BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

OBJECTIVE: To explore clinical effects of bone setting manipulation combined with pry reduction and Kirschner needle internal fixation in treating SandersⅡ-Ⅲ calcaneal fracture. METHODS: Clinical data of 52 patients with types Sanders Ⅱand Ⅲ calcaneal fracture (foot) treated with bone-setting manipulation combined with pry reduction and Kirscher needle internal fixation from July 2017 to July 2019 were retrospectively analyzed, including 43 males and 9 females, aged from 31 to 72 years old with an average of (50.83±10.48) years old; 15 patients with Sanders typeⅡ and 37 patients with Sanders type Ⅲ. The changes of Bühler angle, Gissane angle, calcaneus width and calcaneus height before operation and 24 months after operation were compared, and Maryland foot function score was performed to evaluate clinical effects. RESULTS: All patients were followed up from 24 to 60 months with an average of (41.50±9.86)months. The fracture healed normally and the healing time was (11.00±0.95) weeks. Bühler angle, Gissane angle, calcaneal bone width and calcaneal bone height were increased from (16.37±8.36)°, (96.27±9.62)°, (46.82±4.67) mm, (38.41±3.58) mm before operation to (31.48±8.24)°, (111.62±8.69)°, (42.06±4.83) mm, (44.21±3.82) mm at 24 months after operation, and the difference were statistically significant (P<0.01). Postoperative Maryland score at 24 months was (93.04±8.83), 40 patients got excellent result, 7 good and 5 fair. CONCLUSION Orthopedic manipulation combined with percutaneous reduction and Kirschner wire internal fixation could significantly improve Bühler angle, Gissane angle, width, and height of Sanders typeⅡ and Ⅲ calcaneal fractures, and the curative effect is satisfactory.
Humans ; Male ; Female ; Calcaneus/surgery* ; Middle Aged ; Fracture Fixation, Internal/methods* ; Adult ; Aged ; Fractures, Bone/therapy* ; Retrospective Studies ; Bone Wires ; Manipulation, Orthopedic/methods*

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major chronic respiratory condition with high morbidity and mortality, imposing a serious economic and public health burden. The World Health Organization ranks COPD among the top 4 chronic diseases worldwide. Zangsiwei Qingfei Mixture (ZSWQF), a novel Tibetan herbal formulation independently developed by our research team, has shown therapeutic potential for chronic respiratory diseases. This study aims to evaluate the effects of aerosolized ZSWQF on cigarette smoke-induced COPD in mice and explore its underlying mechanisms. METHODS: Thirty C57 mice were randomly divided into a Control group, a COPD group, and a ZSWQF group. The Control group received saline aerosol inhalation without cigarette smoke exposure; both the COPD group and the ZSWQF group were exposed to cigarette smoke, with the former receiving saline inhalation and the latter treated with ZSWQF aerosol. White blood cell (WBC) count was performed using a fully automatic blood cell analyzer. Serum, alanine transaminase (ALT), and serum creatinine (SCr), as well as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). BALF cell classification was determined using a hematology analyzer. Lung function was assessed with a small animal pulmonary function system, including airway resistance (RI) and cyclic dynamic compliance (CyDN). Lung tissues were stained with hematoxylin and eosin (HE), and mean linear intercept (MLI) and destruction index (DI) were calculated to evaluate morphological changes. Network pharmacology was applied to identify disease-related and ZSWQF-related targets, followed by intersection and protein-protein interaction (PPI) network analysis, and enrichment analysis of biological functions and pathways. Primary type II alveolar epithelial cell (AEC II) from SD rats were isolated and divided into a Control group, a lipopolysaccharide (LPS) group, a normal serum group, a water extract of ZSWQF (W-ZSWQF) group, a ZSWQF containing serum group, and a MLN-4760 [angiotensin-converting enzyme (ACE) 2 inhibitor]. Western blotting was performed to assess protein expression of ACE, p38 [a mitogen-activated protein kinase (MAPK)], phospho (p)-p38, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p-ERK1/2, c-Jun N-terminal kinase (JNK), p-JNK, inhibitor of nuclear factor-kappa B alpha (IκBα), p-IκBα, and p-p65 subunit of nuclear factor-kappa B (NF-κBp65). RESULTS: WBC counts were significantly higher in the COPD group than in controls (P<0.01) and decreased following ZSWQF treatment (P<0.05). No significant intergroup differences were found in organ weights, ALT, or SCr (all P>0.05). Serum and BALF levels of IL-6, IL-8, and TNF-α, as well as total BALF cells, neutrophils, and macrophages, were elevated in the COPD group compared with controls and reduced by ZSWQF treatment (P<0.05). COPD mice exhibited increased RI, decreased CyDN, marked alveolar congestion, inflammatory infiltration, thickened septa, and higher MLI and DI values versus controls (P<0.05); ZSWQF treatment significantly reduced MLI and DI (P<0.05). Network pharmacology identified 151 potential therapeutic targets for ZSWQF against COPD, with key nodes including TNF, IL-6, protein kinase B (Akt) 1, albumin (ALB), tumor protein p53 (TP53), non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT) 3, matrix metalloproteinase (MMP)-9, and beta-catenin (CTNNB1). Enrichment analysis indicates involvement of cancer-related, phosphatidylinositol 3-kinase (PI3K)/Akt, hypoxia-inducible factor (HIF)-1, calcium, and MAPK signaling pathways. Western blotting results showed that compared with the LPS group, AEC II treated with ZSWQF-containing serum exhibited decreased expression of ACE, p-p38/p38, p-ERK1/2/ERK1/2, p-JNK/JNK, p-IκBα/IκBα, and p-NF-κBp65, while ACE2 expression was upregulated, consistent with the MAPK/nuclear factor-kappa B (NF-κB) pathway regulation predicted by network pharmacology. CONCLUSIONS Aerosolized ZSWQF provides protective effects in COPD mice by reducing airway inflammation and remodeling.
Animals ; Pulmonary Disease, Chronic Obstructive/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Mice, Inbred C57BL ; Male ; Network Pharmacology ; Smoke/adverse effects* ; Bronchoalveolar Lavage Fluid ; Administration, Inhalation ; Inflammation/drug therapy* ; Tumor Necrosis Factor-alpha ; Lung/drug effects* ; Interleukin-6/blood*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Purpose::Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.Methods::This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q 1, Q 3). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve. Results::According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval ( CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ 2= 13.82, adjusted R2 = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ 2= 18.48, adjusted R2 = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively. Conclusion::Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

