ObjectiveTo detect the proportion of splenic follicular helper T （Tfh） cells and their functionally related cytokine expression levels in the incomplete embryo implantation disorder （EID） model mice， and to explore the immunological mechanism of Tfh in infertility caused by embryo implantation disorder. MethodsSixteen female Kunming mice were randomly divided into two groups， with eight mice in each group. On day 4 of pregnancy， an incomplete EID mouse model was established by oral gavage of mifepristone suspension， while an equal volume of saline was administered to the control group. On day 8 of pregnancy， the mice were euthanized. Flow cytometry was used to detect the levels of Tfh cells in the spleen lymphocytes of both incomplete EID mice and normal control mice. qRT-PCR was performed to measure the mRNA levels of B-cell lymphoma 6 （Bcl-6） and C-X-C chemokine receptor type 5 protein （CXCR5） in the spleen lymphocytes of both groups. Western blot was employed to assess the protein expression levels of Bcl-6 and CXCR5 in the spleen lymphocytes of both groups. Serum levels of interleukin-4 （IL-4）， IL-6， and IL-21 were measured by ELISA. Immunohistochemistry （IHC） was used to observe the expression levels of progesterone receptor （PR）， Bcl-6， and CXCR5 proteins in the uterine endometrial tissue of mice in both groups. ResultsIncomplete-type EID mice had a reduced number of embryo implantation points and reduced endometrial PR expression. Flow assay results showed that the proportion of CD4⁺CXCR5⁺Tfh cells in splenic lymphocytes of incomplete-type EID mice was significantly higher than that of normal controls （P<0.05）. Compared with the normal control group， Bcl-6 and CXCR5 mRNA levels and protein levels were elevated in splenic lymphocytes of incomplete EID mice， with statistically significant differences （P<0.05）； serum IL-4， IL-6， and IL-21 levels were elevated in incomplete EID mice， and Bcl-6 and CXCR5 proteins in the endometrium were significantly elevated （P<0.05）. ConclusionThe increase of Tfh cells and their associated cytokines Bcl-6 and CXCR5 is associated with the development of incomplete EID， and may be involved in the development of female immune infertility.

In recent years,significant breakthroughs have been achieved in the immunotherapy for Alzheimer's disease.In line with global advancements,two anti-amyloid-β monoclonal antibodies have been approved and successfully launched in China for clinical use.Lecanemab and Donanemab were officially used in June 2024 and April 2025 in China,respectively.In order to standardize the rational and safe application of anti-amyloid-β monoclonal antibodies for Alzheimer's disease in China,this article integrates recom-mendations from the clinical trials and real-world experience from the author's team and domestic peers to further update the recom-mendations for the clinical use of anti-amyloid-β monoclonal antibody based on the 2024 version.It includes indications for therapy,pre-treatment evaluation and preparation,administration protocols and safety measures during treatment,and post-treatment monitor-ing strategies.

