order to simultaneously collect the diverse precursors attributed to [M+H], [M + NH] and [M + Na] ions. A practical and effective erMS workflow is established to rapidly identify and compare the saponins in the analyzed samples. In total, 111 TSs of structure are estimated, including 44 new compounds that had not been identified previously in A. elata. Of the five aglycones detected in the samples, a sapogenin 3β, 16α, 23-trihydroxyoleana-11,13-dien-28-oic acid (A5) that is identified for the first time in A. elata leaves. Compared to the buds, the leaves number twice as many hederagenin-type (A2) compounds. Although the number of other aglycones does not vary significantly between the buds and the leaves, A5 compounds are exclusively detected in the latter. Moreover, the C-3 sugar chains of TSs in A. elata leaves are mainly neutral (e.g., Hex+Hex, Hex+Hex+Hex and Hex+Hex+Hex+Hex), whereas those of bud TS compounds are primarily acidic (e.g., Pen+HexA, Hex+HexA and Hex+Pen+HexA). Some of the identified TS compounds, e.g., 27, 28, 32, 46, 54, 57, 71 and 105 can be used as indices to evaluate the quality of the plant leaves and buds. Overall, this study is of great significance for the comparative study of triterpenoid saponins in the leaves and buds of Aralia elata.
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http://dx.doi.org/10.1016/j.jpba.2021.114176DOI Listing
September 2021

Fibrinogen-Albumin Ratio Index (FARI) as a Certain Prognostic Biomarker in Pretreated Patients with Immunotherapy.

Authors:
Ziwei Guo Jun Liang

Cancer Manag Res 2021 24;13:4169-4180. Epub 2021 May 24.

Medical Oncology, Peking University Cancer Hospital and Institute, Beijing, People's Republic of China.

Purpose: Immunotherapy has become the standard treatment for advanced tumors so that many biomarkers play parts in predicting prognosis and clinical outcome. Use of FARI is increasing, but there are no studies on its use prior to immunotherapy.

Patients And Methods: A retrospective study prior to immunotherapies in advanced carcinoma used FARI and other biomarkers as clinical parameters from which to analyse data from January 2014 to November 2020. Data were presented in GraphPad Prism 7 and X-Tile and analyzed using IBM SPSS.

Results: A total of 146 patients were enrolled in our study. FARI (with an optimal cut-off value of 11.1%) was divided into a high group, in connection with shorter OS mainly in patients with bone metastasis (120m vs 11.5m, 95% Cl: 12.17-23.83, SE: 2.974, =0.03), and a low group with a longer PFS (11.0m vs 5.0m, 95% Cl: 3.303-12.697, SE: 2.397, =0.03) in NSCLC but a shorter PFS (3.5m vs 5.5m, 95% Cl: 3.757-6.243, SE: 0.634, =0.01) in liver metastasis. FARI was not determined as an independent predictor of OS in patients undergoing medical therapies (>11.1% vs ≤11.1%, HR: 1.296, 95% Cl: 0.687-2.032, =0.314). ECOG (HR: 2.892, 95% Cl: 1.911-4.378, <0.001) can be an independent predictor for PFS and OS in advanced carcinoma.

Conclusion: Our findings highlight certain potential values for predicting prognosis but no outstanding biomarkers prior to immunotherapy according to FARI.
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http://dx.doi.org/10.2147/CMAR.S307272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163584PMC
May 2021

Effects of prenatal exposure to bisphenols on newborn leucocyte telomere length: a prospective birth cohort study in China.

Environ Sci Pollut Res Int 2021 May 24. Epub 2021 May 24.

Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, Nanning, 530021, Guangxi, China.

