Publications by authors named "Ming Zhao"

1,755 Publications

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A Generative Adversarial Network technique for high-quality super-resolution reconstruction of cardiac magnetic resonance images.

Magn Reson Imaging 2021 Oct 23. Epub 2021 Oct 23.

School of Computer Science and Engineering, Central South University, Changsha 410000, China; Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China. Electronic address:

Purpose: In this paper, we proposed a Denoising Super-resolution Generative Adversarial Network (DnSRGAN) method for high-quality super-resolution reconstruction of noisy cardiac magnetic resonance (CMR) images.

Methods: The proposed method is based on feed-forward denoising convolutional neural network (DnCNN) and SRGAN architecture. Firstly, we used a feed-forward denoising neural network to pre-denoise the CMR image to ensure that the input is a clean image. Secondly, we use the gradient penalty (GP) method to solve the problem of the discriminator gradient disappearing, which improves the convergence speed of the model. Finally, a new loss function is added to the original SRGAN loss function to monitor GAN gradient descent to achieve more stable and efficient model training, thereby providing higher perceptual quality for the super-resolution of CMR images.

Results: We divided the tested cardiac images into 3 groups, each group of 25 images. Then, we calculated the Peak Signal to Noise Ratio (PSNR) /Structural Similarity (SSIM) between Ground Truth (GT) and the images generated by super-resolution, used them to evaluate our model. We compared with the current widely used method: Bicubic ESRGAN and SRGAN, our method has better reconstruction quality and higher PSNR/SSIM score.

Conclusion: We used DnCNN to denoise the CMR image, and then using the improved SRGAN to perform super-resolution reconstruction of the denoised image, we can solve the problem of high noise and artifacts that cause the cardiac image to be reconstructed incorrectly during super-resolution.
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http://dx.doi.org/10.1016/j.mri.2021.10.033DOI Listing
October 2021

A1-R Exquisitely Targets and Arrests a Matrix-producing Triple-negative Breast Carcinoma in a PDOX Model.

In Vivo 2021 Nov-Dec;35(6):3067-3071

AntiCancer Inc, San Diego, CA, U.S.A.;

Background/aim: Triple-negative matrix-producing breast carcinoma (MPBC) is rare, recalcitrant, and highly aggressive. The present study aimed to determine the efficacy of tumor-targeting leucine-arginine auxotroph Salmonella typhimurium (S. typhimurium) A1-R on a triple-negative MPBC in a patient-derived orthotopic xenograft (PDOX) model.

Materials And Methods: The PDOX MPBC model was established in the left second mammary gland of nude mice by surgical orthotopic implantation (SOI). PDOX models were randomized into two groups when the tumor volume reached over 70 mm: a control group (n=6); and a tumor-targeting S. typhimurium A1-R group (n=7), [intravenous (i.v.) injection of S. typhimurium A1-R via the tail vein, weekly, for two weeks]. All mice were sacrificed on day 14. Tumor volume and body weight were measured once per week.

Results: S. typhimurium A1-R exquisitely targeted and arrested the growth of the MPBC PDOX compared to the control group (p=0.017).

Conclusion: S. typhimurium A1-R has future clinical potential for triple-negative MPBC patients.
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http://dx.doi.org/10.21873/invivo.12602DOI Listing
August 2021

Diagnosis experience and literature review of patients with cervical, thoracic and lumbar multi-segment spinal stenosis: A case report.

Prog Brain Res 2021 13;266:377-385. Epub 2021 Aug 13.

International Experimental Central Nervous System Injury & Repair (IECNSIR), Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden. Electronic address:

Background: The incidence of cervical, thoracic and lumbar spinal canal stenosis is low. It is difficult to identify the main focus and responsible segment, and it is also difficult to select the sequence of staging surgery. We report a patient with triple stenosis.

Case Presentation: In this paper, we introduced a 61-year-old female patient with cervical, thoracic and lumbar spinal canal stenosis who had previously undergone "lumbar discectomy" in the outer hospital. The postoperative effect was not good and the symptoms were poor. The diagnosis was "cervical spinal stenosis and lumbar spine surgery." The staged spinal canal decompression operation and Duhuo Jisheng Decoction (DHJSD) treatment were conducted in our hospital. After 3 months of follow-up, the functional and imaging results were satisfactory.

Conclusion: We should pay enough attention to the patients with spinal degenerative diseases who need surgery, and must pursue the unity of medical history, signs and images. In case of difficult patients, more comprehensive examination is required, and the main focus and responsible segment are determined through comprehensive analysis. The more important diseases that may exist cannot be covered up by focal lesion manifestations, so as to avoid unnecessary surgical trauma for patients. In addition, surgery combined with Chinese herbal medicine DHJSD therapy may be an effective treatment for this kind of disease.
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http://dx.doi.org/10.1016/bs.pbr.2021.06.019DOI Listing
August 2021

A clinical study of high-dose urokinase for the treatment of the patients with hypertension induced ventricular hemorrhage.

Prog Brain Res 2021 6;266:349-355. Epub 2021 Oct 6.

International Experimental Central Nervous System Injury & Repair (IECNSIR), Department of Surgical Sciences, Anesthesiology & Intensive Care Medicine, Uppsala University Hospital, Uppsala University, Uppsala, Sweden. Electronic address:

Objective: This study discusses the therapeutic effect of high-dose urokinase treatment for hypertension ventricular hemorrhage.

Methods: A total of 60 patients with hypertension ventricular hemorrhage were randomly assigned to two groups: treatment group (n=30) and control group (n=30). Both groups received bilateral external ventricular drain. The treatment group was injected with 50,000IU urokinase to the lateral ventricle every day; the total injection volume per day was 100,000IU. The control group was injected with 20,000IU urokinase to the lateral ventricle every day with a total injection volume per day of 40,000IU. Lumbar puncture was performed in both groups after the later ventricular drain was removed to release cerebrospinal fluid (CSF). Head Computed tomography(CT) examination was performed regularly to observe changes in the ventricular hematoma as well as the occurrence of complications such as intracranial infection and hydrocephalus. Patient prognosis 6 weeks after surgery was compared between the two groups.

