OBJECTIVE: To investigate the current status of long-term quality of life in patients with severe acute pancreatitis (SAP) who have been cured and discharged, and to analyze the influencing factors affecting long-term quality of life in SAP cured patients after discharge. METHODS: A retrospective collection was conducted. Patients who were received standardized treatment before being cured and discharged from the hospital admitted to the first department of critical care medcine of the Second Affiliated Hospital of Anhui Medical University from January 2017 to December 2023 were enrolled. According to the 36-item short form health survey scale (SF-36) score, patients were divided into high score group (high quality of life, the top 50% of patients with total SF-36 score) and low score group (low quality of life, the bottom 50% of patients with total SF-36 score). The gender, age, history of hypertension and diabetes, etiology of pancreatitis, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), CT severity index (CTSI), laboratory indicators such as C-reactive protein (CRP), procalcitonin (PCT), blood glucose, and triglycerides upon admission, use of vasoactive drugs, non-invasive/high-flow ventilation, invasive ventilation, retroperitoneal puncture and drainage, open pancreatic surgery treatment and secondary infection during hospitalization were collected, as well as the retention of abdominal drainage tubes at discharge from hospital. Distribute follow-up questionnaires or telephone follow-up surveys through WeChat and Question Star programs to investigate the pancreatic secretion function, chronic abdominal pain, and recurrence of pancreatitis of patients after discharge. Multivariable Logistic regression was used to analyze the relevant factors affecting the long-term quality of life of cured patients with SAP. RESULTS: A total of 86 patients were ultimately enrolled. There were 43 patients in both the high and low score groups. Among 86 patients, 20 experienced acute pancreatitis recurrence, with a recurrence rate of 23.26%. Twenty-two (25.58%) experienced chronic abdominal pain after discharge, and 5 patients (5.81%) needed medication to relieve pain. Thirty-three patients (38.37%) had pancreatic exocrine dysfunction after discharge, characterized by abdominal distension, constipation or diarrhea. Twenty-two patients (25.58%) suffered from pancreatic endocrine dysfunction, and were diagnosed with diabetes. Univariate analysis showed that compared with the high score group, the low score group had more patients with hypertension, initial renal dysfunction, initial severe metabolic acidosis, initial serum calcium < 2.0 mmol/L, blood glucose > 11.1 mmol/L and cultured Gram positive bacteria (from blood/body fluid/pancreatic necrotic tissue) during treatment (48.84% vs. 16.28%, 60.47% vs. 32.56%, 18.60% vs. 4.65%, 88.37% vs. 62.79%, 55.81% vs. 30.23%, 34.88% vs. 13.95%), had higher CTSI score (6.60±1.61 vs. 5.77±1.32), lower hemoglobin level at discharge (g/L: 102.30±18.78 vs. 110.72±16.68), and a lower proportion of etiological interventions after discharge (34.88% vs. 67.44%), the differences were statistically significant (all P < 0.05). Multivariate Logistic regression analysis showed that hypertension [odds ratio (OR) = 4.814, 95% confidence interval (95%CI) was 1.196-19.378], initial serum calcium < 2.0 mmol/L (OR = 6.688, 95%CI was 1.321-33.873) and initial blood glucose > 11.1 mmol/L (OR = 6.473, 95%CI was 1.399-29.950) were risk factors for long-term quality of life in cured SAP patients (all P < 0.05), while post discharge prophylactic intervention was a protective factor for long-term quality of life (OR = 0.092, 95%CI was 0.020-0.425, P < 0.01). CONCLUSIONS Cured SAP patients have varying degrees of impaired secretion function and the possibility of recurrence of acute pancreatitis. Hypertension, initial serum calcium < 2.0 mmol/L and blood glucose > 11.1 mmol/L are independent influencing factors for low long-term quality of life in cured SAP patients. Prevention and intervention targeting the etiology of pancreatitis after discharge can improve the long-term quality of life of cured SAP patients.
Humans ; Quality of Life ; Retrospective Studies ; Pancreatitis/therapy* ; Patient Discharge ; Male ; Female ; Middle Aged ; APACHE ; Adult ; Acute Disease ; Aged

