Purpose This study aimed to investigate the expression of CTLA-4 and PD-L1 in pulmonary lympho-epithelial carcinoma(PLEC)and to explore their relationships with patient prognosis and with tumor-infiltrating lym-phocytes(TILs).Methods Fifty cases of PLEC were retrospectively collected,together with 23 samples of adjacent normal lung tissue.Immunohistochemistry was performed to detect CTLA-4 and PD-L1 expression in both PLEC and adjacent normal lung tissues,as well as to quantify CD4+and CD8+T-lymphocytes infiltration within the tumor micro-environment.CTLA-4,PD-L1,and the distributions of CD4+T cells and CD8+T cells were then correlated with the clinicopathological features of PLEC.Results The positive rate of CTLA-4 in PLEC was significantly higher than that in adjacent normal lung tissue(P＜0.05).PD-L1 expression differed significantly across TNM stages of PLEC(P＜0.05)and was positively correlated with TNM stages(r=0.31,P=0.03).CD4+and CD8+T-lymphocytes were pre-dominantly localized in the tumor stroma,with CD4+T cells density exceeding that of CD8+(P＜0.05).Within canc-er nests,CD8+T cells density was significantly higher than CD4+(P＜0.05).Conclusion Both PD-L1 and CTLA-4 are frequently expressed in PLEC,suggesting they represent potential immunotherapeutic targets.In the PLEC micro-environment,lymphocytes primarily infiltrated the stromal compartment,and CD4+T cells are more abundant than CD8+T cells in that locale.

OBJECTIVE To explore the mechanism of Yishen Qingli Huoxue Formula(YQHF)improving renal fibrosis by inhib-iting HIF1-α using data mining,molecular docking,and in vivo and in vitro experiments.METHODS The expression changes of HIF1-α in renal biopsy tissues of patients with chronic kidney disease(CKD)in the GEO database were analyzed.Molecular docking was used to clarify the interaction mode between YQHF effective monomers and HIF1-α.Thirty SD rats were randomized to sham,model,low-dose YQHF,high-dose YQHF,and losartan potassium groups(n=6 per group).Unilateral ureteral obstruction(UUO)was used to induce renal fibrosis.Serum creatinine(Scr)and blood urea nitrogen(BUN)were measured,and kidney sections were stained with HE and Masson to assess pathology and fibrosis.Renal HIF1-α protein expression was quantified by Western blot.A renal fibro-sis cell model was established by inducing NRK-52E cells with TGF-β1,and the cells were divided into control,model,YQHF,HIF1-α inhibitor,HIF1-α inhibitor+YQHF,HIF1-α agonist,and HIF1-α agonist+YQHF groups.Western blot analysis was used to detect the protein expression levels of HIF1-α,COL-1,and α-SMA,and to observe the mechanism of YQHF-containing serum in protecting renal tubular epithelial cells.RESULTS Data mining showed HIF1-α expression in the CKD group was significantly higher than in the control group(P<0.01).Molecular docking indicated YQHF core components had good binding affinity to HIF1-α.In vivo,com-pared with the sham group,HE staining revealed tubular atrophy and inflammatory-cell infiltration,and Masson staining showed in-creased collagen deposition in UUO model rats(P<0.01).Serum creatinine and blood urea nitrogen were also elevated in the model group(P<0.05),together with up-regulated renal expression of COL-1,α-SMA and HIF-1α(P<0.01).After intervention with either high-dose or low-dose YQHF or losartan potassium,these pathological changes were attenuated:collagen deposition decreased(P<0.01),creatinine and BUN fell to varying degrees(P<0.05),and renal COL-1,α-SMA and HIF-1α levels were down-regulated(P<0.01);immunohistochemistry confirmed reduced HIF-1α in UUO kidneys(P<0.01).In NRK-52E cells,TGF-β1 stimulation mark-edly increased COL-1,α-SMA and HIF-1α protein levels(P<0.01).Both YQHF and chloramphenicol alone down-regulated these proteins(P<0.05,P<0.01),and their combination produced stronger inhibition of HIF-1α than YQHF alone(P<0.05).Conversely,the HIF-1α agonist fenbendazole-d3 reversed YQHF's anti-fibrotic effect,re-elevating COL-1,α-SMA and HIF-1α(P<0.01),with no significant difference versus agonist alone.CONCLUSION YQHF may inhibit extracellular matrix deposition and delay renal fi-brosis progression by suppressing HIF1-α accumulation,providing new theoretical evidence for traditional Chinese medicine in treat-ing renal fibrosis.

