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.

OBJECTIVE To investigate the effects and potential mechanism of curcumin on neurological injury in neonatal rats with bacterial meningitis based on the signal transducer and activator of transcription 1（ STAT1）/ nucleotide-binding domain leucine- rich repeat and pyrin domain-containing receptor 3 （NLRP3） signaling pathway. METHODS Neonatal rats， with an equal number of males and females， were randomly divided into control group， model group， curcumin low-dose （Cur-L）， medium-dose （Cur- M） and high-dose （Cur-H） groups， and Cur-H+STAT1 transcription enhancer [2-（1，8-naphthyridin-2-yl）phenol] group （Cur-H+2- NP group）， with 15 rats in each group. Except for the control group， rats in other groups were injected with a suspension of group B Streptococcus （1×104 cfu/mL， 10 μL） into the cerebellomedullary cistern to establish a bacterial meningitis model. After successful model establishment， rats in Cur-L， Cur-M and Cur-H groups were intraperitoneally injected with 1.25， 2.5 and 5 mg/kg curcumin， respectively， and those in the Cur-H+2-NP group were intraperitoneally injected with 5 mg/kg curcumin and 0.5 mg/kg 2- NP， once a day， for 3 consecutive weeks. After the last administration， modified Loeffler score was conducted， white blood cells （WBC） count in cerebrospinal fluid as well as the contents of inflammatory factors [tumor necrosis factor-α， interleukin-6 （IL-6）， IL-1β and IL-18]， brain water content and blood-brain barrier permeability were detected； the histopathological changes of hippocampus and cortex tissues were observed. The percentage of apoptosis in hippocampal/cortical tissue cells， the positive expression of ionized calcium-binding adapter molecule-1 （Iba-1）， the co-localization of Iba-1 and NLRP3， as well as the expressions of proteins related to the STAT1/NLRP3 signaling pathway （phosphorylated STAT1， NLRP3， apoptosis-associated speck-like protein containing a CARD， gasdermin D， caspase-1， IL-1β and IL-18） were examined. RESULTS Compared with the control group， the neurons in the hippocampal/cortical tissues of rats in the model group exhibited significant morphological abnormalities， accompanied by neuronal edema and necrosis， as well as infiltration of inflammatory cells. The modified Loeffler score and the number of Nissl bodies were significantly decreased/reduced in the model group， while the WBC count， levels of inflammatory factors， brain water content， blood-brain barrier permeability， HE staining score， number of degenerated neurons， percentage of apoptotic cells， positive expression of Iba-1， percentage of Iba-1 and NLRP3 co-localization- positive cells， and expressions of pathway-related proteins were all significantly rose/increased/upregulated （P＜0.05）. Compared with the model group， the histopathological changes in the hippocampal/cortical tissues of rats in all curcumin dosage groups were alleviated to varying degrees， with significant improvements in all quantitative indicators （P＜0.05）； conversely， 2-NP significantly reversed the ameliorative effects of curcumin on these quantitative indicators （P＜0.05）. CONCLUSIONS Curcumin can alleviate cerebral edema and blood-brain barrier damage， reduce neuroinflammation， inhibit cell apoptosis and pyroptosis， and thereby alleviate neuronal injury in neonatal rats with bacterial meningitis. The underlying mechanism may be related to the inhibition of the STAT1/NLRP3 signaling pathway.

Pulmonary rehabilitation (PR) has become an indispensable component of the modern care continuum for lung cancer. Substantial evidence confirms its definitive value in improving perioperative outcomes, mitigating treatment-related side effects, and enhancing quality of life in patients with advanced disease. However, a significant "implementation gap" exists between its proven clinical benefits and widespread application, primarily characterized by the lack of standardized protocols, uncertainty in optimal timing, and low patient adherence. Bridging this gap requires a dual-driven approach: harnessing technological innovations such as telerehabilitation, wearable devices, and artificial intelligence to enhance accessibility and personalization, alongside optimizing care models through multidisciplinary team collaboration. This review systematically analyzes the evidence, implementation barriers, and innovative pathways for PR in lung cancer care, aiming to catalyze its transition from an ancillary option to a core standard of care, and envisions a new paradigm of personalized PR that is patient-centered, data-driven, and technologically integrated.