Objective:To evaluate inflammation early in the infarct zone and its dynamic changes after acute myocardial infarction (AMI) using 18F-FDG PET imaging, and analyze its relationship with left ventricular remodeling progression (LVRP). Methods:Sixteen Bama miniature pigs (4-6 months old, 8 females) were selected. AMI models were established by balloon occlusion of the left anterior descending artery. 18F-FDG PET imaging was performed before AMI and at days 1, 5, 8, and 14 post-AMI to evaluate the regional inflammation response. 18F-FDG SUV ratio (SUVR) and the percentage of uptake area of left ventricle (F-extent) in the infarct zone, and the SUVRs of the spleen and bone marrow, were measured. Echocardiography and 99Tc m-methoxyisobutylisonitrile(MIBI) SPECT myocardial perfusion imaging (MPI) were performed at the above time points and on day 28 post-AMI to assess left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and myocardial perfusion defect extent. The degree of LVRP at day 28 post-AMI was defined as ΔLVESV(%)=(LVESV AMI 28 d-LVESV AMI 1 d)/LVESV AMI 1 d×100%. Data were analyzed using repeated measures analysis of variance, Kruskal-Wallis rank sum test and Pearson correlation analysis. Results:Twelve pigs were successfully modeled and completed the study. Inflammation in the infarct zone persisted until day 14 post-AMI. The SUVR of the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 1.03±0.08, 3.49±1.06, 2.93±0.90, 2.38±0.76, and 1.63±0.62, respectively ( F=49.31, P<0.001). The F-extent values in the infarct zone pre-AMI and at days 1, 5, 8, and 14 post-AMI were 0, (40.08±12.46)%, (40.00±12.76)%, (31.08±12.82)%, and 16.50%(7.25%, 22.00%), respectively ( H=37.61, P=0.001). There were no significant differences in the SUVRs of bone marrow and spleen before and after AMI ( F values: 0.69 and 0.77, both P>0.05). At day 1 post-AMI, both SUVR and F-extent in the infarct zone were significantly correlated with LVRP ( r values: 0.82 and 0.70, P values: 0.001 and 0.035). Conclusions:18F-FDG PET imaging can be used to evaluate inflammation in the infarct area and its dynamic changes after AMI. Inflammation in the infarct area is severe at day 1, and then gradually decreases. The extent and severity of inflammation visible on 18F-FDG PET imaging 1 d after AMI are closely related to LVRP.

Objective:This study aims to establish an early warning diagnosis model for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and to provide a simple, rapid, and accurate auxiliary diagnosis basis for clinical practice.Methods:The sample bank of subjects (patients admitted to the Eighth Medical Center of the PLA General Hospital from September 10, 2021, to July 25, 2023) was constructed, including the model establishment cohort [SCOPD group 49, 42 males and 7 females, (69.71±11.16) years old; AECOPD group 53, 49 males and 4 females, (72.60±10.19) years old] and the model validation cohort [SCOPD group 35, 28 males and 7 females, (69.97±10.40) years old; AECOPD group 35, 33 males and 2 females, (71.43±9.67) years old]. Fasting peripheral blood samples were collected, and the expression levels of IL-5, IL-17A, and IFN-α were detected by flow cytometry. Different expression levels were analyzed by Mann-Whitney U test. Binary logistic regression analysis was used to screen the related risk factors of COPD patients in acute exacerbation. The diagnostic efficacy of the model was evaluated by the receiver operating characteristic (ROC) curve.Results:The levels of IL-5 [1.64 (0.60, 2.86) pg/ml], IL-17A [1.42 (0.88, 2.29) pg/ml], and IFN-α [0.91 (0.59, 1.81) pg/ml] in the SCOPD group were significantly decreased compared with the AECOPD group IL-5 [4.68 (2.34, 9.40) pg/ml, Z=-5.033, P<0.001], IL-17A [2.33 (1.59, 4.62) pg/ml, Z=-3.919, P<0.001], IFN-α [2.83 (0.91, 3.75) pg/ml, Z=-4.127, P<0.01] in the cohort of model establishment. The results of binary logistic regression analysis between SCOPD and AECOPD groups showed that IL-5, IL-17A, and IFN-α were independent risk factors for acute exacerbation of patients with COPD ( P<0.05). And the regression equation is Y=-2.861+0.364×IL-5+0.385×IL-17A+0.445×IFN-α. The AUC value of IL-5, IL-17A, IFN-α and combined detection was 0.866 ( P<0.001). Compared to the SCOPD group and the AECOPD group in the cohort of model validation, the receiver operating characteristic (ROC) curve showed that the combined model of three (AUC=0.858, P<0.001) could be used to diagnose the AECOPD. And the Kappa value was 0.773( P<0.05). Conclusion:The combined detection of IL-5, IL-17A, and IFN-α has high diagnostic efficacy for patients with acute exacerbation of COPD. This method provides a new potential tool for the clinical diagnosis of AECOPD and has the value of further exploration and optimization, promotion, and application.

