ObjectiveTo evaluate the clinical efficacy of Huayu Tongluo Formula （化瘀通络方， HTF） in patients with mid-stage diabetic kidney disease of blood stasis syndrome and explore its potential mechanisms. MethodsA multi-center， randomized， double-blind， placebo-controlled clinical trial was conducted. Ninety patients of mid-stage diabetic kidney disease of blood stasis syndrome were divided into a control group of 46 cases and a treatment group of 44 cases. Both groups received conventional western medicine treatment， the treatment group additionally taking HTF， while the control group taking a placebo of the formula. The treatment was administered once daily for 24 weeks. The primary outcomes included 24-hour urine total protein （24 h-UTP）， serum albumin （Alb）， glycated hemoglobin （HbA1c）， and serum creatinine （Scr）.The secondary outcomes included changes in levels of endothelin-1 （ET-1）， nitric oxide （NO）， vascular endothelial growth factor （VEGF）， and traditional Chinese medicine （TCM） syndrome scores before and after treatment. Clinical efficacy was evaluated based on TCM syndrome scores and overall disease outcomes. Adverse reactions and endpoint events were recorded. ResultsIn the treatment group after treatment， 24 h-UTP， ET-1， and VEGF levels significantly decreased （P＜0.05）， Alb and NO levels significantly increased （P＜0.05）； while the TCM syndrome scores for edema， lumbar pain， numbness of limbs， dark purple lips， dark purple tongue or purpura， and thin， rough pulse all significantly decreased （P＜0.05）. In the control group， no significant changes were observed in any of the indicators after treatment （P＞0.05）.Compared with the control group， the treatment group showed significant reductions in 24 h-UTP， ET-1， and VEGF levels， and increases in Alb and NO levels （P＜0.05）. The TCM syndrome scores for edema， lumbar pain， dark purple tongue or purpura， and thin， rough pulse were all lower in the treatment group than in the control group （P＜0.05）. The total effective rate of TCM syndrome in the treatment group was 59.09% （26/44）， and the overall clinical effective rate was 45.45% （20/44）. In the control group， these rates were 15.22% （7/46） and 8.7% （4/46）， respectively， with the treatment group showing significantly better outcomes （P＜0.05）. A total of 7 adverse events occurred across both groups， with no significant difference （P＞0.05）. No endpoint events occurred during the study. ConclusionOn the basis of conventional treatment of Western medicine， HTF can further reduce urinary protein levels and improve clinical symptoms in patients with mid-stage diabetic kidney disease of blood stasis syndrome. The mechanism may be related to its effects on endothelial function.

[摘 要] 目的：观察白细胞介素-37（IL-37）在乳腺癌患者的表达变化对CD8+ T细胞活性的影响。方法：纳入2020年7月至2022年9月在新乡医学院第一附属医院就诊的46例乳腺癌患者、24例乳腺良性肿瘤患者、20例对照者。采集外周血，分离血浆和外周血单个核细胞（PBMC），收集接受手术治疗的乳腺癌患者肿瘤组织和癌旁组织，分离组织中肿瘤浸润淋巴细胞（TIL），纯化CD8+ T细胞。ELISA法检测IL-37、可溶型单免疫球蛋白IL-1受体相关蛋白（SIGIRR）表达，实时定量PCR法检测组织中IL-37 mRNA，流式细胞术检测CD8+ T细胞中IL-18受体α链（IL-18Rα）和SIGIRR表达。外源性IL-37刺激纯化的CD8+ T细胞，与乳腺癌细胞系MCF-7共培养，通过测定乳酸脱氢酶水平计算靶细胞死亡比例，ELISA法检测上清中穿孔素、颗粒酶B、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）水平。结果：乳腺癌患者血浆IL-37水平高于乳腺良性肿瘤患者[（554.17 ± 96.63）pg/mL vs （499.52 ± 78.66）pg/mL，P = 0.020]和对照者[（483.97 ± 47.23）pg/mL，P = 0.003]。乳腺癌患者肿瘤组织中IL-37 mRNA相对表达量高于癌旁组织[（1.88 ± 0.21） vs （1.00 ± 0.53）pg/mL，P < 0.001]。外周血IL-18Rα+ CD8+细胞比例、SIGIRR+ CD8+细胞比例、血浆可溶型SIGIRR水平在乳腺癌患者、乳腺良性肿瘤患者、对照者之间的差异无统计学意义（均P > 0.05）。CD8+ TIL表达IL-18Rα和SIGIRR的比例在肿瘤组织和癌旁组织之间的差异无统计学意义（P > 0.05）。重组人IL-37刺激后，CD8+ T细胞诱导靶细胞死亡比例、上清中IFN-γ和TNF-α水平在直接接触和间接接触共培养系统中均低于无刺激（均P < 0.05）。在直接接触共培养系统中，IL-37刺激后上清中穿孔素和颗粒酶B水平均低于无刺激（均P < 0.001），但在间接接触共培养系统中，上清中穿孔素和颗粒酶B水平在无刺激和IL-37刺激之间的差异无统计学意义（均P > 0.05）。结论：乳腺癌患者中IL-37水平升高可能参与诱导外周血和肿瘤微环境中CD8+ T细胞功能衰竭。

