Rheumatoid arthritis （RA） is a common chronic systemic autoimmune disease with synovitis as the main manifestation， which often causes joint swelling and pain or even deformity. It is considered to be an incurable lifelong disease. Although the current Western medicine treatment can alleviate the progression of the disease， it has the clinical limitations of liver injury， cardiovascular complications， and other adverse reactions， along with easy recurrence. Traditional Chinese medicine （TCM） has a long history and has the advantages of individualized treatment and fewer adverse reactions. It can effectively relieve the symptoms of joint swelling and pain in RA patients and slow down the progression of bone destruction， which has attracted wide concern in the medical community. Janus kinase （JAK）/signal transducer and activator of transcription （STAT） signaling pathway is an important intracellular pathway involved in cell proliferation， differentiation， apoptosis， immune regulation， and other biological behaviors， and plays an important role in the pathophysiological process of RA. In recent years， many studies have confirmed that TCM monomers and compounds can inhibit inflammation and angiogenesis by regulating the JAK/STAT signaling pathway， induce apoptosis and inhibit proliferation of fibroblast-like synoviocytes （FLS）， regulate immune response， and thus exert an effect in the treatment of RA. However， there is still a lack of comprehensive and systematic induction and overview. Therefore， by searching the relevant literature in China National Knowledge Infrastructure （CNKI） and PubMed databases from 2009 to 2024， this study described the mechanism of the JAK/STAT signaling pathway in the occurrence and development of RA and summarized the research progress of TCM monomers and compounds in regulating the JAK/STAT signaling pathway in RA intervention. The study aims to provide new ideas and strategies for the clinical treatment of RA with TCM and the research and development of new drugs.

目的 系统评估阻塞性睡眠呼吸暂停（OSA）与脑小血管病（CSVD）影像特征的关系，以期深入探索OSA在CSVD发生、发展中的潜在机制，并为优化临床管理策略提供新的科学依据。方法 收集自2021年5月—2023年10月期间入院的首发缺血性脑卒中合并CSVD的患者。完善头部MRI，评估CSVD影像学特征，并完善睡眠呼吸检测，计算OSA的特异性指标“低氧负荷（HB）”，并与传统指标对比，采用多因素Logistic回归分析研究这些缺氧指标与CSVD之间的关系，并绘制ROC曲线以比较缺氧指标与结局指标的相关性。结果 共纳入243例首发急性缺血性脑卒中患者，男性155例（63.8%），女性88例。多因素Logistic回归分析发现HB（OR=1.037，95%CI 1.020~1.055，P<0.001）和呼吸暂停低通气指数（AHI）（OR=1.044，95%CI 1.020~1.070，P<0.001）均与脑白质高信号（WMH）呈显著正相关。绘制ROC曲线结果显示，HB（AUC=0.722）与WMH的相关性优于AHI（AUC=0.670）。而睡眠期间血氧饱和度低于90%的时间总和（T90）、血氧饱和度下降指数（ODI）与WMH无关。OSA与扩大的血管周围间隙（EPVS）、脑微出血（CMB）、腔隙性脑梗死（LI）无相关性。结论 相较于传统评估指标，HB与WMH关联性更强，可作为OSA患者风险评估的更有效指标，为个体化干预提供精准依据。 Abstract Objective To systematically evaluate the association between obstructive sleep apnea （OSA） and the radiological features of cerebral small vessel disease （CSVD）， to investigate the potential mechanism of OSA in the development and progression of cerebrovascular diseases， and to provide a new scientific basis for optimizing clinical management strategies. Methods The patients with first-episode ischemic stroke and CSVD who were admitted from May 2021 to October 2023 were enrolled according to the inclusion and exclusion criteria. Cranial MRI was performed to evaluate the radiological features of CSVD， and sleep respiration testing was conducted to calculate hypoxic burden （HB）， a specific indicator for OSA， which was compared with traditional indicators. The multivariate logistic regression analysis was used to investigate the association between these hypoxic indicators and CSVD， and the receiver operating characteristic （ROC） curve was plotted to compare the correlation between hypoxic indicators and outcome measures. Results A total of 243 patients with first-episode acute ischemic stroke were enrolled in this study， among whom there were 155 male patients （63.8%） and 88 female patients. The multivariate logistic regression analysis showed that both HB OR=1.037， 95%CI 1.020-1.055， P<0.001） and apnea-hypopnea index （AHI）（OR=1.044， 95% CI 1.020-1.070， P<0.001） were significantly positively correlated with white matter hyperintensities （WMH）.The ROC curve analysis showed that the correlation between HB and WMH （AUC=0.722） was better than that between HB and AHI（AUC=0.670）. However， sleep time with oxygen saturation below 90% and oxygen desaturation index were not associated with WMH. OSA was not associated with enlarged perivascular spaces， cerebral microbleeds， or lacunar infarction. Conclusion Compared with traditional indicators， HB has a stronger correlation with WMH and can be used as a more effective indicator for risk assessment in OSA patients， thereby providing a precise basis for individualized intervention.