The abuse and irrational use of antibiotics in human veterinary medicine has seriously endangered the ecological environment and human health.In this study,a fully automatic solid-phase disk extraction-stable isotope dilution-ultra-high performance liquid chromatography-mass spectrometry method for determination of 17 kinds of sulfonamides antibiotics(SAs)in water was established,which was then applied to determination of SAs in real samples including tap water,river water and seawater,respectively.Meanwhile,the residual characteristics were discussed and the ecological risks were assessed.With this method,1.0 L water sample with 0.5 g/L Na2EDTA(pH=3)was extracted and enriched by 3M SDB-XC disk,and eluted by 10 mL of mixture of methanol and acetone(1:1,V/V),and the pretreatment time of the sample was about 60 min per six samples.Under the optimized conditions,the linearity of the method for detection of 17 kinds of SAs ranged from 0.05 to 100 μg/L,with correlation coefficients(R2)>0.999.In addition,the detection limits(S/N=3)were as low as 0.012-0.052 ng/L,and the recoveries were in the range of 76%-110%,with relative standard deviations of 0.5%-9.6%(n=5).The results showed that no SAs was detected in tap water,while 3 and 9 kinds of SAs were detected in river water of Zhoushan,and seawater of Wenzhou Sea area in Zhejiang province,respectively.The total concentrations of the detected SAs were 0.875-21.826 ng/L and 1.024-20.768 ng/L in river water and seawater,respectively,and among which,sulfamethoxazole(SMX)was the predominant compound in river water and seawater,accounting for 81%and 74%of the total SAs,respectively.The ecological risk assessment showed that the risk quotients of the detected SAs in the river water and seawater in the study area for the three kinds of trophic organisms(algae,Daphnia and fish)were far less than 0.01,meaning that the ecological risk was low.