[摘 要] 目的：探讨异位表达血红蛋白亚基（HBA/HBB）对缺氧条件下嵌合抗原受体T细胞（CAR-T细胞）功能障碍的改善作用及其对肿瘤细胞的杀伤效应。方法：全基因合成技术合成靶向HER2的CAR序列，构建共表达HBA或HBB的CAR慢病毒载体，包装慢病毒后感染人原代T淋巴细胞，制备异位表达HBA/HBB的CAR-T细胞，命名为HBA CAR-T和HBB CAR-T。采用缺氧探针检测小鼠实体瘤缺氧状态。通过流式细胞术检测瘤内CAR-T细胞占比、异位表达血红蛋白亚基的CAR-T细胞阳性率及CAR-T细胞的活性氧、凋亡水平。WB法检测HBA CAR-T和HBB CAR-T内相关血红蛋白亚基表达情况，采用细胞计数板计数检测细胞增殖水平，通过萤光素酶报告基因法检测CAR-T细胞对肿瘤细胞的杀伤能力，qPCR检测CAR-T细胞中缺氧诱导因子-1α（HIF-1α）表达水平，利用MitoXpress Intra试剂盒检测CAR-T细胞内氧气含量。结果：不同细胞构建的实体瘤模型均存在明显缺氧情况，且CAR-T细胞浸润水平与缺氧程度呈显著负相关（P < 0.000 1）。HBA CAR-T与HBB CAR-T构建成功（阳性率 > 60%），相应血红蛋白亚基可稳定表达。缺氧环境下HBA CAR-T和HBB CAR-T的ROS水平、凋亡水平显著下降，增殖、对肿瘤细胞的体外杀伤能力显著强于传统CAR-T细胞（均P < 0.05）。HBA CAR-T与HBB CAR-T内HIF-1α表达降低（均P < 0.001），且缺氧程度显著降低（均P < 0.001）。结论：异位表达血红蛋白亚基可改善缺氧条件下CAR-T细胞功能障碍并增强其对肿瘤细胞的体外杀伤作用。

AIM:To investigate the protective effects of soy isoflavones on retinal ganglion cells(RGCs)damage in diabetic rats and related mechanisms.METHODS: Totally 80 male SD rats(80 eyes), aged 4-6 weeks, were randomly divided into four groups(n=20 per group): a control group, a diabetic model group, a low-dose soy isoflavone treatment group, and a high-dose soy isoflavone treatment group. Among them, the control group was fed normal chow, while the diabetic group, soy isoflavone low-dose-treated group, and soy isoflavone high-dose-treated group were fed high-fat chow. After a feeding period of 4 wk, rats in the diabetic group, as well as those in the soy isoflavone low-dose and high-dose treatment groups, were injected intraperitoneally with streptozotocin(STZ)at a dose of 50 mg/kg to establish a diabetic model. Rats in the control group received an equivalent volume of sodium citrate buffer acid. The soy isoflavone low-dose-treated group was administered 360 mg/kg of soy isoflavones daily via gavage, while the soy isoflavone high-dose-treated group received 540 mg/kg of soy isoflavones daily via gavage. Both the control group and the diabetic group were given an equal amount of purified water daily via gavage. Body weight and blood glucose levels were measured at 4 and 8 wk post-gavage treatment. The eyes were extracted and the retinas were dissected at 8 wk following the gavage treatment. The number of RGCs in each group was determined using immunochemical tissue staining and protein blotting techniques, while the superoxide dismutase(SOD)activity and malondialdehyde(MDA)content of the rat retinal tissue were measured through histochemical methods.RESULTS: Compared with diabetic rats, treatment with high-dose soy isoflavones for 8 wk resulted in a reduction of blood glucose to 8.9±1.23 mmol/L, an increase in intraretinal SOD activity to 849.93±63.71 U/mgprot, a decrease in MDA content to 45.77±0.59 nmol/mgprot, and an increase in the number of RGCs to 76±1 cells/mm2, which is comparable to the control group's data(all P<0.05).CONCLUSION: Soy isoflavones can reduce retinal oxidative stress in diabetic rats and protect RGCs.

