BACKGROUND: Neoadjuvant therapeutic strategies play a pivotal role in the comprehensive treatment of non-small cell lung cancer (NSCLC). However, lung squamous cell carcinoma (SCC) generally exhibits a more favorable response to neoadjuvant therapy compared with lung adenocarcinoma (ADC). The aim of this study is to elucidate how baseline cancer-associated fibroblasts (CAFs) and tumor-associated endothelial cells (TAECs) influence the differential therapeutic outcomes of neoadjuvant treatment in SCC versus ADC. METHODS: We retrospectively collected pretreatment biopsy samples from 104 patients with stage II-III NSCLC who underwent neoadjuvant chemotherapy (NAC) or neoadjuvant chemoimmunotherapy (NAIC) at Shandong Cancer Hospital between January 1, 2018 and December 31, 2023. Tissue microarrays were constructed using an automated arrayer, and multiplex immunofluorescence staining (α-SMA/CD31/CK/DAPI) was performed to identify CAFs (α-SMA+/CK-) and TAECs (CD31+/CK-). Quantitative analyses included CAFs and TAECs densities, the nearest neighbor distance (NND) between CAFs and TAECs, and their spatial proximity (30 μm). Differences in major pathological response (MPR) between groups, defined as residual viable tumor cells ≤10% in resected specimens after neoadjuvant therapy, were assessed using the χ² test. The Mann-Whitney U test was applied to analyze intergroup differences in quantitative indicators, and receiver operating characteristic (ROC) curve analysis was conducted to evaluate the predictive performance of immune-related markers for MPR in the NAIC cohort. RESULTS: Among the 104 NSCLC patients who received neoadjuvant therapy, 35 underwent NAIC and 69 received NAC. Overall, patients with SCC were more likely to achieve MPR compared with those with ADC (50.0% vs 22.4%, P=0.006). This trend persisted in the NAIC subgroup (72.7% vs 30.8%, P=0.038), whereas no significant difference in MPR rates was observed between SCC and ADC in the NAC subgroup. At baseline, prior to NAIC or NAC, programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression, CAFs and TAECs densities, CAFs-TAECs NND, and CAFs-TAECs proximity (30 μm) showed no significant differences between SCC and ADC. In patients with SCC receiving NAIC, baseline PD-L1/PD-1 expression, CAFs density, and TAECs density showed not significant differences between MPR and NMPR groups. However, the CAFs-TAECs distance was significantly greater in the MPR group (NND: 31.2 vs 24.7 μm, P=0.038), and the number of TAECs within 30 μm of CAFs was significantly lower (proximity: 1.1 vs 3.6, P=0.038). Univariate Cox regression analysis indicated that low TAECs density was associated with MPR following NAIC (OR=36.00, 95%CI: 2.68-1486.88, P=0.019). Furthermore, ROC analysis demonstrated that baseline CAFs-TAECs NND and proximity (30 μm) exhibited strong predictive performance for MPR in SCC patients treated with NAIC, with an area under the curve (AUC) of 0.893, sensitivity of 0.857, and specificity of 1.000. CONCLUSIONS CAFs are more spatially distant from TAECs and more prone to MPR after NAIC in SCC, which may be related to the reduced interaction of CAFs with TAECs and reduced tumor-associated angiogenesis.
