BACKGROUND: This study aimed to investigate programmed death-ligand 1 tumor proportion score in predicting the safety and efficacy of PD-1/PD-L1 antibody-based therapy in treating patients with advanced non-small cell lung cancer (NSCLC) in a real-world setting. METHODS: This retrospective, multicenter, observational study enrolled adult patients who received PD-1/PD-L1 antibody-based therapy in China and met the following criteria: (1) had pathologically confirmed, unresectable stage III-IV NSCLC; (2) had a baseline PD-L1 tumor proportion score (TPS); and (3) had confirmed efficacy evaluation results after PD-1/PD-L1 treatment. Logistic regression, Kaplan-Meier analysis, and Cox regression were used to assess the progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs) as appropriate. RESULTS: A total of 409 patients, 65.0% ( n = 266) with a positive PD-L1 TPS (≥1%) and 32.8% ( n = 134) with PD-L1 TPS ≥50%, were included in this study. Cox regression confirmed that patients with a PD-L1 TPS ≥1% had significantly improved PFS (hazard ratio [HR] 0.747, 95% confidence interval [CI] 0.573-0.975, P = 0.032). A total of 160 (39.1%) patients experienced 206 irAEs, and 27 (6.6%) patients experienced 31 grade 3-5 irAEs. The organs most frequently associated with irAEs were the skin (52/409, 12.7%), thyroid (40/409, 9.8%), and lung (34/409, 8.3%). Multivariate logistic regression revealed that a PD-L1 TPS ≥1% (odds ratio [OR] 1.713, 95% CI 1.054-2.784, P = 0.030) was an independent risk factor for irAEs. Other risk factors for irAEs included pretreatment absolute lymphocyte count >2.5 × 10 9 /L (OR 3.772, 95% CI 1.377-10.329, P = 0.010) and pretreatment absolute eosinophil count >0.2 × 10 9 /L (OR 2.006, 95% CI 1.219-3.302, P = 0.006). Moreover, patients who developed irAEs demonstrated improved PFS (13.7 months vs. 8.4 months, P <0.001) and OS (28.0 months vs. 18.0 months, P = 0.007) compared with patients without irAEs. CONCLUSIONS A positive PD-L1 TPS (≥1%) was associated with improved PFS and an increased risk of irAEs in a real-world setting. The onset of irAEs was associated with improved PFS and OS in patients with advanced NSCLC receiving PD-1/PD-L1-based therapy.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Male ; Female ; Retrospective Studies ; Middle Aged ; Lung Neoplasms/metabolism* ; Aged ; B7-H1 Antigen/metabolism* ; Programmed Cell Death 1 Receptor/metabolism* ; Adult ; Aged, 80 and over ; Immune Checkpoint Inhibitors/therapeutic use*

Objective:To summarize the diagnosis and treatment experience of kidney graft’s ureteral obstruction secondary to ureteral inguinal hernia.Methods:Clinical data of a patient with kidney graft’s ureteral obstruction secondary to ureteral inguinal hernia in the Second Xiangya Hospital of Central South University in December 2023 was retrospectively analyzed.This was a male patient with 44 years old. Eleven years after kidney transplantation, he was admitted to the hospital because his serum creatinine increased for one day, accompanied by oliguria and edema of both lower limbs. His previous basal creatinine was maintained in the range of 60-70 μmol/L. Physical examination showed a mass of about 4 cm×3 cm in the right groin. The patient complained of anuria lasting for 7 hours on the second day after admission, and the serum creatinine increased to 406 μmol/L. B-ultrasound showed obstruction of the transplanted kidney and ureteral hydrops. Abdominal CT scan suggested that the right inguinal hernia (transplanted kidney ureteral hernia) was suspected.Preoperative diagnosis of ureteral obstruction secondary to inguinal hernia of the transplanted kidney was made. Percutaneous nephrostomy was performed under local anesthesia, and postoperative anti-infection and indwelling catheter treatments were given. The serum creatinine dropped significantly and the inguinal mass disappeared. A follow-up color ultrasound showed that the transplanted kidney ureteral obstruction and hydrops were alleviated than before. The patient was discharged 2 days after the nephrostomy operation. He was recommended to visit the general surgeon for hernia repairment in a timely manner after a stable renal function was achieved. The patient's renal function basically returned to normal during the following 3 weeks after discharge, and no hernia repair was performed. He was then readmitted to the hospital in order to remove the nephrostomy tube. The patient's nephrostomy tube and urinary catheter both drained almost 1000ml every day. After being informed of the risk of recurrence of obstruction among others, the nephrostomy was removed. Oliguria occurred on the day of nephrostomy tube removal, slight swelling and pain in the transplanted kidney area, and recurrence mass in the groin was seen. The color ultrasound showed recurrence of hydroureteral obstruction and hydrops in the transplanted kidney, and a transplanted nephrostomy was performed again along the original stoma. The postoperative recovery was smooth. One week later, a MDT by general surgeons and the urologists were conducted for choices of surgery. Traditional inguinal hernia repair (Bassini method) and double J-tube insertion under flexible ureteroscope were performed. Results After the operation, anti-infection with cefuroxime, immunosuppression, wound dressing change were given among other treatments. The nephrostomy tube and urinary catheter were removed before discharge. The double J-tube was removed 2 months after discharge. The outpatient follow-up was carried out until 9 months after the initial nephrostomy. The follow-up serum creatinine was at 62 umol/L. The color Doppler ultrasound showed only localized fluid accumulation and no recurrence of ureteroinguinal hernia.Conclusions:Ureteral inguinal hernia of the transplanted kidney is rare and can lead to hydroureteral obstruction and renal insufficiency in the transplanted kidney. Abdominal CT examination is the first choice, combined with abdominal physical examination for diagnosis. Nephrostomy is an effective measure to relieve obstruction and promote recovery of renal function. Hernia repair surgery is an effective measure to prevent the recurrence of kidney graft’s ureteral inguinal hernia, and Bassini method hernia repair is a feasible treatment measure.

