Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Objective:To investigate the influencing factors for gastroesophageal reflux disease (GERD) after laparoscopic Heller-Dor surgery for esophageal achalasia.Methods:The retrospective case-control study was conducted. The clinical data of 210 patients with esophageal achalasia who were admitted to Shanxi Provincial Cancer Hospital from January 2021 to December 2023 were collected. There were 119 males and 91 females, aged (47±12)years. All patients underwent laparoscopic Heller-Dor surgery. Observation indicators: (1) surgical situations; (2) follow-up; (3) influencing factors for GERD after laparoscopic Heller-Dor surgery; (4) development and evaluation of a predictive model for GERD after laparoscopic Heller-Dor surgery. Univariate and multivariate analyses were performed using stepwise Logistic regression. Results of multivariate analysis were used to construct a nomogram in predicting GERD. The predictive performance was assessed using the area under the receiver operating characteristic curve. The calibration curve was used to evaluate the accuracy of the model, and the decision curve was used to assess the overall net benefit of the model.Results:(1) Surgical situations. All 210 patients underwent laparoscopic Heller-Dor surgery. The operation time was (128±31)minutes, volume of intraoperative blood loss was (25±9)mL, and length of lower esophageal sphincter (LES) myotomy was (5±3)cm. The length of low esophageal myotomy >6 cm was performed in 49 patients, and length of gastric fundus myotomy >2 cm was performed in 58 patients. Intraoperative mucosal perforation occurred to 3 patients and was repaired intraoperatively. One patient required conversion to open surgery. Postoperative complications occurred in 18 patients. The duration of postoperative hospital stay was (4.3±2.4)days. (2) Follow-up. All 210 patients were followed up for 4(range,7-33)months after surgery. During follow-up, 32 pati-ents had GERD, including 17 cases presenting dysphagia and 25 cases presenting acid regurgitation and heartburn (the same patient may have two symptoms). There were 29 cases with body mass index (BMI) >28 kg/m2. Symptom severity scores of 210 patients showed heartburn of 0.6(range, 0-3.0), reflux of 0.7(range, 0-3.0), chest pain of 0.4(range, 0-2.0), cough and hoarseness of 0.5(range, 0-2.0), nausea and vomiting 0.3(range, 0-2.0), dysphagia 0.8(range, 0-3.0). The LES pressure was (15±8)mmHg (1 mmHg=0.133 kPa), LES relaxation rate was 81%±13.0%, and integrated relaxation pressure was (9±6)mmHg. Esophageal manometry classification showed type Ⅰ, Ⅱ, and Ⅲ in 0, 8, and 0 patients, respectively. There were 208 patients achieved symptom relief after drug or symptomatic treatment. Only two patients with severe symptoms were unresponsive to medication and subsequently underwent surgery at another hospital, with symptoms improving postoperatively. (3) Influen-cing factors for GERD after laparoscopic Heller-Dor surgery. Results of multivariate analysis showed that male, smoking history, length of lower esophageal myotomy >6 cm, and postoperative BMI >28 kg/m2 were independent risk factors for GERD after laparoscopic Heller-Dor surgery ( odds ratio=4.02, 6.34, 5.41, 7.38, 95% confidence interval as 1.50-10.78, 3.31-12.31, 1.77-13.47, 2.80-15.42, P<0.05). (4) Development and evaluation of a predictive model for GERD after laparoscopic Heller-Dor surgery. A predictive nomogram model for GERD was constructed based on the results of multivariate analysis. The receiver operating characteristic curve of predictive nomogram model for GERD had an area under curve of 0.91 (95% confidence interval as 0.82-0.97), demonstrating good discrimination. The calibration curve showed good agreement between predicted and observed probabilities, with a mean absolute error of 0.033. The decision curve demonstrated that within a threshold probability range of 0.2-0.8, the predictive model had greater net benefit than "treat-all" or "treat-none" strategies, indicating clinical utility of this model in clinical decision. Conclusions:Male, smoking history, length of lower esophageal myotomy >6 cm, and postoperative BMI >28 kg/m2 are independent risk factors for GERD after laparoscopic Heller-Dor surgery for esophageal achalasia. The predictive model for GERD after laparoscopic Heller-Dor surgery based on these factors shows strong predictive accuracy.