Objective To assess the situation and influencing factors of occupational burnout among the staff at the Center for Disease Control and Prevention (CDC) in Sichuan Province. Methods A total of 1 038 CDC staff members in Sichuan Province were selected as the study subjects using the stratified random sampling method. Occupational burnout of the staff was assessed using the Maslach Burnout Inventory General Survey via an online questionnaire. Results The detection rate of occupational burnout was 42.3% (439/1 038). Binary logistic regression analysis result showed that, after controlling for confounding factors such as education level and alcohol consumption, CDC staffs aged at 20-<31, 31-<41, and 41-<51 years were at higher risk of occupational burnout compared with those ≥51 years (all P<0.05). CDC staffs with 5-<10 or ≥10 years of service had higher occupational burnout risk compared with those with <5 years (both P<0.05). CDC staffs with poor or fair health status, irregular diet, and poor sleep quality had higher risk of occupational burnout compared with those healthy, have regular diet, and good sleep quality (all P<0.05). The risk of occupational burnout increased with higher overtime frequency (all P<0.05). Conclusion Occupational burnout among CDC staffs in Sichuan Province is relatively high. Age, years of service, health status, diet, sleep quality, and overtime frequency are key influencing factors.

Phosphatidylinositol 4 kinases are the initial and key molecules of the phosphatidyl inositol signaling pathway.Among them,the phosphatidylinositol 4-kinaseⅢ β(PI4KⅢβ)is in-volved in the synthesis of the Golgi PI4P pool,playing a vital role in numerous physiological processes.Meanwhile,the en-zyme is an important host factor mediating the replication of some pathogenic RNA viruses,and participating in other patho-logical processes such as bacterial infection and malaria.In ad-dition,studies have shown that the function of PI4KⅢβ is regu-lated by numerous factors,including host and viral protein bind-ing partners.This review will discuss the structure and the phys-iopathology regulatory mechanism of PI4KⅢβ.

Objective:To explore the effects of Zhiyan mixture on the activation of classically activated macrophages(M1)and T helper cells 2(Th2)immune responses in mice with mycoplasma pneumoniae(MP)infection.Methods:C57BL/6J mice were divided into control group,MP group,Zhiyan mixture group and azithromycin group.Except control group,models of MP infection were prepared by nasal drip of MP bacterial solution(1×107 CFUs/ml)in the other groups.Zhiyan mixture group was given intragastric administration of Zhiyan mixture,azithromycin group was given intragastric administration of azithromycin,control group and MP group were given the same volume of normal saline.The pathological damage of lung tissues were observed by HE staining,and patho-logical scoring was conducted.The changes of MP load in lung tissues were detected by solid culture method.M1 level was detected by flow cytometry.The mRNA levels of inducible nitric oxide synthase(iNOS),TNF-α and CXC chemokine 1(CXCL1)in lung tissues were detected by PCR.The levels of IL-4,IL-5,IL-10 and IL-13 in lung tissues were detected by ELISA.The expressions of NF-κB pathway-related proteins in lung tissues were detected by Western blot.Results:The pathological scores of lung tissues,MP load,F4/80+cell level,ratios of CD86+/F4/80+and MHC Ⅱ+/F4/80+,and mRNA levels of iNOS,TNF-α and CXCL1 in MP group,Zhiyan mix-ture group and azithromycin group were higher than those in control group(P<0.05),levels of IL-4,IL-5,IL-10 and IL-13,and ex-pressions of p-p65/p65 and p-IKK/IKK in lung tissues were all higher than those in control group(P<0.05).The pathological scores of lung tissues,MP load,F4/80+level,ratios of CD86+/F4/80+and MHC Ⅱ+/F4/80+,and mRNA levels of iNOS,TNF-α and CXCL1 in Zhiyan mixture group and azithromycin group were lower than those in MP group(P<0.05),levels of IL-4,IL-5,IL-10 and IL-13 were higher than those in MP group(P<0.05),and protein expressions of p-p65/p65 and p-IKK/IKK in lung tissues were lower than those in MP group(P<0.05).Conclusion:Zhiyan mixture can improve lung injury in mice with MP infection,which may be related to reducing M1 activity,increasing Th2 immune response and inhibiting NF-κB pathway.

