BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

OBJECTIVE: Psoriasis, a common chronic inflammatory skin condition with genetic underpinnings, is traditionally managed with cupping therapy. Although used historically, the precise mechanical effects and therapeutic mechanisms of cupping in psoriasis remain largely unexamined. This study aimed to evaluate cupping therapy's efficacy for psoriasis and investigate its role in modulating inflammatory responses and cellular metabolism. METHODS: Psoriasis was induced in mice using topical imiquimod (IMQ). The effects of cupping on psoriatic lesions were assessed using the Psoriasis Area and Severity Index score, histology, immunohistochemistry, and immunofluorescence staining. polymerase chain reaction sequencing (RNA-seq) and Western blotting were conducted to examine changes in mRNA expression and the AMP-activated protein kinase (AMPK) signaling pathway. RESULTS: Cupping therapy significantly reduced inflammation, epidermal thickness, and inflammatory cell infiltration in mice with IMQ-induced psoriasis. Immunohistochemistry and immunofluorescence showed lower expression of inflammatory markers and a shift in T-cell populations. RNA-seq and Western blotting indicated that cupping upregulated Piezo1 and activated the AMPK pathway, improving energy metabolism in psoriatic skin. CONCLUSION Cupping therapy reduces epidermal hyperproliferation and inflammation in psoriasis, rebalancing the local immune microenvironment. Mechanistically, cupping promotes calcium influx via Piezo1, activates AMPK signaling, and supports metabolic homeostasis, suggesting therapeutic potential for psoriasis. Please cite this article as: Xi RF, Liu X, Wang Y, Lu HZ, Yuan SJ, Guo DJ, Zhu JY, Li FL, Duan YJ. Mechanosensory activation of Piezo1 via cupping therapy: Harnessing neural networks to modulate AMPK pathway for metabolic restoration in a mouse model of psoriasis. J Integr Med. 2025; 23(6):721-732.
Animals ; Psoriasis/chemically induced* ; Mice ; AMP-Activated Protein Kinases/metabolism* ; Disease Models, Animal ; Cupping Therapy/methods* ; Signal Transduction ; Imiquimod ; Ion Channels/genetics* ; Male ; Mechanotransduction, Cellular

Objective To investigate the expression of SORT1 in the gastric cancer tissue and analyze its relationship with clinical prognosis of patients as well as the pathways and mechanisms involved in gastric cancer progression.Methods The Gene Expression Profiling Interaction Analysis database,Western blot,and immunohistochemistry were employed to predict and analyze the expression of SORT1 in the gastric cancer and the adjacent tissue.The clinical case information of 109 patients who underwent radical surgery for gastric cancer in the First Affiliated Hospital of Bengbu Medical University from April 2015 to April 2017 was collected to analyze the relationship of SORT1 with the clinicopathological parameters and prognosis of the patients.Cell proliferation was detected by the CCK-8 assay and colony formation assay,while cell migration and invasion were assessed by the scratch assay and Transwell assay,respectively.Western blot was employed to determine the expression of proteins related to epithelial-mesenchymal transition(EMT)in gastric cancer cells,followed by further analysis on molecular mechanism through which SORT1 regulates EMT in gastric cancer cells.Results Western blot and immunocytochemistry results showed that SORT1 was highly expressed in the gastric cancer tissue(P=0.003,P<0.001),which was positively correlated with malignant progression of tumors(all P<0.05).The Kaplan-Meier survival analysis revealed shortened postoperative survival periods for the patients with high expression of SORT1(P<0.001).The Cox regression model indicated that SORT1 expression was an independent risk factor affecting the 5-year survival rate after surgery for gastric cancer patients(P<0.001).Up-regulation of SORT1 expression promoted the proliferation,migration,invasion,and EMT of gastric cancer cells(all P<0.05),while down-regulation of SORT1 showed the opposite effects(all P<0.05).Western blot results showed that high expression of SORT1 promoted the expression of β-catenin,cyclin D1,and c-Myc(all P<0.05).Moreover,in vitro use of the Wnt/β-catenin pathway inhibitor(XAV939)effectively suppressed the EMT enhancement caused by high expression of SORT1 in gastric cancer cells(all P<0.05).Conclusions SORT1 is highly expressed in gastric cancer and affects patients' postoperative survival periods.It is involved in the proliferation,migration,and invasion of gastric cancer cells and may promote the EMT of gastric cancer cells by activating the Wnt/β-catenin pathway.
Humans ; Stomach Neoplasms/pathology* ; Cell Proliferation ; Epithelial-Mesenchymal Transition ; Cell Movement ; Prognosis ; Cell Line, Tumor ; Adaptor Proteins, Vesicular Transport/metabolism* ; Male ; Female ; Middle Aged