Diabetic retinopathy(DR), the most common microvascular complication of diabetes, has become a leading cause of visual impairment and blindness across all age groups. The early diagnosis and severity assessment of DR rely on the precise evaluation of retinal microvascular alterations. The periarterial capillary-free zone(paCFZ), a physiological avascular region surrounding retinal arteries, has recently been recognized as an important biomarker reflecting the status of retinal microcirculation. Advances in optical coherence tomography angiography(OCTA)have enabled noninvasive, high-resolution quantification of the paCFZ, offering a novel approach for the early detection and stratification of DR. This review systematically summarizes the definition and developmental mechanism of the paCFZ, as well as its morphological characteristics across different stages of DR, with a particular focus on the advantages of OCTA in visualizing and quantifying the paCFZ. We further discuss the differential manifestations of the paCFZ in nonproliferative DR and proliferative DR, and its associations with retinal ischemia and oxygenation status. In addition, the potential clinical value of paCFZ in evaluating responses to anti-vascular endothelial growth factor(VEGF)therapy and predicting disease progression is summarized. Finally, the challenges in clinical translation and future research directions are addressed, aiming to provide theoretical support and new perspectives for early screening, risk stratification, and personalized management of DR.

[摘 要] 目的：探讨DNA甲基转移酶1（DNMT1）通过稳定zeste基因增强子同源物2（EZH2）促进结直肠癌（CRC）HCT8细胞增殖与迁移的机制。方法：利用生物信息学方法分析DNMT1在CRC组织中的表达水平。WB法检测DNMT1在CRC细胞HCT8、SW620和正常结肠上皮细胞NCM460中的表达。通过siRNA或慢病毒载体转染HCT8细胞，分为siNC组、siDNMT1组、Vector组、DNMT1-OE组、siTRAF6组、siEZH2组、siEZH2 + DNMT1-OE组。采用克隆形成实验、CCK-8法、Transwell实验和划痕愈合实验检测敲低或过表达DNMT1对HCT8细胞增殖与迁移的影响，WB和qPCR法检测EZH2蛋白和mRNA水平，免疫沉淀（IP）法检测EZH2泛素化水平，免疫荧光双染检测肿瘤坏死因子受体相关因子6（TRAF6）与EZH2的细胞内共定位情况，克隆形成和划痕愈合实验验证EZH2对DNMT1功能的逆转作用。收集2022—2025年间郑州大学附属洛阳中心医院手术切除的12例CRC患者的癌及癌旁组织标本，采用免疫组化法检测CRC组织中DNMT1、TRAF6和EZH2的表达水平。结果：DNMT1在CRC组织中表达显著高于癌旁组织（P < 0.01），且在CRC细胞中表达上调（P < 0.05）；DNMT1敲低显著抑制HCT8细胞增殖及迁移（均P < 0.01），过表达则相反（均P < 0.01）。DNMT1正向调控EZH2的蛋白水平（P < 0.01），而mRNA水平不变（P > 0.05）。MG132可恢复siDNMT1组的EZH2蛋白表达（P < 0.01），且siDNMT1组EZH2泛素化水平升高。DNMT1负向调控TRAF6的表达（P < 0.01），且TRAF6与EZH2在细胞质中共定位，IP证实两者直接结合。敲低TRAF6可减弱EZH2的泛素化水平，敲低EZH2可逆转DNMT1对HCT8细胞增殖、迁移的促进作用（均P < 0.01）。DNMT1和EZH2在CRC组织中呈高表达（P < 0.01），TRAF6在CRC组织中表达显著低于癌旁组织（P < 0.05）。结论：DNMT1通过抑制TRAF6稳定EZH2促进CRC细胞的增殖和迁移，DNMT1、TRAF6和EZH2可能是CRC治疗的潜在靶点。