This study was aimed at investigating the pathogenic and molecular characteristics of Klebsiella pneumoniae(KP)in fecal samples of diarrhea cases in a district of Beijing.Fecal samples from diarrhea cases in an outpatient department in a district of Beijing from 2018 to 2021 were collected,and used for isolation and culture of KP.The KP strains isolated strains were subjected to drug resistance phenotype testing and whole-genome sequencing.Multilocus sequence typing and whole-genome phyletic evolution analysis were performed on the sequencing results.The cases'epidemiological and clinical characteristics were analyzed.From 2018 to 2021,1 103 fecal samples were collected and detected.The total detection rate of KP was 10.43％(115/1 103),and the infection rate of KP mixed with other diarrhea-causing pathogens was 42.61％(49/115).The positivity rate was slightly high(12.47％,61/489)a-mong females and was highest in young adults 16-45 years of age.Small peaks were observed in January,April to May,and August to September.The gastrointestinal symptoms in cases were mainly nausea and watery stool,and the suspicious food was unknown.Ampicillin,tetracycline,and sulfafurazole were the top three antibiotics to which these 115 KP strains showed resistance,and 29 strains were resistant to multiple antibiotics.The strains were divided into 72 sequence types,among which ST23 was dominant.According to the phylogenetic tree,the strains were divided into four main branches,among which 14 ST23 strains had a very close genetic relationship with the highly virulent NTUH-K2044 reference strain.KP infection persisted in fecal samples from diarrhea cases in the district of Beijing.Women and young adults were particularly susceptible.The drug resistance of KP strains in this region was very serious,and the ST types were diverse.Moreover,the ST23 pathogenic strains were closely related to high virulence strains.

AIM To analyze the metabolites of nobiletin in rats in vivo based on characteristic ions.METHODS Ten rats were assigned into administration group and control group,and given intragastric administration of the 0.5％CMC-Na suspension of nobiletin(250 mg/kg)and 0.5％CMC-Na solution,respectively,after which plasma,urine and feces were collected,solid phase extraction method was adopted in pretreatment,UHPLC-HRMS analysis was performed.The candidate metabolites were systematically described according to diagnostic product ions,chromatographic retention time,accurate molecular weight and neutral loss fragments,after which accurate metabolites were obtained in the established metabolite data set with-CH3(m/z 15)characteristic ions as a baits.RESULTS A total of 64 metabolites were identified,whose main metabolic pathways were glucuronidation,sulfation,hydrogenation and their compound reactions.CONCLUSION This experiment elucidates the metabolites of nobiletin in rats in vivo,which provides a new reference for its further development.

Objective:To observe the clinical efficacy of exercise-based acupuncture in treating ischemic stroke and its effects in improving the patient's motor function and daily living ability. Methods:A total of 106 patients with motor dysfunction due to cerebral infarction were randomized into a trial group and a control group,each consisting of 53 cases.Both groups received conventional rehabilitation;in addition,the control group was given point-toward-point acupuncture at scalp points,and the trial group was offered exercise-based acupuncture,3 times weekly for 4 consecutive weeks.Before treatment,after 2 and 4 weeks of treatment,and at the 2-month follow-up,the Fugl-Meyer assessment(FMA)scale,Lovett scale for muscle strength,modified Ashworth scale(MAS),and activities of daily living(ADL)scale were used to assess the patient's motor function,muscle strength,muscle tension,and daily living ability. Results:After treatment,both groups gained improvements in motor function and daily living ability;after 4-week treatment and at the 2-month follow-up,the trial group had higher FMA and ADL scores than the control group(P<0.05).The MAS score decreased after treatment in both groups;after 2 and 4 weeks of treatment and at the 2-month follow-up,the MAS score was lower in the trial group than in the control group(P<0.05).After the intervention,the Lovett score increased in both groups;after 4 weeks of treatment,the Lovett score was higher in the trial group than in the control group(P<0.05). Conclusion:Based on routine rehabilitation,exercise-based acupuncture and scalp point-toward-point acupuncture both can improve the motor function and daily living ability in ischemic stroke patients;exercise-based acupuncture performs better than scalp point-toward-point acupuncture.