Results: In the treatment group, the intraventricular hemorrhage clearance time and the number of instances of urokinase treatment were significantly less than those of the control group (P<0.05). The total urokinase dosage of the treatment group was significantly higher than that of the control group (P<0.05). With respect to post-surgery complications, in the treatment group, there were three cases of hydrocephalus and one case of intracranial infection. In the control group, there were four cases of hydrocephalus and three cases of intracranial infection. Intraventricular re-hemorrhage was not observed in either group. Intracranial infection was relieved after strengthened anti-infective therapy and continuous drainage. There was a statistically significant difference in the occurrence of complications between the treatment group and the control group (P<0.05). The rate of good prognosis in the treatment group was higher than that of the control group (P<0.05), and the inefficiency rate was lower (P<0.05).

Conclusions: High-dose urokinase treatment produces a significant therapeutic effect in hypertension ventricular hemorrhage. This treatment can quickly eliminate intraventricular hemorrhage, shorten the ventricular drain tube indwelling time, decrease the occurrence of intracranial infection, and increase the likelihood of a good prognosis.
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http://dx.doi.org/10.1016/bs.pbr.2021.06.017DOI Listing
October 2021

Carotid arterial wall MRI of apolipoprotein e-deficient mouse at 7 T using DANTE-prepared variable-flip-angle rapid acquisition with relaxation enhancement.

Magn Reson Imaging 2021 Oct 21. Epub 2021 Oct 21.

Department of Biomedical Engineering, The Sixth Affiliated Hospital, School of Basic Sciences, Guangzhou Medical University, Guangzhou, China. Electronic address:

Purpose: To optimize a sequence combining the delay alternating with nutation for tailored excitation (DANTE) preparative module with the variable-flip-angle rapid acquisition with relaxation enhancement (VF-RARE) sequence (DANTE-VF-RARE) and to investigate its feasibility for vessel wall imaging in Apolipoprotein E-Deficient (ApoE) mouse at 7 Tesla (T).

Materials And Methods: Specific T1/T2 values were used for producing a sharper vessel wall in the variable-flip-angle optimization scheme. The DANTE RF pulse flip angle and pulse train length were optimized for maximizing the wall-lumen contrast. ApoE (fed high fat diet for 20/40/ 60 weeks, n = 9/4/4) and wild-type mice (controls, n = 3) were imaged at 7 T using VF-RARE, DANTE-VF-RARE, time-of-flight (TOF) angiography, and multi-slice T1-weighted 2D RARE coupled with inflow outflow saturation bands (IOSB-RARE). Wall-lumen contrast-to-noise-ratio efficiency (CNR), lumen area (LA), and wall area (WA) were compared between DANTE-VF-RARE and 2D IOSB-RARE sequences. Additionally, linear regression analysis was conducted between MR measurements and histomorphometric planimetry results.

Results: Residual blood signal was observed in the four out of eighteen carotids on VF-RARE images, whereas it was significantly suppressed on DANTE-VF-RARE images. Compared with IOSB-RARE, DANTE-VF-RARE offered significantly improved CNR (P < 0.001). The LA and WA were both comparable (P = 0.085 and 0.112, respectively) and showed excellent agreement between DANTE-VF-RARE and IOSB-RARE (ICC = 0.96 and 0.95, respectively). The luminal stenosis identified by DANTE-VF-RARE was in consistent with the results of TOF. Strong correlations were found between MR measurements and histopathological analysis for both WA (DANTE-VF-RARE: r = 0.92, slope = 0.94, P < 0.001; IOSB-RARE: r = 0.93, slope = 0.94, P < 0.001) and LA (DANTE-VF-RARE: r = 0.82, slope = 0.54, P < 0.001; IOSB-RARE: r = 0.78, slope = 0.50, P < 0.001).

Conclusion: DANTE-VF-RARE achieves effective blood signal suppression and is a feasible approach for the 3D carotid arterial wall imaging of ApoE mouse at 7 T.
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http://dx.doi.org/10.1016/j.mri.2021.10.026DOI Listing
October 2021

Cell adhesion suppresses autophagy via Src/FAK-mediated phosphorylation and inhibition of AMPK.

Cell Signal 2021 Oct 18;89:110170. Epub 2021 Oct 18.

Cancer Center, Sanford Burnham Prebys Medical Discovery Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address:

Autophagy is a multi-step process regulated in part by AMP-activated protein kinase (AMPK). Phosphorylation of threonine 172 on the AMPK α-subunit enhances AMPK kinase activity, resulting in activation of downstream signaling. Integrin-mediated cell adhesion activates Src/ Focal Adhesion Kinase (FAK) signaling complex, which regulates multiple cellular processes including cell survival. We show here that Src signaling leads to direct phosphorylation of the AMPK-α subunit on a novel site, tyrosine 179, resulting in suppression of AMPK-T172 phosphorylation and autophagy upon integrin-mediated cell adhesion. By using chemical inhibitors, genetic cell models and targeted mutagenesis, we confirm an important role for Src and FAK in suppressing AMPK signaling and autophagy induced by various additional stimuli, including glucose starvation. Furthermore, we found that autophagy suppression by hydroxychloroquine promotes apoptosis in a cancer cell model that had been treated with Src inhibitors. Our findings reveal a link between the Src/ FAK complex and AMPK/ autophagy regulation, which may play an important role in the maintenance of normal cellular homeostasis and tumor progression.
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http://dx.doi.org/10.1016/j.cellsig.2021.110170DOI Listing
October 2021

Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors.

Nat Commun 2021 Oct 15;12(1):6043. Epub 2021 Oct 15.

Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.

