INTRODUCTION: Hydroxychloroquine (HCQ), originally an antimalarial drug, is currently used to treat multiple disorders, especially rheumatic diseases. Given its good efficacy and safety, HCQ is widely administered in pregnant patients. However, the safety profile of HCQ during pregnancy remains controversial due to limited research. In addition, HCQ has been reported to reduce preeclampsia in patients with systemic lupus erythematosus (SLE) and could potentially alleviate the symptom of preeclampsia. However, the clinical profile and molecular mechanism of HCQ in preeclampsia is yet to be fully understood. METHOD: We reviewed the literature on HCQ treatment in pregnancy with rheumatic diseases and preeclamp-sia in PubMed and Web of Science. We also discussed the safety of long-term therapy with HCQ during pregnancy. RESULTS: HCQ mainly modulates autoimmune response through inhibition of lysosomal function, toll-like receptor (TLR) signalling, nicotinamide adenine dinucleotide phosphate-mediated oxidative stress and autophagy. Benefits of HCQ in treating rheumatic diseases, including antiphospholipid syndrome, rheumatoid arthritis and Sjogren's syndrome during pregnancy, has been demonstrated in clinics. In particular, multiple clinical guidelines recommend HCQ as an indispensable therapeutic drug for pregnant patients with SLE. Additionally, it may potentially function in preeclampsia to improve clinical symptoms. CONCLUSION HCQ is effectively used for rheumatic diseases during pregnancy. The benefits of HCQ treatment in rheumatic diseases outweigh the risk of adverse reactions it induces in pregnant women.
Humans ; Hydroxychloroquine/pharmacology* ; Pregnancy ; Female ; Antirheumatic Agents/pharmacology* ; Rheumatic Diseases/drug therapy* ; Pregnancy Complications/drug therapy* ; Pre-Eclampsia/prevention & control* ; Lupus Erythematosus, Systemic/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Antiphospholipid Syndrome/drug therapy* ; Sjogren's Syndrome/drug therapy*

With the emergence of deep learning techniques based on convolutional neural networks, artificial intelligence (AI) has driven transformative developments in the field of medical image analysis. Recently, large language models (LLMs) such as ChatGPT have also started to achieve distinction in this domain. Increasing research shows the undeniable role of AI in reshaping various aspects of medical image analysis, including processes such as image enhancement, segmentation, detection in image preprocessing, and postprocessing related to medical diagnosis and prognosis in clinical settings. However, despite the significant progress in AI research, studies investigating the recent advances in AI technology in the aforementioned aspects, the changes in research hotspot trajectories, and the performance of studies in addressing key clinical challenges in this field are limited. This article provides an overview of recent advances in AI for medical image analysis and discusses the methodological profiles, advantages, disadvantages, and future trends of AI technologies.
Artificial Intelligence ; Humans ; Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer ; Deep Learning ; Diagnostic Imaging/methods*

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

Objective:To investigate the clinical phenotype and genetic etiology of a patient with tall stature and primary amenorrhea presenting with 47, XYY Disorder of sex development (DSD).Methods:A female patient presenting with " tall stature and primary amenorrhea" at Nanjing Drum Tower Hospital in July 2024 was selected as the study subject. A retrospective study design was employed to collect the patient′s clinical data. Peripheral venous blood sample was collected. Following the extraction of genomic DNA, genetic testing was performed including chromosomal karyotyping analysis, copy number variation sequencing (CNV-seq), multiplex PCR for the AZF regions and sex-determining genes Y ( SRY), and whole-exome sequencing (WES). Candidate variants were validated by Sanger sequencing and classified for pathogenicity based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Nanjing Drum Tower Hospital (Ethics No.: 2022-451-01). Results:The patient had a height of 188 cm and a body weight of 50 kg, in addition with infantile uterus, absent ovaries, and primary amenorrhea. G-banded karyotyping analysis of peripheral blood sample revealed 47, XYY. CNV-seq indicated Seq[GRCh37]Yp11.32q12×2. No deletion was detected in the AZF regions of Y chromosome, and SRY was positive. WES identified a heterozygous c. 86C>A (p.Thr29Lys) variant of the NR5A1 gene, leading to substitution of threonine with lysine at position 29 of the encoded protein. Sanger sequencing confirmed the presence of the variant. According to the ACMG guidelines, this variant was classified as variant of uncertain significance (VUS) with supporting evidence (PS3_Moderate+ PM5+ PP3+ PM2_Supporting+ PS4_Supporting). Reviewing the nearly 60 years of previously reported cases, all 7 documented 47, XYY DSD patients were assigned a female social gender and presented with abnormal gonadal and external genitalia development. Among them, 5 cases underwent SRY testing, all of which were positive. Only 1 case underwent whole-exome sequencing (WES), but no pathogenic or likely pathogenic variants were identified. Conclusion:This DSD patient presented with the clinical features of tall stature and primary amenorrhea. The NR5A1 gene variant c. 86C>A (p.Thr29Lys) probably underlay the disorder of sex development in this patient. Above finding has enriched the spectrum of pathogenic variants of the NR5A1 gene.