Telomere length (TL) at birth is related to diseases that may arise in the future and long-term health. Bisphenols exhibit toxic effects and can cross the placenta barrier. However, the effects of prenatal exposure to bisphenols on newborn TL remain unknown. We aimed to explore the effects of prenatal exposure to bisphenols (i.e., bisphenol A [BPA], bisphenol B [BPB], bisphenol F [BPF], bisphenol S [BPS] and tetrabromobisphenol A [TBBPA]) on relative TL in newborns. A total of 801 mother-infant pairs were extracted from the Guangxi Zhuang Birth Cohort. The relationship between bisphenol levels in maternal serum and relative TL in cord blood was examined by generalized linear models and restricted cubic spline (RCS) models. After adjusting for confounders, we observed a 3.19% (95% CI: -6.08%, -0.21%; P = 0.037) reduction in relative cord blood TL among mothers ≥ 28 years old, with each onefold increase in BPS. However, in each onefold increase of TBBPA, we observed a 3.31% (95% CI: 0.67%, 6.01%; P = 0.014) increase in relative cord blood TL among mothers < 28 years old. The adjusted RCS models revealed similar results (P overall < 0.05, P non-linear > 0.05). This study was the first to establish a positive association between serum TBBPA levels and relative TL in newborns born to young mothers. However, BPS levels were inversely correlated with TL in fetus born to old mothers. The results suggested that the fetus of old pregnant women may be more sensitive to BPS exposure. Moreover, BPS exposure early in life may accelerate aging or increase the risk of developing BPS-related diseases in later life.
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http://dx.doi.org/10.1007/s11356-021-14496-zDOI Listing
May 2021

Infection is associated with elevated serum concentrations of antipsychotic drugs.

Int Clin Psychopharmacol 2021 May 20. Epub 2021 May 20.

Department of Pharmacy, Hefei Fourth People's Hospital Psychopharmacology Research Laboratory, Anhui Mental Health Center Department of Pharmacy, Affiliated Psychological Hospital of Anhui Medical University, Hefei, China.

We aimed to investigate the effects of infection on serum concentrations of different antipsychotics in inpatients with respiratory tract infections treated with psychiatric drugs, including risperidone, clozapine, quetiapine, and aripiprazole. All patients underwent therapeutic drug monitoring (TDM) and routine blood tests during infection and noninfection periods. The Wilcoxon signed-rank test was used to analyze intra-individual differences in dose-corrected serum concentrations (C/D) levels in infection and noninfection periods. To study the effects of infection intensity on drug concentrations, white blood cells (WBCs) parameters and C/D levels were analyzed by Spearman's correlation analysis using all samples. The median C/D levels of risperidone (risperidone + 9-OH, n = 36) and clozapine (n = 42) were significantly higher (P < 0.001), whereas the median C/D levels of quetiapine (n = 21) and aripiprazole (n = 13) were slightly significantly higher (P < 0.01) in infection than in noninfection period. A significant positive association between C/D levels and WBC parameters was observed for risperidone, clozapine, and quetiapine. These results indicated reduced clearance of all drugs evaluated, especially clozapine and risperidone, due to infection. Therefore, during infection in patients receiving risperidone, clozapine, quetiapine, or aripiprazole, TDM should be performed to minimize the possible adverse effects associated with elevated drug concentrations.
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http://dx.doi.org/10.1097/YIC.0000000000000366DOI Listing
May 2021

Intensity modulated radiation therapy may improve survival for tracheal-bronchial adenoid cystic carcinoma: A retrospective study of 133 cases.

Lung Cancer 2021 07 8;157:116-123. Epub 2021 May 8.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Department of Radiation Oncology, National Cancer Center/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China. Electronic address:

Purposes: This study aimed to evaluate the role of radiotherapy (RT) and intensity modulated radiation therapy (IMRT) in adjuvant and definitive settings of tracheal-bronchial adenoid cystic carcinoma (TACC) treatment.

Materials/methods: TACC patients (n = 133) treated with surgery and/or RT curatively in our institution between January 1, 1984 and December 31, 2017 were analyzed retrospectively.

Results: Among the 116 patients undergoing surgery, 50 (43.1 %) achieved complete resections and 66 (56.9 %) had positive surgical margins. For patients with positive margins, overall adjuvant RT was correlated with no significantly improved OS (10-year: 58.0 % vs. 47.9 %; P =  0.340) and a slight LRFS benefit (5-year: 81.9 % vs.75.6 %; P =  0.056), but adjuvant IMRT showed significant superiority in both OS (10-year: 82.9 % vs. 47.9 %; P =  0.031) and LRFS (5-year: 100.0 % vs. 75.6 %; P =  0.001) in comparison with no postoperative RT. Multivariate analysis also identified adjuvant IMRT as a significant favorable factor with OS (HR = 0.186, 95 %CI: 0.039-0.883; P =  0.034). For 17 patients receiving definitive RT, IMRT achieved promising 5-year OS of 88.9 % and LRFS of 64.3 %, yet no significant difference from non-IMRT group was reached (P = 0.447 and 0.706). Different therapies presented no significantly different impact on DMFS, whilst DMFS explained more of the OS variances (P < 0.001, R = 0.480) than LRFS (P < 0.001, R = 0.323).