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Objective:To analyze the detection strategy and basic detection situation of markers of infectious diseases transmitted by transfusion in blood testing laboratories of blood stations in China.Methods:Based on the data of practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021, the data on the testing strategies and the basic detection information of the markers for the transmission of infectious diseases through transfusion in the member laboratories of the practice comparison working party of Blood Stations in Mainland of China from 2017 to 2021 were collected, and the situation of the selection for testing markers, testing strategy and the testing method and other relevant aspects were sorted out and analyzed by charts.Results:The selection of the testing markers was consistent, but HTLV testing item was added in some member laboratories. The detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously was adopted in 47 member blood stations; 3) NAT method was dominated by mini pool-NAT in member laboratories. The number of members adopting mini-pools of 8 (MP8)-NAT decreased from 17 in 2017 to 14 in 2021, while the number of members adopting mini-pools of 6 (MP6)-NAT increased from 13 in 2017 to 22 in 2021; Roche NAT system accounted for the largest proportion.Conclusions:In order to ensure blood safety and avoid missing detection, the blood stations still adopt the detection strategy of using two ELISA reagents and one nucleic acid testing (NAT) reagent simultaneously; Meanwhile, in order to increase the NAT positive rate, the proportion of mini pool-NAT mainly decreased year by year despite its dominating role, while the proportion of individual donation-NAT increased year by year; NAT method is transiting from mini-pools of 8 (MP8) to mini-pools of 6 (MP6); The proportion of imported NAT system used in NAT laboratory is relatively large.

Objective:This study aimed to investigate the viability and safety of a novel defecator in managing rectal fecal impaction.Methods:In a descriptive case series, this new defecator was administered to constipated individuals among the ages of 18 and 80 years who met the diagnostic criteria for rectal fecal impaction and were identified with acute rectal fecal impaction through CT scans. The contraindications for this defecator included: (1) Anal stenosis, acute intestinal obstruction, and intestinal perforation; (2) Concomitant rectal malignant tumors; (3) Coagulation dysfunction, low platelet counts, gastrointestinal bleeding, or other bleeding risks; (4) Patients with severe underlying conditions affecting the heart, brain, lungs, or other systems; (5) Individuals with mental health disorders. Based on these criteria, clinical data from 42 patients with rectal fecal impaction who underwent treatment with the new defecator at Deyang People's Hospital between July 2020 and April 2023 were retrospectively analyzed.The defecator comprises three components: a head, a spiral rod, and a handle, constructed from disposable stainless steel wire. The treatment procedure involves the following steps: The patient assumes a flexed, supine position on their left side with their buttocks slightly protruding from the bed's edge. A transparent sealing bag is affixed to the buttocks, centered around the anus. With gloved hands inserted through the bag's entrance, a cotton ball soaked in liquid paraffin lubricates the anal canal and the head of the defecator's spiral rod. The defecator is then slowly rotated and inserted into the anus, with careful attention to any changes in resistance. Once the spiral rod is fully inserted, the patient is instructed to inhale and defecate while the defecator is slowly withdrawn, carrying the dislodged fecal matter, and depositing it into the sealed bag. This operation is repeated 2 to 3 times, followed by the injection of either 100 ml of 36°C normal saline or 60 ml of liquid paraffin into the rectum. After a 5 to 8-minute wait, the patient assumes a squatting position to expel any remaining feces from the rectum. The study assessed the operation time, single treatment success rate, pain levels during treatment, and the occurrence of complications.Results:All 42 patients successfully underwent treatment with the new defecator device, achieving a single treatment success rate of 100%. The average operation time was 11.0 minutes (range: 9.0 to 13.3 minutes). During treatment, 20 cases (47.6%) reported moderate to severe anal pain, with 1 case (2.4%) experiencing anal fissure bleeding, and 6 cases (14.3%) reporting discomfort such as palpitations and sweating. No serious complications, including rectal perforation, were observed in any case.Conclusion:The new defecator device demonstrates ease of use and safety, making it a feasible option for treating acute rectal fecal impaction.