Objective To investigate the effects of simulated-microgravity on the osteogenic differentiation,primary cilia status,cytoskeleton structure,and the YAP(Yes-associated protein)expression in primary osteoblasts.Methods Primary osteoblasts were isolated from the skull bones of neonatal Wistar rats and cultured in random positioning machine system to simulate the cellular effects of microgravity.The calcified nodules were stained with Arlizarin to assess the cellular mineralization ability,the primary cilia and cytoskeleton were detected by immunofluorescence staining of Arl13b/γ-Tubulin and α-Tubulin,respectively,and the expression of YAP was measured by western blot.Results The cellular osteogenic differentiation were markedly suppressed after treated with simulated microgravity for 24 h,and the ciliated cells decreased from(58.44±3.65)%to(15.76±1.84)%in parallel with a decline of average cilium length from(3.19±0.51)μm to(1.59±0.46)μm.In addition,simulated microgravity induced disassembly of microtubules.Notably,simulated microgravity interfered YAP expression and the inhibition of YAP into nucleus.Furthermore,knockdown of YAP expression in osteoblasts notably reduced primary cilia expression and inhibited osteogenic differentiation.Conclusion Primary cilia is a key organelle of osteoblasts in sensing microgravity and regulating osteogenic differentiation.Interference with YAP expression and inhibition of nuclear YAP entry may play an important role in the deaggregation of primary cilia induced by microgravity.

Objective: To explore the differential lipid metabolites in the plasma of mice with idiopathic pulmonary fibrosis(IPF). Methods : Thirty SPF C57BL/6 male mice were randomly divided into 2 groups with 15 mice in each group. The experimental groups were divided into control group and bleomycin(BLM) group. The model of idiopathic pulmonary fibrosis was induced by one-time intratracheal infusion of BLM(1 mg/kg). Hematoxylin-eosin(HE) staining was used to observe the lung histopathology. The collagen fiber deposition in lung tissue was observed by Sirius red staining. The differential lipid metabolites in plasma of IPF mice were screened and enriched by lipidomics. Results : HE staining showed that the pulmonary tissue structure was disordered, alveolar septum was broken and alveolar wall was destroyed in BLM group. Sirius red staining showed a large amount of collagen fiber deposition in the lung interstitium of BLM group. The results of lipidomics analysis showed that the lipid metabolism profile of BLM group changed, 15 differential lipid metabolites were screened out, of which 11 differential lipid metabolites were up-regulated, and 4 differential lipid metabolites were down-regulated, mainly concentrated in glycerophosphoglycerophosphates, glycerophosphocholines, steroid lactones, etc. Conclusion The lipid metabolism profile of BLM group mice changes, differential lipid metabolites such as phosphoglycolate phosphatase(PGP)(18:0/18:0), PGP(i-12:0/i-24:0), PGP(i-13:0/a-25:0), and phosphatidylcholine(PC)(18:0/14:0), PC(18:3/16:0), lysophosphatidylcholine(LPC)(16:1), and LPC(18:3) may play an important role in the progression of IPF. These findings provide a new reference for further study of the molecular mechanism of IPF, and also provide a potential new target for clinical treatment.

Objective To elucidate how the overexpression of cystathionine-β-synthase(CBS)plays an antihypertensive role by affecting peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α)expression.Methods The adeno-associated viruses(AAVs),ones that overexpressed CBS,and another knocked down PGC-1α,were injected into the hypothalamic paraventricular nucleus(PVN)of spontaneously hypertensive rats(SHRs).The rats'blood pressure was monitored,and the level of norepinephrine(NE)was examined by ELISA;PVN inflammatory response,oxidative stress and tyrosine hydroxylase(TH)expression were detected with RT-qPCR and immunofluorescence.Results PVN overexpression of CBS could increase the transcription level of CBS(by 3.8 times,P＜0.05)and PGC-1α(by 1.6 times,P＜0.05)in PVN of SHR.PVN overexpression of CBS could reduce blood pressure in SHR(from 177.81 mmHg to 128.77 mmHg,P＜0.001),but PVN knockdown of PGC-1αweakened such effect(from 128.77 mmHg to 152.79 mmHg,P＜0.05).PVN overexpression of CBS could alleviate PVN inflammatory response and oxidative stress,but this effect was weakened or even eliminated when knocking down PGC-1α was performed at the same time.Conclusion PVN overexpression of CBS can reduce blood pressure in SHR,and this effect may be achieved by increasing the transcriptional level of PGC-1α,alleviating PVN inflammatory response,oxidative stress,and improving sympathetic nerve excitation.

Autism spectrum disorder(ASD) is a neurodevelopmental disorder, and social impairment was one of the core symptoms of ASD, which can seriously affects the social life of patients.The pathogenesis of social impairment in ASD is unclear and it may involves many brain abnormalities.The related theories and hypotheses are numerous and there is no unified conclusion. Studies have shown that the cerebellum has extensive connections with brain networks and is involved in the regulation of social cognition, but its role in ASD has not been fully emphasized.The structural and functional abnormalities of the cerebellar-cortex (CC) loop in ASD patients can lead to language communication disorders, empathy disorders, difficulties in interpreting social cues, abnormal social reward processing and emotional regulation disorders, which are closely related to ASD social impairment. Noninvasive brain stimulation of the superficial cerebellum can improve the abnormal CC circuit in ASD patients, and the cerebellum can be considered as a target for the treatment of social disorders in ASD in the future.Based on the clinical and basic researches on social impairment in ASD in recent years, this article reviews the relevant manifestations of disorders which cerebellar and CC circuit involved, aiming to promote the development of related research in the future.