ObjectiveThis paper aims to observe the protective effect of Huamoyan granules on knee osteoarthritis （KOA） and explore whether its protective effect is oriented toward an anti-inflammatory direction by regulation of macrophage polarization， which can effectively inhibit the progression of pathological inflammatory response， reduce the release of inflammatory pain mediators， and downregulate the protein expression level of transient receptor potential vanilloid 1 （TRPV1）， so as to provide experimental evidence for its clinical application and investigate its action mechanism. MethodsAfter adaptive feeding， Sprague-Dawley （SD） rats were randomly divided into six groups： sham group， model group， celecoxib group， and high， medium， and low-dose synovitis granule groups （9.6， 4.8， 2.4 g·kg^-1）. The administration dose of celecoxib capsules was 20 mg·kg^-1. There were 10 rats in the sham group and 12 rats in the model group and each administration group. A KOA animal model was established by means of intra-articular injection of sodium iodoacetate into the knee joint. From the 10^th day of the experiment， each administration group was given intragastric administration at a dose of 10 mL·kg^-1 for 4 weeks. General conditions of rats in each group were assessed daily. The pressure pain threshold （PPT） to mechanical stimulation and joint diameter were recorded. X-ray examination was performed on the right knee joints of rats for imaging analysis. Enzyme linked immunosorbent assay （ELISA） was performed to detect the tumor necrosis factor-α （TNF-α）， serum interleukin-1β （IL-1β）， and other pro-inflammatory cytokines in rat serum samples， as well as the expression levels of neurogenic inflammatory mediators such as nerve growth factor （NGF） and calcitonin gene-related peptide （CGRP）. Histopathological changes in the knee joint synovial tissues were examined by hematoxylineosin （HE） staining. Safranin O-fast green staining was performed to observe and evaluate the degree of knee cartilage lesions. Western blot was employed to quantitatively analyze TRPV1， p38 mitogen-activated protein kinase （p38 MAPK）， and phosphorylated （p）-p38 MAPK in rat knee synovial tissues. Immunofluorescence （IF） was used to measure and assess M1/M2 macrophage polarization. ResultsCompared with those in the sham group， the circumference and joint diameter of the right knee were markedly enlarged in the model group （P<0.01）， while PPTs of rats showed a significant reduction （P<0.01）. The contents of IL-1β， TNF-α， CGRP， and NGF in rats' serum were significantly elevated （P<0.01）， and the synovial Krenn score was increased （P<0.01）. The Mankin score of cartilage tissue was increased （P<0.01）， and the protein expressions of TRPV1 and p-p38 MAPK/p38 MAPK were significantly upregulated （P<0.01）. The experimental intervention significantly reduced the proportion of pro-inflammatory M1 macrophages in the total macrophage population （P<0.01）， and the percentage of M2 macrophages was decreased （P<0.01）. The M1/M2 macrophage ratio was significantly elevated （P<0.01）. Knee joint diameters of all dose groups of Huamoyan granules and the celecoxib group were reduced （P<0.01） compared with those of the model group， and the PPT recovery speeds in the high and medium-dose groups of Huamoyan granules were more obvious （P<0.05）. The contents of IL-1β， CGRP， and NGF in the rats' serum in all administration groups were significantly reduced （P<0.05， P<0.01）， and the content of TNF-α in rats' serum was significantly reduced （P<0.01）. All dose groups of Huamoyan granules demonstrated significant reductions in both synovial Krenn score （P<0.05， P<0.01） and protein expression of TRPV1 and p-p38 MAPK/p38 MAPK in rats' synovial tissues （P<0.01）. The percentage of M1 macrophages in the synovial tissues of the celecoxib group and all dose groups of Huamoyan granules was decreased （P<0.01）. The percentage of M2 macrophages was increased （P<0.05）， and the M1/M2 ratio was decreased （P<0.01）. ConclusionHuamoyan granules can alleviate the inflammatory response of KOA， reduce the release of inflammatory pain mediators， and downregulate TRPV1 protein expression by regulating macrophage polarization. Its mechanism may be related to the TRPV1/p38 MAPK signaling pathway， thereby achieving the effect of improving peripheral pain hypersensitivity in KOA.