Conclusion: IMRT could confer greatly improved OS and LRFS in postoperative setting for TACC patients with positive surgical margins. IMRT was also a good therapeutic option for definitive TACC with promising survival and local control.
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http://dx.doi.org/10.1016/j.lungcan.2021.05.006DOI Listing
July 2021

Cucurbituril-Encapsulating Metal-Organic Framework via Mechanochemistry: Adsorbents with Enhanced Performance.

Angew Chem Int Ed Engl 2021 Jul 9;60(28):15365-15370. Epub 2021 Jun 9.

Hoffmann Institute of Advanced Materials, Shenzhen Polytechnic, 7098 Liuxian Blvd, Nanshan District, Shenzhen, 518055, China.

The first examples of monolithic crystalline host-guest hybrid materials are described. The reaction of 1,3,5-benzenetricarboxylic acid (H BTC) and Fe(NO ) ⋅9 H O in the presence of decamethylcucurbit[5]uril ammonium chloride (MC5⋅2 NH Cl⋅4 H O) directly affords [email protected](Fe) hybrid monoliths featuring hierarchical micro-, meso- and macropores. Particularly, this "bottle-around-ship" synthesis and one-pot shaping are facilitated by a newly discovered Fe-MC5 flowing gel formed by mechanochemistry. The designed [email protected](Fe) hybrid material with MC5 as active domains shows enhanced CH and lead(II) uptake performance, and selective capture of lead(II) cations at low concentrations. This shows that host-guest hybrid materials can exhibit synergic properties that out-perform materials based on individual components.
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http://dx.doi.org/10.1002/anie.202100675DOI Listing
July 2021

Concurrent chemoradiotherapy versus radiotherapy alone for patients with locally advanced esophageal squamous cell carcinoma in the era of intensity modulated radiotherapy: a propensity score-matched analysis.

Thorac Cancer 2021 06 5;12(12):1831-1840. Epub 2021 May 5.

Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: To investigate the survival benefit of concurrent chemoradiotherapy (CCRT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) during the years of intensity-modulated radiotherapy (IMRT).

Methods: Medical records of 1089 patients with ESCC who received IMRT from January 2005 to December 2017 were retrospectively reviewed. A total of 617 patients received CCRT, 472 patients received radiotherapy (RT) alone. Propensity score matching (PSM) method was used to eliminate baseline differences between the two groups. Survival and toxicity profile were evaluated afterward.

Results: After a median follow-up time of 47.9 months (3.2-149.8 months), both overall survival (OS) and progression-free survival (PFS) of the CCRT group were better than those of the RT alone group, either before or after PSM. After PSM, the 1-, 3-, and 5-year OS of RT alone and CCRT groups were 59.0% versus 70.2%, 27.7% versus 40.5% and 20.3% versus 33.1%, respectively (p < 0.001). The 1-, 3-, and 5-year PFS were 39.4% versus 49.0%, 18.3% versus 30.4% and 10.5% versus 25.0%, respectively (p < 0.001). The rates of ≥ grade 3 leukopenia and radiation esophagitis in the CCRT group were higher than that of RT alone group (p < 0.05). There was no significant difference in the probability of radiation pneumonitis between the two groups (p = 0.167). Multivariate Cox analysis indicated that female, EQD2 ≥60 Gy and concurrent chemotherapy were favorable prognostic factors for both OS and PFS.

Conclusions: Concurrent chemotherapy can bring survival benefits to patients with locally advanced ESCC receiving IMRT. For patients who cannot tolerate concurrent chemotherapy, RT alone is an effective alternative with promising results.
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http://dx.doi.org/10.1111/1759-7714.13971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201542PMC
June 2021

Barriers to preventive care utilization among Hong Kong community-dwelling older people and their views on using financial incentives to improve preventive care utilization.

Health Expect 2021 May 5. Epub 2021 May 5.

School of Optometry, The Hong Kong Polytechnic University, Kowloon, Hong Kong.

Background: Financial incentive is increasingly used as a mean to promote preventive care utilization (PCU), but the current Elderly Health Care Voucher Scheme (EHCVS) in Hong Kong is ineffective for encouraging PCU.

Objective: To explore the older people's barriers to PCU and their views on financial incentive, including EHCVS, for improving private PCU.