Objective:To investigate the impact of vitamin D deficiency on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with polycystic ovary syndrome (PCOS) and normal ovarian reserve (NOR). Methods:A retrospective cohort study was conducted on infertile women undergoing their first IVF-ET cycle in the Department of Reproductive Genetics, Zhengzhou Maternity and Child Health Care Hospital from January 2018 to December 2023, including 318 PCOS patients (group P) and 528 NOR patients (group N). Each group was divided into three subgroups according to serum 25-hydroxyvitamin D [25(OH)D] levels: severe deficiency [25(OH)D<12 μg/L], deficiency [12 μg/L≤25(OH)D<20 μg/L], and non-deficiency [25(OH)D≥20 μg/L]. The impact of vitamin D deficiency on pregnancy outcomes was analyzed in each group. 1∶1 propensity score matching was applied to match the baseline characteristics between group P and group N , resulting in 158 matched cases of PCOS (group P) and NOR (group N). Pregnancy outcomes were compared between the two groups under the same vitamin D status.Results:1) Among PCOS patients, there were no significant differences in general characteristics and pregnancy outcomes among the three subgroups (all P>0.05). The two pronuclei (2PN) rate in the severe deficiency subgroup [59.93% (721/1 203)] was significantly lower than that in the deficiency subgroup [63.70% (1 032/1 620)], with a statistically significant difference ( P=0.045), and both were lower than that in the non-deficiency subgroup [68.06% (554/814)], with a statistically significant difference ( P<0.001, P=0.037). There were no statistically significant differences in the number of oocytes retrieved and MⅡ oocytes, MⅡ oocyte rate, 2PN number, 2PN rate, cleavage number, cleavage rate, number of available embryos on day 3 (day 3, D3), number of high-quality embryos on D3, D3 high-quality embryo rate, clinical pregnancy rate, embryo implantation rate, early miscarriage rate, live birth rate, and premature birth rate among subgroups (all P>0.05). Female age ( OR=0.930, 95% CI: 0.871-0.992, P=0.028), endometrial thickness on the day of transfer ( OR=0.877, 95% CI: 0.791-0.971, P=0.012), number of D3 high-quality embryos ( OR=1.135, 95% CI: 1.050-1.228, P=0.001), and ovulation stimulating protocol ( OR=2.230, 95% CI: 1.153-4.314, P=0.017) were independent factors influencing clinical pregnancy. 2) Among NOR patients, there were no significant differences in general characteristics, pregnancy outcomes, laboratory parameters, or other outcome-related indices among the three subgroups (all P>0.05). Female age ( OR=0.944, 95% CI: 0.900-0.990, P=0.018), number of D3 high-quality embryos ( OR=1.070, 95% CI: 1.004-2.597, P=0.037), and number of transferred embryos ( OR=1.753, 95% CI: 1.184-2.597, P=0.005) were independent factors influencing clinical pregnancy. 3) After matching, there were no significant differences in baseline characteristics and pregnancy outcomes between group P and group N (all P>0.05). In the severe vitamin D deficiency state, group P had significantly lower MⅡ oocyte rate [76.64% (525/685)], 2PN rate [59.69% (345/578)], embryo implantation rate [35.71% (30/84)], and live birth rate [34.00% (17/50)] compared with group N [81.58% (465/570), P=0.033; 67.00% (335/500), P=0.013; 51.28% (40/78), P=0.046; 55.32% (26/47), P=0.035]. In the vitamin D deficiency state, the 2PN rate in group P [66.50% (532/800)] was significantly lower than that in group N [72.00% (725/1 007), P=0.012]. Conclusion:Vitamin D deficiency may adversely affect IVF-ET outcomes in patients with PCOS, with more pronounced effects in cases of severe deficiency. However, it has no impact on the assisted reproductive outcomes in NOR patients.