Clinical evidence has established that concomitant traumatic brain injury (TBI) accelerates bone healing, but the underlying mechanism is unclear. This study shows that after TBI, injured neurons, mainly those in the hippocampus, release osteogenic microRNA (miRNA)-enriched small extracellular vesicles (sEVs), which targeted osteoprogenitors in bone to stimulate bone formation. We show that miR-328a-3p and miR-150-5p, enriched in the sEVs after TBI, promote osteogenesis by directly targeting the 3'UTR of FOXO4 or CBL, respectively, and hydrogel carrying miR-328a-3p-containing sEVs efficiently repaires bone defects in rats. Importantly, increased fibronectin expression on sEVs surface contributes to targeting of osteoprogenitors in bone by TBI sEVs, thereby implying that modification of the sEVs surface fibronectin could be used in bone-targeted drug delivery. Together, our work unveils a role of central regulation in bone formation and a clear link between injured neurons and osteogenitors, both in animals and clinical settings.
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http://dx.doi.org/10.1038/s41467-021-26302-yDOI Listing
October 2021

Regulatory utility of pharmacometrics in the development and evaluation of antimicrobial agents and its recent progress in China.

CPT Pharmacometrics Syst Pharmacol 2021 Oct 15. Epub 2021 Oct 15.

Institute of Antibiotics, Huashan Hospital Affiliated to Fudan University, Shanghai, China.

Pharmacometrics is an emerging science that interprets drug, disease, and trial information in a mathematical fashion to inform and facilitate efficient drug development and/or regulatory decisions. Pharmacometrics study is increasingly adopted in the regulatory review of new antimicrobial agents. We summarized the 31 antimicrobial agents approved by the US Food and Drug Administration (FDA) and the 26 antimicrobial agents approved by European Medicines Agency (EMA) from January 2001 to May 2019. We also reviewed recent examples of utilizing pharmacometrics to support antimicrobial agent's registration in China, including modeling and simulation methods, effects of internal/external factors on pharmacokinetic (PK) parameters, safety and efficacy evaluation in terms of exposure-response analysis, refinement of the wording of product labeling and package leaflet, and possible postmarketing clinical trial. Ongoing communication among regulator, academia, and industry regarding pharmacometrics is encouraged to streamline and facilitate the development of new antimicrobial agents. The industry can maximize its benefit in drug development through continued pharmacometrics education/training.
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http://dx.doi.org/10.1002/psp4.12716DOI Listing
October 2021

Desmoplastic small round cell tumour presenting as cervical lymph nodes metastases with solid pattern morphology and novel EWSR1-WT1 fusion transcript.

Pathology 2021 Oct 11. Epub 2021 Oct 11.

Department of Pathology, Laboratory Medicine Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China. Electronic address:

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http://dx.doi.org/10.1016/j.pathol.2021.07.009DOI Listing
October 2021

Accelerating precision anti-cancer therapy by time-lapse and label-free 3D tumor slice culture platform.

Theranostics 2021 13;11(19):9415-9430. Epub 2021 Sep 13.

Cancer Center, Faculty of Health Sciences, University of Macau, Macau SAR, China.

The feasibility of personalized medicine for cancer treatment is largely hampered by costly, labor-intensive and time-consuming models for drug discovery. Herein, establishing new pre-clinical models to tackle these issues for personalized medicine is urgently demanded. We established a three-dimensional tumor slice culture (3D-TSC) platform incorporating label-free techniques for time-course experiments to predict anti-cancer drug efficacy and validated the 3D-TSC model by multiphoton fluorescence microscopy, RNA sequence analysis, histochemical and histological analysis. : Using time-lapse imaging of the apoptotic reporter sensor C3 (C3), we performed cell-based high-throughput drug screening and shortlisted high-efficacy drugs to screen murine and human 3D-TSCs, which validate effective candidates within 7 days of surgery. Histological and RNA sequence analyses demonstrated that 3D-TSCs accurately preserved immune components of the original tumor, which enables the successful achievement of immune checkpoint blockade assays with antibodies against PD-1 and/or PD-L1. Label-free multiphoton fluorescence imaging revealed that 3D-TSCs exhibit lipofuscin autofluorescence features in the time-course monitoring of drug response and efficacy. : This technology accelerates precision anti-cancer therapy by providing a cheap, fast, and easy platform for anti-cancer drug discovery.
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http://dx.doi.org/10.7150/thno.59533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490519PMC
September 2021

Cavernous lymphangioma of the urinary bladder in an adult woman: an additional case report of a rare lesion and literature review.

BMC Urol 2021 Oct 13;21(1):145. Epub 2021 Oct 13.

Department of Pathology, Laboratory Medicine Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, 310014, Zhejiang, China.

Background: Urinary bladder lymphangioma is a rare and benign lesion that is often causes symptoms related to irritation and urinary tract obstruction. Because a lymphangioma may resemble a true neoplasm of the urinary bladder clinically, the lesion must be removed for accurate histologic diagnosis and to rule out malignancy.

Case Presentation: We present a case of a 40-year-old female who was evaluated for painless gross hematuria. Clinical and diagnostic work up revealed a sharply defined mass involving the wall and bulging into the cavity on the dome of the bladder. Partial cystectomy was performed and histologic findings were compatible with cavernous lymphangioma. The symptom of hematuria relieved after the procedure and the patient was in good status without evidence of recurrence by cystoscopy at follow-up 6 months later.

Conclusions: Lymphangioma of the urinary bladder is treated with surgical excision and seems to have no recurrence once completely resected, but long-time follow-up may be needed.
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http://dx.doi.org/10.1186/s12894-021-00907-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8513249PMC
October 2021

Primary Adrenal Glomus Tumor: The First Case Report.

Urol Int 2021 Oct 13:1-4. Epub 2021 Oct 13.

Department of Pathology, Laboratory Medicine Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

We report a unique case of a 25-year-old man who was incidentally identified to have a mass in the left adrenal gland region by computerized tomography scan. The image revealed a 1.8 × 1.6 cm, well-defined adrenal mass with moderately homogeneous enhancement. The mass was laparoscopically completely removed, and the diagnosis of a solid variant glomus tumor of the adrenal gland was rendered. There were no histologic features indicating atypia or malignance and no primary tumors anywhere else. The patient was free of disease at the 6-month follow-up. To our knowledge, this is the first case of primary adrenal glomus tumor described in the literature.
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http://dx.doi.org/10.1159/000519482DOI Listing
October 2021

Experimental Study on the Evaluation and Influencing Factors on Individual's Emergency Escape Capability in Subway Fire.

Int J Environ Res Public Health 2021 09 28;18(19). Epub 2021 Sep 28.