Objective:This study aimed to investigate the viability and safety of a novel defecator in managing rectal fecal impaction.Methods:In a descriptive case series, this new defecator was administered to constipated individuals among the ages of 18 and 80 years who met the diagnostic criteria for rectal fecal impaction and were identified with acute rectal fecal impaction through CT scans. The contraindications for this defecator included: (1) Anal stenosis, acute intestinal obstruction, and intestinal perforation; (2) Concomitant rectal malignant tumors; (3) Coagulation dysfunction, low platelet counts, gastrointestinal bleeding, or other bleeding risks; (4) Patients with severe underlying conditions affecting the heart, brain, lungs, or other systems; (5) Individuals with mental health disorders. Based on these criteria, clinical data from 42 patients with rectal fecal impaction who underwent treatment with the new defecator at Deyang People's Hospital between July 2020 and April 2023 were retrospectively analyzed.The defecator comprises three components: a head, a spiral rod, and a handle, constructed from disposable stainless steel wire. The treatment procedure involves the following steps: The patient assumes a flexed, supine position on their left side with their buttocks slightly protruding from the bed's edge. A transparent sealing bag is affixed to the buttocks, centered around the anus. With gloved hands inserted through the bag's entrance, a cotton ball soaked in liquid paraffin lubricates the anal canal and the head of the defecator's spiral rod. The defecator is then slowly rotated and inserted into the anus, with careful attention to any changes in resistance. Once the spiral rod is fully inserted, the patient is instructed to inhale and defecate while the defecator is slowly withdrawn, carrying the dislodged fecal matter, and depositing it into the sealed bag. This operation is repeated 2 to 3 times, followed by the injection of either 100 ml of 36°C normal saline or 60 ml of liquid paraffin into the rectum. After a 5 to 8-minute wait, the patient assumes a squatting position to expel any remaining feces from the rectum. The study assessed the operation time, single treatment success rate, pain levels during treatment, and the occurrence of complications.Results:All 42 patients successfully underwent treatment with the new defecator device, achieving a single treatment success rate of 100%. The average operation time was 11.0 minutes (range: 9.0 to 13.3 minutes). During treatment, 20 cases (47.6%) reported moderate to severe anal pain, with 1 case (2.4%) experiencing anal fissure bleeding, and 6 cases (14.3%) reporting discomfort such as palpitations and sweating. No serious complications, including rectal perforation, were observed in any case.Conclusion:The new defecator device demonstrates ease of use and safety, making it a feasible option for treating acute rectal fecal impaction.