Aim To investigate the effect of interdialytic serum potassium levels on thrombosis of autologous ar-teriovenous fistula(AVF)in patients with chronic kidney disease(CKD)on maintenance haemodialysis(MHD).Methods 159 CKD patients who underwent MHD in our hospital from October 2021 to October 2022 were retrospectively analyzed.They were divided into hyperkalemia group(n=53),normal serum potassium group(n=61)and hypokalemia group(n=45)according to the mean serum potassium level of patients with different dialysis intervals,and all patients were followed up for 1 year or followed up until AVF thrombosis.General datas were collected and the following indicators were detected at the time of patient enrolment,including biochemical indicators,inflammatory factors,ultrasound indicators of AVF and oxidative stress factors levels.Multifactorial Logistic regression equations were used to analyze the effects of clinical indicators on AVF thrombosis in MHD patients,receiver operating characteristic(ROC)curve was used to assess the predictive efficacy of clinical indicators on AVF thrombosis;And interval likelihood ratio was used to stratify interdialyt-ic serum potassium levels,and further observe whether the relationship was stability between AVF thrombosis and interdia-lytic serum potassium levels in MHD patients.Results Compared with the normal serum potassium group,the levels of C-reactive protein(CRP),intact parathyroid hormone(iPTH),procalcitonin(PCT),triglyceride(TG),malondial-dehyde(MDA),myeloperoxidase(MPO),brachial artery resistance index(RI),brachial artery pulsatility index(PI)and radial artery PI were significantly elevated in hyperkalemia group and hypokalemia group,while the levels of albumin(Alb),total cholesterol(TC),superoxide dismutase(SOD)and fistula blood flow were significantly reduced(P＜0.05).Systolic blood pressure,diastolic blood pressure,fistula blood flow,Alb and SOD levels were significantly lower in patients with AVF thrombosis than those in patients with AVF unthrombosis(P＜0.05);Interdialytic mean serum potassium level,CRP,iPTH,PCT,brachial artery RI,brachial artery PI,radial artery PI,radial artery RI,MDA and MPO levels were significantly higher in patients with AVF thrombosis(P＜0.05).The ROC curve was used to analyse the model estab-lished by the multifactorial Logistic regression equation,and it was found that model 1 and model 2 had good predictive effi-cacy,and model 2 had the best predictive efficacy.The results of the interval likelihood ratio showed that:when the patient's interdialytic serum potassium level was 3.5～4.5 mmol/L,the possibility of the patient's AVF thrombosis was the lowest,and when the patient's interdialytic serum potassium level was＞5.5 mmol/L or＜3.5 mmol/L,the possibility of the patient's AVF thrombosis was higher,and when the patient's serum potassium level was＞5.5 mmol/L,the probability of AVF thrombosis was the highest in patients,which was 3.925 times higher than that of patients without AVF thrombosis.Conclusion Abnormal interdialytic serum potassium levels may induce AVF thrombosis in CKD patients.Serum potassium levels can be monitored during MHD treatment to enable timely intervention and improve clinical treatment outcomes for patients.

OBJECTIVE To explore the mechanism of Yishen Qingli Huoxue Formula(YQHF)improving renal fibrosis by inhib-iting HIF1-α using data mining,molecular docking,and in vivo and in vitro experiments.METHODS The expression changes of HIF1-α in renal biopsy tissues of patients with chronic kidney disease(CKD)in the GEO database were analyzed.Molecular docking was used to clarify the interaction mode between YQHF effective monomers and HIF1-α.Thirty SD rats were randomized to sham,model,low-dose YQHF,high-dose YQHF,and losartan potassium groups(n=6 per group).Unilateral ureteral obstruction(UUO)was used to induce renal fibrosis.Serum creatinine(Scr)and blood urea nitrogen(BUN)were measured,and kidney sections were stained with HE and Masson to assess pathology and fibrosis.Renal HIF1-α protein expression was quantified by Western blot.A renal fibro-sis cell model was established by inducing NRK-52E cells with TGF-β1,and the cells were divided into control,model,YQHF,HIF1-α inhibitor,HIF1-α inhibitor+YQHF,HIF1-α agonist,and HIF1-α agonist+YQHF groups.Western blot analysis was used to detect the protein expression levels of HIF1-α,COL-1,and α-SMA,and to observe the mechanism of YQHF-containing serum in protecting renal tubular epithelial cells.RESULTS Data mining showed HIF1-α expression in the CKD group was significantly higher than in the control group(P<0.01).Molecular docking indicated YQHF core components had good binding affinity to HIF1-α.In vivo,com-pared with the sham group,HE staining revealed tubular atrophy and inflammatory-cell infiltration,and Masson staining showed in-creased collagen deposition in UUO model rats(P<0.01).Serum creatinine and blood urea nitrogen were also elevated in the model group(P<0.05),together with up-regulated renal expression of COL-1,α-SMA and HIF-1α(P<0.01).After intervention with either high-dose or low-dose YQHF or losartan potassium,these pathological changes were attenuated:collagen deposition decreased(P<0.01),creatinine and BUN fell to varying degrees(P<0.05),and renal COL-1,α-SMA and HIF-1α levels were down-regulated(P<0.01);immunohistochemistry confirmed reduced HIF-1α in UUO kidneys(P<0.01).In NRK-52E cells,TGF-β1 stimulation mark-edly increased COL-1,α-SMA and HIF-1α protein levels(P<0.01).Both YQHF and chloramphenicol alone down-regulated these proteins(P<0.05,P<0.01),and their combination produced stronger inhibition of HIF-1α than YQHF alone(P<0.05).Conversely,the HIF-1α agonist fenbendazole-d3 reversed YQHF's anti-fibrotic effect,re-elevating COL-1,α-SMA and HIF-1α(P<0.01),with no significant difference versus agonist alone.CONCLUSION YQHF may inhibit extracellular matrix deposition and delay renal fi-brosis progression by suppressing HIF1-α accumulation,providing new theoretical evidence for traditional Chinese medicine in treat-ing renal fibrosis.