School of Mechanics and Safety Engineering, Zhengzhou University, Zhengzhou 450001, China.

Studying an individual's emergency escape capability and its influencing factors is of great practical significance for evacuation and escape in subway emergencies. Taking Zhengzhou Zijing Mountain Subway station as the prototype, and using VR technology, a virtual subway fire escape scene was built. Combined with the total escape time, the total contact time with fire, and the total contact time with smoke, it proposed a calculation formula on emergency escape capability. A total of 34 participants with equal gender distribution were recruited to carry out the virtual subway fire escape experiment, and participants' physiological data (heart rate variability, skin conductance) were real-time recorded by ErgoLAB V3.0 throughout the whole experiment. The emergency escape capability of each participant was evaluated quantitatively, and the related influencing factors were analyzed. The results show that for the age ranges (19-22 years old) in the experiment, the emergency escape capability of women is significantly lower than that of men ( < 0.05); although there is no significance in emergency escape capability in DISC personality types ( > 0.05), the mean emergency escape capability of people with influence personality type is the worst, and that of people with compliance type is the best; during virtual fire escape vs. baseline, Mean_SC and Mean_HR both increased very significantly (all < 0.01), and participants were under stress during their virtual fire escape. There is a significant negative correlation between emergency escape capability and LF_increase_rate ( < 0.05), and a remarkably significant negative correlation between emergency escape capability and LF/HF_increase_rate ( < 0.01); the greater the increase rate of LF or LF/HF, the smaller the emergency escape capability, with excessive stress probably not being conducive to emergency escape. There is a very significant negative correlation between an individual's emergency escape capability and the degree of familiarity with the Zijing Mountain subway station ( < 0.01). The findings provide references and suggestions on the emergency management and emergency evacuation for government and subway departments.
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http://dx.doi.org/10.3390/ijerph181910203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8508343PMC
September 2021

BRAF-rearranged spindle cell mesenchymal neoplasm with a predominant lipofibromatosis-like neural tumor pattern and co-expression of CD34, S100 protein, and markers associated with perineurial differentiation: A rare case with potential diagnostic pitfall.

J Cutan Pathol 2021 Oct 9. Epub 2021 Oct 9.

Department of Pathology, Laboratory Medicine Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Recently, a distinctive group of S100 protein/CD34-positive spindle cell mesenchymal neoplasms characterized by a predominant lipofibromatosis-like neural pattern harboring recurrent gene rearrangements involving NTRK1-3, RAF1, RET, ROS1, ALK, and MET has been identified. BRAF rearrangements have been rarely documented in this group of neoplasms. Herein, we report a 54-year-old man with a 1.3-cm painless mass located in the subcutis of left back. The tumor was composed of mildly atypical, short-spindle shaped to ovoid cells with fascicles and whorls intervening between and admixed with the subcutaneous adipose tissues and nerve bundles. Focally abundant thick, band-like stromal hyalinization was also noted. The neoplastic cells showed diffuse reactivity for S100 protein and CD34 and multifocal immunopositivity for markers associated with perineurial differentiation including epithelial membrane antigen, GLUT1, and claudin-1. Fluorescence in situ hybridization analyses showed positive for BRAF rearrangement and negative for rearrangements involving NTRK1, RET, and ROS1. The tumor was narrowly excised and recurred after 24 months of follow-up. To our knowledge, we report the second case of BRAF-rearranged spindle cell mesenchymal tumor with predominant lipofibromatosis-like neural tumor pattern. Expression of markers associated with perineurial differentiation is exceptional and represents a potential diagnostic pitfall, which may cause significant diagnostic confusion with a peripheral nerve sheath tumor.
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http://dx.doi.org/10.1111/cup.14149DOI Listing
October 2021

MEX3A knockdown inhibits the tumorigenesis of colorectal cancer via modulating CDK2 expression.

Exp Ther Med 2021 Nov 22;22(5):1343. Epub 2021 Sep 22.

Clinical Medical College, Follow-up Research Center, Jiangsu Vocational College of Medicine, Yancheng, Jiangsu 224005, P.R. China.

Colorectal cancer (CRC) is a malignant tumor of the gastrointestinal tract and a leading cause of cancer-associated mortality worldwide. Mex-3 RNA binding family member A (MEX3A) promotes the progression of multiple types of cancer, including ovarian and cervical cancer. However, to the best of our knowledge, the role of MEX3A in CRC is not completely understood. Therefore, the present study aimed to investigate the function of MEX3A in CRC. The mRNA and protein expression levels of MEX3A in CRC cells were analyzed using reverse transcription-quantitative PCR and western blotting, respectively. Cell Counting Kit-8 assays were used to measure cell viability. Cell apoptosis and cell cycle distribution were detected via flow cytometry, and CRC cell invasion was analyzed by performing Transwell assays. Moreover, the mitochondrial membrane potential in CRC cells was measured via JC-1 staining. The results of the present study revealed that the expression levels of MEX3A were upregulated in CRC tissues compared with adjacent healthy tissues. MEX3A knockdown notably inhibited CRC cell viability, and induced apoptosis and mitochondrial injury. In addition, MEX3A knockdown markedly induced G phase cell cycle arrest in CRC cells via downregulating CDK2 expression. In conclusion, the findings of the present study suggested that MEX3A knockdown may inhibit the tumorigenesis of CRC cells by regulating CDK2 expression. Therefore, MEX3A may serve as a novel target for CRC treatment.
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http://dx.doi.org/10.3892/etm.2021.10778DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8495542PMC
November 2021

One hundred twelve cases of 46, XY DSD patients after initial gender assignment: a short-term survey of gender role and gender dysphoria.

Orphanet J Rare Dis 2021 Oct 9;16(1):416. Epub 2021 Oct 9.

Department of Endocrinology, Genetics and Metabolism, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, 100045, China.

Background: 46, XY disorders of sex development (46, XY DSD) are congenital disorders with 46, XY chromosomal karyotype but inconsistent gonadal/phenotypic sex. One of the biggest concerns for parents and clinicians is the gender assignment. However, there is no standard uniform of care nor consensus at present. We sought to evaluate the current treatment's rationality and provide a reference basis for the gender reassignment in 46, XY DSD patients with a specific diagnosis.