Objective:To analyze the clinical characteristics and treatment of patients with acute Q fever in Dali Bai Autonomous Prefecture, Yunnan Province.Methods:A total of 26 patients with acute Q fever admitted to People′s Hospital of Yunnan Dali Bai Autonomous Prefecture from October 2022 to December 2023 were enrolled. A retrospective cross-sectional study analysis was performed to analyze the demographic characteristics, epidemiology, clinical manifestations, laboratory tests and pathogen detection of these patients.Results:Of the 26 patients, 25 were male and one was female. The age ranged from 18 to 82 years with an average age of (45.6±17.2) years. All of them were sporadic cases. The neighbors of eight patients had sheep and cattle, 11 cases had a history of field work, and four cases had a history of field trip. Coxiella burnetii was detected in 26 patients by different molecular diagnostic techniques, including 21 cases by blood quantitative polymerase chain reaction (qPCR), three cases by sputum multi-pathogen targeted next-generation sequencing (tNGS), one case by alveolar lavage fluid tNGS, and one case by cerebrospinal fluid metagenomic next-generation sequencing (mNGS). Routine blood cultures of 19 cases were negative. All 26 patients presented with chills and fever, 21 cases (80.8%) with headache, 19 cases (73.1%) with fatigue, 14 cases (53.8%) with generalized aches and pains, 12 cases (46.2%) with poor appetite, and 14 cases (53.8%) with cough. Twenty-four cases had concurrent hepatitis, 12 cases had pneumonia, one had encephalitis, and 19 cases had myocardial damage. The laboratory tests showed that 23 cases (88.5%) had normal white blood cell count, eight cases (30.8%) had decreased platelet count, 25 cases (96.2%) had C-reactive protein elevated, 24 cases (92.3%) had procalcitonin elevated, 14 out of 17 cases had elevated erythrocyte sedimentation rate, and 19 cases had elevated D-dimer levels. Liver function tests showed that alanine aminotransferase increased in 24 cases (92.3%) (all less than 10 times of upper limit of normal (ULN)), aspartate aminotransferase increased in 23 cases (88.5%) (all less than 10 times of ULN), alkaline phosphatase increased in 10 cases (38.5%)(all less than two times of ULN), and γ-glutamyl transpeptidase increased in 19 cases (73.1%), which were all less than 10 times of ULN. Myocardial enzymes were detected in 21 cases, of which seven cases (33.3%) had elevated lactate dehydrogenase and 12 cases (57.1%) had elevated hydroxybutyrate dehydrogenase (all less than three times of ULN). In terms of treatment, 16 cases were treated with doxycycline alone, and nine cases were treated with doxycycline combined with azithromycin or quinolones or rifampicin, and one with tigecycline. After treatment, the conditions of patients improved. The overall length of hospital stay was (7.7±5.0) d, and that of eight patients treated with doxycycline combined with quinolones or azithromycin was 4.8 to 6.0 days. Conclusions:Acute Q fever often has no clear epidemiological history, and the clinical manifestations and laboratory tests are lack of specificity. qPCR, tNGS, mNGS can provide pathogenic diagnostic evidence for suspected cases. In terms of treatment, doxycycline is the first choice for treatment of acute Q fever, and combined treatment with azithromycin or quinolones could result in a shorter hospital stay.

Estrogen receptor α36(ERα36),a splice variant of ERα66,is crucial in the pathogenesis,progression,and therapeutic resistance of female estrogen-related tumors(e.g.,breast,cervical,and endometrial cancers)as it uniquely activates non-genomic signaling pathways.This review provides a comprehensive summary of the structural features of ERα36 and its molecular mechanisms in regulating tumor prolif-eration,migration,and drug resistance via membrane-mediated pathways,including phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT)and mitogen-activated protein kinase/extracellular signal-regulated kinase(MAPK/ERK).The interaction between ERα36 and epi-dermal growth factor receptor/human epidermal growth factor receptor2(EGFR/HER2)forms a positive feedback loop that exacerbates ma-lignant transformation.High ERα36 expression is associated with decreased sensitivity to chemotherapy and resistance to tamoxifen.Recent studies have demonstrated that natural compounds and synthetic inhibitors targeting ERα36 can reverse drug resistance and suppress can-cer stem cell activity by blocking non-genomic signaling.This review provides novel insights into overcoming drug resistance and optimizing targeted therapies for female estrogen-related malignancies.