The Baihe Dihuang Decoction(BDD) is a representative traditional Chinese medicine formula that has been used to treat depression. This study employed metabolomics and network pharmacology to investigate the mechanism of BDD in the treatment of depression. Fifty male Sprague-Dawley(SD) rats were randomly assigned to the normal control group, model group, fluoxetine group, and high-and low-dose BDD groups. A rat model of depression was established through chronic unpredictable mild stress(CUMS), and the behavioral changes were detected by forced swimming test and open field test. Metabolomics technology was used to analyze the metabolic profiles of serum and hippocampal tissue to screen differential metabolites and related metabolic pathways. Additionally, network pharmacology and molecular docking techniques were used to investigate the key targets and core active ingredients of BDD in improving metabolic abnormalities of depression. A "component-target-metabolite-pathway" regulatory network was constructed. BDD could significantly improve depressive-like behavior in CUMS rats and regulate 12 differential metabolites in serum and 27 differential metabolites in the hippocampus, involving tryptophan metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis, alanine, aspartate, and glutamate metabolism, tyrosine metabolism, and purine metabolism. Verbascoside, isorbascoside, and regaloside B were the key active ingredients for improving metabolic abnormalities in depression. Epidermal growth factor receptor(EGFR), protooncogene tyrosine-protein kinase(SRC), glycogen synthase kinase 3β(GSK3β), and androgen receptor(AR) were the key core targets for improving metabolic abnormalities of depression. This study offered a preliminary insight into the mechanism of BDD in alleviating metabolic abnormalities of depression through network regulation, providing valuable guidance for its clinical use and subsequent research.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Rats ; Metabolomics ; Depression/genetics* ; Antidepressive Agents/chemistry* ; Network Pharmacology ; Hippocampus/drug effects* ; Humans ; Molecular Docking Simulation ; Behavior, Animal/drug effects* ; Disease Models, Animal

Objective Itproposes a WISN staffing demand model for clinical physicians to address the challenge that current physicians staffing standards fail to meet the operational needs of general hospitals.Methods Collect the 2023 annual operation data of a tertiary general hospital,using inpatient visits and surgeries as benchmarks to measure the workload demands of physicians in internal medicine and surgery,respectively.Additionally,integrate non-clinical workloads of physicians and the workload of resident physicians in standardized training to address the limitation of traditional models that focus solely on clinical tasks.Results The good applicability and robustness of the model in practical applications are verified through model comparison and sensitivity analysis,accurately reflecting the demand for physicians.Conclusion The model accurately reflects the workload of physicians in general hospitals,providing a quantitative estimation formula for physicians staffing.It has broad applicability and significant potential for wider adoption.