Methods: We conducted a cross-sectional survey of gender role with the Pre-school Activities Inventory (PSAI), the Children's Sex Role Inventory (CSRI) in 46, XY DSD patients and set up control groups comparison. Psychiatrist assessed gender dysphoria in patients ≥ 8-year-old with the criteria of diagnostic and statistical manual of mental disorders, 5th edition (DSM-5).

Results: A total of 112 responders of 136 patients participated in this study (82.4%, aged 2-17.8 years, median age: 4-year-old). The follow-up period was from 6 months to 10 years (median: 2 years). Twenty-five females were reassigned to the male gender after a specific diagnosis (16/25 (64%) in 5 alfa-reductase-2 deficiency (5α-RD2), 5/25 (20%) in partial androgen insensitivity syndrome (PAIS), 4/25 (16%) in NR5A1gene mutation). Male gender assignment increased from 55.3 (n = 62) to 77.7% (n = 87). The median PSAI score was similar to the control males in 5α-RD2, PAIS, and NR5A1 gene mutation groups (p > 0.05); while identical to the control females in complete androgen insensitivity syndrome (CAIS) and CYP17A1 gene mutation groups (p > 0.05). PSAI score of children raised as male was higher than those of CAIS and CYP17A1 groups raised as female (p < 0.05). CSRI scale showed no statistical differences in the consistency of gender roles and reassigned gender between 46, XY DSD patients and control groups (p > 0.05). None of the patients over 8-year-old (n = 44) had gender dysphoria.

Conclusion: The reassigned gender in 46, XY DSD patients is consistent with their gender role during early childhood. None of them had gender dysphoria. The molecular diagnosis, gonadal function, and the gender reassignment are congruent within our Chinese cohort. Long-term follow-up and more evaluation are still required.
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http://dx.doi.org/10.1186/s13023-021-02039-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501610PMC
October 2021

Dedifferentiated liposarcoma with abrupt transition of low-grade and high-grade dedifferentiation: A rare case report.

Int J Immunopathol Pharmacol 2021 Jan-Dec;35:20587384211048565

Departments of Pathology, 74678Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

Dedifferentiated liposarcoma is a unique subtype of liposarcoma, which has obvious histological heterogeneity. In affected patients, the condition typically manifests as the dedifferentiation of high-grade histological morphology, but it may also manifest as the dedifferentiation of low-grade histological morphology. In some cases, unique histological or immunophenotypic characteristics are observed. We describe, herein, a rare case of dedifferentiated liposarcoma, in which the high-grade and low-grade dedifferentiated components coexisted with a relatively sharp transition in pathology.
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http://dx.doi.org/10.1177/20587384211048565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8504230PMC
October 2021

Interactions between glial cells and the blood-brain barrier and their role in Alzheimer's disease.

Ageing Res Rev 2021 Oct 2;72:101483. Epub 2021 Oct 2.

Institute of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China. Electronic address:

Alzheimer's disease (AD), which is an irreversible neurodegenerative disorder characterized by senile plaques and neurofibrillary tangles, is the most common form of dementia worldwide. However, currently, there are no satisfying curative therapies for AD. The blood-brain barrier (BBB) acts as a selective physical barrier and plays protective roles in maintaining brain homeostasis. BBB dysfunction as an upstream or downstream event promotes the onset and progression of AD. Moreover, the pathogenesis of AD caused by BBB injury hasn't been well elucidated. Glial cells, BBB compartments and neurons form a minimal functional unit called the neurovascular unit (NVU). Emerging evidence suggests that glial cells are regulators in maintaining the BBB integrity and neuronal function. Illustrating the regulatory mechanism of glial cells in the BBB assists us in drawing a glial-vascular coupling diagram of AD, which may offer new insight into the pathogenesis of AD and early intervention strategies for AD. This review aims to summarize our current knowledge of glial-BBB interactions and their pathological implications in AD and to provide new therapeutic potentials for future investigations.
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http://dx.doi.org/10.1016/j.arr.2021.101483DOI Listing
October 2021

Patient-Derived Organoids Can Guide Personalized-Therapies for Patients with Advanced Breast Cancer.

Adv Sci (Weinh) 2021 Oct 4:e2101176. Epub 2021 Oct 4.

Cancer Centre, Faculty of Health Sciences, University of Macau, Macau, SAR, 999078, China.

Most breast cancers at an advanced stage exhibit an aggressive nature, and there is a lack of effective anticancer options. Herein, the development of patient-derived organoids (PDOs) is described as a real-time platform to explore the feasibility of tailored treatment for refractory breast cancers. PDOs are successfully generated from breast cancer tissues, including heavily treated specimens. The microtubule-targeting drug-sensitive response signatures of PDOs predict improved distant relapse-free survival for invasive breast cancers treated with adjuvant chemotherapy. It is further demonstrated that PDO pharmaco-phenotyping reflects the previous treatment responses of the corresponding patients. Finally, as clinical case studies, all patients who receive at least one drug predicate to be sensitive by PDOs achieve good responses. Altogether, the PDO model is developed as an effective platform for evaluating patient-specific drug sensitivity in vitro, which can guide personal treatment decisions for breast cancer patients at terminal stage.
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http://dx.doi.org/10.1002/advs.202101176DOI Listing
October 2021

Investigation and dynamic profiling of oligopeptides, free amino acids and derivatives during Pu-erh tea fermentation by ultra-high performance liquid chromatography tandem mass spectrometry.

Food Chem 2021 Sep 17;371:131176. Epub 2021 Sep 17.