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.
Female ; Humans ; Uterine Cervical Neoplasms/drug therapy* ; Prospective Studies ; Quality of Life ; Neoplasm Staging ; Chemoradiotherapy ; Chemotherapy, Adjuvant/adverse effects* ; Adjuvants, Immunologic ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Retrospective Studies

Clinical data from 11 previously diagnosed and treated patients with hyperthyroidism(Graves′ disease) complicated by liver failure were collected. Among them, 4 cases were drug-induced liver injury leading to liver failure, 1 case had a history of schistosomal liver cirrhosis combined with hyperthyroidism, and 6 cases had hyperthyroidism-induced liver injury(HILI) leading to liver failure. During hospitalization, all patients received supportive therapy and symptomatic treatment with β-blockers. Nine patients were treated with glucocorticoids and artificial liver support therapy. Among the 11 patients, 2 died, 8 patients achieved normal thyroid and liver function within 1-12 months after treatment, and 1 patient with liver cirrhosis had stable liver function in the later stage. After improvement in liver function, 7 patients received isotope therapy, 1 patient underwent total thyroidectomy, and 1 patient received medication. These results indicate that the clinical characteristics differ for drug-induced liver injury and HILI-related liver failure. Early initiation of artificial liver support therapy, in addition to β-blockers and glucocorticoids, is important in alleviating thyroid toxicity and liver damage, thus creating an opportunity for subsequent radioactive iodine or surgical treatment.

Background:Gastroesophageal reflux disease(GERD)is a common digestive system disease with typical symptoms of acid reflux and heartburn,and high sensitivity of esophagus is an important cause of heartburn and other symptoms.TRPV1 and NaV1.8 may play an important role in the regulation of esophageal hypersensitivity,and the specific mechanism is not yet clear.Aims:To detect the expression levels of TRPV1 and NaV1.8 in esophageal sensory neuron in GERD state and explore their role in mediating esophageal hypersensitivity.Methods:Twelve guinea pigs were randomly divided into control group and GERD group.The GERD guinea pig model was established by drinking hydrochloric-pepsinogen acid water,the body mass of guinea pigs was monitored,the esophageal inflammatory histological score was performed,and the successful construction of the GERD model was verified by measuring the expression indicators of inflammatory factors.The heart rate variability method was used to detect whether the guinea pigs were in the state of visceral hypersensitivity.The expression and co-expression of TRPV1 and NaV1.8 in esophagus,nodular ganglion and jugular ganglion were detected by immunofluorescence,Western blot and real-time fluorescence quantification.Results:Compared with the control group,the score of esophageal inflammatory histology in GERD group was much higher than that in the control group(0.96 vs.0.22).The contents of esophageal inflammatory factors interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α were significantly increased(P<0.05),while the contents of anti-inflammatory factor IL-10 were decreased(P<0.05).The index of heart rate variability,low frequency to high frequency ratio(LF/HF)had no significant difference between the GERD group and the control group(P>0.05),and the LF/HF in the GERD group was higher than that in the control group after the molding(P<0.05).In esophagus and jugular,the expression levels of TRPV1 and NaV1.8 in GERD group were increased and the co-expression levels were up-regulated(P<0.05),while the expression levels in nodose were not significantly changed(P>0.05).Conclusions:In the case of esophageal acid exposure,the expression levels of TRPV1 and NaV1.8 in the esophageal mucosal epithelium increased,while the expression levels in jugular ganglion were up-regulated,thus promoting the transmission of pain signals in the vagus nerve pathway,and ultimately leading to the occurrence of esophageal hypersensitivity.