Humans ; Lung Neoplasms/therapy* ; Neoadjuvant Therapy ; Male ; Female ; Middle Aged ; Retrospective Studies ; Endothelial Cells/drug effects* ; Aged ; Cancer-Associated Fibroblasts/drug effects* ; Immunotherapy ; Carcinoma, Squamous Cell/drug therapy* ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Adult

Objective To investigate the impact of succinate dehydrogenase(SDH)on the modulation of human sperm functions.Methods The isolated human sperm were co-incubated with different concentrations(10,20,40 mmol/L)of SDH inhibitor disodium malonate for one or two hours.The activity of the SDH was measured by commercially available reagent kit,while the protein level of the SDH catalytic subunit SDHA was determined through Western blot analysis.Sperm functions were analyzed:1)The impact of disodium malonate on important mo-tility parameters of un-capcitated sperm including progressive motility rate(PR),total motility(TM),average pathvelocity(VAP)and the ability of capacitated sperm to penetrate viscous media were be assessed using a com-puter aided semen analysis system.2)Effect of disodium malonate on sperm survival rate was evaluated using the Eosin-Nigrosin microscopy.3)The incidence of acrosome reaction in capacitated sperm was be detected by PSA-FITC staining assay following disodium malonate treatment.Results Disodium malonate had no effect on expression of SDH catalytic subunit SHDA protein in human sperm.However,it inhibited the catalytic activity of the SDH,sperm forward motility,total motility,and the ability of sperm to penetrate viscous media.These inhibitory effects were positively correlated with the concentration of disodium malonate.Furthermore,disodium malonate had no any influence on the occurrence of spontaneous acrosome reaction in capacitated sperm.Conclusions Disodium mal-onate impairs human sperm motility by inhibiting succinate dehydrogenase activity.

Objective:To analyze the necessity of anastomosis of the cutaneous nerve by comparing anterolateral femoral flaps with versus without anastomosis of the anterolateral femoral cutaneous nerve in the repair of extremity soft tissue defects.Methods:A retrospective analysis was made of the clinical data of 30 patients with extremity soft tissue defects who had been admitted to Department of Orthopedics, The Sixth People＇s Hospital affiliated to Shanghai Jiaotong University School of Medicine from September 2019 to March 2022. The patients were assigned into 2 groups according to whether the anterolateral femoral cutaneous nerve was anastomosed or not in the repair of extremity soft tissue defects using anterolateral femoral flaps. In the anastomosis groups of 14 cases, there were 7 males and 7 females, with an age of (46.4±15.2) years and a flap size of (22.4±7.3) cm×(8.5±1.3) cm. In the non-anastomosis group of 16 cases, there were 11 males and 5 females, with an age of (39.9±15.8) years and a flap size of (23.0±6.4) cm×(9.0±2.1) cm. The 2 groups were compared in terms of flap survival, Semmes-Weinstein recovery degree and area of monofilament tactile sensation, and time periods for temperature sensation and two-point discrimination.Results:There was no statistically significant difference between the 2 groups in the preoperative general data, showing they were comparable ( P>0.05). All the flaps survived completely without vascular crisis. In the anastomosis group, the time periods required for Semmes-Weinstein recovery of monofilament tactile sensation to the areas of 20.0%, 50.0%, and 80.0% [(2.5±0.7) months, (6.7±1.1) months, and (11.0±1.2) months] were significantly shorter than those in the non-anastomosis group [(3.6±1.3) months, (8.6±1.4) months, and (15.0±2.2) months], the recovery area at the last follow-up [100.0% (100.0%, 100.0%)] was significantly larger than that in the non-anastomosis group [84.6% (81.7%, 89.9%)], and the time period for recovery of temperature sensation [(3.9±0.7) months] significantly shorter than that in the non-anastomosis group [(6.1±1.1) months] (all P<0.05). The time for recovery of two-point discrimination in the 14 patients in the anastomosis group was (10.4±1.7) months while only 7 of the 16 patients in the non-anastomosis group recovered two-point discrimination after (14.7±1.4) months, showing a significant difference between the 2 groups ( P<0.05). Conclusion:In the repair of extremity soft tissue defects using anterolateral femoral flaps, compared with no anastomosis of the cutaneous nerve, anastomosis of the anterolateral femoral cutaneous nerve may ensure more or less the sensory recovery of the flaps.