State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau SAR, China. Electronic address:

Microbial fermentation is the critical step of Pu-erh tea manufacture, which will induce dramatic changes in the chemical composition and content of tea. In this research, we applied multi-methods based on UHPLC-Q-TOF/MS to profile the dynamic changes of oligopeptides, free amino acids, and derivatives (OPADs) during Pu-erh fermentation and predicted the potential bioactivities in silico. A total of 60 oligopeptides, 18 free amino acids, and 42 amino acid derivatives were identified, and the contents of most of them decreased after fermentation. But several N-acetyl amino acids increased 7-36 times after fermentation, and they might be the potential inhibitors of neurokinin-1 receptor. Moreover, the results of metamicrobiology showed Aspergillus niger and Aspergillus luchuensis were more prominent to metabolize protein, oligopeptides, and amino acids. Overall, these findings provide valuable insights about dynamic variations of OPADs during Pu-erh tea fermentation and are beneficial for guiding practical fermentation and quality control of Pu-erh tea.
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http://dx.doi.org/10.1016/j.foodchem.2021.131176DOI Listing
September 2021

Soft tissue perineurioma involving the kidney: a report of two cases with an emphasis on differential diagnosis.

Diagn Pathol 2021 Sep 30;16(1):87. Epub 2021 Sep 30.

Department of Pathology, Laboratory Medicine Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, 310014, Hangzhou, Zhejiang, China.

Background: Soft tissue perineurioma of the kidney is rare, with only a few reported cases. We report two additional cases with histologic, immunohistochemical and genetic analyses.

Case Presentation: Both tumors were from adults (1 female aged 49 years and 1 male aged 42 years) and grossly had maximum diameters of 6.5 and 10 cm, respectively. The tumors were overall well circumscribed but unencapsulated, with focally entrapped benign native renal tubules in one case; both tumors seemed to arise in the capsular areas. The tumors had histologic and immunohistochemical profiles consistent with soft tissue perineurioma. Fluorescence in situ hybridization analyses demonstrated that the tumors were negative for amplification of MDM2 and rearrangements of ESWR1, FUS, and KMT2A. Targeted next-generation sequencing revealed a low tumor mutation burden and likely pathogenic mutations (CYP2B6 and FLT1 mutations for 1 each). Follow-up data were available for both patients; neither had tumor recurrence or metastasis.

Conclusions: In conclusion, renal perineurioma is rare, usually arises in the capsular areas, and is cured by resection. Low-grade dedifferentiated liposarcoma and low-grade fibromyxoid sarcoma as well as other spindle cell lesions should be considered in the differential diagnosis.
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http://dx.doi.org/10.1186/s13000-021-01149-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482618PMC
September 2021

Nodular fasciitis of the breast: Report of two cases illustrating the diagnostic implications for USP6 gene rearrangement and brief review of the literature.

Exp Mol Pathol 2021 Sep 28;123:104690. Epub 2021 Sep 28.

Department of Breast Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, China. Electronic address:

Nodular fasciitis is a benign, self-limited, pseudosarcomatous neoplasm that is cytogenetically characterized by recurrent USP6 gene rearrangement. Involvement of the breast by nodular fasciitis is very rare with only a few documented cases. It can clinically, radiologically and histologically mimic a malignancy, posing significant diagnostic challenges to clinicians, radiologists, and pathologists. In this study, we report 2 cases of nodular fasciitis occurring in the female breast, reviewing the literature and emphasizing the application of fluorescence in situ hybridization analysis of USP6 gene rearrangement in its diagnosis and differential diagnosis.
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http://dx.doi.org/10.1016/j.yexmp.2021.104690DOI Listing
September 2021

Association of Methylenetetrahydrofolate Reductase C677T Gene Polymorphisms with Mild Cognitive Impairment Susceptibility: A Systematic Review and Meta-Analysis.

Behav Neurol 2021 18;2021:2962792. Epub 2021 Sep 18.

Department of Geratology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.

Background: Methylenetetrahydrofolate reductase () C677T (rs1801133) gene polymorphisms are related to a growing risk of Alzheimer's disease; however, whether this association applies to mild cognitive impairment (MCI) remains unclear.

Objective: We conducted this meta-analysis to evaluate the contribution of C677T (rs1801133) gene variants to the risk of MCI.

Methods: PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched from their inception to March 21, 2021, with language restricted to English or Chinese. We used fixed or random effects to examine the association between C677T (rs1801133) gene variants and MCI susceptibility. Forest plots of pooled odds ratios (ORs) and 95% confidence intervals (CIs) were generated.

Results: Eight articles with 2,175 participants were included in the present meta-analysis. There was no significant association between C677T (rs1801133) gene variants and MCI susceptibility under the allelic (OR, 1.318; 95% CI, 0.964-1.801; = 0.084), dominant (OR, 1.296; 95% CI, 0.925-1.817; = 0.132), recessive (OR, 1.397; 95% CI, 0.845-2.312; = 0.193), heterozygous (OR, 1.031; 95% CI, 0.855-1.243; = 0.749), or homozygous (OR, 1.506; 95% CI, 0.850-2.667; = 0.160) models.

Conclusion: The results suggest that C677T (rs1801133) gene polymorphisms are not associated with MCI susceptibility. However, large-scale studies covering various factors are required.
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http://dx.doi.org/10.1155/2021/2962792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464412PMC
September 2021

A PHF1-TFE3 fusion atypical ossifying fibromyxoid tumor with prominent collagenous rosettes: Case report with a brief review.

Exp Mol Pathol 2021 Sep 22;123:104686. Epub 2021 Sep 22.

Department of Pathology, Laboratory Medicine Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, China. Electronic address:

Ossifying fibromyxoid tumor (OFMT) is a rare mesenchymal neoplasm of uncertain line of differentiation that can be subdivided into typical, atypical, and malignant tumors. Cytogenetically, OFMT is characterized by recurrent gene rearrangement involving PHF1 in up to 85% of cases. The most common PHF1 fusion partner is EP400, present in approximately half of cases. Most recently, a novel fusion of PHF1-TFE3 was identified in about 10% of PHF1-rearranged OFMTs. Herein, we report a unique case of PHF1-TFE3 fusion atypical OFMT with prominent collagenous rosettes. A 50-year-old male patient presented with a slowly growing, painless mass in the right foot for 4 years. Gross examination showed a 3.5-cm, subcutaneous well-circumscribed, lobulated mass. Microscopic examination revealed a well-demarcated but un-encapsulated tumor without a peripheral bony shell. The neoplasm was composed of mildly atypical spindle to ovoid cells with increased mitosis (2 mitoses per 10 high-power fields) arranged in a multinodular manner within a fibromyxoid stroma, which contained numerous small, irregular collagenous rosettes surrounded by radiating growth of tumor cells. The neoplastic cells were diffusely positive for TFE3 and CD10. RNA sequencing revealed an in-frame fusion between PHF1 exon 12 and TFE3 exon 7. Subsequent Fluorescence in-situ hybridization analyses demonstrated positive for rearrangements of both the PHF1 and TFE3 loci. The patient was free of disease at 63 months' follow-up. Our case exhibits atypical features and prominent collagenous rosettes, expanding the morphological spectrum of OFMT with PHF1-TFE3 fusion.
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http://dx.doi.org/10.1016/j.yexmp.2021.104686DOI Listing
September 2021

Three-Dimensional Computed Tomography Bronchography and Angiography-Guided Thoracoscopic Segmentectomy for Pulmonary Nodules.