OBJECTIVE: Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. METHODS: We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro. RESULTS: SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells. CONCLUSION Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals ; Apoptosis/drug effects* ; Particulate Matter/adverse effects* ; Mice ; Male ; Inflammation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Myocardial Ischemia/drug therapy* ; Cell Line

Widespread utilization of glyphosate has led to environmental residues,posing potential threats to ecological systems and human health.Traditional methods for detection of glyphosate are limited by specialized equipment and operational techniques,resulting in inefficient responses.Therefore,it is urgent to develop a convenient,sensitive and accurate detection method for detection of glyphosate.Herein,a new naphthalenesulfonamide-based"Turn-on"fluorescent probe was synthesized using 2-chloroaniline and dansyl chloride as raw materials through a one-step process,which showed a good linear relationship between the glyphosate concentration in concentration range of 0.003-70 μmol/L and the fluorescence intensity(R2=0.995),with a detection limit of 2.73 nmol/L(S/N=3).Analytical techniques such as nuclear magnetic resonance(NMR)spectroscopy and high-resolution mass spectrometry(HRMS)were used to investigate the interaction mechanism between the fluorescent probe and glyphosate.The results indicated that a nucleophilic substitution reaction occurred between the probe and the secondary amine(—NH—)of glyphosate,inducing a photoinduced electron transfer(PET)effect which enhanced the fluorescence intensity by 11.2 times.The probe showed good anti-interference ability towards coexisting metal ions,anions and pesticides in water.When applied to determination of glyphosate in the samples such as tap water,river water(Xiangxi River Reservoir),soil,soybeans,and corn,the spiking recoveries ranged from 94.7％to 109.9％,demonstrating the high accuracy and broad applicability of this detection method.A portable test strip based on this fluorescent probe was developed for rapid semi-quantitative analysis of glyphosate.The developed method was rapid,sensitive,and portable,providing theoretical and technical support for on-site measurement of environmental contaminants.

Aim To investigate the high expression of LINC00626 in colorectal cancer,and explore the effects of LINC00626 on the proliferation,apoptosis,and drug sensitivity of colorectal cancer SW480 cells,as well as its underlying mechanisms.Methods Flu-orescence in situ hybridization(FISH)was used to de-tect the expression levels of LINC00626 in 38 colorec-tal cancer tissues and their corresponding adjacent nor-mal tissues.The JASPAR database was utilized to pre-dict co-expressed genes and their possible binding sites.Cell transfection technology was employed to knockdown LINC00626.Western blot and qRT-PCR techniques were used to verify the transfection efficien-cy.CCK-8 assay,cell apoptosis and necrosis staining,and Western blot were used to detect the changes in the proliferation,apoptosis,drug sensitivity,and ap-optotic proteins of SW480 cells,respectively.Results The FISH results indicated that LINC00626 was highly expressed in colorectal cancer tissues(P＜0.05).The expression of LINC00626 was not associat-ed with the age or gender of patients,but was related to the TNM stage and the presence of lymph node me-tastasis($ P＜0.05 $).The results of CCK-8 assay and cell apoptosis and necrosis staining showed that af-ter knockdown of LINC00626,the proliferation ability of SW480 cells decreased,the apoptosis level in-creased,and the drug resistance decreased(P＜0.05).Western blot results showed that with the de-crease in the expression level of LINC00626,the ex-pression of caspase-3 protein decreased,the expression of cleaved caspase-3 protein increased,and the expres-sion of Bcl-2 protein decreased(P＜0.05).Conclu-sions LINC00626 is highly expressed in colorectal cancer and is associated with the TNM stage and the presence of lymph node metastasis.LINC00626 can af-fect the proliferation,apoptosis,and drug sensitivity of SW480 cells and alter the expression of apoptotic pro-teins.

Objective Itproposes a WISN staffing demand model for clinical physicians to address the challenge that current physicians staffing standards fail to meet the operational needs of general hospitals.Methods Collect the 2023 annual operation data of a tertiary general hospital,using inpatient visits and surgeries as benchmarks to measure the workload demands of physicians in internal medicine and surgery,respectively.Additionally,integrate non-clinical workloads of physicians and the workload of resident physicians in standardized training to address the limitation of traditional models that focus solely on clinical tasks.Results The good applicability and robustness of the model in practical applications are verified through model comparison and sensitivity analysis,accurately reflecting the demand for physicians.Conclusion The model accurately reflects the workload of physicians in general hospitals,providing a quantitative estimation formula for physicians staffing.It has broad applicability and significant potential for wider adoption.

