OBJECTIVE: To explore the clinical characteristics, diagnosis, and treatment methods of one patient with idiopathic multicentric Castleman disease (iMCD), in order to strengthen the understanding of this rare disease. METHODS: The clinical manifestations, diagnosis and treatment process, and prognosis of one patient with iMCD admitted to our hospital were retrospectively analyzed. RESULTS: The patient was a 45-year-old female with swollen bilateral orbit, edema of lower limbs, multiple serosal cavity effusion, thrombocytopenia, renal insufficiency, and multiple lymph node enlargement. Lymph node biopsy suggested mixed type of Castleman disease. Combined with pathology, imaging and laboratory examination, the patient was finally diagnosed with mixed type of iMCD. After six cycles of R-COP regimen chemotherapy, the patient achieved complete remission. CONCLUSIONS Castleman disease with renal and orbit involvement is rare in clinic and easy to be misdiagnosed. It should be distinguished from lymphoma. The patient has been treated with R-COP regimen, and obtained good short-term efficacy.
Humans ; Castleman Disease/diagnosis* ; Middle Aged ; Female ; Retrospective Studies ; Orbit/pathology* ; Kidney/pathology*

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Reflux esophagitis is an inflammatory disease of esophageal mucosa damage caused by the reflux of gastric contents into the esophagus. Its incidence is on the rise， and it has become an important precancerous disease of esophageal cancer. Studies have shown that the continuous inflammatory response stimulates the esophageal mucosa， causing abnormal proliferation of esophageal epithelial cells and damage to esophageal mucosal tissue， which eventually leads to the occurrence of heterogeneous hyperplasia and even carcinogenesis. The nuclear transcription factor-kappa B （NF-κB） signaling pathway is one of the most classical inflammatory and cancer signaling pathways. It has been found that abnormal activation of the NF-κB signaling pathway is crucial to the development and prognosis of reflux esophagitis and esophageal cancer. It is widely involved in the proliferation， autophagy， apoptosis， and inflammatory response of esophageal epithelial cells and tumor cells， accelerating the transformation of reflux esophagitis to esophageal cancer and making it a potential target for the treatment of reflux esophagitis and esophageal cancer. Currently， there is no specific treatment for reflux esophagitis and esophageal cancer， and large side effects often appear. Therefore， finding a promising and safe drug remains a top priority. In recent years， traditional Chinese medicine scholars have conducted a lot of research on NF-κB signaling pathway， and the results indicate that NF-κB signaling pathway is an important potential target for traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， but there is a lack of comprehensive and systematic elaboration. Therefore， this paper summarized the relevant studies in recent years， analyzed the relationship among NF-κB signaling pathway， reflux esophagitis， esophageal cancer， and transformation from inflammation to cancer， and reviewed the research literature on the regulation of the NF-κB signaling pathway in traditional Chinese medicine to prevent and treat reflux esophagitis and esophageal cancer， so as to provide new ideas for the prevention and treatment of reflux esophagitis and esophageal cancer.

Esophageal cancer （EC） is a common malignant tumor of the digestive system with an extremely poor prognosis. MicroRNA （miRNA） is an important regulator in tumor occurrence and development， and can participate in malignant biological behaviors such as tumor cell proliferation， invasion， metastasis and apoptosis. Traditional Chinese medicine has the characteristics of accurate curative effects， wide range of effects， and few side effects. The review uses miRNA as the entry point to systematically elaborate on the mechanism of traditional Chinese medicine-mediated miRNA intervening in EC. The results showed that active ingredients of traditional Chinese medicine （including curcumin， Tussilago farfara polysaccharides， Atractylodes macrocephala polysaccharides and ophiopogonin B） and Dougen guanshitong oral liquid could up-regulate the expressions of miRNAs such as miRNA-532-3p （miR-532-3p）， miR-551b-3p， miR-99a， miR-34a， miR-199a-3p and miR-377； and the active ingredients/parts of traditional Chinese medicine （including chrysin and Actinidia arguta extract）， and Chinese herbal formulas （including Chaihu shugan san combined with Xuanfu daizhe decoction and Modified jupi zhuru decoction） could down-regulate the expressions of miRNAs such as miR-199a-3p， miR-451 and miR-21， which could regulate the expressions of signaling pathways （phosphoinositide 3-kinase/protein kinase B， etc.） or their downstream protein（zinc-finger and homeobox protein 1， etc.） or enzymes（thymidine kinase-1， etc.）， inhibit the proliferation， invasion and metastasis of EC cells and induce apoptosis， thereby ultimately achieving the purpose of preventing the disease from aggravating.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To investigate the clinical manifestations,molecular genetics and gonadal pathol-ogy characteristics of patients with disorders of sex development(DSD),and to summarize the clinical experi-ence of identifying rare diseases from common symptoms.Methods The clinical data of 416 patients with DSD diagnosed and treated in the multidisciplinary center of DSD of Guangzhou Women and Children's Medical Cen-ter from May 2018 to August 2023 were retrospectively analyzed,summarized and discussed.Results Accord-ing to chromosome karyotype,416 cases of DSD were classified into three types:92 cases(22.1％)of abnormal sex chromosome karyotype,285 cases(68.5％)of 46,XY karyotype and 39 cases(9.4％)of 46,XX karyotype.Among the 92 patients with abnormal sex chromosome karyotype,59 cases were raised as males,18 cases(30.5％)complained of short penis with hypospadias and cryptorchidism.The most common karyotype was 45,X/46,XY(58 cases,63.0％).Among the 285 patients with 46,XY karyotype,238 cases were raised as males,and 63 cases(26.5％)complained of short penis and hypospadias;47 cases were raised as females,and 13 ca-ses(27.7％)complained of inguinal mass.A total of 216 patients with 46,XY karyotype were subjected to whole exome gene detection,and 155 cases(71.8％)were found to have molecular pathogenesis with the clinical phe-notype.Among the 39 patients with 46,XX karyotype,19 cases were raised as males,and 8 cases(42.1％)com-plained of short penis and hypospadias.In the 18 cases of gonad biopsy,17 cases showed testicular tissue in go-nads.Whole exome sequencing was performed in 14 cases.NR5A1 gene heterozygous mutation,SRY gene muta-tion and SOX3 gene mutation were found in 2 cases,respectively(14.3％).Twenty cases were raised as females,and 14 cases(70.0％)complained of clitoral hypertrophy.Gonad biopsy was performed in 8 cases,with 7 cases of ovotestis(87.5％)and 1 case of NR5A1 gene heterozygous mutation(14.3％).Conclusions The etiologies of DSD are complex and diverse,and the clinical manifestations are various,which can be manifested as hypospa-dias,micropenis,cryptorchidism and other common symptoms of the urinary system.Different etiologies have dif-ferent treatment options.Therefore,chromosome karyotype,molecular genetic testing and gonadal pathology can be used to clarify the cause of disease,especially for rare diseases,improve the detection rate,reduce the rate of missed diagnosis,and ensure reasonable treatment,especially sex selection.

