Body, qi, and spirit are the essential elements that constitute life. Based on the holistic view of life that integrates body, qi, and spirit, we aim to understand the pathogenesis of gastroesophageal reflux disease with emotional disorders. Our team believes that the fundamental characteristic of this disease is the coexistence of body, qi, and spirit disorders, manifested as physical tissue damage accompanied by functional decline, and the emergence of emotional disorders such as anxiety and depression. Among these, the body disorder is the intuitive sign, the qi disorder serves as the basis for the onset of the disease, and the spirit disorder represents the pathological essence of the comorbid emotional disorders. The treatment of this disease employs a holistic approach that addresses body, qi, and spirit simultaneously. Among these, adjusting the body is the first priority, with controlling acidity and protecting the mucous membrane as the crucial step. This helps control acid reflux and facilitates the repair of esophageal mucosal damage. Regulating qi is essential, with harmonizing the ascending and descending movements of qi at its core. This involves adjusting the qi movement of the internal organs and promoting the metabolism and transformation of essential substances. Nurturing the spirit is fundamental, with alleviating depression and nourishing the spirit as the focus. This improves emotional well-being and ensures that the spirit is nourished. Understanding the pathogenesis and treatment of gastroesophageal reflux disease with emotional disorders from the perspectives of body, qi, and spirit can provide new insights and strategies for clinical treatment of this disease.

Hemophilia is a hereditary coagulation disorder, in which patients often suffer from joint dysfunction due to recurrent joint bleeding, with the knee joint being particularly susceptible to involvement, thereby significantly impairing their ability to walk.Gait analysis, as an objective, quantitative, and comprehensive assessment tool, can be employed to accurately evaluate the walking function of patients and provide a scientific basis for the rehabilitation management of individuals with hemophilia.With the deepening of medical research, the role of gait analysis in the rehabilitation management of hemophilia is increasingly being recognized.This review article summarizes the application of gait analysis in the rehabilitation management of hemophilia, including changes in gait parameters, kinematic and kinetic characteristics of joints in patients with hemophilia, as well as the relationships between these parameters and the severity of the disease and treatment outcomes in hemophilia patients, exploring the role of gait analysis in the rehabilitation management of hemophilia to better apply it in clinical practice.

BACKGROUND: In the interim analysis of MONARCH plus, adding abemaciclib to endocrine therapy (ET) improved progression-free survival (PFS) and objective response rate (ORR) in predominantly Chinese postmenopausal women with HR+/HER2- advanced breast cancer (ABC). This study presents the final pre-planned PFS analysis. METHODS: In the phase III MONARCH plus study, postmenopausal women in China, India, Brazil, and South Africa with HR+/HER2- ABC without prior systemic therapy in an advanced setting (cohort A) or progression on prior ET (cohort B) were randomized (2:1) to abemaciclib (150 mg twice daily [BID]) or placebo plus: anastrozole (1.0 mg/day) or letrozole (2.5 mg/day) (cohort A) or fulvestrant (500 mg on days 1 and 15 of cycle 1 and then on day 1 of each subsequent cycle) (cohort B). The primary endpoint was PFS of cohort A. Secondary endpoints included cohort B PFS (key secondary endpoint), ORR, overall survival (OS), safety, and health-related quality of life (HRQoL). RESULTS: In cohort A (abemaciclib: n  = 207; placebo: n  = 99), abemaciclib plus a non-steroidal aromatase inhibitor improved median PFS vs . placebo (28.27 months vs . 14.73 months, hazard ratio [HR]: 0.476; 95% confidence interval [95% CI]: 0.348-0.649). In cohort B (abemaciclib: n  = 104; placebo: n  = 53), abemaciclib plus fulvestrant improved median PFS vs . placebo (11.41 months vs . 5.59 months, HR: 0.480; 95% CI: 0.322-0.715). Abemaciclib numerically improved ORR. Although immature, a trend toward OS benefit with abemaciclib was observed (cohort A: HR: 0.893, 95% CI: 0.553-1.443; cohort B: HR: 0.512, 95% CI: 0.281-0.931). The most frequent grade ≥3 adverse events in the abemaciclib arms were neutropenia, leukopenia, anemia (both cohorts), and lymphocytopenia (cohort B). Abemaciclib did not cause clinically meaningful changes in patient-reported global health, functioning, or most symptoms vs . placebo. CONCLUSIONS: Abemaciclib plus ET led to improvements in PFS and ORR, a manageable safety profile, and sustained HRQoL, providing clinical benefit without a high toxicity burden or reduced quality of life. TRIAL REGISTRATION ClinicalTrials.gov (NCT02763566).
Humans ; Female ; Fulvestrant/therapeutic use* ; Breast Neoplasms/metabolism* ; Aminopyridines/therapeutic use* ; Benzimidazoles/therapeutic use* ; Middle Aged ; Aromatase Inhibitors/therapeutic use* ; Aged ; Receptor, ErbB-2/metabolism* ; Adult ; Letrozole/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Anastrozole/therapeutic use*