Objective To analyze the predictive value of serum inflammatory factors in multidrug-re-sistant pulmonary tuberculosis.Methods A total of 151 newly treated pulmonary tuberculosis patients admit-ted to Quzhou Hospital Affiliated to Wenzhou Medical University from February 2021 to February 2023 were enrolled for standardized treatment.Based on whether multidrug resistance developed after treatment,patients were divided into multidrug-resistant group and non-multidrug-resistant group.Pretreatment serum levels of inflammatory factors were measured and compared between groups,including hypersensitive C-reactive pro-tein(hs-CRP),procalcitonin(PCT),IL-1α,IL-1β,IL-1 receptor antagonist(IL-1RA),IL-2,IL-4,IL-5,IL-6,IL-8,IL-9,IL-10,IL-12,IL-13,IL-15,IL-17,IL-18,IL-22,IL-35,tumor necrosis factor-α(TNF-α),TNF-γ,and CD40 ligand(CD40L).Logistic regression identified influencing factors for multidrug-resistant pulmonary tu-berculosis.Receiver operating characteristic(ROC)curves evaluated the predictive value of these indicators.Results The incidence of multidrug-resistant pulmonary tuberculosis was 21.85%(33/151).The levels of se-rum inflammatory factors in the drug-resistant group were higher than those in the non-drug-resistant group before treatment(P<0.05).History of alcohol consumption,presence of cavities,severe illness,adherence to treatment,and pre-treatment serum hs-CRP,PCT,IL-6,IL-18,TNF-α levels were all influencing factors for multidrug resistance in pulmonary tuberculosis patients(P<0.05).The sensitivity and area under curve(AUC)of the combined prediction of serum hs-CRP,PCT,IL-6,IL-18,TNF-α levels before treatment for multidrug-resistant pulmonary tuberculosis were higher than those of individual predictions.Conclusion The levels of serum inflammatory factors are related to multidrug resistance in pulmonary tuberculosis,and the combina-tion of serum hs-CRP,PCT,IL-6,IL-18,TNF-α can predict multidrug resistance in pulmonary tuberculosis.

OBJECTIVE: To explore the clinical and genetic characteristics of a Chinese pedigree affected with Hypertrophic cardiomyopathy (HCM) due to a truncating variant of ALPK3 gene. METHODS: A 44-year-old male admitted to Taizhou Hospital of Zhejiang Province on December 29, 2018 was selected as the study subject. Whole-exome sequencing (WES) was carried out, and candidate variant was interpreted by following the guidelines from the American College of Medical Genetics and Genomics (ACMG). For ALPK3 was considered an autosomal recessive gene, the WES results was considered insufficient to explain his phenotype. In April 2023, the proband's WES data were re-analyzed using updated annotation pipelines, and peripheral blood samples were collected from his first-degree relatives (mother and brother) for Sanger sequencing validation. Conservation analysis and protein structural modeling were performed to assess the impact of the variant. Clinical evaluation and genetic counseling were provided to the proband's family members. Relevant literature on ALPK3tv-induced HCM patients were searched in Wanfang Data Knowledge Service Platform, CNKI, and PubMed database using "ALPK3" and "hypertrophic cardiomyopathy" as keywords. Clinical characteristics of HCM patients with heterozygous ALPK3tv variants were summarized and compared with the clinical characteristics of HCM patients with positive sarcomere-associated gene variants (SARC+). This study was approved by the Medical Ethics Committee of Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University (Ethics No.: K20230314). RESULTS: The proband was a 44-year-old male who was transferred to our institution on December 29, 2018 due to "chest tightness and pain for 6 months, exacerbated for 2 days". Emergency coronary angiography was performed, which led to a preliminary diagnosis of "acute coronary syndrome", and the patient was admitted to the Cardiology Department for treatment. Based on electrocardiogram and echocardiogram findings, the diagnosis was revised as HCM. The patient's condition has stabilized post-coronary angiography, and he was discharged with improved condition. On January 2019, WES was conducted to determine the etiology of the proband's HCM. WES results identified a novel heterozygous c.2156dupC (p.Pro720ThrfsTer53) truncating variant in the ALPK3 gene. At that time, the inheritance pattern could not explain the phenotype. In 2022, a literature indicated that heterozygous ALPK3tv could lead to autosomal dominant HCM. Consequently, in April 2023, the proband's whole-exome data were re-annotated, revealing changes in the transcript and protein versions, with the updated site annotated as ALPK3 (NM_020778.5): c.1550dupC (p.Pro518ThrfsTer53). Sanger sequencing confirmed that the proband's mother and brother also carried this variant. The mother exhibited obstructive HCM, while the brother showed no related phenotype. Bioinformatics analysis demonstrated conservation of this site across multiple species, and the variant has resulted in the loss of a protein domain. Based on ACMG guidelines, the variant was classified as likely pathogenic. Literature review and Bayesian calculation further elevated the pathogenicity rating, indicating that this variant was the cause of HCM in the patient. Literature study revealed distinctions between HCM caused by this variant type and SARC+ HCM. The age of onset among heterozygous ALPK3tv patients was delayed by approximately 10 years compared to SARC+ patients. Both forms of HCM exhibited a male predominance, which was particularly marked in individuals with ALPK3tv. Electrocardiographic left ventricular hypertrophy was more prevalent in heterozygous ALPK3tv patients than in SARC+ patients. The incidence of apical or concentric hypertrophy patterns was higher in heterozygous ALPK3tv patients compared to asymmetric septal hypertrophy, which predominated in SARC+ patients. ALPK3tv patients exhibited lower penetrance and later onset compared to SARC+ patients. A positive correlation between left ventricular wall thickness and age was noted in female patients only. CONCLUSION In this pedigree, the proband has presented with HCM, characterized by echocardiographic evidence of apical left ventricular hypertrophy without significant outflow tract obstruction or extracardiac phenotypes. Although his mother and brother had carried the same heterozygous ALPK3 (NM_020778.5) c.1550dupC (p.Pro518ThrfsTer53), the mother exhibited severe obstructive HCM, while the brother was asymptomatic, suggesting incomplete or age-dependent penetrance within the family. This study has enriched the evidence for the pathogenicity of ALPK3tv among Chinese HCM pedigrees and underscored the importance of periodic literature reviews and genetic re-analysis for unresolved genetic testing results.
Humans ; Male ; Pedigree ; Adult ; Cardiomyopathy, Hypertrophic/genetics* ; Heterozygote ; Asian People/genetics* ; Exome Sequencing ; Mutation ; China ; Female ; East Asian People