ObjectiveTo explore the mechanism by which Tangbikang granules improve diabetic peripheral neuropathy based on ferroptosis mediated by the adenosine monophosphate-activated protein kinase/nuclear factor erythroid 2-related factor 2 （AMPK/Nrf2） signaling pathway. MethodsA diabetes model was established using spontaneous male Zucker diabetic fatty （ZDF） rats. After successful modeling， the rats were divided into a normal group， a model group， high-， medium-， and low-dose Tangbikang granules groups， and a metformin hydrochloride group. The high-， medium-， and low-dose Tangbikang granules groups were administered by gavage at doses of 2.5， 1.25， 0.625 g·kg^-1， respectively. The metformin hydrochloride group received 0.135 g·kg^-1 by gavage， while the remaining groups received an equal volume of deionized water. Administration continued for 12 weeks. Blood glucose levels were measured after administration， and at 4， 8， 12 weeks. Following the 12-week intervention， the thermal pain threshold and the sciatic nerve conduction velocity （SNCV） were measured. The levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， and adenosine triphosphate （ATP） in the sciatic nerve were measured using enzyme-linked immunosorbent assay （ELISA）. Morphological changes in the sciatic nerve were observed using hematoxylin and eosin （HE） staining， and the ultrastructural changes were examined using transmission electron microscopy. The levels of glutathione peroxidase 4 （GPx4） were detected using immunofluorescence （IF） assay. The protein expression levels of p-AMPK， Nrf2， GPx4， and acyl-CoA synthetase long-chain family member 4 （ACSL4） were detected using Western blot. ResultsCompared with the normal group， the model group had significantly higher blood glucose levels after administration and at weeks 4， 8 and 12 （P<0.01）. The thermal pain threshold was significantly prolonged （P<0.01）， and the SNCV was significantly slowed down （P<0.01）. The SOD and ATP levels significantly decreased （P<0.01）， while the MDA levels significantly increased （P<0.01）. Pathologically， the sciatic nerve fibers in the model group showed a dispersed structure， disordered and sparse arrangement， axonal atrophy， irregular myelin sheath halo， increased and swollen Schwann cell nuclei， obvious endoneurial fibrosis， and collagen hyperplasia. Immunofluorescence assay revealed fragmented red fluorescence and significantly reduced expression of GPx4 （P<0.01）. Western blot analysis showed significantly decreased protein expression levels of p-AMPK， Nrf2， and GPx4 （P<0.01）， and significantly increased expression of ACSL4 （P<0.01） in the model group. Compared with the model group， fasting blood glucose level decreased significantly in the high-dose Tangbikang granules group at weeks 4 and 12 （P<0.05）. The thermal pain threshold was significantly shortened in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SNCV was significantly accelerated in the high- and medium-dose Tangbikang granules groups （P<0.01）. The SOD levels were significantly elevated in the high-dose Tangbikang granules group （P<0.01）. The MDA levels significantly decreased in all Tangbikang granules groups （P<0.01）. Both the metformin hydrochloride group and the high-dose Tangbikang granules group exhibited relatively orderly and densely arranged sciatic nerve fibers with more regular myelin sheath halos. The GPx4 expression significantly increased in both the metformin hydrochloride group and all Tangbikang granules groups （P<0.01）. The protein expression levels of p-AMPK， Nrf2， and GPx4 were significantly increased （P<0.01）， while ACSL4 protein expression significantly decreased （P<0.01）. ConclusionTangbikang granules may improve peripheral neuropathy by suppressing ferroptosis through the regulation of the AMPK/Nrf2 signaling pathway.