B lymphocytes (B cells) play a complex and paradoxical role in tumorigenesis. They can recognize tumor-associated antigens, present these antigens to T cells, and produce antibodies that directly target and eliminate tumor cells. This makes B cells a potentially powerful ally in combating cancer. However, B cells also exhibit immunosuppressive functions, secreting cytokines like IL-10 or generating tumor-promoting antibodies that dampen the anti-tumor immune response, and some tumor cells have even been shown to exploit B cells to promote their growth and metastasis. This dual nature of B cells presents both opportunities and challenges for tumor immunotherapy. In this review, we summarize the mechanisms underlying the multifaceted functions of B cells and their current applications in cancer immunotherapy. Furthermore, we also explore the key issues and future directions in this field, emphasizing the need for further research to fully harness the anti-tumor potential of B cells in the fight against cancer.
Humans ; B-Lymphocytes/immunology* ; Neoplasms/therapy* ; Carcinogenesis/immunology* ; Immunotherapy/methods* ; Animals

As a biocatalyst, laccase has been widely studied and applied in the papermaking industry. However, the low catalytic efficiency and poor stability of natural laccase limit its application in the pulping process. To develop the laccase with high activity and strong tolerance, we carried out directed evolution for modification of the laccase derived from Bacillus pumilus and screened out the mutants F282L/F306L and Q275P from the random mutant library by high-throughput screening. The specific activities of F282L/F306L and Q275P were 280.87 U/mg and 453.94 U/mg, respectively, which were 1.42 times and 2.30 times that of the wild-type laccase. Q275P demonstrated significantly improved thermal stability, with the relative activity 20% higher than that of the wild-type laccase after incubation at 40 ℃, 50 ℃, and 70 ℃ for 4 h. F282L/F306L and Q275P showed greater tolerance to metal ions and organic solvents than the wild-type laccase. The K_m value of the wild-type laccase was 374.97 μmo/L, and those of F282L/F306L and Q275P were reduced to 318.96 μmo/L and 360.71 μmo/L, respectively, which suggested that the substrate affinity of laccase was improved after mutation. The k_cat values of F282L/F306L and Q275P for the substrate ABTS were 574.00 s^-1 and 898.03 s^-1, respectively, which were 1.1 times and 1.7 times that of the wild-type laccase, indicating the improved catalytic efficiency. Q275P demonstrated better performance than the wild-type laccase in pulping, as manifested by the reduction of 0.82 in the Kappa number and the increases of 2.00% ISO, 7.8%, and 7.2% in whiteness, tensile index, and breaking length, respectively. This work lays a foundation for improving the adaptation of laccase to the environment of the papermaking industry.
Laccase/chemistry* ; Directed Molecular Evolution ; Enzyme Stability ; Bacillus pumilus/genetics* ; Mutation ; Biocatalysis ; Catalysis

ObjectiveTo analyze the epidemiological characteristics of clustered vomiting and diarrhea outbreaks in Minhang District of Shanghai, to identify the influencing factors of outbreak scale and duration of epidemic, and to provide scientific evidence for further strengthening surveillance early-warning efforts in key settings and for optimizing prevention and control measures. MethodsThe data for describing epidemiological characteristics of clustered vomitting and diarrhea outbreaks in Minhang District from 2018 to 2023 were collected, multivariable logistic regression models were applied to analyze the influencing factors for epidemic scale,and Spearman rank correlation analyses were applied to analyze the factors duration. ResultsA total of 136 clustered vomiting and diarrhea outbreaks were reported in Minhang District from 2018 to 2023, all occurring in school settings, with an overall attack rate of 0.90%. The outbreaks exhibited distinct seasonality, predominantly occurring from October to December (43.38%) and March to May (32.35%). The primary settings were preschools (45.59%) and elementary schools (44.12%), with students accounted for the majority of cases (99.48%). The predominant clinical manifestation was vomiting (90.44%), with person-to-person contact being the primary transmission route (98.53%). Norovirus genogroup Ⅱ was identified as the main pathogen (71.32%). Standardized terminal disinfection of outbreak sites (OR=0.39, 95%CI=0.20‒0.74) and effective isolation of affected classes (OR=0.23, 95%CI=0.09‒0.57) were significant protective factors for reducing outbreak scale. Both response time (r=0.64, P<0.001) and the number of case generations (r=0.71, P<0.001) showed positive correlations with outbreak duration. ConclusionSchools are the key settings for the prevention and control of clustered vomiting and diarrhea outbreaks in Minhang District, with peak occurring in autumn and spring. Early detection, timely reporting, and prompt response to outbreaks are crucial. Strengthening school-based surveillance systems and standardizing outbreak management protocols are of particular importance.