Design And Setting: Focus-group discussions were conducted in community elderly centres located in five districts of Hong Kong.

Participants: Community-dwelling older people aged 60 years or above.

Results: Lack of understanding about preventive care and low awareness of the need for preventive care were key factors for the low motivation for PCU. Uncertainty over the level of service fee charged and concerns over service quality hindered the choice of using the private service providers under the current EHCVS. Financial incentives specific for preventive care services were thought to be cues to actions and guides for service promotion. However, some flexibility in service coverage and a set time limit of the financial incentives were preferred to accommodate individual needs.

Conclusions: Apart from promoting knowledge of preventive care, official monitoring for service fee and quality is important for empowering older people to choose private service providers for preventive care. Financial incentives for preventive care services should be more specific to cue service promotion and uptake of preventive care while maintaining flexibility to accommodate individual needs.

Patient Or Public Contribution: Participants were recruited using purposive sampling with the coordination of community elderly centres. Data were analysed using thematic coding.
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http://dx.doi.org/10.1111/hex.13256DOI Listing
May 2021

Preparation and Characterization of Hydroxyapatite Coating on AZ31 Magnesium Alloy Induced by Carboxymethyl Cellulose-Dopamine.

Materials (Basel) 2021 Apr 8;14(8). Epub 2021 Apr 8.

State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physic, Chinese Academy of Sciences, Lanzhou 730000, China.

Magnesium and its alloys have become potential implant materials in the future because of light weight, mechanical properties similar to natural bone, good biocompatibility, and degradability in physiological environment. However, due to the rapid corrosion and degradation of magnesium alloys in vivo, especially in the environment containing chloride ions, the application of magnesium alloys as implant materials has been limited. Therefore, improving the corrosion resistance of magnesium alloy and ensuring good biocompatibility is the main focus of the current research. In this study, hydroxyapatite coating was prepared on magnesium alloy surface using carboxymethyl cellulose-dopamine hydrogel as inducer to improve corrosion resistance and biocompatibility. Surface characterization techniques (scanning electron microscopy, Fourier-transformed infrared spectroscopy, energy dispersive X-ray spectroscopy- and X-ray diffraction) confirmed the formation of hydroxyapatite on the surface of AZ31 alloy. Corrosion resistance tests have proved the protective effect of Carboxymethyl cellulose-Dopamine/hydroxyapatite (CMC-DA/HA) coating on the surface of AZ31 alloy. According to MC3T3-E1 cell viability and Live/Dead staining, the coating also showed good biocompatibility. The results will provide new ideas for the biological application of magnesium alloys.
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http://dx.doi.org/10.3390/ma14081849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068241PMC
April 2021

Discrimination and characterization of Panax polysaccharides by 2D COS-IR spectroscopy with chemometrics.

Int J Biol Macromol 2021 Jul 24;183:193-202. Epub 2021 Apr 24.

Key Laboratory of Chinese Materia Medica (Heilongjiang University of Chinese Medicine), Ministry of Education, 24 Heping Road, Harbin 150040, PR China. Electronic address:

In this study, a novel two-dimensional correlation infrared spectroscopy (2DCOS-IR) is presented to rapidly characterize and discriminate polysaccharides in Panax ginseng (PGP), P. notoginseng (PNP), and P. quinquefolius (PQP) using attenuated total reflection Fourier transform infrared spectroscopy-based on single-characteristic temperature as the external disturbance (2D-sATR-FTIR). Compared with two existing 2DCOS-IR methods based on gradient heating pathways using KBr pellet (100 min; 2D-KBr-FTIR) and attenuated total reflection (30 min; 2D-gATR-FTIR), the new procedure took an average of just 2 min to finish a sample measurement, which resolved previously tedious and time-consuming dilemmas. It offered advantages in the quality evaluation of natural polysaccharides and featured nondestructive, high-throughput, and high-efficiency characteristics. An intuitive analysis of the 2D-sATR-FTIR demonstrated that PNP was first identified because it had fewer auto-peaks. Posteriorly, PGP and PQP were distinguished according to the ratio of the auto-peaks 6 and 9, with the former greater than 1 and the latter less than 1. Furthermore, characteristic auto-peaks 1, 5, and 6 were unambiguously determined as Quality-markers using PCA and PLS-DA for visualized identifications. LDA was successfully used to establish a predictive model of the PGP, PNP, and PQP based on the positions and intensity of these three characteristic auto-peaks.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.04.124DOI Listing
July 2021

Richer fusion network for breast cancer classification based on multimodal data.