Objective:To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy.Methods:Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores.Results:Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46–63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44–58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1–2 in 246 patients (50.5%) and 3–4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8–16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7–133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8–16, and >16 were 85.1%, 80.5%, and 66.4%, respectively ( P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408–0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559–4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer ( P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62–0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49–0.60). The two scores differed significantly in accuracy ( Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion:The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.

Objective:To investigate the correlation between the neoadjuvant rectal (NAR) score and long-term survival in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy.Methods:Clinical and pathological data of 487 patients diagnosed with rectal adenocarcinoma from October 2004 to April 2014 at Sun Yat-sen University Cancer Center who had received neoadjuvant chemoradiotherapy were retrospectively analyzed and the impact of NAR score on prognosis studied. Disease-free-survival (DFS) was calculated by the Kaplan-Meier method and survivals compared using the log-rank test. Cox models were used for univariate and multivariate analyses. Receiver operating characteristic curves were utilized to evaluate the predictive capability of NAR and tumor regression grade scores for the risk of 10-year postoperative recurrence and metastasis. The Delong test was employed to compare the diagnostic performance of the two scores.Results:Of the 487 patients included in the study, 166 were men (34.1%). The median age was 56 years (interquartile range [IQR]: 46–63). All patients completed adequate preoperative chemoradiotherapy and underwent R0 resection.The median interval between the end of chemoradiotherapy and surgery was 51 days (IQR: 44–58). Post-chemoradiotherapy downstaging occurred in 329 patients (67.6%). Tumor regression grades (TRGs) were 1–2 in 246 patients (50.5%) and 3–4 in 241 patients (49.5%). A total of 394 patients (80.9%) received postoperative chemotherapy. NAR scores were <8 in 182 patients (37.4%), 8–16 in 180 (37.0%), and >16 in 125 (25.6%). The median follow-up time was 111.5 months (IQR: 70.7–133.7 months). One hundred and thirteen patients died of rectal cancer, among whom 13 patients developed local recurrence, 88 patients developed distant metastasis, and 12 patients had unknown recurrence patterns. The 10-year DFS and overall survival rate of f the whole group were 68.9% and 71.5% respectively. The 10-year DFS rates for patients with NAR scores <8, 8–16, and >16 were 85.1%, 80.5%, and 66.4%, respectively ( P<0.001). Multivariate analyses revealed that the Dixon operation (HR=0.606, 95%CI: 0.408–0.902, P=0.014), and >16 (HR=2.569, 95%CI: 1.559–4.233, P<0.001) were independent predictors of the 10-year DFS of patients with locally advanced rectal cancer ( P<0.05 for all). In the entire patient cohort, the AUC of the receiver operating characteristic curve for NAR score predicting 10-year recurrence and metastasis was 0.67 (95%CI: 0.62–0.72), whereas the AUC for TRG score was 0.54 (95%CI: 0.49–0.60). The two scores differed significantly in accuracy ( Z=-4.06, P<0.001), the NAR score being a significantly better predictor of risk of 10-year recurrence and metastasis than the TRG score. Conclusion:The NAR score is a reliable predictor of 10-year DFS in patients with locally advanced rectal cancer who have undergone neoadjuvant chemoradiotherapy followed by curative surgery.