Background At present, high level of depression is a serious problem in medical staff and may affect their immune function. The role of psychological resilience between depression and immunity cannot be ignored. However, it is still lack of research report in this area. Objective To explore the mediating effect of psychological resilience on the association between depression and humoral immunological biomarkers in medical staff. Methods A total of 108 medical staff from a tertiary hospital in Henan Province were selected using stratified cluster sampling from September 2022 to December 2022. The Connor-Davidson Resilience Scale and Patient Health Questionnaire-9 were used to evaluate their psychological resilience and depression. Serum immunoglobulin (Ig) M (IgM), IgG, IgA, complement 3 (C3), and complement 4 (C4) were detected in fasting venous blood samples. Mann-Whitney U test, Kruskal-Wallis H test, independent-samples t-test, and One-way ANOVA were used for comparisons among different demographic groups. Spearman correlation was used to evaluate correlations among measured variables. PROCESS plug-in was used to verify potential mediating effect of psychological resilience on the relationship between depression and humoral immunological biomarkers. Results The M (P₂₅, P₇₅) score of psychological resilience was 65.50 (53.25, 75.00) in the participating medical staff. The ratios of low, medium, and high levels of psychological resilience were 2.78% (3/108), 51.85% (56/108), and 45.37% (49/108), respectively. The M (P₂₅, P₇₅) score of depression was 6.00 (2.00, 8.00). The positive rate of depression was 61.11% (66/108). The correlation analysis results showed that psychological resilience was negatively correlated with depression and serum complement C3 (r=−0.416 and −0.309, P＜0.01), positively correlated with serum IgG and serum IgA (r=0.302 and 0.517, P＜0.01); optimism, self-improvement, and resilience were negatively correlated with depression (r=−0.387, −0.446, and −0.312, P<0.01), positively correlated with IgG (r=0.194, 0.284, and 0.239, P<0.05), and positively correlated with IgA (r=0.377, 0.378, and 0.444, P<0.01), respectively; resilience was negatively correlated with C3 (r=−0.304, P<0.01), and depression was negatively correlated with serum IgG and serum IgA (r=−0.516 and −0.522, P＜0.01), positively correlated with serum complement C3 (r=0.195, P＜0.05). The mediating effect test showed that psychological resilience showed mediating effects on the relationship between depression and serum IgA and serum complement C3, with mediating effect values of −0.148 (95%CI: −0.051, −0.012) and 0.111 (95%CI: 0.001, 0.010), and their mediating effect ratios were 28.30% and 56.92%. Conclusion The mental health status of the target medical staff is not optimistic. Depression is associated with changes in some humoral immunological biomarkers. Psychological resilience can mediate the correlations between depression and humoral immunological biomarkers. The managers should take measures to improve the levels of psychological resilience and promote the physical and mental health of medical staff.

OBJECTIVE: To observe the clinical efficacy of acupuncture based on the "head qijie" theory combined with endovascular intervention in the treatment of ischemic stroke (IS). METHODS: Sixty-six IS patients were randomly divided into an experimental group (33 cases, 3 cases dropped out) and a control group (33 cases, 3 cases dropped out). The control group received endovascular intervention. On the basis of the treatment in the control group, the experimental group received acupuncture based on the "head qijie" theory starting from the second day after surgery, Baihui (GV20) and bilateral Fengchi (GB20), Tianzhu (BL10), etc. were selected, once a day, 6 times a week for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Barthel index (MBI) and modified Rankin scale (mRS) were observed in the two groups, the clinical efficacy and safety were evaluated. RESULTS: After treatment, the NIHSS and mRS scores were decreased compared with those before treatment in both groups (P<0.01), the NIHSS and mRS scores in the experimental group were lower than those in the control group (P<0.05). After treatment, the MBI scores were increased compared with those before treatment in both groups (P<0.01), the MBI score in the experimental group was higher than that in the control group (P<0.05). The total effective rate in the experimental group was 86.7% (26/30), which was higher than 66.7% (20/30) in the control group (P<0.05). The incidence of adverse events in the experimental group was 6.7% (2/30), which was lower than 13.3% (4/30) in the control group (P<0.05). CONCLUSION Acupuncture based on the "head qijie" theory combined with endovascular intervention in treating IS has good efficacy, improves neurological function, and enhances daily living ability.
Humans ; Male ; Female ; Acupuncture Therapy ; Middle Aged ; Aged ; Ischemic Stroke/therapy* ; Acupuncture Points ; Endovascular Procedures ; Treatment Outcome ; Adult ; Combined Modality Therapy

Inflammatory bowel disease (IBD) is an idiopathic intestinal inflammatory condition with chronic and relapsing manifestations and is characterized by a disturbance in the interplay between the intestinal microbiota, the gut, and the brain. The microbiota-gut-brain axis involves interactions among the nervous system, the neuroendocrine system, the gut microbiota, and the host immune system. Increasing published data indicate that psychological stress exacerbates the severity of IBD due to its negative effects on the microbiota-gut-brain axis, including alterations in the stress response of the hypothalamic-pituitary-adrenal (HPA) axis, the balance between the sympathetic nervous system and vagus nerves, the homeostasis of the intestinal flora and metabolites, and normal intestinal immunity and permeability. Although the current evidence is insufficient, psychotropic agents, psychotherapies, and interventions targeting the microbiota-gut-brain axis show the potential to improve symptoms and quality of life in IBD patients. Therefore, further studies that translate recent findings into therapeutic approaches that improve both physical and psychological well-being are needed.
Humans ; Inflammatory Bowel Diseases/metabolism* ; Stress, Psychological/microbiology* ; Gastrointestinal Microbiome/physiology* ; Brain/metabolism* ; Hypothalamo-Hypophyseal System ; Pituitary-Adrenal System ; Animals