ObjectiveTo analyze the reported cases of infectious diseases across different tiers of public medical and healthcare institutions in Minhang District, Shanghai from 2013 to 2023, to investigate the status and changes in reported infectious diseases in this district from a temporal, etiological, and demographic perspectives, so as to provide a scientific basis for the construction of a hierarchica early-warning surveillance system under the grading diagnosis and treatment model in medical institutions, as well as for optimizing sentinel surveillance at facilities of different levels. MethodsA retrospective analysis was performed using surveillance data from the China Disease Prevention and Control Information System in Minhang District from 2013 to 2023. Reported infectious diseases were categorized into three categories based on transmission routes: respiratory infectious diseases, intestinal infectious diseases, and sexually transmitted and blood borne infectious diseases. According to the implementation phase of the grading diagnosis and treatment policy, the research time was divided into four time periods: 2013‒2016, 2017‒2019, 2020‒2022, and 2023. The distribution and temporal changes of reported cases of infectious diseases were compared across community health service centers (CHCs), secondary hospitals, tertiary grade-A hospitals and tertiary grade-B hospitals. Chi-square test was used for univariate analysis of differences in the number of reported cases. Quantitative data with normal distribution were analyzed using parametric tests, otherwise, Kruskal⁃Wallis H tests were used. ResultsThe proportions of total reported cases of infectious diseases in medical institutions at all levels in Minhang District, Shanghai from 2013 to 2023 were 10.66% in CHCs, 9.10% in secondary hospitals, 64.95% in tertiary grade-B hospitals, and 15.29% in tertiary grade-A hospitals, with an overall decline and then rebound trend in the reported cases. After the implementation of grading diagnosis and treatment policy, the number of reported cases in CHCs and secondary hospitals showed a trend of first decreasing and then increasing, while that in tertiary grade-B hospitals showed a steady decreasing trend and that in tertiary grade-A hospitals showed an increasing trend. In terms of the research periods divided above, a total of 10 392 cases were reported in 2013‒2016 (70.34% from tertiary grade-B hospitals and 12.59% from CHCs), including 2 922 cases of respiratory infectious diseases, 1 241 cases of intestinal infectious diseases, and 6 229 cases of sexually transmitted and blood-borne infectious diseases. Between 2017 and 2019, a total of 6 967 cases were reported (73.49% from tertiary grade-B hospitals and 11.84% from tertiary grade-A hospitals), including 2 983 cases of respiratory infectious diseases, 279 cases of intestinal infectious diseases, and 3 705 cases of sexually transmitted and blood-borne infectious diseases. Between 2020 and 2022, a total of 4 599 cases were reported (69.92% from tertiary grade-B hospitals and 24.57% from tertiary grade-A hospitals), including 1 627 cases of respiratory infectious diseases, 123 cases of intestinal infectious diseases, and 2 849 cases of sexually transmitted and blood-borne infectious diseases. In 2023, a total of 4 648 cases were reported (35.20% from tertiary grade-B hospitals and 27.50% from tertiary grade-A hospitals), including 3 165 cases of respiratory infectious diseases, 69 cases of intestinal infectious diseases, and 1 414 cases of sexually transmitted and blood-borne infectious diseases. The proportion of reported cases from tertiary grade-B hospitals was the highest in all the four research periods, but exhibited an obvious decrease in 2023. The differences in the reported cases of infectious diseases with different transmission routes among medical institutions at all levels were statistically significant (χ²=3 225.628, P<0.05). The differences in the mean age of patients among medical institutions at all levels were statistically significant (H=1 325.927, P<0.05). ConclusionThere are significant differences in the number of reported cases of infectious disease in the medical institutions at different levels. Tertiary grade-B hospitals have historically dominated the number of reported cases, but its share has declined recently. Whereas, CHCs and tertiary grade-A hospitals have played an increasingly important role in the surveillance and early warning of respiratory and intestinal infectious diseases. Therefore, it is recommended to leverage the strengths of grading diagnosis and treatment to establish targeted sentinel sites and deploy specialized teams tailored to the epidemiological characteristics of specific disease categories.