Aim To investigate the effect of interdialytic serum potassium levels on thrombosis of autologous ar-teriovenous fistula(AVF)in patients with chronic kidney disease(CKD)on maintenance haemodialysis(MHD).Methods 159 CKD patients who underwent MHD in our hospital from October 2021 to October 2022 were retrospectively analyzed.They were divided into hyperkalemia group(n=53),normal serum potassium group(n=61)and hypokalemia group(n=45)according to the mean serum potassium level of patients with different dialysis intervals,and all patients were followed up for 1 year or followed up until AVF thrombosis.General datas were collected and the following indicators were detected at the time of patient enrolment,including biochemical indicators,inflammatory factors,ultrasound indicators of AVF and oxidative stress factors levels.Multifactorial Logistic regression equations were used to analyze the effects of clinical indicators on AVF thrombosis in MHD patients,receiver operating characteristic(ROC)curve was used to assess the predictive efficacy of clinical indicators on AVF thrombosis;And interval likelihood ratio was used to stratify interdialyt-ic serum potassium levels,and further observe whether the relationship was stability between AVF thrombosis and interdia-lytic serum potassium levels in MHD patients.Results Compared with the normal serum potassium group,the levels of C-reactive protein(CRP),intact parathyroid hormone(iPTH),procalcitonin(PCT),triglyceride(TG),malondial-dehyde(MDA),myeloperoxidase(MPO),brachial artery resistance index(RI),brachial artery pulsatility index(PI)and radial artery PI were significantly elevated in hyperkalemia group and hypokalemia group,while the levels of albumin(Alb),total cholesterol(TC),superoxide dismutase(SOD)and fistula blood flow were significantly reduced(P＜0.05).Systolic blood pressure,diastolic blood pressure,fistula blood flow,Alb and SOD levels were significantly lower in patients with AVF thrombosis than those in patients with AVF unthrombosis(P＜0.05);Interdialytic mean serum potassium level,CRP,iPTH,PCT,brachial artery RI,brachial artery PI,radial artery PI,radial artery RI,MDA and MPO levels were significantly higher in patients with AVF thrombosis(P＜0.05).The ROC curve was used to analyse the model estab-lished by the multifactorial Logistic regression equation,and it was found that model 1 and model 2 had good predictive effi-cacy,and model 2 had the best predictive efficacy.The results of the interval likelihood ratio showed that:when the patient's interdialytic serum potassium level was 3.5～4.5 mmol/L,the possibility of the patient's AVF thrombosis was the lowest,and when the patient's interdialytic serum potassium level was＞5.5 mmol/L or＜3.5 mmol/L,the possibility of the patient's AVF thrombosis was higher,and when the patient's serum potassium level was＞5.5 mmol/L,the probability of AVF thrombosis was the highest in patients,which was 3.925 times higher than that of patients without AVF thrombosis.Conclusion Abnormal interdialytic serum potassium levels may induce AVF thrombosis in CKD patients.Serum potassium levels can be monitored during MHD treatment to enable timely intervention and improve clinical treatment outcomes for patients.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Purpose This study aimed to investigate the expression of CTLA-4 and PD-L1 in pulmonary lympho-epithelial carcinoma(PLEC)and to explore their relationships with patient prognosis and with tumor-infiltrating lym-phocytes(TILs).Methods Fifty cases of PLEC were retrospectively collected,together with 23 samples of adjacent normal lung tissue.Immunohistochemistry was performed to detect CTLA-4 and PD-L1 expression in both PLEC and adjacent normal lung tissues,as well as to quantify CD4+and CD8+T-lymphocytes infiltration within the tumor micro-environment.CTLA-4,PD-L1,and the distributions of CD4+T cells and CD8+T cells were then correlated with the clinicopathological features of PLEC.Results The positive rate of CTLA-4 in PLEC was significantly higher than that in adjacent normal lung tissue(P＜0.05).PD-L1 expression differed significantly across TNM stages of PLEC(P＜0.05)and was positively correlated with TNM stages(r=0.31,P=0.03).CD4+and CD8+T-lymphocytes were pre-dominantly localized in the tumor stroma,with CD4+T cells density exceeding that of CD8+(P＜0.05).Within canc-er nests,CD8+T cells density was significantly higher than CD4+(P＜0.05).Conclusion Both PD-L1 and CTLA-4 are frequently expressed in PLEC,suggesting they represent potential immunotherapeutic targets.In the PLEC micro-environment,lymphocytes primarily infiltrated the stromal compartment,and CD4+T cells are more abundant than CD8+T cells in that locale.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.