Background: Studies have shown that transient receptor potential (TRP) channels play important roles in gastroesophageal reflux disease (GERD), however, the relationship between TRPV1 and TRPM8 in reflux esophagitis (RE) remains unclear. Aims: To investigate the expressions of TRPV1, TRPM8 and their correlation in guinea pigs with RE. Methods: Thirty male guinea pigs aged 3⁃4 weeks were randomly divided into 3 groups: blank control group, negative control group and model group, with 10 animals in each group. Guinea pigs in model group and negative control group were given esophageal perfusion with 0.1 mol/L HCl containing 0.5% pepsin and normal saline, respectively, once a day for 14 days; guinea pigs in blank control group were free to drink sterile water for 14 days. On day 15, the esophagus was dissected for macroscopic and histopathological examination, and Western blotting and/or real⁃time PCR were used to detect the expression levels of TRPV1, TRPM8, GNAQ (an isoform of G protein), and the tight junction proteins and proinflammatory cytokines in esophageal tissue. The co⁃localization of TRPV1 and TRPM8 was assessed by immunofluorescence. Results: Esophageal mucosal congestion, hyperplasia of esophageal epithelial cells, infiltration of inflammatory cells, as well as up⁃regulation of proinflammatory cytokines and down⁃regulation of tight junction proteins were observed in esophageal tissue of guinea pigs in model group, which indicated the successful RE model construction. As compared with the negative control group, expression levels of TRPV1 and GNAQ mRNA and protein were significantly increased, while expression levels of TRPM8 mRNA and protein were significantly reduced in esophageal tissue of guinea pigs in model group (all P<0.05). TRPV1 and TRPM8 channels were co ⁃ localized in the lamina propria of esophageal mucosa. Conclusions: There is a certain equilibrium mechanism between TRPV1 and TRPM8 channels in RE models. G protein⁃coupled receptor signaling pathway and the downstream TRPV1/TRPM8 might be involved in the occurrence and development of GERD.

In China, hepatocellular carcinoma (HCC) accounts for about 50% of cases in the world, which is still challenging. The implementation of multi-disciplinary treatment (MDT) and whole course management of HCC are conducive to improve the prognosis of patients, so as to achieve the goal of increasing by 15% of overall survival of HCC patients as proposed by the "Healthy China 2030" . The standardized management of HCC includes several key points, such as exact diagnosis of the HCC, selection of proper treatment methods, individual postoperative adjuvant therapy and regular follow-up. MDT is the key measure to implement the standardized and whole course management of HCC. Herein, the author tends to summary the experience on standardized management of HCC.

Objective:To retrospectively analyze the clinical and serological characteristics in rehabilitated patients with common novel coronavirus pneumonia(COVID-19).Methods:A total of 165 patients with common COVID-19 were enrolled in this retrospective study, in which clinical data was collected from February 23 to March 15, 2020 in Leishenshan Hospital(Wuhan, China). The patients with COVID-19 were divided into elderly group and non-elderly group according to their age, and the differences in the clinical and serological metabolic characteristics between these two groups were analyzed.Results:49.7% patients were over 60 years old. The most common clinical symptoms were fever, cough, and fatigue, followed by muscle soreness. Expectoration and digestive tract symptoms were rare. Dyspnea occurred more frequently in the elderly group than in non-elderly group(47.56% vs 25.30%, P<0.01). Hypertension was the most common concomitant disease(accounting for 29.1%)followed by diabetes. Hypertension was more common in the elderly group than in non-elderly group(41.46% vs 16.86%, P<0.01), but without significant difference in diabetes between the two groups. The counts of leukocytes and lymphocytes in all patients were in the normal range, and no difference was observed between the groups. The comparison of serological indicators showed that serum creatinine in the elderly group was higher than that in the non-elderly group( P<0.01)while serum albumin, glomerular filtration rate, and serum calcium were lower in the elderly group. After serum albumin correction, the levels of albumin corrected calcium in all patients were in the normal range, without significant difference between these two groups. There was no significant difference between the two groups when the length of hospital stay was taken as the index of outcome [(34.01±10.24) vs(30.97±10.51)d, P>0.05]. Conclusion:Fever, cough, and fatigue are the most common clinical symptoms in patients with ordinary COVID-19. The elderly are more likely to develop dyspnea. The blood routine and metabolic characteristics in patients with common COVID-19 are normal, but serum albumin level is more likely to decrease in elderly patients with COVID-19.