Objective:To explore the effect of sleep deprivation on hair growth cycle in mice.Methods:Seventy-two adult C57BL/6J mice were randomly divided into a control group of 36 mice and an experimental group of 36 mice using a lottery method. After hair removal, in the control the group the mice were subjected to routine feeding in a horizontal platform environment for 16 hours per day, while in the experimental group the mice were subjected to sleep deprivation using an improved water platform for 16 hours per day. On the 1st, 9th, and 19th day after the experiment, the skin tissue from the hair removal area of the two groups of mice was taken for HE staining. Then the mouse hair was staged and scored by observing hair follicle morphology under an optical microscope. The cycle and score of the hair was started from the telogen, which was set as 0 points; the anagen Ⅰ to V were set as 1-5 points; the anagen Ⅵ and catagen Ⅰ were set as 6 points; the catagen Ⅱ to Ⅷ were set at 7-13 points. Statistical analysis was conducted by SPSS 26.0. The hair cycle score was expressed as Mean±SD. Student’s t-test was used for comparison between groups at the same time point, and Welch-test was used for comparison of scores at different time points within the group. P<0.05 indicated a statistically significant difference. Results:On the 1st, 9th, and 19th day, the hair cycle scores of the control group were 1.00 ± 0.57, 5.04 ± 0.94, and 9.52 ± 0.87 points, while the hair cycle scores of the experimental group were 0.85 ± 0.62, 2.40 ± 0.50 and 6.08 ± 0.42 points. Inter group comparison showed that the hair cycle scores of the experimental group were lower than those of the control group at all three time points. There was no statistically significant difference on the 1st day ( t=1.03, P=0.307), while the differences were statistically significant on the 9th day ( t=13.38, P<0.001) and the 19th day ( t=16.41, P<0.001). Intragroup comparison showed that there was a statistically significant difference in hair cycle scores between the control group and the experimental group at different time points( P<0.01), and the scores increased over time. Conclusion:Sleep deprivation can cause a lag in the hair growth cycle of mice, but it does not cause a cessation of the hair growth cycle. The degree of lag gradually increases with the number of deprivation days.