Objective:Chronic obstructive pulmonary disease(COPD)is a significant global public health issue.Modern medical treatments have both benefits and limitations,prompting increasing attention from scholars worldwide on traditional ethnic medicine,and the Zangsiwei Qingfei Mixture is a newly developed formula derived from the effective components of classical Tibetan medicine to treat chronic respiratory diseases.This study aims to investigate the clinical efficacy and safety of the Zangsiwei Qingfei Mixture combined with conventional treatment in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD). Methods:Sixty AECOPD patients admitted to the Second Xiangya Hospital of Central South University from May 2021 to May 2023 were enrolled and randomly divided into 2 groups,with 30 patients in each group.The control group received conventional treatment,including bronchodilators,anti-infection agents,expectorants,and oxygen therapy.The experimental group received the Zangsiwei Qingfei Mixture in addition to conventional treatment.The treatment duration was 7 d for both groups.Baseline data such as gender,age,body mass index(BMI),smoking status,Global Initiative for Chronic Obstructive Lung Disease(GOLD)classification,COPD course,and the number of COPD exacerbations in the past year were collected.The primary efficacy indicators were assessed using the modified Medical Research Council(mMRC)dyspnea scale and the modified Borg scale.Secondary indicators included arterial lactic acid(LAC)and serum tumor necrosis factor alpha(TNF-α)levels.Safety indicators included liver and kidney function[alanine transaminase(ALT),aspartate transaminase(AST),serum creatinine(SCr),serum uric acid(SUA)],coagulation function[activated partial thromboplastin time(APTT),prothrombin time(PT),fibrinogen(FIB),and D-dimer].The generalized linear mixed model(GLMM)was used to evaluate the clinical efficacy and safety of the Zangsiwei Qingfei Mixture. Results:Before treatment,there were no statistically significant differences in general baseline data,grading of mMRC dyspnea scale,score of modified Borg scale,arterial LAC,ALT,AST,SCr,SUA,APTT,FIB,and D-dimer between the 2 groups(all P＞0.05).However,serum TNF-α and PT levels in the experimental group were significantly lower than those in the control group(both P＜0.05).GLMM analysis showed that after adjusting for pre-and post-treatment,gender,age,BMI,smoking status,GOLD classification,COPD course,and the number of COPD exacerbations in the past year,the experimental group demonstrated significantly lower grading of mMRC dyspnea scale(coefficient=-0.329,P=0.036),score of modified Borg scale(coefficient=-1.077,P=0.001),serum TNF-α level(coefficient=-14.378,P＜0.001),and arterial LAC level(coefficient=-0.409,P=0.012)compared to the control group.The Zangsiwei Qingfei Mixture had no significant effect on liver,kidney,or coagulation function indicators(all P＞0.05). Conclusion:The Zangsiwei Qingfei Mixture combined with conventional treatment can improve clinical symptoms and promote homeostasis in AECOPD patients,demonstrating safety and reliability.Combining modem medicine with traditional ethnic medicine offers a feasible approach to treating chronic respiratory diseases in the future.

Objective To investigate factors influencing the occurrence of early haematoma expansion(HE)in patients with spontaneous intracerebral hemorrhage(sICH),to develop a predictive model and evaluate its predictive efficacy.Methods A retrospective cohort of 238 patients with sICH,admitted to General Hospital of Western Theater Command between January 2017 and December 2022,was analyzed.Patients were categorized into two groups based on the criteria of HE exceeding 33%in relative volume or 6 ml in absolute volume:HE group(n=62)and non-haematoma expansion(NHE)group(n=176).Clinical characteristics,laboratory findings,Non-contrast Computed Tomography(NCCT)imaging,and Glasgow Coma Scale(GCS)scores were compared between the two groups.Multifactorial logistic regression analysis was employed to identify risk factors for HE and to model the probability of its occurrence.The R language rms package was utilized to construct a nomogram model for predicting HE in sICH patients,Additionally,the related clinical,NCCT,and GCS models were constructed.The predictive efficacy of each model for HE in sICH patients was evaluated using area under Receive Operative Characteristic(ROC)curve(AUC),and the clinical application value of each model was assessed using accuracy,sensitivity,specificity,and Jordon's index.The Delong test was applied to analyze differences in the predictive values of the models.Results Significant differences in satellite sign,vortex sign,and history of anticoagulant treatment were observed between two groups(P<0.05).Multifactorial logistic regression analysis revealed independent risk factors for HE in sICH patients,including the first CT examination time,homogeneity,history of anticoagulant medication,volume,maximal diameter,hypodensity sign,island sign,satellite sign,and vortex sign(P<0.05).The AUCs for the constructed clinical model,NCCT model,GCS model and nomogram model in predicting the occurrence of HE in sICH patients were 0.672,0.706,0.518 and 0.754,respectively.The nomogram model demonstrated higher accuracy,sensitivity,Jordon's index and AUC compared with those in the clinical and NCTT models.Conclusions The first CT examination time,homogeneity,history of anticoagulant treatment,volume,maximum diameter,hypodensity sign,island sign,satellite sign,and vortex sign are independent predictors of early HE in sICH patients.The nomogram model,constructed with the above parameters,demonstrated high predictive efficacy for HE and holds potential for clinical application.

Purpose/Significance The paper discusses the surrogate seeking behavior of online health information surrogate seeker of rural elderly,analyzes the characteristics of surrogate seeker in the process of behavior,and probes into the influencing factors of surrogate seeking behavior.Method/Process Semi-structured interviews are conducted with the surrogate seekers most frequently chosen by the rural elderly,and the interview results are coded.Result/Conclusion 37 initial concepts,15 sub-categories and 6 main categories are sorted out through three levels of coding,and a theoretical model of online health information surrogate seeking behavior for surrogate seeker is constructed.The influencing factors of surrogate seeking behavior include behavioral motivation,information ability,information awareness,environmental char-acteristics and intergenerational support.Surrogate seeking behavior can be divided into information retrieval,screening,processing and trans-mission processes,and surrogate seekers show the behavioral characteristics of firmness,emotional drive and subsidiarity.