Rheumatic diseases are a group of chronic disorders characterized by abnormalities in the immune system， while portal hypertension occurs due to increased blood flow or heightened resistance in the portal venous system or obstruction of hepatic venous outflow. Both rheumatic diseases and their medications can lead to noncirrhotic portal hypertension. The hypercoagulable state associated with rheumatic diseases can result in thrombosis within the portal and hepatic venous systems， and damage to the intrahepatic portal system and hepatic sinusoidal endothelial system can lead to porto-sinusoidal vascular disease and hepatic sinusoidal obstruction syndrome. Moreover， drugs used for the treatment of rheumatic diseases may cause liver parenchymal injury， which further leads to liver fibrosis and cirrhosis， or they may damage the hepatic vascular endothelium and thus cause noncirrhotic portal hypertension. This article elaborates on the mechanisms and characteristics by which common rheumatic diseases and their therapeutic agents lead to portal hypertension， in order to provide insights and assistance for clinical diagnosis， treatment， and follow-up monitoring.

Objective To observe the effects of electroacupuncture on RhoA/ROCK2 signaling pathway in cerebral cortex of mice with amyotrophic lateral sclerosis(ALS);To explore the mechanism of electroacupuncture in improving the motor function of ALS mice.Methods The male hSOD1G93A mice were divided into model group and electroacupuncture group,and wild-type male mice in the same litter were set as blank group,with 12 mice in each group.After the mice were 60 days old,"Baihui"and both side of"Tianzhu","Tianshu"were selected for electroacupuncture for 10 min per day,5 days of continuous treatment and 2 days off for 3 weeks.Rotating rod experiment and open field experiment were used to evaluate the motor function of mice,the damage of neurons in cerebral cortex was observed by Nissl staining,Western blot was used to detect the expressions of Tar DNA binding protein-43(TDP-43),tumor necrosis factor(TNF)-α,interleukin(IL)-1β,RhoA and ROCK2 protein in cerebral cortex.Immunofluorescence staining was used to detect the positive expressions of ion calcium binding adapter molecule 1(Iba-1)and glial fibrillary acidic protein(GFAP)in cerebral cortex.Results Compared with the blank group,the incubation period of rod turning and the total distance of open field movement in the model group were reduced(P<0.01),the neuron damage was obvious in the cerebral cortex,with Nissl body shrinkage and reduction in quantity(P<0.01),the relative expressions of TDP-43,TNF-α,IL-1β,RhoA and ROCK2 protein increased(P<0.01),and the positive expression of Iba-1 and GFAP increased(P<0.01).Compared with the model group,the incubation period of rod turning and the total distance of open field movement increased in electroacupuncture group(P<0.05),the damage of neuron in cerebral cortex was reduced,the number of Nissl bodies increased(P<0.05),the expressions of TDP-43,TNF-α,IL-1β,RhoA and ROCK2 decreased(P<0.05),and the positive expression of Iba-1 and GFAP reduced(P<0.05).Conclusion Electroacupuncture can improve motor function in ALS model mice,and the mechanism may be related to the inhibition of RhoA/ROCK2 signaling pathway activity and then relieve neuroinflammation.

Colorectal cancer(CRC)is one of the most prevalent gastrointestinal tumors;however,its pathogenesis is poorly understood.Therapeutic strategies for CRC vary according to molecular typing.Immune checkpoint inhibitors(ICIs)have shown significant efficacy in pa-tients with mismatch repair-deficient/microsatellite instability-high(dMMR/MSI-H)CRC.However,ICIs are less effective in patients with mis-match repair-proficient/microsatellite instability-low(pMMR/MSI-L).Intestinal flora have been found to enhance immunotherapy for CRC and ameliorate immunotherapy-related adverse effects by modulating immune responses through multiple mechanisms,particularly in pa-tients with pMMR/MSI-L CRC.This article reviews the key role of intestinal flora in regulating immunotherapy for CRC,discusses the pro-gress of related studies,and considers the clinical translational prospects of diet,probiotics,and fecal microbiota transplantation(FMT).