Aim To investigate the high expression of LINC00626 in colorectal cancer,and explore the effects of LINC00626 on the proliferation,apoptosis,and drug sensitivity of colorectal cancer SW480 cells,as well as its underlying mechanisms.Methods Flu-orescence in situ hybridization(FISH)was used to de-tect the expression levels of LINC00626 in 38 colorec-tal cancer tissues and their corresponding adjacent nor-mal tissues.The JASPAR database was utilized to pre-dict co-expressed genes and their possible binding sites.Cell transfection technology was employed to knockdown LINC00626.Western blot and qRT-PCR techniques were used to verify the transfection efficien-cy.CCK-8 assay,cell apoptosis and necrosis staining,and Western blot were used to detect the changes in the proliferation,apoptosis,drug sensitivity,and ap-optotic proteins of SW480 cells,respectively.Results The FISH results indicated that LINC00626 was highly expressed in colorectal cancer tissues(P＜0.05).The expression of LINC00626 was not associat-ed with the age or gender of patients,but was related to the TNM stage and the presence of lymph node me-tastasis($ P＜0.05 $).The results of CCK-8 assay and cell apoptosis and necrosis staining showed that af-ter knockdown of LINC00626,the proliferation ability of SW480 cells decreased,the apoptosis level in-creased,and the drug resistance decreased(P＜0.05).Western blot results showed that with the de-crease in the expression level of LINC00626,the ex-pression of caspase-3 protein decreased,the expression of cleaved caspase-3 protein increased,and the expres-sion of Bcl-2 protein decreased(P＜0.05).Conclu-sions LINC00626 is highly expressed in colorectal cancer and is associated with the TNM stage and the presence of lymph node metastasis.LINC00626 can af-fect the proliferation,apoptosis,and drug sensitivity of SW480 cells and alter the expression of apoptotic pro-teins.

Objective:To summarize the diagnosis and treatment experience of kidney graft’s ureteral obstruction secondary to ureteral inguinal hernia.Methods:Clinical data of a patient with kidney graft’s ureteral obstruction secondary to ureteral inguinal hernia in the Second Xiangya Hospital of Central South University in December 2023 was retrospectively analyzed.This was a male patient with 44 years old. Eleven years after kidney transplantation, he was admitted to the hospital because his serum creatinine increased for one day, accompanied by oliguria and edema of both lower limbs. His previous basal creatinine was maintained in the range of 60-70 μmol/L. Physical examination showed a mass of about 4 cm×3 cm in the right groin. The patient complained of anuria lasting for 7 hours on the second day after admission, and the serum creatinine increased to 406 μmol/L. B-ultrasound showed obstruction of the transplanted kidney and ureteral hydrops. Abdominal CT scan suggested that the right inguinal hernia (transplanted kidney ureteral hernia) was suspected.Preoperative diagnosis of ureteral obstruction secondary to inguinal hernia of the transplanted kidney was made. Percutaneous nephrostomy was performed under local anesthesia, and postoperative anti-infection and indwelling catheter treatments were given. The serum creatinine dropped significantly and the inguinal mass disappeared. A follow-up color ultrasound showed that the transplanted kidney ureteral obstruction and hydrops were alleviated than before. The patient was discharged 2 days after the nephrostomy operation. He was recommended to visit the general surgeon for hernia repairment in a timely manner after a stable renal function was achieved. The patient's renal function basically returned to normal during the following 3 weeks after discharge, and no hernia repair was performed. He was then readmitted to the hospital in order to remove the nephrostomy tube. The patient's nephrostomy tube and urinary catheter both drained almost 1000ml every day. After being informed of the risk of recurrence of obstruction among others, the nephrostomy was removed. Oliguria occurred on the day of nephrostomy tube removal, slight swelling and pain in the transplanted kidney area, and recurrence mass in the groin was seen. The color ultrasound showed recurrence of hydroureteral obstruction and hydrops in the transplanted kidney, and a transplanted nephrostomy was performed again along the original stoma. The postoperative recovery was smooth. One week later, a MDT by general surgeons and the urologists were conducted for choices of surgery. Traditional inguinal hernia repair (Bassini method) and double J-tube insertion under flexible ureteroscope were performed. Results After the operation, anti-infection with cefuroxime, immunosuppression, wound dressing change were given among other treatments. The nephrostomy tube and urinary catheter were removed before discharge. The double J-tube was removed 2 months after discharge. The outpatient follow-up was carried out until 9 months after the initial nephrostomy. The follow-up serum creatinine was at 62 umol/L. The color Doppler ultrasound showed only localized fluid accumulation and no recurrence of ureteroinguinal hernia.Conclusions:Ureteral inguinal hernia of the transplanted kidney is rare and can lead to hydroureteral obstruction and renal insufficiency in the transplanted kidney. Abdominal CT examination is the first choice, combined with abdominal physical examination for diagnosis. Nephrostomy is an effective measure to relieve obstruction and promote recovery of renal function. Hernia repair surgery is an effective measure to prevent the recurrence of kidney graft’s ureteral inguinal hernia, and Bassini method hernia repair is a feasible treatment measure.