Microbiology and Immunology is one of core basic curriculums for medical college undergraduates.Combining with characteristics of this course,our teaching comprehension and background calling for curriculum ideological and political education,we consider blending traditional sinology classic"Thirty-Six Stratagems"in teaching of this curriculum.Meanwhile,its practical signif-icance on many aspects will be elucidated.This paper will provide useful reference for blending other sinology classics into ideological and political education of specialized curriculums.

Purpose To explore the diagnostic value of beak sign in fetal annular pancreas by analyzing the ultrasonographic features of fetal annular pancreas.Materials and Methods The ultrasound images and clinical data of 13 cases of fetal annular pancreas diagnosed by prenatal ultrasound in Shandong Provincial Maternal and Child Health Hospital from September 2019 to December 2021 and confirmed by surgery after birth were retrospectively analyzed.The degree of duodenal stenosis at the obstruction site was observed,especially whether the angle formed by the intestinal wall could identify the fetal annular pancreas,and the ultrasonic characteristics were summarized and analyzed.Results A total of 13 fetuses with annular pancreas showed double bubble sign,3 cases showed clamp sign,and 7 cases showed beak sign at the end of duodenal dilatation.All the 13 cases underwent surgical treatment after birth,including 2 cases with duodenal atresia and 1 case with atypical intestinal malrotation.All the children had good prognosis after operation.Conclusion By observing the dilated end of duodenum and the relationship with pancreatic head,prenatal ultrasound combined with beak sign and double bubble sign could improve the diagnostic accuracy of fetal annular pancreas,which has significant value in prenatal diagnosis of fetal annular pancreas.

Objective:To assess the value of cerebral small vessel disease (CSVD) burden in predicting prognosis in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO) after endovascular therapy (EVT).Methods:The study was a cross-sectional study. A total of 242 patients with AIS due to anterior circulation LVO received EVT in the First Affiliated Hospital of Nanjing Medical University from February 2018 to September 2022. The clinical and imaging data of all patients were analyzed retrospectively. On follow-up MRI within 7 days after EVT, CSVD features [white matter hyperintensity (WMH), lacune, perivascular space, cerebral microbleed, cerebral atrophy] and CSVD burden score (0-5) was evaluated. Modified Rankin scale (mRS) score at 90 days after EVT was assessed. Patients were categorized into a mild burden group (0-1 points) and a moderate-severe burden group (2-5 points) based on CSVD burden score. Meanwhile, patients were categorized into a good prognosis group (0-2 points) and a bad prognosis group (3-6 points) based on mRS score at 90 days after EVT. Mann-Whitney U test and χ2 test were used to compare the difference of clinical and imaging indexes between the 2 groups, and variables with P<0.1 in the univariate analysis were included in the multifactorial logistic regression to screen for independent factors to predict the prognosis. Results:There were 169 patients in the good prognosis group and 73 patients in the bad prognosis group out of 242 patients. Compared with the good prognosis group, age, incidence of hyperlipidemia, baseline National Institutes of Health Stroke Scale (NIHSS) scores, incidence of hemorrhagic conversion, CSVD burden scores, incidence of periventricular WMH scores of 3 and/or deep WMH scores≥2, and incidence of moderate-severe cerebral atrophy of patients in the bad prognosis group were higher, and the incidence of complete recanalization was lower (all P<0.05). Multivariate analysis showed hyperlipemia ( OR=8.438, 95% CI 1.691-42.119, P=0.009), baseline NIHSS score ( OR=1.103, 95% CI 1.047-1.162, P<0.001), complete recanalization ( OR=0.131, 95% CI 0.038-0.454, P=0.001) and hemorrhage transformation ( OR=1.952, 95% CI 1.031-3.697, P=0.040) were independent factors for the prognosis of EVT in patients with LVO AIS. There were 157 cases in the mild burden group and 85 cases in the moderate-severe burden group. The 90-day mRS score was higher in the moderate-severe burden group compared with the mild burden group ( Z=-2.24, P=0.025). Conclusion:CSVD burden has some clinical implications in predicting the prognosis of EVT in patients with anterior circulation LVO AIS.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.