Surg Innov 2021 Sep 24:15533506211044389. Epub 2021 Sep 24.

Department of Thoracic Surgery, ShanXi Cancer Hospital (the Affiliated Cancer Hospital of Shanxi Medical University), Taiyuan, China.

Background: Three-dimensional computed tomography bronchography and angiography (3D-CTBA) provides detailed imaging information for pulmonary segmentectomy. This study was performed to verify the feasibility of 3D-CTBA-guided thoracoscopic segmentectomy for the treatment of pulmonary nodules.

Methods: A retrospective analysis was performed on all patients who underwent 3D-CTBA-guided uniport thoracoscopic segmentectomies or subsegmentectomies for pulmonary nodules in the period from May 2019 to May 2020. All of the information related to perioperative management and surgical operations was retrieved from the medical records and operating notes for detailed analysis.

Results: A total of 104 eligible operations involving the resection of 110 nodules with diameters in the range of 5-20 mm were included. Under 3D-CTBA guidance, the pulmonary nodules were located with an accuracy of 100% (110/110) and the median resection margin was 24.3 mm (17-33 mm). Additionally, the segmental (subsegmental) bronchi, arteries, and veins were identified with accuracy rates of 100% (104/104), 96.2% (100/104), and 94.2% (98/104), respectively. The postoperative complications consisted of 3 cases of pulmonary infection (2.9%), 6 cases of arrhythmia (5.8%), 2 cases of hemoptysis (1.9%), 4 cases of air leak (3.8%), and 2 cases of subcutaneous emphysema (1.9%). No perioperative death occurred.

Conclusion: 3D-CTBA-guided thoracoscopic segmentectomy is an effective surgical approach for the management of pulmonary nodules.
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http://dx.doi.org/10.1177/15533506211044389DOI Listing
September 2021

A high-efficient nano pesticide-fertilizer combination fabricated by amino acid-modified cellulose based carriers.

Pest Manag Sci 2021 Sep 22. Epub 2021 Sep 22.

Innovative Institute for Plant Health, Key Laboratory of Agricultural Green Fine Chemicals of Guangdong Higher Education Institution, School of Chemistry and Chemical Engineering, Zhongkai University of Agriculture and Engineering, Guangzhou, China.

Background: As the global population grows, large quantities of agrochemicals are used to secure food demand and there is an urgent need to develop efficient and environmentally friendly pesticides and fertilizers. Compared with traditional pesticides, nanopesticide formulations can achieve better foliar wettability, chemical stability, and water dispersibility without or with the minimal use of organic solvents, in line with the development of sustainable agriculture.

Results: In this research, glycidyl methacrylate (GMA) was used as an intermediate and glycine methyl ester (GLY) was used as an organic nitrogen source to modify carboxymethyl cellulose (CMC) to synthesize a pesticide nanocarrier CMC-PGMA-GLY. A nanopesticide [email protected] ([email protected]) was formed by the hydrophobic and electrostatic interactions of emamectin benzoate (EB), which had good water dispersion. The good affinity of the composite towards leaves led to the effective moistening of the leaf surface by the pesticide and through the pH control pesticide release. Biological experiments show that nanopesticides can maintain high insecticidal activity and have no toxicity to seed germination. The results of pot experiment showed that the nanocarriers could be used as an organic nitrogen fertilizer to increase the fresh weight of plants by 39.77%.

Conclusions: This environmentally friendly pesticide carrier can be used as a fertilizer to provide sufficient nutrients for crops, opening a new method for the development of sustainable agriculture.
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http://dx.doi.org/10.1002/ps.6655DOI Listing
September 2021

Surveillance Strategy for Barcelona Clinic Liver Cancer B Hepatocellular Carcinoma Achieving Complete Response: An Individualized Risk-Based Machine Learning Study.

Front Bioeng Biotechnol 2021 31;9:667641. Epub 2021 Aug 31.

Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, China.

For patients with complete response (CR) of Barcelona Clinical Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), there is no consensus regarding the monitoring strategy. Optimal surveillance strategies that can detect early progression of HCC within a limited visit after treatment have not yet been investigated. A retrospective, real-world study was conducted to investigate surveillance strategies for BCLC stage B HCC (BBHCC) patients with CR after curative treatment to support clinical decision making. From January 2007 to December 2019, 546 BBHCC patients with CR after radical treatment were collected at Sun Yat-sen University Cancer Center. Seventy percent of patients were subjected to the train cohort randomly; the remaining patients comprised the validation cohort to verify the proposed arrangements. The random survival forest method was applied to calculate the disease progression hazard per month, and follow-up schedules were arranged to maximize the capability of progression detection at each visit. The primary endpoint of the study was the delayed-detection months for disease progression. The cumulative 1, 2, and 3-years risk-adjusted probabilities for the train/validation cohorts were 32.8%/33.7%, 54.0%/56.3%, and 64.0%/67.4%, respectively, with peaks around approximately the 9th month. The surveillance regime was primarily concentrated in the first year posttreatment. The delayed-detection months gradually decreased when the total follow-up times increased from 6 to 11. Compared with controls, our schedule reduced delayed detection. Typically, the benefits of our surveillance regimes were obvious when the patients were followed seven times according to our schedule. The optional schedules were 5, 7, 9, 11, 17, 23, and 30 months. The proposed new surveillance schedule may provide a new perspective concerning follow-up for BBHCC patients with CR.
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http://dx.doi.org/10.3389/fbioe.2021.667641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447402PMC
August 2021

Influencing factors of coronary artery stenosis in patients with stable coronary heart disease and a correlation analysis.