ObjectiveTo explore the possible mechanism of Changweiqing （肠胃清） in the treatment of colorectal cancer. MethodsHCT 116 cancer cells were used to prepare intestinal cancer cells with silenced polypyrimidine region binding protein 3 （PTBP3） gene and stably transfected cells with overexpressed PTBP3 gene. Stably transfected cells with silenced PTBP3， stably transfected cells with overexpressed PTBP3 and untransfected cancer cells were injected into the armpit of 72 nude mice to construct three different subcutaneous transplanted tumor models of colorectal cancer cells， including the silenced model， the overexpressed model and the control model， with 24 mice per model. Mice of each transplanted tumor modelwere randomly divided into Changweiqing （CWQ） group， oxaliplatin （OXA） group and normal saline （NS） group， with 8 mice in each group. The CWQ groups were given intragastric administration of 35.9625 g/kg of Changweiqing oral liquid and were intraperitoneally injected with 0.2ml of normal saline； the NS groups were given 0.5ml of normal saline by gavage， and intraperitoneal injection of 0.2ml of normal saline； the OXA groups were intraperitoneally injected with 5 mg/kg （0.2 ml） of oxaliplatin and given 0.5ml of normal saline by gavage. Each group was given intragastric administration once a day and intraperitoneal injection three times a week. After 31 days， the weight of subcutaneous tumors in each group was measured， and the tumor inhibition rate of the groups in each model were measured. Immunohistochemistry and other methods were used to detect the expression level of cell proliferation cell nuclear antigen Ki67 and apoptosis index. Real-time PCR and Western Blot were used to detect mRNA and protein expressions of PTBP3， signal transducer and activator of transcription 3 （STAT3） splicing isoform α （STAT3α）， STAT3 splicing isoform β （STAT3β）， B-cell lymphoma/leukemia-2 （Bcl-2） splicing isoform α （Bcl-2α）， and Bcl-2 splicing isoform β （Bcl-2β） in subcutaneous tumor cells in each group. ResultsFor all three transplanted tumor models， the weight of the subcutaneous tumors and Ki67 expression level of subcutaneous tumor tissue in all CWQ groups and OXA groups were lower than those of the corresponding NS groups， while the apoptosis level were higher （P＜0.05 or P＜0.01）. The mRNA and protein expressions of PTBP3， STAT3α， and Bcl-2α in the subcutaneous tumor tissues of the silenced model CWQ group and the overexpressed model CWQ group were lower than those of the corresponding NS groups， while the mRNA and protein expression levels of STAT3β and Bcl-2β were higher （P＜0.05 or P＜0.01）. All there groups of silenced model had lower subcutaneous tumor weight， Ki67 expression level， and mRNA and protein expression levels of PTBP3， STAT3α， and Bcl-2α in subcutaneous tumor tissue， as well as higher apoptosis level and mRNA and protein expression levels of STAT3β and Bcl-2β than those in all groups of control model； all groups of overexpressed model had higher subcutaneous tumor weight， Ki67 expression level， and mRNA and protein expression levels of PTBP3， STAT3α， and Bcl-2α ， while lower apoptosis level and mRNA and protein expression levels of STAT3β and Bcl-2β than those in all control model groups （P＜0.05 or P＜0.01）. In the control model， compared with the NS group， The tumor inhibition rate of all OXA groups was higher than that of corresponding CWQ groups， respectively. Compared to that of each control model group， the tumor inhibition rate was positive value of each silenced model group， and negative value of each overexpressed model group. ConclusionPTBP3 can promote the proliferation and inhibit apoptosis of intestinal cancer cells， upregulate the expression of STAT3α and Bcl-2α， and downregulate the expression of STAT3β and Bcl-2β in intestinal cancer cells. The meachnism of action of Changweiqing in the treatment of colorectal cancer maybe related to the inhibition of PTBP3， and regulation of the expression of STAT3α， STAT3β， Bcl-2α， and Bcl-2β.