BMC Med Inform Decis Mak 2021 04 22;21(Suppl 1):134. Epub 2021 Apr 22.

Department of Oncology, Peking University International Hospital, Beijing, China.

Background: Deep learning algorithms significantly improve the accuracy of pathological image classification, but the accuracy of breast cancer classification using only single-mode pathological images still cannot meet the needs of clinical practice. Inspired by the real scenario of pathologists reading pathological images for diagnosis, we integrate pathological images and structured data extracted from clinical electronic medical record (EMR) to further improve the accuracy of breast cancer classification.

Methods: In this paper, we propose a new richer fusion network for the classification of benign and malignant breast cancer based on multimodal data. To make pathological image can be integrated more sufficient with structured EMR data, we proposed a method to extract richer multilevel feature representation of the pathological image from multiple convolutional layers. Meanwhile, to minimize the information loss for each modality before data fusion, we use the denoising autoencoder as a way to increase the low-dimensional structured EMR data to high-dimensional, instead of reducing the high-dimensional image data to low-dimensional before data fusion. In addition, denoising autoencoder naturally generalizes our method to make the accurate prediction with partially missing structured EMR data.

Results: The experimental results show that the proposed method is superior to the most advanced method in terms of the average classification accuracy (92.9%). In addition, we have released a dataset containing structured data from 185 patients that were extracted from EMR and 3764 paired pathological images of breast cancer, which can be publicly downloaded from http://ear.ict.ac.cn/?page_id=1663 .

Conclusions: We utilized a new richer fusion network to integrate highly heterogeneous data to leverage the structured EMR data to improve the accuracy of pathological image classification. Therefore, the application of automatic breast cancer classification algorithms in clinical practice becomes possible. Due to the generality of the proposed fusion method, it can be straightforwardly extended to the fusion of other structured data and unstructured data.
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http://dx.doi.org/10.1186/s12911-020-01340-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061018PMC
April 2021

Risk Factors for Adverse Pregnancy Outcomes among Zhuang Ethnic Pregnant Women: A Cohort Study in Guangxi, China.

Curr Med Sci 2021 Apr 20;41(2):219-227. Epub 2021 Apr 20.

Department of Sanitary Chemistry, School of Public Health, Guangxi Medical University, Nanning, 530021, China.

Risk factors for adverse pregnancy outcomes among Zhuang ethnic pregnant women are unclear. This study analyzed the incidence and risk factors related to preterm birth (PB), low birth weight (LBW) and macrosomia in Zhuang population. We conducted a prospective cohort study of 9965 Zhuang pregnancy women in Guangxi, China. Information on mothers and newborns was obtained by using questionnaires and referring to medical records. Multivariate logistic regression analyses were used to evaluate the association between related factors and adverse pregnancy outcomes. Our results showed that the incidence of PB, LBW and macrosomia in Zhuang people was 5.55%, 5.64% and 2.19%, respectively. Maternal age ≥36 years (OR=2.22, 95% CI: 1.51-3.27) was related to a higher incidence of PB. Those with pre-pregnancy body mass index (BMI) <18.5 kg/m (OR=1.91, 95% CI: 1.45-2.51), and had a female fetus (OR=1.74, 95% CI: 1.36-2.23) were more likely to have LBW infants. Maternal age between 31 and 35 years (OR=1.76, 95% CI: 1.03-2.99) and pre-pregnancy overweight or obesity (OR=1.79, 95% CI: 1.15-2.80) were associated with a higher risk of macrosomia. The protective factors of macrosomia were maternal pre-pregnancy BMI <18.5 kg/m (OR=0.30, 95% CI: 0.15-0.60) and female fetus (OR=0.41, 95% CI: 0.28-0.59). Our study provided a reference for maternal and childcare administration among Zhuang population.
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http://dx.doi.org/10.1007/s11596-021-2339-9DOI Listing
April 2021

Azithromycin alleviates systemic lupus erythematosus via the promotion of M2 polarisation in lupus mice.

Cell Death Discov 2021 Apr 16;7(1):82. Epub 2021 Apr 16.

Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China.