Objective:To observe the effect of ankle joint proprioception training on ankle joint proprioception, balance and gait in patients with thalamic infarction.Methods:Fifty-six patients with thalamic infarction were divided into a control group and a treatment group, each of 28, using a random number table. Both groups were given conventional lower limb rehabilitation training, but the treatment group was additionally provided with ankle joint proprioception training. Before and after 4 weeks of the treatment, the Tecnobody proprioception testing system was used to determine the average trajectory error rate (ATE) and the time taken in the test. The Berg Balance Scale (BBS) and a balance tester were used to assess balance. A gait analyzer was used to collect spatial-temporal measures of the patients′ walking, including the stride amplitude, stride rate, the proportion of the time spent in the swing phase, and foot dorsiflexion and plantarflexion angles.Results:After the treatment, the time used, ATE, ankle proprioception, BBS scores, static balance test scores, stability limits, stride length, stride rate, swing phase time percentage, and foot dorsiflexion and plantarflexion angles had improved in both groups compared with before the treatment ( P≤0.05). Compared with the control group, the treatment group had a smaller average ATE, spent less time on the ankle proprioception test, had higher BBS scores, had lower scores on the static balance test, had larger limits of stability, took longer strides at a faster rate, and spent a greater percentage of time in the swing phase. That group also showed greater ankle dorsiflexion and plantarflexion on average ( P≤0.05). ATE difference of the affected lower limb and the time to complete the ankle proprioception test were positively correlated with the gap in the static balance ability test, and negatively correlated with the gaps in the BBS score, the limits of stability, stride length, stride rate, and the time share of the swing phase, as well as the dorsiflexion and plantarflexion angles of the foot. Conclusions:Ankle proprioception training, in addition to effectively improving ankle proprioception, can improve the balance and gait of persons with thalamic infarction. It is worthy of clinical application and promotion.

Objective:To analyze the efficacy of phantom-less quantitative computer tomography (PL-QCT) for the diagnosis of osteoporosis in patients with lumbar degenerative diseases.Methods:From October 2021 to October 2023, a total of 1 248 patients with lumbar degenerative disease who did not receive anti-osteoporosis treatment in the Department of Spine Surgery, Tianjin Hospital were retrospectively analyzed. There were 520 males and 728 females, aged 62.31±9.37 years (range, 40-87 years), height 1.66±0.08 m (range, 1.43-1.89 m), weight 69.04±8.27 kg (range, 49-93 kg). The mean body mass index was 26.11±3.67 kg/m 2 (range, 14.40-37.11 kg/m 2). Dual-energy X-ray absorptiometry (DXA) and PL-QCT were used to diagnose osteoporosis, and the detection rates of the two diagnostic methods were compared. The receiver operating characteristic (ROC) curve of PL-QCT for the diagnosis of osteoporosis was drawn, the area under the curve (AUC) and 95% confidence interval (CI), sensitivity and specificity were calculated. Results:Among 1 248 patients with lumbar degenerative diseases, 626 (50.2%) were diagnosed as osteoporosis by PL-QCT, 423(33.9%) were diagnosed by spine DXA, 488(39.1%) were diagnosed by hip DXA and 539 patients(43.2%) were diagnosed by dual-site DXA. The detection rate of osteoporosis of PL-QCT was higher than that of spine DXA (χ 2=193.557, P<0.001), hip DXA (χ 2=322.201, P<0.001) and dual-site DXA (χ 2=94.683, P<0.001), and the difference was statistically significant. Taking the diagnostic results of spinal DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 79%, a specificity of 81%, and an AUC and 95% CI of 0.82(0.79, 0.85). Taking the diagnostic results of hip DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 85%, a specificity of 55%, and an AUC and 95% CI of 0.75(0.71, 0.78). Taking the diagnostic results of two-site DXA for osteoporosis as a reference, the ROC curve of PL-QCT for the diagnosis of osteoporosis showed a sensitivity of 72%, a specificity of 75%, and an AUC and 95% CI of 0.81(0.78, 0.83). Conclusion:Compared with DXA, PL-QCT has a higher detection rate of osteoporosis in patients with degenerative lumbar spine disease and good diagnostic efficacy.