Am J Transl Res 2021 15;13(8):9522-9529. Epub 2021 Aug 15.

Department of Cardiology III, Cangzhou Central Hospital Cangzhou 061001, Hebei, China.

Objective: To explore the relationship of the size and concentration of low density lipoprotein (LDL) particles and high density lipoprotein (HDL) particles and the coronary stenotic degree of stable coronary artery disease.

Methods: Altogether 62 patients with coronary disease confirmed by coronary angiography treated in our hospital from March 2019 to March 2020 were selected as the observation group, and 62 healthy persons in the same period were chosen as the control group. The particle size of LDL and HDL protein complexes were measured and we then calculated the concentration ratio to explore the relationship between the two types of lipoprotein particles and the degree of coronary artery disease. The Gensini integral method and the lesion numbers were used to evaluate the coronary stenotic degree.

Results: In comparison with the control group, the mean diameter of the average LDL particle in the observation group was smaller, but the type B ratio and Gensini score were higher (P<0.05). In comparison with the control group, the observation group had a higher Sd-LDL concentration ratio, as well as concentration of small-particle HDL, percentage of concentration of small-particle HDL in the whole HDL concentration and Gensini score (P<0.05). In comparison with the single-vessel disease group, the multi-vessel disease group had a smaller LDL concentration, as well as smaller large-particle HDL concentration and percentage of large-particle HDL concentration in the whole HDL concentration, and SD-LDL concentration ratio, small-particle HDL concentration, and percentage of small-particle HDL concentration in the whole HDL concentration and Gensini points were considerably higher (P<0.05). The Gensini score in the observation group showed negative correlations with LDL particle size (r=-0.375, P<0.05), and positive correlations with the concentration of large-particle HDL (r=0.301, P<0.05).

Conclusion: The size and concentration of LDL and HDL are significantly related to the coronary stenotic degree in SCAD disease, suggesting that they play a role in the coronary stenotic degree.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430167PMC
August 2021

Targeted design of a recombinant tracer for SPECT renal imaging.

Theranostics 2021 27;11(18):9118-9132. Epub 2021 Aug 27.

Division of Nephrology and Hypertension, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.

A robust radiopharmaceutical has high uptake in the target and low retention in non-target tissues. However, traditional tracers for renal imaging that chemically chelate Tc are excreted through the renal route with transient resident time in the kidney. Following a rational design approach, we constructed a protein-based radiotracer, designated PBT-Fc, to sequentially bind tubular neonatal Fc-receptor and subsequently proximal tubular basement membrane for its targeted sequestration in kidney parenchyma. In this process, the tracer participates in physiologic glomerular filtration and tubular reabsorption while escaping lysosomal catabolism and urinary clearance. To specifically target renal receptors in navigating the urinary passage in the kidney, we produced a recombinant fusion protein with two separate functional parts: a polybasic PBT segment derived from human Vascular Endothelial Growth Factor and Fc segment of IgG1. The chimeric fusion of PBT-Fc was labeled with radionuclide Tc and tested in rodent models of kidney diseases. Planar scintigraphy and single-photon emission computerized tomography (SPECT) were performed to evaluate renal-specificity of the tracer. When injected in mouse and rat, following a brief 10 - 15 min dynamic redistribution phase in circulation, ~ 95% of the [Tc]-PBT-Fc signal was concentrated in the kidney and lasted for hours without urinary loss or surrounding tissue activities. Long-lasting tracer signals in the kidney cortex in conjunction with SPECT greatly augmented the image quality in detecting pathological lesions in a variety of disease models, including ischemic acute kidney injury, drug-induced renal toxicity, and chronic kidney disease from renin-angiotensin system (RAS) overactivation. Exclusive renal retention of the recombinant radiotracer greatly facilitated static-phase signal acquisition by SPECT and achieved submillimeter spatial resolution of kidney alternations in glomerular and tubular disease models.
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http://dx.doi.org/10.7150/thno.60132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419037PMC
August 2021

AIM2 deficiency in B cells ameliorates systemic lupus erythematosus by regulating Blimp-1-Bcl-6 axis-mediated B-cell differentiation.

Signal Transduct Target Ther 2021 Sep 14;6(1):341. Epub 2021 Sep 14.

Department of Dermatology, Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Medical Epigenomics, Changsha, Hunan, China.

Absent in melanoma 2 (AIM2) has been reported to be a component of inflammasomes in innate immune cells. Surprisingly, AIM2 is expressed by B cells, and higher AIM2 expression is observed in the B cells from lupus patients. To date, the inflammasome-independent function of AIM2 in B cells remains unclear. Here, we report increased expression of AIM2 in human tonsil memory and germinal center (GC) B cells and in memory B cells and plasma cells from the circulation and skin lesions of lupus patients. Conditional knockout of AIM2 in B cells reduces the CD19 B-cell frequency in lymph nodes and spleens, and dampens KLH-induced IgG1-antibody production. In a pristane-induced mouse model of lupus, AIM2 deficiency in B cells attenuates lupus symptoms and reduces the frequency of GC B cells, T follicular helper (Tfh) cells, plasmablast cells, and plasma cells. Furthermore, the loss of AIM2 in human B cells leads to the increased expression of Blimp-1 and reduces the expression of Bcl-6. However, the silencing of Blimp-1 and Bcl-6 has no significant effect on AIM2 expression, indicating that AIM2 might be the upstream regulator for Blimp-1 and Bcl-6. In addition, IL-10 is found to upregulate AIM2 expression via DNA demethylation. Together, our findings reveal that AIM2 is highly expressed in the B cells of lupus patients and promotes B-cell differentiation by modulating the Bcl-6-Blimp-1 axis, providing a novel target for SLE treatment.
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http://dx.doi.org/10.1038/s41392-021-00725-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440614PMC
September 2021
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