Objective:To investigate the status of lymph node metastasis in transverse colon cancer and its association with clinicopathological characteristics and prognosis.Methods:A retrospective cohort study was performed. Clinical data from patients with transverse colon cancer at stages T1-4, N0-2, M0 who were consecutively admitted in the Department of Colorectal Surgery, Fudan University Shanghai Cancer Center from 2010 to 2022 were retrospectively analyzed. Patients were excluded if they had a history of prior tumors, developed a second or subsequent primary malignancy during the follow-up after the current primary transverse colon cancer, or underwent emergency surgery due to complications such as gastrointestinal bleeding or obstruction. The observation indicators included: (1) lymph node metastasis status and its impact on prognosis; (2) lymph node dissection status and the impact of dissection of <12 lymph nodes on prognosis; (3) factors influencing the dissection of <12 lymph nodes. Postoperative follow-up was performed to evaluate tumor recurrence, metastasis, and survival, with a follow-up cutoff date of March, 2025. Chi-squared tests, one-way ANOVA, multivariate logistic regression, the Kaplan-Meier method, and log-rank tests were used to analyze the relevant factors of lymph node dissection and its impact on patient prognosis. Postoperative follow-up was conducted via outpatient visits and telephone interviews to assess tumor recurrence, metastasis, and survival.Results:A total of 336 transverse colon cancer patients were included, including 219 males and 117 females, with a median age of 60 years (range: 24-84 years). There were 212, 83, and 41 patients with stage N0, N1, and N2, respectively. The median number of metastatic lymph nodes in the entire cohort was 0 (range: 0-18), with an overall lymph node metastasis rate of 36.9% (124/336). The metastasis rates of the 1st, 2nd, and 3rd station lymph nodes were 30.4% (102 cases), 19.6% (66 cases), and 2.4% (8 cases), respectively. Within the T1, T2, T3, and T4 stage groups, the 1st, 2nd, and 3rd station lymph node metastasis rates were 3.1% (1/32), 0, and 0 in T1; 14.6% (6/41), 2.4% (1/41), and 0 in T2; 31.6% (54/171), 23.4% (40/171), and 2.3% (4/171) in T3; and 44.6% (41/92), 27.2% (25/92), and 4.3% (4/92) in T4, respectively. There was a statistically significant difference in the total lymph node metastasis rates among different T stages (χ2=36.816, P<0.001). Additionally, statistically significant differences were also observed in the metastasis rates of lymph nodes at Station 1 and Station 2 among different stages (χ2=24.924, P<0.001; χ2=20.338, P<0.001). However, no statistically significant difference was found in the metastasis rate of lymph nodes at station 3 (χ2=3.313, P=0.346). Skip metastasis was observed in 23 patients (6.8%), including 14 cases in T3 stage and 9 cases in T4 stage, with no skip metastasis found in T1 or T2 stages. The median follow-up time was 39 months (95%CI: 36-42). 1-, 3-, and 5-year overall survival (OS) rates were 96.6%, 87.8%, and 85.8%, respectively, and disease-free survival (DFS) rates were 94.7%, 82.6%, and 74.7%, respectively. The 5-year DFS rates in N0, N1, and N2 stages were 85.4%, 66.1%, and 41.3%, respectively (χ2=67.408, P<0.001). Patients with station 1 lymph node metastasis had a significantly lower 5-year DFS than those without metastasis (56.8% vs. 83.0%, χ2=32.348, P<0.001). Similarly, patients with station 2 lymph node metastasis had a significantly lower 5-year DFS than those without (50.2% vs. 81.0%, χ2=28.313, P<0.001). However, no significant difference in 5-year DFS was found between patients with station 3 lymph node metastasis and those without (51.4% vs. 75.1%, χ2=2.759, P=0.097). There was also no significant difference in 5-year DFS between patients with and without skip metastasis (65.0% vs. 75.5%,χ2=0.879, P=0.349). The median number of dissected lymph nodes in the entire cohort was 16 (range: 3-52). Using 12 lymph nodes as the cutoff, 286 patients (85.1%) had ≥12 lymph nodes dissected, and 50 patients (14.9%) had <12. The 5-year DFS in the <12 lymph nodes group was lower than that in the ≥12 group (62.1% vs. 76.6%), but the difference was not statistically significant (χ2=2.863, P=0.091). Univariate analysis showed that age, tumor length, high-moderate differentiation, and T stage were influencing factors for dissecting <12 lymph nodes (all P<0.1). Going further, multivariate logistic regression analysis revealed that age ≥50 years (OR=2.564, 95%CI: 1.085-6.054, P=0.032), high-moderate tumor differentiation (OR=2.582, 95% CI: 1.265-5.271, P=0.009), and T1-2 stage (OR=2.520, 95%CI: 1.177-5.396, P=0.017) were independent risk factors for dissecting <12 lymph nodes (all P<0.05). Conclusions:Lymph node metastasis in transverse colon cancer mainly occurs at the 1st and 2nd stations. Skip metastasis may occur in T3-T4 stages. For T1-2 stage transverse colon cancer, D2 radical resection can be performed, but for cancers in T3 to T4, D3 radical operation should be carried out.