Objective To collect the data of hospitalized death cases in a provincial grade A tertiary general hospital,analysis the characteristics,changing trends,rescue conditions and related influencing factors of inpatient death cases,and provide a reference for the hospital's death case management and improvement of medical quality.Methods The gender,age,inpatient department,length of hospitalization,cause of death,rescue measures,sequential organ failure assessment(SOFA)score,and the date of death cases in a grade A tertiary general hospital from January 1,2012,to December 31,2022,were collected from the hospital medical record database.The characteristics of death cases were then statistically summarized through data aggregation.Spearman's rank correlation coefficient was used to analyze the relationship between the two research variables,while multivariate Logistic regression analysis was employed to explore the relevant factors affecting the implementation of rescue measures when death events occur in hospitalized patients,and draw the receiver operator characteristic curve(ROC curve)to analyze the relevant factors affecting the implementation of cardiopulmonary resuscitation in the event of death in hospitalized patients.Results ① The in-hospital mortality rate of inpatients in this hospital in the past 10 years was 0.26％,the mortality rate of males was significantly higher than that of females[0.32％(1 959/607 170)vs.0.19％(1 021/549 802),χ2 = 210.615,P<0.01],the mortality rate of hospitalized patients increased with age(r = 0.860,P = 0.037),and elderly patients>65 years old were the main group of hospital deaths;②The top 5 main causes of death among patients in this hospital were tumors,circulatory system diseases,respiratory system diseases,digestive system diseases and the symptoms,signs,clinical and laboratory abnormal findings,and those who died due to these 5 types of diseases accounted for 82.05％(2 445/2 980)of the total number of deaths;③Before the death event,the electrocardiogram(ECG)monitoring rate of inpatients in this hospital was 77.99％,the epinephrine usage rate was 83.46％,the endotracheal intubation rate was 57.55％,the cardiopulmonary resuscitation implementation rate was 44.93％,and the defibrillation rate was 12.85％.The epinephrine usage rate[86.17％(1 688/1 959)vs.78.26％(799/1 021)],the endotracheal intubation rate[59.37％(1 163/1 959)vs.54.06％(552/1 021)]and the cardiopulmonary resuscitation implementation rate[46.30％(907/1 959)vs.42.31％(432/1 021)]of male patients was significantly higher than that of female patients(all P<0.05);the cardiopulmonary resuscitation implementation rate for patients who died over 65 years old was significantly lower than those in other age groups[43.25％(734/1 697)vs.47.16％(605/1 283),P<0.05],before the death of inpatients in the surgical department,the ECG monitoring rate[68.63％(641/934)vs.82.26％(1 679/2 041)],the epinephrine usage rate[75.48％(705/934)vs.87.21％(1 780/2 041)]and the cardiopulmonary resuscitation implementation rate[31.16％(291/934)vs.51.34％(1 048/2 041)]were significantly lower than those in other department(all P<0.05).Patients who died from tumors had the lowest implementation rate of rescue measures when the death event occurred.Except for tumor patients,the ECG monitoring rate[68.33％(233/341)vs.93.07％(1 356/1 457)],the epinephrine usage rate[86.22％(294/341)vs.95.47％(1 391/1 457)],the endotracheal intubation rate[60.12％(205/341)vs.71.31％(1 039/1 457)],the cardiopulmonary resuscitation rate[40.18％(137/341)vs.55.66％(811/1 457)]and the defibrillation rate[7.92％(27/341)vs.19.42％(283/1 457)]of patients who died due to digestive system diseases were significantly lower than those who died due to circulatory diseases,respiratory diseases,and symptoms,signs,clinical and laboratory abnormalities(all P<0.05);④Multivariate Logistic regression analysis showed that urban household registration and SOFA score≥14 points before death were independent factors influencing the likelihood of cardiopulmonary resuscitation being performed in patients with severe death[odds ratio(OR)and 95％confidence interval(95％ CI)were 6.731(1.891-23.958)and 10.023(3.169-31.704),P values are 0.003 and<0.001 respectively];⑤ROC curve analysis shows that urban household registration,SOFA score≥14 points before death and their combination had a certain predictive value for cardiopulmonary resuscitation in hospitalized patients with digestive diseases(all P<0.05),and the combined value was higher,the area under ROC curve(AUC)= 0.840,95％ CI was 0.742-0.934.sensitivity was 82.76％,specificity was 75.51％,positive predictive value was 78.18％,and negative predictive value was 73.91％.Conclusions Hospitals should specifically strengthen the medical quality management of inpatient death cases,enhance the early warning system for high-risk patients,and consistently standardize the rescue measures and procedures for inpatients.Additionally,hospitals should prioritize the care of elderly and male patients with circulatory and respiratory-related critical illnesses,they should also strive to improve their ability to identify and treat critically ill surgical patients,as well as enhance their expertise in managing severe digestive system diseases.