Objective: To investigate the trends in incidence and mortality of lung cancer in Huangpu District, Shanghai Municipality from 2002 to 2019, so as to provide the evidence for formulating lung cancer prevention and control measures. Methods: Data of lung cancer incidence and mortality among residents in Huangpu District from 2002 to 2019 were collected through the Shanghai Cancer Registration and Reporting Management System. The crude incidence and mortality of lung cancer was calculated, and standardized by the data from the Chinese Fifth National Population Census in 2000 (Chinese-standardized rate) and the Segi's world standard population in 1960 (world-standardized rate). The trends in incidence and mortality of lung cancer among residents by age and gender were evaluated using annual percent change (APC). Results: A total of 12 965 cases of lung cancer were reported in Huangpu District from 2002 to 2019, and the crude incidence rate was 80.66/105, the Chinese-standardized incidence rate was 34.54/105, and the world-standardized incidence rate was 31.30/105, all showing upward trends (APC=4.588%, 2.933% and 3.247%, all P<0.05). A total of 10 102 deaths of lung cancer were reported, and the crude mortality rate was 62.30/105, showing an upward trend (APC=0.959%, P<0.05); the Chinese-standardized mortality was 25.93/105, and the world-standardized mortality was 22.05/105, both showing downward trends (APC=-1.282% and -1.263%, both P<0.05). The crude incidence and mortality rates of lung cancer in males were higher than those in females (101.39/105 vs. 60.52/105, 85.45/105 vs. 39.87/105, both P<0.05). The crude incidence and mortality rates of lung cancer showed upward trends with age (both P<0.05), reaching their peaks in the age groups of 80-<85 years (341.37/105) and 85 years or above (355.97/105), respectively. Conclusions The incidence of lung cancer showed an upward trend, while the mortality showed a downward trend in Huangpu District from 2002 to 2019. Elderly men were the high-risk group for lung cancer incidence and mortality.

Objective:To investigate the influencing factors for gastroesophageal reflux disease (GERD) after laparoscopic Heller-Dor surgery for esophageal achalasia.Methods:The retrospective case-control study was conducted. The clinical data of 210 patients with esophageal achalasia who were admitted to Shanxi Provincial Cancer Hospital from January 2021 to December 2023 were collected. There were 119 males and 91 females, aged (47±12)years. All patients underwent laparoscopic Heller-Dor surgery. Observation indicators: (1) surgical situations; (2) follow-up; (3) influencing factors for GERD after laparoscopic Heller-Dor surgery; (4) development and evaluation of a predictive model for GERD after laparoscopic Heller-Dor surgery. Univariate and multivariate analyses were performed using stepwise Logistic regression. Results of multivariate analysis were used to construct a nomogram in predicting GERD. The predictive performance was assessed using the area under the receiver operating characteristic curve. The calibration curve was used to evaluate the accuracy of the model, and the decision curve was used to assess the overall net benefit of the model.Results:(1) Surgical situations. All 210 patients underwent laparoscopic Heller-Dor surgery. The operation time was (128±31)minutes, volume of intraoperative blood loss was (25±9)mL, and length of lower esophageal sphincter (LES) myotomy was (5±3)cm. The length of low esophageal myotomy >6 cm was performed in 49 patients, and length of gastric fundus myotomy >2 cm was performed in 58 patients. Intraoperative mucosal perforation occurred to 3 patients and was repaired intraoperatively. One patient required conversion to open surgery. Postoperative complications occurred in 18 patients. The duration of postoperative hospital stay was (4.3±2.4)days. (2) Follow-up. All 210 patients were followed up for 4(range,7-33)months after surgery. During follow-up, 32 pati-ents had GERD, including 17 cases presenting dysphagia and 25 cases presenting acid regurgitation and heartburn (the same patient may have two symptoms). There were 29 cases with body mass index (BMI) >28 kg/m2. Symptom severity scores of 210 patients showed heartburn of 0.6(range, 0-3.0), reflux of 0.7(range, 0-3.0), chest pain of 0.4(range, 0-2.0), cough and hoarseness of 0.5(range, 0-2.0), nausea and vomiting 0.3(range, 0-2.0), dysphagia 0.8(range, 0-3.0). The LES pressure was (15±8)mmHg (1 mmHg=0.133 kPa), LES relaxation rate was 81%±13.0%, and integrated relaxation pressure was (9±6)mmHg. Esophageal manometry classification showed type Ⅰ, Ⅱ, and Ⅲ in 0, 8, and 0 patients, respectively. There were 208 patients achieved symptom relief after drug or symptomatic treatment. Only two patients with severe symptoms were unresponsive to medication and subsequently underwent surgery at another hospital, with symptoms improving postoperatively. (3) Influen-cing factors for GERD after laparoscopic Heller-Dor surgery. Results of multivariate analysis showed that male, smoking history, length of lower esophageal myotomy >6 cm, and postoperative BMI >28 kg/m2 were independent risk factors for GERD after laparoscopic Heller-Dor surgery ( odds ratio=4.02, 6.34, 5.41, 7.38, 95% confidence interval as 1.50-10.78, 3.31-12.31, 1.77-13.47, 2.80-15.42, P<0.05). (4) Development and evaluation of a predictive model for GERD after laparoscopic Heller-Dor surgery. A predictive nomogram model for GERD was constructed based on the results of multivariate analysis. The receiver operating characteristic curve of predictive nomogram model for GERD had an area under curve of 0.91 (95% confidence interval as 0.82-0.97), demonstrating good discrimination. The calibration curve showed good agreement between predicted and observed probabilities, with a mean absolute error of 0.033. The decision curve demonstrated that within a threshold probability range of 0.2-0.8, the predictive model had greater net benefit than "treat-all" or "treat-none" strategies, indicating clinical utility of this model in clinical decision. Conclusions:Male, smoking history, length of lower esophageal myotomy >6 cm, and postoperative BMI >28 kg/m2 are independent risk factors for GERD after laparoscopic Heller-Dor surgery for esophageal achalasia. The predictive model for GERD after laparoscopic Heller-Dor surgery based on these factors shows strong predictive accuracy.