In recent years,the surgical treatment model for rectal cancer has undergone profound changes.The therapeutic goal has gradually shifted from single tumor radical resection to balancing functional preservation,and the therapeutic concept has transformed from merely emphasizing surgical techniques to attaching importance to comprehensive treatment.Especially in the treatment of low rectal cancer,the neoadjuvant therapy model has been continuously optimized.For patients with good tumor regression after neoadjuvant therapy,"watch and wait"and transanal local excision have become important optional strategies.This not only avoids some severe surgery-related complications but also maximizes the preservation of patients'organ functions,bringing a qualitative leap in their quality of life.This treatment strategy is gradually expanding from locally advanced low rectal cancer to relatively early-stage low rectal cancer.In terms of surgical techniques,based on the traditional intermediate approach of"first plane,then vessels",the concept of a"vessel-centered"approach is proposed.By managing vessels first and then expanding the plane,it enables thorough dissection of lymph nodes at the root of the inferior mesenteric artery while preserving the left colic artery.With the aid of dual-fluorescence intraoperative navigation technology[indocyanine green(ICG)fluorescence and intraoperative real-time imaging system(IRIS)ureter fluorescence imaging],real-time visualization of lymph nodes and ureters is achieved,ensuring the completeness of lymph node dissection and helping to reduce the risk of ureteral injury.The angulation-free double anastomosis technique used during surgery effectively reduces the incidence of anastomotic leakage and improves surgical safety.For patients with high-risk factors for anastomotic leakage,intestinal stent bypass is expected to replace the traditional prophylactic end ileostomy,thus avoiding complications associated with prophylactic end ileostomy and the trauma caused by secondary stoma closure.In general,the development trend of surgical treatment for rectal cancer is to minimize patient trauma,preserve organ functions,and improve quality of life under the premise of ensuring oncological efficacy,promoting the development of surgical techniques towards standardization and precision to maximize patients'perioperative safety.

Objective To explore the therapeutic mechanism of berberine in atopic dermatitis(AD)rats based on PI3K/Akt/NF-kappa B signaling pathway.Methods Sixty adult male Wistar rats were randomly divided into the blank group(normal rats),the control group(AD model,50 mg/kg berberine treatment)and the experimental group(AD model,200 mg/kg berberine treatment),with 20 rats in each group.The levels of interleukin-4(IL-4),interleukin-13(IL-13)and tumor necrosis factor-α(TNF-α)were determined by enzyme-linked immunosorbent assay(ELISA)at 1 d,7 d and 14 d of intervention.The protein levels of PI3K,p-PI3K,Akt,p-Akt and NF-κB p65 were detected by Western blot assay.Pathological changes of rat skin tissue were analyzed by HE staining.Results After intervention for 1 d,7 d and 14 d,serum levels of IL-4,IL-13,TNF-α and PI3K,p-PI3K,Akt,p-Akt and NF-kappa B p65 were higher in the control group than those in the blank group(P＜0.05).After intervention for 7 d and 14 d,the levels of the above indicators were lower in the experimental group than those in the control group(P＜0.05).After 14 days of intervention,compared with the blank group,the skin tissue of rats in the control group and the experimental group showed obvious pathological changes,including thickening of epidermis layer,excessive keratinization of the stratum comeum,thickening of spinous layer and a large infiltration of inflammatory cells in dermis.The pathological damage of rat skin tissue was significantly alleviated in the experimental group.Conclusion Berberine can inhibit the activation of PI3K/Akt/NF-kappa B signaling pathway,reduce serum level of inflammatory factors and reduce pathological damage of skin tissue in AD rats.

OBJECTIVE: To investigate the clinical and genetic features of a Chinese pedigree with Progressive familial intrahepatic cholestasis (PFIC) and explore its genotype-phenotype correlation. METHODS: A patient with PFIC diagnosed at Xinxiang Central Hospital in 2023 was selected as the study subject. The patient was subjected to abdominal magnetic resonance imaging (MRI) and painless gastroscopy. Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA and trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing. This study has been approved by the Medical Ethics Committee of Xinxiang Hospital (Ethics No. 2023-241). RESULTS: MRI scan showed that the patient had significantly enlarged liver and spleen. WES revealed that he has harbored compound heterozygous variants of the ATP8B1 gene, including a c.1710_1711insCCTC (p.A571Pfs*12) frameshifting variant in exon 16 and a c.2989G>A (p.V997M) missense variant in exon 24, which were respectively inherited from his father and mother, and rated as pathogenic (PVS1+PM2_Supporting+PM3+PP1) and likely pathogenic (PM2_Supporting+PM3+PP1) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION WES can clarify the genetic etiology of patients with speed and accuracy, and facilitate clinical decision-making. The detection of pathogenic variants has provided a basis for clinical diagnosis and enriched the mutational spectrum of the ATP8B1 gene.
Humans ; Male ; Pedigree ; Cholestasis, Intrahepatic/diagnostic imaging* ; Adenosine Triphosphatases/genetics* ; Female ; Adult ; Exome Sequencing ; Mutation ; East Asian People