OBJECTIVE To investigate the effects of salidroside （Sal） on myocardial fibrosis and pyroptosis and its potential mechanism. METHODS The mice were randomly divided into control group， model group and Sal low-dose， medium-dose and high-dose groups， with 10 mice in each group. Except for the control group， the mice in other groups were injected subcutaneously with isoproterenol 5 mg/（kg·d）to prepare the myocardial fibrosis model. Since modeling， mice in the Sal low-dose， medium-dose and high-dose groups were given 10， 30 and 50 mg/kg of Sal by intragastric administration every day； control group and model group were given 10 mL/kg of normal saline by intragastric administration every day， for 14 consecutive days. After the last medication， the mice were sacrificed； hematoxylin-eosin staining was used to observe pathological change of myocardial tissue and calculate the diameter of myocardial cell； Masson and Sirius Red staining were used to observe the degree of myocardial fibrosis in mice and calculate the collagen volume fraction （CVF）； quantitative real-time PCR was performed to detect the mRNA expressions of collagen type Ⅰ （Col Ⅰ）， α-smooth muscle actin （α-SMA）， Toll-like receptor 4 （TLR4）， NOD-like receptor pyrin domain containing 3 （NLRP3）， caspase-1 andgasdermin D （GSDMD） in myocardial tissues. The total protein expressions of Col Ⅰ， α-SMA， TLR4， NLRP3，caspase-1 and GSDMD in myocardial tissues and protein-positive cell score were measured by Western blot assay and immunohistochemistry. RESULTS Compared with control group， the myocardial cells in the model group were enlarged， the arrangement of myocardial fibers was disordered， the matrix metabolism was significantly increased， the CVF in myocardial tissue was significantly increased， and the mRNA and protein expression levels of Col Ⅰ， α-SMA， TLR4， NLRP3， caspase-1 and GSDMD were elevated and protein-positive cell score was increased significantly （P＜0.01）. Compared with model group， the myocardial cell morphology was clearer， myocardial fibrosis was alleviated， and the levels of the above indicators in myocardial tissue of Sal medium-dose and high-dose groups had been reversed to varying degrees， especially in Sal high-dose group（P＜0.05 or P＜0.01）. In addition， the Sal low-dose group also reversed some fibrosis and pyroptosis-related indicators to some extent. CONCLUSIONS Sal can significantly prevent the occurrence and development of myocardial fibrosis， and the mechanism of action may be related to the inhibition of TLR4-mediated pyroptosis pathway in myocardial tissue.

Backgrounds::Inadequate sleep duration is associated with a higher risk of type 2 diabetes and the relationship is nonlinear. We aim to assess the curve relationship between night sleep duration and the incidence of type 2 diabetes in China.Methods::A cohort of 11,539 participants from the REACTION study without diabetes at baseline (2011) were followed until 2014 for the development of type 2 diabetes. The average number of hours of sleep per night was grouped. Incidence rates and odds ratios (ORs) were calculated for the development of diabetes in each sleep duration category.Results::Compared to people who sleep for 7 to 8 h/night, people with longer sleep duration (≥9 h/night) had a greater risk of type 2 diabetes (OR: 1.27; 95% CI: 1.01-1.61), while shorter sleep (<6 h/night) had no significant difference in risk of type 2 diabetes. When the dataset was stratified based on selected covariates, the association between type 2 diabetes and long sleep duration became more evident among individuals <65 years of age, male, body mass index <24 kg/m 2 or with hypertension or hyperlipidemia, no interaction effects were observed. Furthermore, compared to people persistently sleeping 7 to 9 h/night, those who persistently slept ≥9 h/night had a higher risk of type 2 diabetes. The optimal sleep duration was 6.3 to 7.5 h/night. Conclusions::Short or long sleep duration was associated with a higher risk of type 2 diabetes. Persistently long sleep duration increased the risk.

