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 explore the relationship between peripheral blood lymphocyte subsets, interleukin-6 (IL-6) levels, and prognosis in patients with viral pneumonia.Methods:A total of 100 patients with viral pneumonia admitted to the Emergency Department of the Chuiyangliu Hospital Affiliated to Tsinghua University from December 2021 to November 2023 were selected and divided into a survival group and a death group. 20 healthy individuals who underwent physical examinations during the same period were selected as the control group. General information of the patients was collected, and peripheral blood lymphocyte subsets and related cytokine IL-6 were detected. Differences in peripheral blood lymphocyte subsets and IL-6 levels among different groups were analyzed, And multiple logistic regression was used to analyze the influencing factors of viral pneumonia disease and death.Results:The proportion of death group with diabetes was significantly higher than that of survival group ( P<0.05). The mortality of patients with diabetes was higher than that of patients without diabetes [60.7%(17/28) vs 12.5%(9/72), P<0.05]. The total number of peripheral blood T lymphocytes, helper/inducible T lymphocytes (Th), CD4 + /CD8 + ratio, B lymphocyte count, and natural killer (NK) cells in patients with viral pneumonia were significantly lower than those in the healthy control group (all P<0.05), and the level of IL-6 was significantly higher than that in the healthy control group ( P<0.05); The total number of peripheral blood T lymphocytes, Th cells, CD4 + /CD8 + ratio, B lymphocyte count, and NK cells in the death group were significantly lower than those in the survival group (all P<0.05), and the level of IL-6 was significantly higher than that in the survival group ( P<0.05). The results of multivariate logistic regression analysis showed that T lymphocyte subsets and IL-6 were all influencing factors for the disease and death of viral pneumonia (all P<0.05). Conclusions:The mortality of viral pneumonia patients with diabetes increased; The absolute number of lymphocyte subsets decreases and the level of IL6 increases in patients with viral pneumonia; The difference in changes between the death group and the survival group is more significant; Early detection of peripheral blood lymphocyte subsets and IL6 levels is beneficial for evaluating the prognosis of patients with viral pneumonia and has certain guiding value for clinical practice.

Objective:To retrospectively analyze the feasibility of undergoing day surgery at 3rd week after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children.Methods:The clinical data from children who underwent day surgery from November 1, 2022 to February 28, 2023, with operation time ≤1 h, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, regardless of gender, aged≤14 yr, with body mass index of 10-30 kg/m 2, were divided into SARS-CoV-2 group and control group according to whether the children had been infected with the SARS-CoV-2. The main outcome measure was the incidence of respiratory system-related complications within 30 days after surgery. Secondary outcome measures included the rate of unplanned ventilation, delayed discharge and secondary admission within 30 days after surgery. Preoperative creatine kinase isoenzyme (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), hemoglobin (Hb), white blood cell count, C-reactive protein (CRP) level, grade of oropharyngeal mucosa inflammation, operation time, emergence time, intraoperative respiratory depression, laryngeal spasm, hypoxemia, hypotension, incidence of sinus bradycardia and rate of additional rescue drugs were recorded. Results:There were 337 cases in SARS-CoV-2 group and 1 396 cases in control group. Compared with control group, CK-MB concentrations were significantly increased, and the Hb concentration was decreased before surgery in SARS-CoV-2 group ( P<0.05). There were no statistically significant differences in the incidence of respiratory system-related complications, unplanned ventilation, delayed discharge and rate of postoperative secondary admission, preoperative AST and ALT concentrations, white blood cell count, CRP concentrations, grade of oropharyngeal mucosa inflammation, operation time, intraoperative respiratory depression, laryngeal spasm, hypoxemia, hypotension, incidence of sinus bradycardia, rate of additional rescue drugs and emergence time between the two groups ( P>0.05). Conclusions:Feasibility of undergoing day surgery is good at the third week after being infected with the SARS-CoV-2 in children.

The correlation between hearing loss (HL) and physical performance in patients receiving maintenance hemodialysis (MHD) remains poorly investigated. This study explored the association between HL and physical performance in patients on MHD. Methods: This multicenter cross-sectional study was conducted between July 2020 and April 2021 in seven hemodialysis centers in Shanghai and Suzhou, China. The hearing assessment was performed using pure-tone average (PTA). Physical performance was assessed using the Timed Up and Go Test (TUGT), handgrip strength, and gait speed. Results: Finally, 838 adult patients (male, 516 [61.6%]; 61.2 ± 2.6 years) were enrolled. Among them, 423 (50.5%) had mild to profound HL (male, 48.6% and female, 53.4%). Patients with HL had poorer physical performance than patients without HL (p < 0.001). TUGT was positively correlated with PTA (r = 0.265, p < 0.001), while handgrip strength and gait speed were negatively correlated with PTA (r = –0.356, p < 0.001 and r = –0.342, p < 0.001, respectively). Physical performance in patients aged <60 years showed significant dose-response relationships with HL. After adjusting for confounders, the odds ratios (95% confidence intervals) for HL across the TUGT quartiles (lowest to highest) were 1.00 (reference), 1.15 (0.73–1.81), 1.69 (1.07–2.70), and 2.87 (1.69–4.88) (p for trend = 0.005). Conclusion: Lower prevalence of HL was associated with a faster TUGT and a stronger handgrip strength in patients on MHD.