Objective To study the relationship between vaginal microecological balance and serum T cell subsets,Toll-like receptor 2(TLR2)and Toll-like receptor 4(TLR4)after hysterectomy.Methods The clinical data of 120 patients who underwent laparoscopic total hysterectomy in Daxing Teaching Hospital of Capital Medical University from June 2020 to June 2022 were retrospectively analyzed.The patients were assigned to normal group(n=50)and unbalanced group(n=70)according to postoperative vaginal microecological changes.General information,such as age,body mass index(BMI),disease type,expression of CD+4,CD+8,CD+4/CD+8,TLR2,and TLR4 were compared between the two groups.The risk factors affecting vaginal microecological balance after hysterectomy were analyzed by multivariate Logistic regression.Receiver operating characteristic(ROC)curve was drawn to evaluate the efficacy of serum T cell subsets,TLR2,and TLR4 in predicting vaginal microecological imbalance after hysterectomy.Results The levels of CD+4 and CD+4/CD+8 in the unbalanced group were significantly lower than those in the normal group,while the levels of CD+8,TLR2 and TLR4 in the unbalanced group were significantly higher than those in the normal group(P<0.05).Multivariable Logistic regression analysis showed that CD+4,CD+8,CD+4/CD+8,TLR2 and TLR4 expression were the influence factors of vaginal microecological imbalance after hysterectomy(P<0.05).ROC analysis confirmed that the expression of CD+4,CD+8 and CD+4/CD+8 and the levels of TLR2 and TLR4 could be used to predict vaginal microecological imbalance after hysterectomy,and the areas under the curve were 0.718,0.813,0.785,0.851,and 0.945,respectively(all P<0.05).Conclusion CD+4,CD+8,CD+4/CD+8,TLR2 and TLR4 expression levels are the influence factors of vaginal microecological imbalance after hysterectomy.They can be used as biological indicators for evaluating vaginal microecological balance after hysterectomy.

Objective To explore the valve regurgitation status of left heart after the implantation of left ventricular assist device (LVAD) and its effect on prognosis of patients with LVAD implantation. Methods A total of 35 patients with cardiomyopathy who underwent magnetic levitation LVAD implantation at Zhongshan Hospital, Fudan University from February 2021 to July 2024 were retrospectively selected. Clinical data during hospitalization were collected, including preoperative basic data and postoperative valve regurgitation status. Telephone follow-ups were conducted to monitor patients’ survival status and transthoracic echocardiography was used to assess left valve function. Kaplan-Meier survival curves and log-rank test were employed to compare the survival rate of patients with different levels of valve regurgitation. Results The 35 patients had a mean age of (53.9±11.1) years, with 85.7% male, and 3 patients (8.6%) died during hospitalization. Preoperatively, 17 patients (48.6%) had moderate or greater mitral regurgitation, while all 35 patients had less than moderate aortic regurgitation. One month postoperatively, thirty patients were followed up, among which 24 patients (80%) had less than moderate mitral regurgitation, including 11 cases with alleviated regurgitation compared to pre-surgery; 6 patients (20%) had moderate or greater mitral regurgitation, including 4 cases with stable regurgitation and 2 cases with progression of regurgitation compared to pre-surgery; 2 patients (6.7%) had progression of aortic regurgitation to moderate or greater. The follow-up time was 1.2 (1.0, 2.1) years, with 1-year survival rate of 91.4% and 3-year survival rate of 71.1%. Survival analysis showed that the 3-year survival rate of patients with moderate or greater mitral regurgitation one month postoperatively was significantly lower than that of patients with less than moderate regurgitation (66.7% vs 83.3%, P＝0.046). Conclusions After the implantation of magnetic levitation LVAD, most patients showed improvement in mitral regurgitation, while aortic regurgitation remained unchanged. The degree of mitral regurgitation one month postoperatively is associated with prognosis.