Objective:To analyze the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Beijing in 2024, to investigate the infection status of reservoir hosts, vector organisms, and baseline human populations, and provide a scientific basis for formulating prevention and control strategies.Methods:Epidemiological surveys were conducted on all confirmed cases. Serum samples from healthy populations and reservoir hosts were collected for SFTSV antibody detection. Questing ticks were monitored using the flagging method. Real-time fluorescent quantitative PCR was employed to detect SFTSV in cases, reservoir hosts, and ticks. Positive samples underwent whole-genome sequencing and genetic evolution analysis.Results:In 2024, Beijing reported 15 locally infected cases with 4 deaths. The age of onset ranged from 50 to 80 years (median: 66 years). Cases showed a certain degree of geographical clustering, with June being the peak month of onset. The affected population was predominantly farmers, with a male-to-female ratio of 3∶2. Animal contact history emerged as a significant risk factor alongside tick bites. Parthenogenetic tick populations were identified in Pinggu district, while SFTSV-carrying ticks were detected in endemic areas (Mentougou, Shijingshan, and Fengtai Districts). Viral presence was also confirmed in ticks or dogs from non-endemic areas. Sequencing and phylogenetic analysis revealed stable clustering of strains into two distinct genotypes (A and B). Antibody-positive individuals were identified in healthy populations from non-endemic areas.Conclusions:The incidence of SFTS in Beijing is increasing, with natural viral circulation already established in non-endemic regions. Enhanced surveillance and adjusted prevention strategies are urgently needed.

OBJECTIVE: To observe the effects of "olfactory three needles" on cognition, learning and memory abilities, as well as hippocampal microglia (MG) phagocytic activity in vascular dementia (VD) rats, and explore the mechanisms of acupuncture in regulating MG activation and improving remyelination, so as to ameliorate VD. METHODS: Among 38 SD rats meeting experimental requirements, 9 rats were randomly assigned to a sham-operation group, and the remaining rats underwent permanent bilateral common carotid artery ligation to establish VD model. Eighteen successfully modeled rats were randomly divided into a model group and an electroacupuncture (EA) group, with 9 rats in each one. In the EA group, EA was performed at "olfactory three needles" ("Yintang" [GV24⁺] and bilateral "Yingxiang" [LI20]), at disperse-dense wave, the frequency of 2 Hz/15 Hz and the current intensity of 1 mA, for 15 min per intervention, once daily. One course was composed of 7 days, and 2 courses were required, with the interval of 2 days. The novel object recognition test was employed to assess the cognition of rats, and the Morris water maze was adopted to observe learning and memory abilities. Luxol fast blue (LFB) staining was performed to evaluate myelin sheath loss in the hippocampus, the Western blot was used to detect the protein expression of triggering receptor expressed on myeloid cells-2 (TREM2) and proteolipid protein (PLP) in the hippocampus; and the immunofluorescence staining was used to detect the positive expression of PLP, sex determining region Y-box 10 (SOX10), ionized calcium binding adaptor molecule 1 (Iba1)⁺ TREM2⁺ and Iba1⁺ lysosome-associated membrane protein 1 (LAMP1)⁺ in the hippocampus. RESULTS: Compared with the sham-operation group, the rats in the model group exhibited the prolonged escape latency on day 3 and 4 (P<0.05, P<0.01), the increase of the total distance traveling (P<0.01) and the decrease of the recognition index (RI) and platform crossing frequency (P<0.01). Compared with the model group, the rats in the EA group showed the shortened escape latency on day 3 and 4 (P<0.05), the decrease of total distance traveling (P<0.01) and the increase of RI and platform crossing frequency (P<0.05, P<0.01). When compared with the sham-operation group, the rats of the model group presented uneven staining, sparse arrangement of myelin sheath fibers, unclear contours, and prominent vacuole-like changes in the hippocampal CA1 region. When compared with the model group, the EA group showed more dense staining, the increase of myelin sheath fibers with more orderly alignment, and fewer vacuolar changes in the hippocampal CA1 region. Compared with the sham-operation group, the model group exhibited the increase of TREM2 protein expression and the decrease of PLP protein expression in the hippocampus (P<0.01), whereas the EA group showed the up-regulation of TREM2 and PLP protein expression when compared with the model group (P<0.01, P<0.05). The positive expression of the hippocampal PLP, SOX10, and Iba1⁺LAMP1⁺ in the model group was reduced in comparison with the sham-operation group (P<0.05, P<0.01), and the positive expression of Iba1⁺ TREM2⁺ was elevated (P<0.05). In the EA group, the positive expression of PLP, SOX10, Iba1⁺TREM2⁺, and Iba1⁺ LAMP1⁺ was higher compared with that in the model group (P<0.05, P<0.01). CONCLUSION "Olfactory three needles" can improve the learning and memory, and cognitive functions of VD rats, and its mechanism may be associated with the up-regulation of TREM2 and LAMP1 to adjust MG phagocytic activity and intracellular degradation, and promote remyelination.
Animals ; Dementia, Vascular/metabolism* ; Rats ; Rats, Sprague-Dawley ; Microglia/metabolism* ; Male ; Acupuncture Therapy/instrumentation* ; Acupuncture Points ; Humans ; Remyelination ; Memory ; Hippocampus/cytology* ; Cognition ; Electroacupuncture ; Needles