Respiratory syncytial virus（RSV）is the most common reason for lower respiratory tract infections in children's hospitalization.The burden of RSV disease is widely recognized.Main risk factors for severe disease，such as extreme age（<3 months），chronic cardiopulmonary conditions，and immunosuppression，typically coincide with poorer outcomes.While most RSV hospitalizations involve healthy children，a higher proportion of hospitalized infants with underlying conditions need intensive care.Lower respiratory tract disease caused by RSV may present as bronchiolitis or pneumonitis，a large intrapulmonary shunt and acute respiratory distress syndrome（ARDS）.The bronchiolitis clinical assessment scales were used to determine the severity of the children.Presently，treatment primarily consists of supportive measures.Non-invasive mechanical ventilation and high-flow oxygen therapy represented significant advancements in the management of severe RSV disease in children.Severe respiratory distress and ARDS need invasive mechanical ventilatory support and/or extracorporeal membrane oxygenation therapy.New vaccines for RSV under development and immune passive strategies involving Nirsevimab are expected to reduce the medical burden of severe RSV disease.

Objective The objective of this study was to investigate the expression of interleukin-38(IL-38)in patients with breast cancer and its regulatory function to CD8+T cell activity.Methods 44 patients with breast cancer,25 patients with benign breast tumor,and 20 controls,who were treated in the First Affiliated Hospital of Xinxiang Medical University from July 2020 and Sep-tember 2022.Mononuclear cells from plasma and peripheral blood of all subjects were isolated,tumor-infiltrating lymphocytes from tumor tissues of breast cancer patients were isolated,and CD8+T cells were purified.IL-38 protein level in the plasma was measured by enzyme-linked immunosorbent assay(ELISA).The relative level of IL-38 mRNA in the tissue was semi-quantified by real-time quantitative PCR.Recombinant human IL-38 was used to stimulate CD8+T cells from peripheral blood and tumor tissue from patients with breast cancer.A co-culture system was established between CD8+T cells and breast cancer MCF-7 cell line.The percentage of target cell death was calculated by measuring lactate dehydrogenase level in the supernatants.The levels of perforin,granzyme B,inter-feron-γ and tumor necrosis factor-α(TNF-α)in the supernatants were measured by ELISA.The immune checkpoint molecules ex-pression in CD8+T cells were detected by flow cytometry.Results The levels of plasma IL-38 were significantly higher in patients with breast cancer(74.23±19.88 pg/mL)compared with in patients with benign breast tumor(62.87±16.27 pg/mL,P=0.018)and controls(61.77±12.75 pg/mL,P=0.013).The relative expression of IL-38 mRNA in tumor tissues was significantly higher than in para-tumor tissues(1.57±0.22 vs.1.00±0.18,P<0.001).The proportion of target cell death induced by peripheral and tumor-in-filtrating CD8+T cells,and the levels of perforin and granzyme B secretion in direct contact co-culture group were higher than those in indirect contact co-culture group(P<0.05).There were no significant differences of either interferon-γ or TNF-α levels between di-rect contact and indirect contact co-culture group(P>0.05).In the direct contact co-culture group,the levels of target cell death pro-portion,perforin,granzyme B,interferon-γ and TNF-α l in the IL-38 stimulation group were lower than those in the non-stimulation group(P<0.05).In the indirect contact co-culture group,the target of cell death proportion,interferon-γ and TNF-α the IL-38 stimulation group were also lower than those in the non-stimulation group(P<0.05).However,there were no statistical differences of either perforin or granzyme B levels between the IL-38 stimulation group and non-stimulation group within the indirect contact co-culture group(P>0.05).There were also no differences in the levels of immune checkpoint molecules in CD8+T cells between the non-stimulation group and the IL-38 stimulation group(P>0.05).Conclusion Highly expressed IL-38 in patients with breast cancer may be involved in inducing CD8+T cell functional failure.