Objective:To explore clinical factors of poor prognosis in patients with anti-melanoma differentiation-associated gene 5 andtibody positive dermatomyositis (MDA5-DM).Methods:One hundred and twenty-six enrolled adults with MDA5-DM were divided into the survival group and the deceased group according to the outcomes. Survival time, clinical manifestations, laboratory tests, pulmonary function tests, myositis antibodies and treatments were collected for statistical analysis. Serum concentrations of IL-15, HMGB1, and sCD163 were measured by ELISA in MDA5-DM patients and healthy controls. Mann-Whitney U nonparametric test and Student′s t-test were used to compare the continuous variables between the two groups, and χ2 or Fisher′s exact test were used for comparison of categorical variables. Cox regression analysis was used to assess the survival predictors in MDA5-DM patients. The cumulative survival rate was calculated by Kaplan-Meier curve analysis, and Log-rank tests were used to examine differences in survival curves. P<0.05 was considered statistically significant. Results:Cox multivariate regression analysis revealed that age > 57 years [ HR (95% CI)=3.05 (1.20, 7.80), P=0.020], RP-ILD [ HR (95% CI)=25.07 (5.42, 115.98), P<0.001], and levels of anti-Ro52 antibody [ HR (95% CI)=3.41 (1.36, 8.53), P=0.009] were important prognostic factors independent of multiple clinical parameters. The ELISA test results showed that the levels of serum IL-15[0.91 (0.66, 2.00)pg/ml vs. 0.51(0.39, 0.72)pg/ml, Z=-4.57, P<0.001] and HMGB1 [230.53(90.40, 394.31)ng/ml vs. 32.66 (17.82, 46.21)ng/ml, Z=-6.52, P<0.001] in MDA5-DM patients were significantly higher than those in healthy controls, but there were no significant differences in the level of serum IL-15 [1.21(0.63, 2.12)pg/ml vs. 0.91(0.68, 1.66)pg/ml, Z=-0.30, P=0.766], HMGB1[267.61(167.03, 444.23)ng/ml vs. 228.35(74.74, 344.32)ng/ml, Z=0.82, P=0.413], and sCD163 [112.70(93.45, 148.51)ng/ml vs. 132.72(96.79, 203.18)ng/ml, Z=-0.62, P=0.536] between the survival group and the deceased group. Conclusion:Older age, RP-ILD, and high levels of anti-Ro52 antibody significantly increase the risk of death in MDA5-DM patients. Intensive follow-up of patients with the above factors in the early stages may help to improve the prognosis.

Objective:To assess the prevalence of dentinal hypersensitivity (DH) and related factors in urban adults in China.Methods:The study was designed as an observational, cross-sectional epidemiological study carried out in adults aged 18-69 years old in seven cities (Beijing, Shanghai, Wuhan, Chengdu, Xi′an, Guangzhou, and Harbin) of China. The study was conducted from March 2021 to May 2023. Patients were required to complete a questionnaire regarding the subjects′ socio-economic factors, dietary behavior, oral health behavior and personal antecedent factors. DH was clinically diagnosed by judging whether the tooth cold air stimulation provoked DH or not, and recorded by investigator pain rating Schiff score. Compare the findings of six cities (Harbin excluded) with a similar study conducted in 2008.Results:In total, 11 622 subjects from seven cities in China participated the study. Fifty two point two percent (6 072/11 622) of subjects reported DH in questionnaire, 36.7% (4 266/11 622) of subjects reported experiencing DH in response to cold air stimulation for at least one study tooth. Risk factors including age, sex, city, toothbrush method and acid reflux showed marked associations with DH ( P<0.05). The prevalence of DH of urban residents in six cities (Harbin excluded) was 33.7% (3 335/9 882), higher than that in 2008 [29.7%(2 354/7 939)]. Conclusions:Overall, DH was common among urban adults in China and the prevalence increased in recent years. Better understanding of DH and its associated factors should be considered in its prevention and management by dental professionals.