Objective To explore the roles of transfer RNA-derived small RNAs(tsRNAs)in the oncogenesis and progression of lung adenocarcinoma by analyzing the differential expression of tsRNAs in lung adenocarcinoma and the relationship between the expression levels of tsRNAs in lung adenocarcinoma and the prognosis of patients in order to further screen and validate the tsRNAs associated with lung adenocarcinoma.Methods The differential expression of tsRNAs between lung adenocarcinoma tissues and normal tissues was analyzed based on the database of the Computational Medicine Center.The effects of tsRNAs expression levels on the prognosis of lung adenocarcinoma patients were analyzed based on the Cancer Genome Atlas(TCGA)database(TCGA-LUAD).The target genes were predicted based on TRFtarget2.0 and tRFTar databases.Gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed based on DAVID and KOBA KEGG online websites.The expression levels of target genes in lung adenocarcinoma tissues and normal tissues were analyzed based on the University of ALabama at Birmingham CANcer data analysis Portal(UALCAN)database.In vitro cell proliferation,migration,and invasion assays were performed to investigate the biological functions of tRF-19-69M8LOJX in lung adenocarcinoma cells.Results Compared with the normal tissues,tRF-19-69M8LOJX was up-regulated in lung adenocarcinoma tissues(log2FC=4.28,FDR＜0.05).High expression level of tRF-19-69M8LOJX was associated with shorter progression-free survival(HR=1.565,95％CI=1.142-2.145,P=0.005).And its overexpression promoted cell proliferation and migration(P＜0.001),and invasion(P=0.009)of A549 cells,and up-regulated COL1A1(P=0.002)and VCAN(P=0.022)significantly in the tRF-19-69M8LOJX overexpression cell model.Conclusion tRF-19-69M8LOJX is up-regulated in lung adenocarcinoma tissues.And its high expression is closely associated with poor prognosis.The tsRNA may play an important role in the pathogenesis and development of lung adenocarcinoma.

Objective To investigate the efficacy of varying doses of methylprednisolone(MP)on mice with acute exacerbations of chronic obstructive pulmonary disease(AECOPD)induced with influenza A virus(IAV).Methods Mouse model of COPD was established using LPS combined with smoking for 12 weeks,and then these COPD mice were treated with administration of 40 μL IAV via nasal drip to establish a AECOPD model.A total of 15 AECOPD mice were randomly divided into low-,medium-and high-dose MP groups,oseltamivir group and blank group.The body weight and survival time were monitored within 10 d after IAV infection.On days 1,3,and 5 post-treatment,lung function was assessed using whole-body plethysmography(WBP),inflammatory factors in bronchoalveolar lavage fluid(BALF)were quantified with ELISA,viral titers in BALF were determined using plaque assays,and colony-forming units were evaluated with blood agar plates.Immunofluorescence analysis:① Pulmonary immunofluorescence assay:Mice were randomly categorized into(n=4):LPS 1-day group,LPS 3-day group,and LPS+MP treatment group.All groups received an initial dose of LPS via atomization;subsequently,the LPS+MP treatment group received a single gavage dose of MP.Lung tissues were harvested from the 1-day LPS group on 1 d post-treatment,and from the 3-day LPS and LPS+MP groups on 3 d for immunofluorescence staining.② Cellular immunofluorescence assay:Mouse bone marrow neutrophils were classified into blank control(no intervention),LPS stimulation(LPS group),MP intervention with LPS stimulation(LPS+MP group),and MP intervention alone(MP group).The above cells were collected in 4 h after corresponding interventions for subsequent cellular immunofluorescence analysis.Results ①The medium-dose MP group demonstrated the most significant improvement in survival rate,weight recovery,and lung function when compared to other groups(P＜0.05).② Treatment of medium-dose MP obviously reduced the levels of IL-6 and neutrophil extracellular traps(NETs)(P＜0.05),while,elevated inflammatory factors and NETs were observed in the high-dose MP group on day 5 post-treatment.③ Notable decline in the lung injury score was found in the medium-dose MP group than the other groups(P＜0.05).④The high-dose MP group exhibited substantial bacterial proliferation and delayed viral clearance since day 5 after treatment.Conclusion Medium-dose MP shows best efficacy in treatment of IAV-induced AECOPD,and the dose neither delays viral clearance nor increases the risk of bacterial infection following viral infection.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.