Our previous study demonstrated that azithromycin could promote alternatively activated (M2) macrophages under lupus conditions in vitro, which might be beneficial for lupus treatment. Thus, the aim of this study was to further confirm whether azithromycin can drive M2 polarisation in lupus and ultimately alleviate systemic lupus erythematosus (SLE) in vivo. Lymphocyte-derived DNA (ALD-DNA)-induced mice (induced lupus model) and MRL-Fas mice (spontaneous lupus model) were both used in the experiment. First, we observed symptoms of lupus by assessing the levels of serum anti-dsDNA antibodies and serum creatinine and renal pathology. We found that both murine models showed increased levels of serum anti-dsDNA antibodies and creatinine, enhanced glomerular fibrosis and cell infiltration, basement membrane thickening and elevated IgG deposition. After azithromycin treatment, all these medical indexes were alleviated, and kidney damage was effectively reversed. Next, macrophage polarisation was assessed in the spleen and kidneys. Macrophage infiltration in the spleen was notably decreased after azithromycin treatment in both murine models, with a remarkably elevated proportion of M2 macrophages. In addition, the expression of interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), CD86, toll-like receptor (TLR)2 and TLR4 was extremely downregulated, while the expression of transforming growth factor (TGF)-β, arginase-1 (Arg-1), chitinase-like 3 (Ym-1), found in inflammatory zone (Fizz-1) and mannose receptor (CD206) was significantly upregulated in the kidneys after azithromycin treatment. Taken together, our results indicated for the first time that azithromycin could alleviate lupus by promoting M2 polarisation in vivo. These findings exploited the newly discovered potential of azithromycin, a conventional drug with verified safety, affordability and global availability, which could be a novel treat-to-target strategy for SLE via macrophage modulation.
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http://dx.doi.org/10.1038/s41420-021-00466-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050155PMC
April 2021

Impaired olfactory neural circuit in patients with SLE at early stages.

Lupus 2021 Jun 15;30(7):1078-1085. Epub 2021 Apr 15.

Department of Radiology, Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, China.

Objective: To investigate the changes of olfactory function and odor-induced brain activation in patients with systemic lupus erythematosus (SLE) at early stages compared with healthy controls.

Materials And Methods: Olfactory function and odor-induced brain activation in 12 SLE patients at early stages and 12 age, gender and education matched healthy controls were evaluated using olfactory behavior test and odor-induced task-functional magnetic resonance imaging (task-fMRI).

Results: No significant differences in olfactory behavior scores (including olfactory threshold, olfactory identification, and olfactory memory) were found in the patients with SLE at early stages compared with the healthy controls, while significantly decreased odor-induced activations in olfactory-related brain regions were observed in the patients. In the SLE group, the patients with better performance in the olfactory threshold test had significantly lower levels of anti-dsDNA antibody.

Conclusion: The current study demonstrated that significant alterations in odor-induced brain activations occurred prior to measurable olfactory decline in SLE at early stages, which provided a new method for early diagnosis of olfactory dysfunction in SLE.
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http://dx.doi.org/10.1177/09612033211005556DOI Listing
June 2021

Maternal overweight but not paternal overweight before pregnancy is associated with shorter newborn telomere length: evidence from Guangxi Zhuang birth cohort in China.

BMC Pregnancy Childbirth 2021 Apr 9;21(1):283. Epub 2021 Apr 9.

Department of Epidemiology and Health Statistics, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning, 530021, Guangxi, China.

Background: Telomere length (TL) is variable at birth and is inversely associated with body mass index (BMI) in adulthood. A growing number of evidences suggested that a higher maternal pre-pregnancy BMI results in adverse offspring health outcomes, especially shorter newborn TL. However, a newborn's genetic endowment is equally derived from both parents, the association between parental pre-pregnancy BMI and newborn TL has been rarely discussed. We aimed to determine the association between parental pre-pregnancy BMI and newborn TL.

Methods: A total of 1082 parent-newborn pairs were recruited from the Guangxi Zhuang Birth Cohort (GZBC). TL in cord blood was measured using quantitative real-time polymerase chain reaction (qPCR) and expressed as the ratio of telomere copy number to single-copy gene number (T/S). A series of linear regressions were performed to assess the associations between parental pre-pregnancy BMI and newborn TL.