Short stature(SS) and disorder of sex development(DSD) are two types of conditions characterized by high clinical heterogeneity and complex etiology. There is interplay and mutual influence between the pathways regulated by growth hormone and sex hormones in skeletal and gonadal development. Causing co-occurrence of SS and DSD, as seen in conditions such as Turner syndrome, mixed gonadal dysgenesis, Noonan syndrome, and Prader-Willi syndrome. Patients with these disorders are often accompanied by distinctive facial features, endocrine and metabolic disturbances, cardiovascular disease, and other systemic complications. Genetic factors involved include chromosomal numerical and structural abnormalities; mutations in genes such as SHOX, CHD7, SOX8, and PTPN11, dysregulation of the RAS/mitogen activated protein kinase signaling pathway, and defects in imprinted genes. This article aims to systematically review the relevant research progress, in order to provide a reference for the clinical diagnosis and treatment strategies of patients with coexisting SS and DSD.

OBJECTIVE: To explore the prenatal and postnatal phenotypes of 22q11.2 microdeletion syndrome (22q11.2DS) and enhance clinical understanding of this condition. METHODS: Data were collected from 86 fetuses diagnosed with 22q11.2DS at four prenatal diagnostic centers across China between January 2014 and August 2025. Prenatal imaging findings, pregnancy outcomes, and postnatal conditions were analyzed. RESULTS: Among the 86 fetuses, complete ultrasound data were available for 65 cases. Cardiovascular abnormalities were observed in 42 cases, thymic hypoplasia or aplasia in 7 cases, urinary system anomalies in 6 cases, nuchal translucency (NT) thickening in 7 cases, butterfly vertebrae, clubfoot, omphalocele and diaphragmatic hernia in 1 case each, cleft lip and palate in 2 cases, and ultrasound soft markers in 13 cases. The parents of 9 fetuses opted to continue with the pregnancy. Among these, 6 showed no significant ultrasound abnormalities and no related phenotypes postnatally, while the remaining 3 exhibited ultrasound anomalies with postnatal manifestations including developmental delay, immunodeficiency, and cardiac defects. CONCLUSION Fetuses with 22q11.2DS may exhibit various ultrasound abnormalities in multiple systems before and after birth. In addition to cardiovascular anomalies, they may also present with thymic hypoplasia or aplasia, thickened NT, and urinary abnormalities. Fetuses with thickened NT or thymic anomalies should be closely monitored, and thymic assessment should be included in routine prenatal imaging evaluations. For fetuses with 22q11.2DS who show no ultrasound abnormalities, the risk of developing severe phenotypes after birth is relatively low, but occult palate clefts and psychiatric disorders cannot be ruled out. Due to limitations in sample size and follow-up duration, above conclusions require further validation through large-scale prospective studies.
Humans ; Female ; Pregnancy ; Ultrasonography, Prenatal ; DiGeorge Syndrome/genetics* ; Adult ; Male ; Follow-Up Studies ; Fetus/diagnostic imaging* ; Phenotype ; Infant, Newborn

Polycystic kidney disease (PKD) is a group of inherited disorders characterized by cystic lesions in the kidneys and multiple organs, primarily including autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD). ADPKD is mainly caused by variations in the PKD1 and PKD2 genes. Its clinical manifestations include progressive renal cyst growth, hypertension, and multi-system complications. ARPKD, on the other hand, is primarily caused by mutations in the PKHD1 gene. It commonly occurs in infants and young children, with hepatorenal cystic fibrosis being a key feature. Although there is currently no cure for PKD, the integration of multi-omics and precision medicine strategies holds promise for optimizing patient management and improving outcomes in the future. This review summarizes the genetic basis, pathogenic mechanisms, diagnostic techniques, and therapeutic advances in PKD, providing a reference for clinical practice and research.
Humans ; Polycystic Kidney Diseases/genetics* ; TRPP Cation Channels/genetics* ; Mutation ; Polycystic Kidney, Autosomal Dominant/therapy* ; Receptors, Cell Surface