Objective:To explore the effect of sleep deprivation on hair growth cycle in mice.Methods:Seventy-two adult C57BL/6J mice were randomly divided into a control group of 36 mice and an experimental group of 36 mice using a lottery method. After hair removal, in the control the group the mice were subjected to routine feeding in a horizontal platform environment for 16 hours per day, while in the experimental group the mice were subjected to sleep deprivation using an improved water platform for 16 hours per day. On the 1st, 9th, and 19th day after the experiment, the skin tissue from the hair removal area of the two groups of mice was taken for HE staining. Then the mouse hair was staged and scored by observing hair follicle morphology under an optical microscope. The cycle and score of the hair was started from the telogen, which was set as 0 points; the anagen Ⅰ to V were set as 1-5 points; the anagen Ⅵ and catagen Ⅰ were set as 6 points; the catagen Ⅱ to Ⅷ were set at 7-13 points. Statistical analysis was conducted by SPSS 26.0. The hair cycle score was expressed as Mean±SD. Student’s t-test was used for comparison between groups at the same time point, and Welch-test was used for comparison of scores at different time points within the group. P<0.05 indicated a statistically significant difference. Results:On the 1st, 9th, and 19th day, the hair cycle scores of the control group were 1.00 ± 0.57, 5.04 ± 0.94, and 9.52 ± 0.87 points, while the hair cycle scores of the experimental group were 0.85 ± 0.62, 2.40 ± 0.50 and 6.08 ± 0.42 points. Inter group comparison showed that the hair cycle scores of the experimental group were lower than those of the control group at all three time points. There was no statistically significant difference on the 1st day ( t=1.03, P=0.307), while the differences were statistically significant on the 9th day ( t=13.38, P<0.001) and the 19th day ( t=16.41, P<0.001). Intragroup comparison showed that there was a statistically significant difference in hair cycle scores between the control group and the experimental group at different time points( P<0.01), and the scores increased over time. Conclusion:Sleep deprivation can cause a lag in the hair growth cycle of mice, but it does not cause a cessation of the hair growth cycle. The degree of lag gradually increases with the number of deprivation days.

OBJECTIVE To investigate the cellular uptake and in vivo imaging of paclitaxel(PTX)-loaded polyethylene glycol(PEG)-modified rhein conjugate micelles. METHODS (P4/P2+PTX)/CRmP micelles were prepared by co-loading environment-responsive fluorescent probes P4/P2 and PTX into CRmP micelles. Using MCF-7 cells as cell models, the uptake of the micelles by MCF-7 cells was analyzed by laser confocal microscopy and flow cytometry. The H22 subcutaneous transplanted tumor mice were used as animal models, and the distribution of the micelles in vivo and in vitro were analyzed by in vivo imaging system. RESULTS (P4+PTX)/CRmP micelles in the intact form were internalized by MCF-7 cells and distributed in the cytoplasm. (P2+PTX)/CRmP micelles were more accumulated in the liver and tumor sites in vivo, and gradually accumulated at the tumor sites during the experimental time. CONCLUSION The intact micelles can be taken up by tumor cells, and have liver and tumor targeting properties in vivo.

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has achieved 40%-50% long-term complete response in relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients. However, the underlying mechanism of alterations in the tumor microenvironments resulting in CAR-T cell therapy failure needs further investigation. A multi-center phase I/II trial of anti-CD19 CD28z CAR-T (FKC876, ChiCTR1800019661) was conducted. Among 22 evaluable DLBCL patients, seven achieved complete remission, 10 experienced partial remissions, while four had stable disease by day 29. Single-cell RNA sequencing results were obtained from core needle biopsy tumor samples collected from long-term complete remission and early-progressed patients, and compared at different stages of treatment. M2-subtype macrophages were significantly involved in both in vivo and in vitro anti-tumor functions of CAR-T cells, leading to CAR-T cell therapy failure and disease progression in DLBCL. Immunosuppressive tumor microenvironments persisted before CAR-T cell therapy, during both cell expansion and disease progression, which could not be altered by infiltrating CAR-T cells. Aberrant metabolism profile of M2-subtype macrophages and those of dysfunctional T cells also contributed to the immunosuppressive tumor microenvironments. Thus, our findings provided a clinical rationale for targeting tumor microenvironments and reprogramming immune cell metabolism as effective therapeutic strategies to prevent lymphoma relapse in future designs of CAR-T cell therapy.

The number of benign prostatic obstruction (BPO) patients in China is increasing, and patients tend to be younger and younger. The former "gold standard" scheme of transurethral resection of the prostate (TURP) is more suitable for patients with prostate volume ranging from 40 mL to 80 mL, which may lead to excessive resection in patients with small prostate volume and low efficiency in patients with large prostate volume. New minimally invasive techniques have been introduced,including prostate artery embolization, laser surgery (such as holmium, green, diode, and thulium), minimally invasive simple prostatectomy, transperineal laser ablation, prostatic urethral lift,and robot-assisted water jet ablation of the prostate. These methods are alternatives to TURP and increasingly used in the treatment of BPO. This article reviewed the advances in minimally invasive treatment of BPO.