Background As one of the key populations in the prevention and treatment of iodine deficiency disorders, it is important to continuously monitor the iodine nutritional level of school-age children. The current reference interval for thyroid volume in China is based on age only, without taking into account differences in individual developmental levels, and the distribution of thyroid volume may vary regionally due to economic, demographic, and environmental factors. The current reference cut-off points for thyroid volume proposed by the World Health Organization are not based on the Chinese population. Objective To understand the iodine nutritional status and distribution of thyroid volume (Tvol) among children aged 8-10 years in Huangpu District, Shanghai, China, to identify impact factors of Tvol, and to propose a reference range upper limit for local thyroid health surveillance, so as to provide a basis for goiter control and prevention. Methods Six hundred children aged 8-10 years in Huangpu District were recruited in 2017, 2020, and 2023, and body height, weight, thyroid volume, urinary iodine, and iodine content of household edible salt were determined. A multilevel model was constructed using population density and area as regional variables, and age, body surface area (BSA), and body mass index (BMI) as potential impact factors for at the individual level, to assess their effects on thyroid volume. Quantile regression of thyroid volume was performed, and the 98th percentile (P₉₈) of thyroid volume was predicted based on age and BSA. Results The iodized salt coverage in the households of surveyed children in 2017, 2020, and 2023 was 72.0%, 57.0%, and 48.0%, respectively, and the iodized salt coverage decreased by year (χ²=24.31, P<0.001). The urinary iodine level of children in 2017 was higher than that in 2020 and 2023 (χ²=18.77, P<0.001). The Tvol medians of children in 2017, 2020, and 2023 were 2.29, 2.49, and 2.97 mL, respectively, and the Tvol increased by year (χ²=60.04, P<0.001). The proportion of goiter was higher in children in 2023 than in 2017 and 2020 (χ²=6.57, P<0.05). Sex differences were not statistically significant for urinary iodine levels, thyroid volume, and goiter. The median Tvol was 2.26, 2.58, and 2.76 mL in children of 8, 9, and 10 years old respectively, and the Tvol increased with age (χ²=49.02, P <0.001). Tvol was positively correlated with age, BSA, and BMI with correlation coefficients of 0.2846, 0.3723, and 0.2950, respectively. The final quantile regression model showed that the strongest effect of BSA was associated with the 98th percentile of Tvol. Multilevel models considering population density or area as regional variables failed to achieve convergence. Conclusion To establish the upper limit of the reference interval for thyroid volume of healthy children in Huangpu District, the effects of age and BSA should be considered at the individual level, and the upper limit of the normal interval for goiter screening is suggested to be the 98th percentile value of BSA at the same age. In addition, the adaptability of population density and regional area as indicators of regional aggregation of thyroid volume distribution still needs to be further explored.

Objective To explore the effects of exosomes of mesenchymal stem cells(MSC-Exos)on the proliferation,apoptosis,migration and invasion of esophageal cancer ECA109 cells.Methods Human umbilical cord mesenchymal stem cells were cultured,exosomes were extracted and isolated,and identified by transmission electron microscopy.The nanoparticle size determination and protein characterization(TSG101,CD63)were measured by transmission electron microscope.There were the MSC-Exo group(MSC-Exos co-cultured with esophageal cancer ECA109 cells)and the blank control group(only esophageal cancer ECA109 cells),and cells were cultured for 0,24 and 48 h,respectively.CCK-8 proliferation test and scratch test were used to detect the proliferation and migration ability of esophageal cancer EAC109 cells in each group,respectively.After 48 h of culture,cell apoptosis and cell cycle changes were detected by flow cytometry.The protein expression levels of phosphoinositol 3-kinase phosphorylation(p-PI3K),rabbit phosphorylated protein kinase B phosphorylation(p-Akt)and β-catenin were detected by Western blot assay.Results After identification,the obtained MSC-Exos meeted the required standard.Transmission electron microscopy,particle size measurement and marker protein results confirmed that the extracted exosomes of mesenchymal stem cells meeted the identification criteria.At 0 h of cell culture,there were no significant differences in cell proliferation and migration healing rate between the two groups(P＞0.05).After 24 h culture,the cell proliferation ability was lower in the MSC-Exo group than that of the blank control group(P＜0.05).After 48 h culture,the cell proliferation and migration healing rate were lower in the MSC-Exo group than those of the blank control group(P＜0.05).The apoptosis rate of the MSC-Exo group was higher than that of the blank control group,and the proportion of G2+S phase cells was lower than that of blank control group(P＜0.05).The expression levels of p-PI3K,p-Akt and β-catenin protein were significantly lower in the MSC-Exo group than those in the blank control group(P＜0.05).Conclusion MSC-Exos can inhibit the proliferation and migration of esophageal cancer cells and promote cell apoptosis.The inhibitory effect of MSC-Exos on esophageal cancer cells may be related to inhibiting the activation of PI3K and Akt protein and the down-regulating expression of β-catenin protein.