ObjectiveTo investigate the cardioprotective effects of ginsenoside Rg₂ in regulating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway following acute myocardial infarction （AMI） in rats. Methods（1） Cellular experiment： Cardiomyocytes were isolated from 24-hour-old Sprague-Dawley （SD） neonatal rats and subjected to primary culture. An in vitro model of cardiomyocytes under an ischemic-hypoxic microenvironment was established. Cardiomyocytes were pretreated with ginsenoside Rg₂ （1， 2， 3 mg·L^-1） for 4 hours， then placed in RPMI 1640 serum-free medium and cultured for 24 hours in a three-gas incubator （94% N₂， 5% CO₂， 1% O₂）. The survival rate of cardiomyocytes was assessed using the methyl thiazolyl terazolium （MTT） assay. The levels of lactate dehydrogenase （LDH） leakage， superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px） activity， and malondialdehyde （MDA） content in the cell culture supernatant were measured using spectrophotometry. （2） Animal experiment： Specific-pathogen-free （SPF） SD rats were used to establish an AMI model using the Olivette method combined with previous studies. Rats that survived 24 hours post-surgery were randomly divided into a model group and ginsenoside Rg₂ high-， medium-， and low-dose groups. The normal and model groups received normal saline， while the ginsenoside Rg₂ groups were administered intragastrically at doses of 8， 4， and 2 mg·kg^-1， once daily for 3 days. The levels of SOD， MDA， and GSH-Px in myocardial tissues were detected. Cardiomyocyte apoptosis was assessed using the TdT-mediated dUTP biotin nick end labeling （TUNEL） assay. The mRNA and protein expression levels of PI3K， Akt， mTOR， p62， nuclear factor-κB p65 （NF-κB p65）， and microtubule-associated protein 1 light chain 3 （LC3） Ⅱ/Ⅰ in myocardial tissues were analyzed using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot. Pathological changes in the infarct border zone were observed under a light microscope. Results（1） Cellular experiment： Compared with the normal group， the model group exhibited a significantly decreased cardiomyocyte survival rate， as well as reduced SOD and GSH-Px activity， whereas LDH activity and MDA content were significantly increased （P<0.05）. Compared with the model group， ginsenoside Rg₂ intervention significantly increased cardiomyocyte survival， SOD activity， and GSH-Px activity， while reducing LDH activity and MDA content （P<0.05） in a dose-dependent manner. Pathological examination revealed that ginsenoside Rg₂ alleviated infarct size， myocardial degeneration， and necrosis， while significantly reducing cardiomyocyte apoptosis. （2） Animal experiment： Compared with the normal group， the model group exhibited significantly lower SOD and GSH-Px activity （P<0.05） and higher MDA content （P<0.05） in myocardial tissues. Compared with the model group， all ginsenoside Rg₂ groups showed significantly increased SOD and GSH-Px activity （P<0.05） and reduced MDA content （P<0.05）. Compared with the normal group， the model group exhibited significantly decreased mRNA and protein expression levels of PI3K， Akt， mTOR， p62，and LC3 Ⅱ/Ⅰ，whereas the expression levels of NF-κB p65 were significantly increased （P<0.05）. Compared with the model group， the ginsenoside Rg₂ groups showed significantly increased PI3K， Akt， mTOR， and p62 expression， while NF-κB p65 expression levels were significantly decreased （P<0.05） in a dose-dependent manner，the mRNA and protein expression levels of LC3 Ⅱ/Ⅰ in ginsenoside Rg₂ high-dose groups were significantly increased（P<0.05）. ConclusionGinsenoside Rg₂ exerts cardioprotective effects following AMI in rats， potentially through the regulation of PI3K/Akt/mTOR-related protein expression.

Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.