Oxidative stress(OS)is a major reason for body damage. Studies have shown that a variety of factors, such as ischemia and hypoxia, excessive light and hyperglycemia can cause the increase of reactive oxygen species and free radicals in the retina, thus inducing OS, damaging retina and affecting the normal visual function. Kelch-like ECH-associated protein 1(KEAP1)and nuclear factor erythroid 2 related factor 2(NRF2), which together constitute the main antioxidant stress signaling pathway in the body, play an antioxidant role by regulating retinal energy metabolism and cell proliferation, apoptosis and autophagy through various ways, so as to reduce retinal damage caused by OS. In this paper, the role and mechanism of the KEAP1-NRF2 signaling pathway regulation of OS in the retinal are briefly reviewed, aiming to provide ideas for subsequent research.

Objective The HPLC fingerprints of different varieties of Tibetan medicine"Bangjian"were investigated to compare and analyse the differences in the chemical composition of different varieties and to further classify them,so as to provide reference for their quality control and safe clinical use.Methods HPLC method was used to establish the fingerprints of the different species of"Bangjian",and UPLC-Q-TOF-MS method was used to analyse the similarities and differences of the chemical components of the mainstream species and to identify the characteristic peaks.Chemometrics methods were used for the analysis including cluster analysis(HCA),principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA).Results A total of 11 chromatographic peaks were identified from 93 batches of"Bangjian"samples.The HCA and PCA methods were used to classify the 93 batches into 2 categories,and then OPLS-DA was used to classify them into 3 categories in more detail,while 4 main components were selected according to the principle of VIP>1.The results of UPLC-Q-TOF-MS and chemometric showed that the Tibetan medicine"Bangjian"could be divided into iridoids with benzoyl fragments represented by Gentiana szechenyii Kanitz and monocyclic iridoids represented by Gentiana veitchiorum Hemsl.according to their chemotypes.The latter could be divided into alpine gentian group subtype and multi-branch group ornate subtype according to the content of components.The results of the chemotypic classification proved that the traditional classification of the"Bangjian"has a material basis in science but were also flawed.Conclusion The present study demonstrates that the established HPLC fingerprint can be used to classify the"Bangjian"of the complex base elements effectively,which is expected to provide an effective reference for the improvement of quality standards of"Bangjian"and clinical safety medication.

OBJECTIVE: To evaluate the short-term efficacy of proximal fibula osteotomy in the treatment of knee osteoarthritis, and to analyze the effect of osteotomy on the tension of the lateral knee soft tissue of patients and verify the reliability of the Arch string theory. METHODS: A total of 71 patients with varus knee osteoarthritis from December 2019 to March 2022 were included, 3 patients dropped out, and 68 patients completed all trials, collected 27 males and 41 females, aged from 51 to 79 years old, with an average of (68.0±7.0 ) years old. The follow-up time ranged from 4 to 12 weeks, with an average of (3.76±1.94) weeks. After admission, the patient underwent Proximal fibula osteotomy, and the tension of lateral knee soft tissue, visual analogue scale (VAS) of pain, the western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and other indicators were recorded before surgery and 1 month after surgery in the weight-bearing state. RESULTS: According to the VAS, the curative effect of a single index was evaluated by referring to the score before and after treatment by Bao Zongzhao. Thirty seven cases were markedly effective, 27 cases were effective, and 4 cases were ineffective. After surgery, 3 patients presented with weakness of dorsalis pedis extension and 1 presented with paresthesia of dorsalis pedis, which disappeared after symptomatic treatment . The VAS and WOMAC score at 1 month after operation were lower than those before operation, and the differences were statistically significant(P<0.001). The tension of lateral knee soft tissue 1 month after operation was lower than that before operation, and the difference had statistical significance(P<0.001). CONCLUSION Proximal fibula osteotomy is safe and effective in the treatment of varus knee osteoarthritis in the short term. One month after osteotomy, the tension of lateral knee soft tissue increases under weight-bearing state, but the long-term changes still need further observation and follow-up.
Male ; Female ; Humans ; Middle Aged ; Aged ; Osteoarthritis, Knee/surgery* ; Fibula/surgery* ; Reproducibility of Results ; Tibia/surgery* ; Knee Joint/surgery* ; Osteotomy ; Treatment Outcome ; Retrospective Studies

OBJECTIVE: Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment. METHODS: The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway. RESULTS: According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway. CONCLUSION JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.
Animals ; Mice ; Humans ; Carcinoma, Hepatocellular/genetics* ; beta Catenin/pharmacology* ; Liver Neoplasms/genetics* ; Drugs, Chinese Herbal/therapeutic use* ; RNA, Messenger/therapeutic use* ; Cell Line, Tumor ; Cell Proliferation ; Cell Movement ; Gene Expression Regulation, Neoplastic

Peptides are increasingly important resources for biological and therapeutic development, however, their intrinsic susceptibility to proteolytic degradation represents a big hurdle. As a natural agonist for GLP-1R, glucagon-like peptide 1 (GLP-1) is of significant clinical interest for the treatment of type-2 diabetes mellitus, but its in vivo instability and short half-life have largely prevented its therapeutic application. Here, we describe the rational design of a series of α/sulfono-γ-AA peptide hybrid analogues of GLP-1 as the GLP-1R agonists. Certain GLP-1 hybrid analogues exhibited enhanced stability (t _1/2 > 14 days) compared to t _1/2 (<1 day) of GLP-1 in the blood plasma and in vivo. These newly developed peptide hybrids may be viable alternative of semaglutide for type-2 diabetes treatment. Additionally, our findings suggest that sulfono-γ-AA residues could be adopted to substitute canonical amino acids residues to improve the pharmacological activity of peptide-based drugs.

[This corrects the article DOI: 10.1016/j.apsb.2021.03.043.].