Objective:To summarize the clinical characteristics of patients with coronavirus disease 2019 (COVID-19) infected with Delta variant, so as to provide further references for clinical diagnosis and treatment.Methods:A real-world study was conducted to analyze the characteristics of 166 COVID-19 patients infected with Delta variant at Guangzhou Eighth People’s Hospital, Guangzhou Medical University.Results:The study enrolled 5 asymptomatic cases, 123 non-severe cases (mild and moderate type), and 38 severe cases (severe and critical type). Among these patients, 69 (41.6%) were male and 97 (58.4%) were female, with a mean age of 47.0±23.5 years. Thirty-nine cases (23.5%) had received 1 or 2 doses of inactivated vaccine. The incidence of severe COVID-19 cases was 7.7% in 2-doses vaccinated patients, which was lower than that of 11.5% in 1-dose and 26.8% in unvaccinated patients. The proportion of severe cases in 2 dose-vaccinated patients was 7.7%, which was lower than that of 11.5% in 1-dose vaccinated patients and 26.8% in unvaccinated patients, but the difference was not significant ( P>0.05). The most common clinical symptom was fever (134 cases, 83.2%), and 39.1% of cases presented with high-grade fever (≥39 °C); other symptoms were cough, sputum, fatigue, and xerostomia. The proportion of fever in severe cases was significantly higher than that of non-severe cases (97.4% vs. 76.4%, P<0.01). Similarly, the proportion of severe cases with high peak temperature (≥39 ℃) () was also higher than that of non-severe cases (65.8% vs. 30.9%, P<0.01). The median minimal Cycle threshold (Ct) values of viral nucleic acid N gene and ORFlab gene were 20.3 and 21.5, respectively, and the minimum Ct values were 11.9 and 13.5, respectively. Within 48 h of admission, 9.0% of cases presented with decreased white blood cell counts, and 52.4% with decreased lymphocyte counts. The proportions of increased C-reactive protein, serum amyloid A, interleukin 6, and interleukin 10 were 32.5%, 57.4%, 65.3%, and 35.7%, respectively. The proportions of elevated C-reactive protein, serum amyloid A and interleukin-6 in severe cases were significantly higher than those in non-severe cases ( P<0.01). Logistic regression analysis showed that older age and higher peak temperature were associated with a higher likelihood of severe cases ( OR>3, 95% CI: 2-7, P<0.01). In terms of treatment, traditional Chinese medicine (TCM) was used in 97.6% of non-severe cases and 100% in severe cases. Other treatments included respiratory and nutritional support, immunotherapy (such as neutralizing antibodies and plasma of recovered patients). The median times from admission to progression to severe cases, of fever clearance, and of nucleic acid conversion were 5 days, 6 days and 19 days, respectively. No deaths were reported within 28 days. Conclusions:The symptoms of Delta variant infection in Guangzhou are characterized by a high proportion of fever, high peak temperature, long duration of fever, high viral load, a long time to nucleic acid conversion, and a high incidence of severe cases. The severe cases exhibit a higher percentage of elderly patients, a longer duration of fever and have a higher fever rate and a higher hyperthermia rate than non-severe cases. Age and hyperthermia are independent risk factors for progression to severe disease. The combination of TCM and Western medicine can control the progression of the disease effectively.