Objective:To investigate the correlation between fat distribution and the composite indices of femoral neck strength in obese postmenopausal women.Methods:A total of 293 postmenopausal women with non-low body weight were selected, laboratory tests, body composition analyzer test and double-energy X-ray absorptiometry scan were performed. Based on the body mass index(BMI), they were divided into three groups, the normal BMI group(18.5 kg/m 2≤BMI<24.0 kg/m 2, n=91), the overweight group(24.0 kg/m 2≤BMI<28.0 kg/m 2, n=115), and the obese group(BMI≥28.0 kg/m 2, n=87). The measurement results were analyzed. Results:In the obese group, bone mineral density(BMD) of all sites was higher than that in the normal BMI group and overweight group( P<0.005), compression strength index(CSI), bending strength index(BSI), and impact strength index(ISI) were significantly lower than those in the normal BMI group( P<0.001, P=0.008, P=0.001). In the obese group, waist circumference, waist-hip ratio, total fat mass, appendicular fat mass, and trunk fat mass were risk factors for CSI, BSI and ISI independent of age, fasting blood glucose, and BMI( P<0.05). Visceral fat grade and Chinese visceral adiposity fat index were the risk factors for CSI, BSI, and ISI( P<0.05). Conclusion:The composite indices of femoral neck strength decreased in obese postmenopausal women, and both subcutaneous fat and visceral fat were negatively associated with the composite indices of femoral neck strength.

Objective To investigate the expression of zinc finger protein 382(ZNF382)in diffuse large B-cell lymphoma(DLBCL)tissue and its relationship with clinical pathological characteristics and prognosis of DLBCL patients.Methods A total of 57 DLBCL patients admitted to the Department of Hematology,Luoyang Central Hospital from January 2014 to December 2018 were selected as the research subjects.The biopsy pathological specimens and clinical data of DLBCL patients were collected;another 20 patients of reactive proliferative lymph node tissue preserved in the Department of Pathology,Luoyang Central Hospital were taken as the control group.The expression of ZNF382 in DLBCL tissue and reactive proliferative lymph node tissue was detected by En vision two-step method.The difference of ZNF382 expression was compared between DLBCL tissue and reactive proliferative lymph node tissue.The correlations of ZNF382 expression with the clinical features such as age,gender,primary tumor site,Ann Arbor stage,international prognostic index(IPI)score,Hans typing,B-symptoms,bone marrow infiltration,giant masses,Eastern Cooperative Oncology Group(ECOG)score,β2-microglobulin(β2-MG),serum lactate dehydrogenase(LDH),Ki67,and chemotherapy regimen of DLBCL patients were analyzed by univariate analysis;the survival curve was drawed by Kaplan Meier method,and the univariate and multivariate survival analysis were performed by log-rank tests and Cox proportional risk regression models.Results The expression level of ZNF382 in DLBCL tissue was significantly lower than that in reactive proliferative lymph node tissue(Z=-5.056,P＜0.01).The expression level of ZNF382 was correlated with IPI score,Ann Arbor stage,Hans typing,B-symptoms,bone marrow infiltration and giant masses of DLBCL patients(P＜0.05);the expression level of ZNF382 was not associated to gender,age,primary site,ECOG score,β2-MG,serum LDH,Ki67,and whether the chemotherapy regimen combined with rituximab or not of DLBCL patients(P＞0.05).Among the 57 DLBCL patients,the treatment was effective in 36 patients(63.20％)and ineffective in 21 patients(36.80％);the expression level of ZNF382 in tumor tissue of DLBCL patients with effective treatment was significantly higher than that of DLBCL patients with ineffective treatment(Z=-2.895,P＜0.05).The 2-year event free survival rate of DLBCL patients in the ZNF382 high expression group was significantly higher than that in the ZNF382 low expression group(x2=17.955,P＜0.001).The results of univariate survival analysis showed that female,primary lymph nodes,B-symptoms,bone marrow infiltration,giant masses,IPI score≥3,elevated β2-MG,Ki67＞70％,non-germinal center B-cell-like lymphoma,Ann Arbor stageⅢ-Ⅳ and low expression of ZNF382 were risk factors for poor prognosis in DLBCL patients(P＜0.05).The results of multivariate analysis showed that primary lymph nodes,Ann Arbor stage Ⅲ-Ⅳ and low expression of ZNF382 were independent influencing factors for poor prognosis in DLBCL patients(P＜0.05).Conclusion ZNF382 protein is low expressed in the tumor tissues of DLBCL patients,which is closely related to the occurrence,development and prognosis of DLBCL;and it can be used as an indicator for evaluating the prognosis of DLBCL.