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 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.

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.

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.

Humans ; Asthma/drug therapy* ; Biological Therapy

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

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:To investigate the clinical diagnosis and prognosis in patients with emergency septic encephalopathy.Methods:Case data of 131 patients with septic encephalopathy admitted to the emergency department of Chuiyangliu Hospital Affiliated to Tsinghua University from January 2020 to December 2021 were selected and divided into survival group and death group. Logistic regression was used to analyze the risk factors affecting diagnosis, treatment and prognosis in patients with septic encephalopathy. Receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of each indicator in patients with septic encephalopathy.Results:The mean arterial pressure (MAP) and pH level in the death group were lower than those in the survival group, while the C reactive protein (CRP), troponin T (TNI), D-dimer, lactic acid, creatinine, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) score, Sequential Organ Failure Assessment (SOFA), proportion of ventilator support, proportion of vasoactive drug use in the death group were higher than those in the survival group, with statistically significant difference (all P<0.05). Multivariate logistic regression analysis showed that APACHEⅡ score ( OR=1.290, 95% CI: 1.121-1.485, P<0.001), SOFA score ( OR=1.447, 95% CI: 1.183-1.796, P<0.001), the proportion of vasoactive drug use ( OR=18.720, 95% CI: 4.486-78.108, P<0.001) could predict the prognosis of patients with septic encephalopathy, and the area under the curve (AUC) was 0.823, 0886, 0.787. Conclusions:Elderly age and underlying brain diseases are important factors in the occurrence of septic encephalopathy. APACHE Ⅱ score, SOFA score, and the proportion of vasoactive drug use can predict the prognosis of patients with septic encephalopathy.

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

Objective: To examine the feasibility and surgical approach of removing type D trigeminal schwannoma through nasal cavity and nasal sinus under endoscope. Methods: Eleven patients with trigeminal schwannoma who were treated in the Department of Otorhinolaryngology, Qilu Hospital of Shandong University from December 2014 to August 2021 were analyzed retrospectively in this study. There were 7 males and 4 females, aged (47.5±13.5) years (range: 12 to 64 years). The neoplasm involved the pterygopalatine fossa, infratemporal fossa, ethmoidal sinus, sphenoid sinus, cavernous sinus, and middle cranial fossa. The size of tumors were between 1.6 cm×2.0 cm×2.0 cm and 5.7 cm×6.0 cm×6.0 cm. Under general anesthesia, the tumors were resected through the transpterygoid approach in 4 cases, through the prelacrimal recess approach in 4 cases, through the extended prelacrimal recess approach in 2 cases, and through the endoscopic medial maxillectomy approach in 1 case. The nasal endoscopy and imaging examination were conducted to detect whether neoplasm recurred or not, and the main clinical symptoms during follow-up. Results: All the surgical procedures were performed under endonasal endoscope, including Gross total resection in 10 patients. The tumor of a 12-year-old patient was not resected completely due to huge tumor size and limited operation space. One patient was accompanied by two other schwannomas located in the occipital region and the ipsilateral parotid gland region originating from the zygomatic branch of the facial nerve, both of which were removed concurrently. After tumor resection, the dura mater of middle cranial fossa was directly exposed in the nasal sinus in 2 cases, including 1 case accompanied by cerebrospinal fluid leakage which was reconstructed by a free mucosal flap obtained from the middle turbinate, the other case was packed by the autologous fat to protect the dura mater. The operation time was (M(IQR)) 180 (160) minutes (range: 120 to 485 minutes). No complications and deaths were observed. No recurrence was observed in the 10 patients with total tumor resection during a 58 (68) months' (range: 10 to 90 months) follow-up. No obvious change was observed in the facial appearance of all patients during the follow-up. Conclusion: Type D trigeminal schwannoma involving pterygopalatine fossa and infratemporal fossa can be removed safely through purely endoscopic endonasal approach by selecting the appropriate approach according to the size and involvement of the tumor.
Male ; Female ; Humans ; Child ; Retrospective Studies ; Endoscopy/methods* ; Nasal Cavity/surgery* ; Neurilemmoma/surgery* ; Cranial Nerve Neoplasms/surgery*