Results: Mothers who were overweight before pregnancy had significantly shorter cord blood telomere length in their newborns than those who were normal weight before pregnancy [percentage change: - 7.96% (95% CI: - 14.49 to - 0.69%; P = 0.032)]. Further analysis of the combined effects of parental weight status on newborn TL showed that TL was significantly shortened among newborns whose mothers were overweight and fathers were of healthy weight when compared with those whose mothers and fathers were both of normal weight [percentage change: - 8.38% (95% CI: - 15.47 to - 0.92%; P = 0.028)]. Subgroup analysis indicated these effects were more pronounced among male newborns and those whose paternal age < 31 years or maternal age ≥ 28 years at delivery.

Conclusions: Maternal pre-pregnancy overweight, but not paternal pre-pregnancy overweight is associated with shorter newborn TL. Weight control in reproductive women and effective healthy weight management before pregnancy may be of particular benefit for improving longevity and life quality of offspring.
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http://dx.doi.org/10.1186/s12884-021-03757-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033662PMC
April 2021

[Clinical Recommendations for Perioperative Immunotherapy-induced Adverse Events in Patients with Non-small Cell Lung Cancer].

Zhongguo Fei Ai Za Zhi 2021 Mar;24(3):141-160

Department of Thoracic Surgery, Peking University Cancer Hospital, Beijing 100142, China.

Background: Perioperative treatment has become an increasingly important aspect of the management of patients with non-small cell lung cancer (NSCLC). Small-scale clinical studies performed in recent years have shown improvements in the major pathological remission rate after neoadjuvant therapy, suggesting that it will soon become an important part of NSCLC treatment. Nevertheless, neoadjuvant immunotherapy may be accompanied by serious adverse reactions that lead to delay or cancelation of surgery, additional illness, and even death, and have therefore attracted much attention. The purpose of the clinical recommendations is to form a diagnosis and treatment plan suitable for the current domestic medical situation for the immune-related adverse event (irAE).

Methods: This recommendation is composed of experts in thoracic surgery, oncologists, thoracic medicine and irAE related departments (gastroenterology, respirology, cardiology, infectious medicine, hematology, endocrinology, rheumatology, neurology, dermatology, emergency section) to jointly complete the formulation. Experts make full reference to the irAE guidelines, large-scale clinical research data published by thoracic surgery, and the clinical experience of domestic doctors and publicly published cases, and repeated discussions in multiple disciplines to form this recommendation for perioperative irAE.

Results: This clinical recommendation covers the whole process of prevention, evaluation, examination, treatment and monitoring related to irAE, so as to guide the clinical work comprehensively and effectively.

Conclusions: Perioperative irAE management is an important part of immune perioperative treatment of lung cancer. With the continuous development of immune perioperative treatment, more research is needed in the future to optimize the diagnosis and treatment of perioperative irAE.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2021.101.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143963PMC
March 2021

Novel Compound Heterozygous Pathogenic Mutations of in a Chinese Patient With Congenital Hypothyroidism.

Front Endocrinol (Lausanne) 2021 19;12:620117. Epub 2021 Mar 19.

The Core Laboratory in Medical Center of Clinical Research, Department of Molecular Diagnostics and Endocrinology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Background And Objectives: Defects in the human sodium/iodide symporter () gene have been reported to be one of the causes of congenital hypothyroidism (CH). We aimed to identify mutations in Chinese patients with CH and to evaluate the function of the mutation.

Methods: Two hundred and seventy-three patients with primary CH were screened for mutations in using next-generation sequencing. We investigated the expression and cellular localization of the novel compound heterozygous mutation in . The functional activity of the mutants was further examined .

Results: In 273 patients with CH, two previously undescribed pathogenic mutations p.Gly51AlafsTer45 (G51fs) and p.Gly421Arg (G421R) in a compound heterozygous state in were identified in a pediatric patient. G51fs was located in the first intercellular loop connecting transmembrane segment I and II, whereas G421R was in the transmembrane segment (TMS) XI. G51fs and G421R resulted in a truncated NIS and reduced protein expression, respectively. experiments further showed that the normal function of iodine transport of sodium-iodide symporter (NIS) mutants was markedly impaired.

Conclusion: The undescribed compound heterozygous mutation of was discovered in a Chinese CH patient. The mutation led to significantly reduced NIS expression and impaired iodide transport function accompanied by the impaired location of the NIS on the plasma membrane. Our study thus provides further insights into the roles of in CH pathogenesis.
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http://dx.doi.org/10.3389/fendo.2021.620117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018529PMC
March 2021