Objective:To determine plasma metabonomic profiles of rats with early sepsis, to find the differential metabolites and related metabolic pathways of sepsis at different time points, and to reveal the pathophysiological changes of sepsis rats in the early stage.Methods:Fifteen 8-week-old male SD rats were randomly (random number) divided into the sham operation group (S group, n=6) and sepsis group (C group, n=9). Sepsis rat model was established by cecal ligation and puncture, and rats in the sham operation group only freed the cecum but without ligation and perforation. Plasma was collected from orbital blood at 2, 6 and 12 h after modeling, and metabonomics was determined by gas chromatography-mass spectrometry (GC-MS). The endogenous metabolites were identified by comparing the standard ion fragment spectrum library of NIST database and Feihn metabonomics database. Multivariate regression analysis was carried out through MetaboAnalyst4.0, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) to identify the changes of metabolites, screen the related differential metabolites ( P<0.05, fold change>1.5, VIP >1.5), and then further analyze the related metabolic pathways through KEGG. Results:The PCA and PLS-DA pattern recognition showed that there was a cluster type distribution between the sepsis group and sham operation group at each time point, as well as between sepsis group at different time points. Fourteen, 25 and 21 differential metabolites were respectively detected between S2 h/C2 h group, S6 h/C6 h group and S12 h/C12 h group. The related signal pathways of differential metabolites were starch and sucrose metabolism and galactose metabolism at 2 h; starch and sucrose metabolism, galactose metabolism, cysteine and methionine metabolism, arginine and proline metabolism, glycine, serine and threonine metabolism, arachidonic acid metabolism and aminoacyl tRNA biosynthesis at 6 h; and galactose metabolism, arginine and proline metabolism, arginine biosynthesis, alanine, aspartic acid and glutamate metabolism, D-glutamine and D-glutamate metabolism, and vitamin B6 metabolism at 12 h.Conclusions:The plasma metabolites of sepsis rats in the early stage show significant dynamic differences, and the changes of plasma metabolites may be involved in the pathophysiological process of sepsis.

Acute myocardial infarction with cardiogenic shock (AMI-CS) refers to the rapid decrease in cardiac output in a short period of time, and it leads to severe insufficient perfusion of various organs and causes systemic microcirculatory dysfunction, which is the most common cause of the death of patients with acute myocardial infarction (AMI). At present, the main strategy for clinical treatment of AMI-CS is revascularization, which reduces the mortality of AMI-CS. However, myocardial ischemia and reperfusion can cause ischemia/reperfusion (I/R) injury, induce myocardial mitochondrial dysfunction, and a large amount of reactive oxygen species (ROS) accumulation. Mitochondrial-mediated apoptosis of cardiomyocytes is the main reason of cardiomyocyte death during reperfusion injury. This article summarizes the role of mitochondrial in AMI-CS, which focus on three aspects of mitochondrial permeability transition pore (mPTP) opening, mitochondrial autophagy and mitochondrial fusion/division. It is expected to provide new ideas for clinical AMI-CS and identify potential complications targets.

Objective To investigate the feasibility and clinical effect of palmar venous anastomosis in fingertip replantation.Methods From October,2008 to May,2017,the clinical data of 15 patients with 24 finger replantation were retrospectively analyzed by outpatient,telephone and WeChat followed-up.One artery was anastomosed for revascularization with or without nerve repair,and 1 palmar venous anastomosis was performed to reestablish the outflow system.The finger nerve was sutured randomly according to the injury.Results The patients were followed-up for 18-65 (mean,39.9) months.Except for 1 replantation finger with rotation avulsed injury failed,the remaining 14 cases with 23 fingers survived completely.Excellent restoration of finger motion was observed during the follow-up.The mean regained static 2-point discrimination sensation was 3.6 (2.8-4.0) mm.All patients were satisfied with the treatment effect.Conclusion Successful palmar venous anastomosis can improve the survival rate of replanted fingertips,simplify postoperative care,reduce postoperative complications,and improve the treatment effect.