Objective: To investigate the role of CXCL5 in tumor immune of lung cancer and to explore the potential molecular mechanisms. Methods: A total of 62 cases of patients with lung cancer admitted in the First Affiliated Hospital of Henan University from May 2018 to December 2019 were recruited as study object. Another 20 cases of patients with pulmonary infectious diseases and 20 cases of healthy control were selected as control. Enzyme-linked immunosorbent assay (ELISA) was used to determine serum levels of CXCL5 in patients with lung cancer, pulmonary infectious diseases and healthy control. Immunohistochemical staining (IHC) was used to detect the expressions of CXCL5 and PD-1/PD-L1 in tumor and paracarcinoma tissues of patients with lung cancer. Pearson correlation analysis was used to evaluate the correlation between CXCL5 and PD-1 in tumor and paracarcinoma tissues of patients with lung cancer. Lewis cells either expressing CXCL5 or vector plasmids were used to establish C57BL/6J mice model of lung cancer, and all mice were then divided into vehicle and PD-1 antibody treatment groups, 10 mice for each group. The mice survival and tumor growth curves were recorded. IHC was used to evaluate the expressions of CXCL5, PD-1 as well as the proportions of CD8(+) T and Treg cells in xenograft tumor tissues. Results: In patients with lung cancer, the serum level of CXCL5 [(351.7±51.5) ng/L] was significant higher than that in patients with pulmonary infectious diseases and healthy control [(124.7±23.4) ng/L, P<0.001]. The expression levels of CXCL5 (0.136±0.034), CXCR2 (0.255±0.050), PD-1 (0.054±0.012) and PD-L1 (0.350±0.084) in tumor were significant higher than those in paracarcinoma normal tissues [(0.074±0.022), (0.112±0.023), (0.041±0.007) and (0.270±0.043) respectively, P<0.001]. CXCL5 was significant positively correlated with PD-1 in tumor tissues of lung cancer (r=0.643, P<0.001), but not correlated with PD-1 in paracarcinoma tissues(r=0.088, P=0.496). The vector control group, CXCL5 overexpression group, vector control + anti-PD-1 antibody treatment group and CXCL5 overexpression + anti-PD-1 antibody treatment group all successfully formed tumors in mice, while CXCL5 overexpression increased the tumor growth significantly (P<0.01), which was abrogated by the treatment of anti-PD-1 antibody. CXCL5 overexpression decreased the mice survival time significantly (P<0.01), this effect was also abrogated by the treatment of anti-PD-1 antibody. The proportion of CD8(+) T cells in CXCL5 overexpression group [(10.40±2.00)%] was significant lower than that in vector control group [(21.20±3.30)%, P=0.002]. The proportion of CD4(+) Foxp3(+) Treg cells in CXCL5 overexpression group [(38.40±3.70)%] was significant higher than that in vector control group [(23.30±2.25)%, P<0.001]. After the treatment of anti-PD-1 antibody, no significant difference were observed for the proportion of CD8(+) T cells [(34.10±5.00)% and (33.40±4.00)% respectively] and Treg cells [(14.70±3.50)% and (14.50±3.30)% respectively] in xenograft tumor tissues between CXCL5 overexpression+ anti-PD-1 antibody treatment group and vector control + anti-PD-1 antibody treatment group (P>0.05). Conclusion: The expressions of CXCL5 and PD-1/PD-L1 are all increased significantly in the tumor tissues of patients with lung cancer, CXCL5 may inhibit tumor immune of lung cancer via modulating PD-1/PD-L1 signaling.
Animals ; B7-H1 Antigen/metabolism* ; CD8-Positive T-Lymphocytes ; Chemokine CXCL5/metabolism* ; Humans ; Lung Neoplasms/pathology* ; Mice ; Mice, Inbred C57BL ; Programmed Cell Death 1 Receptor/metabolism*

Recombinant human interferon α2b(rhIFNα2b)is widely used as an antiviral therapy agent for the treatment of hepatitis B and hepatitis C.The current identification test for rhIFNα2b is complex.In this study,an anti-rhIFNα2b nanobody was discovered and used for the development of a rapid lateral flow strip for the identification of rhIFNα2b.RhIFNα2b was used to immunize an alpaca,which established a phage nanobody library.After five steps of enrichment,the nanobody I22,which specifically bound rhIFNα2b,was isolated and inserted into the prokaryotic expression vector pET28a.After subsequent purification,the physicochemical properties of the nanobody were determined.A semiquantitative detection and rapid identification assay of rhIFNα2b was developed using this novel nanobody.To develop a rapid test,the nanobody I22 was coupled with a colloidal gold to produce lateral-flow test strips.The developed rhIFNα2b detection assay had a limit of detection of 1 μg/mL.The isolation of I22 and successful construction of a lateral-flow immunochromatographic test strip demonstrated the feasibility of performing ligand-binding assays on a lateral-flow test strip using recombinant protein products.The principle of this novel assay is generally applicable for the rapid testing of other com-mercial products,with a great potential for routine use in detecting counterfeit recombinant protein products.