An excessive weight loss percentage over the two years before treatment is an independent prognostic factor for operated patients with advanced oral squamous cell carcinoma.

The aim of this study was to assess the prognostic value of the weight loss percentage (WLP) over the 2 years pre-treatment for operated patients with advanced oral squamous cell carcinoma (OSCC). This cohort study included 506 operated patients who were diagnosed with advanced primary OSCC between October 2001 and March 2022, and who were followed up until July 2022. Fine-Gray models, marginal structural models with stabilized inverse probability of treatment weighting, and Cox proportional hazards models were utilized to evaluate the prognostic significance of pre-treatment WLP for disease-specific survival (DSS). The median follow-up time was 32.6 months (interquartile range 13.0-71.6 months). A high pre-treatment WLP (>9.23%) was significantly associated with worse DSS (multivariate Fine-Gray model: hazard ratio (HR) 2.04, 95% confidence interval (CI) 1.29-3.22, P = 0.002; multivariate Cox: HR 2.01, 95% CI 1.28-3.16, P = 0.002). In the weighted cohort, a similar association pattern was observed (marginal structural model: HR 2.26, 95% CI 1.28-3.98, P = 0.005; multivariate Cox: HR 2.28, 95% CI 1.38-3.76, P = 0.001). In subgroup analyses, high WLP could predict worse DSS among patients with buccal mucosa/other cancer sites (not including the oral tongue), moderate tumor differentiation, and larger cancer size (>1.8 cm) (all P < 0.05). Pre-treatment WLP over 2 years might be a useful tool to predict the prognosis of operated patients with advanced OSCC.

Genetic parameter estimation and genetic evaluation of important economic traits in white and yellow broilers.

1. This study calculated descriptive statistics for the production traits of two broiler populations: 1) the Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF white broilers), including fat and lean lines; and 2) the Guangxi yellow broilers. Their genetic parameters were estimated, including (co)variance components, heritability (h2) and genetic correlations (rg), using the REML method.2. Heritability estimates (h2) for NEAUHLF white broilers ranged from 0.07 to 0.61. Traits with high heritability (h2 >0.3) included body weight at 3, 5 and 7 weeks of age (BW3, BW5, BW7), carcass weight (CW), metatarsal circumference (MeC), liver weight (LW), gizzard weight (GW), spleen weight (SW) and testis weight (TeW), while in Guangxi yellow broilers, heritability estimates ranged from 0.18 to 0.76, with every trait exhibiting high heritability, except for SW (0.18).3. Positive genetic correlations for NEAUHLF were found (rg >0.3, ranging from 0.31 to 0.84) between BW7 and metatarsal length (MeL), MeC, body oblique length (BoL), chest angle (ChA), LW, GW, heart weight (HW) and SW. Genetic correlations between abdominal fat weight (AFW) and BW1, BW3, BW5, CW, MeL, keel length (KeL), BoL and LW were positive (rg >0.3, ranging from 0.31 to 0.58).4. Among the Guangxi population, BW (125 d of age) showed strong positive genetic correlations with all other traits (rg >0.3, ranging from 0.30 to 0.99), while AFW displayed strong positive genetic correlations with leg muscle weight (LeW), CW, BW and thigh diameter (TD) (rg >0.3, ranging from 0.44 to 0.51).5. It was concluded that the characteristics of the two populations were different, which means there is a need to use different strategies when performing the breeding work to improve productivity and efficiency in both broiler populations.

Association of gut microbiota with acute kidney injury: a two-sample Mendelian randomisation and case-control study.

Epidemiologic studies have implicated the gut microbiota in acute kidney injury (AKI), but the causal relationship is unclear. Using Mendelian randomisation, we explored the causal role of gut microbiota in the development of acute kidney injury after excluding confounding and reverse causality. Mendel randomised (MR) study was conducted using data from intestinal microbiota and genome-wide association studies (GWAS) disease of acute kidney injury and the sequencing data of case-control study confirmed this finding. The summary statistics of intestinal microbiota (n = 13,266) conducted by MiBioGen Alliance was taken as the exposure, while the statistics of acute kidney injury obtained from FinnGen Alliance data (2,383 cases and 212,841 controls) were taken as the results. A total of 42 patients were included in this case-control study. Evidence for the protective causal associations of the genus Flavonifractor id.2059 with AKI was found in inverse variance weighting (odds ratio = 0.48 [95% confidence interval, 0.32-0.72]; P = 0.0003). Additionally, a case-control study showed that the relative abundance of the genus Flavonifractor id.2059 ( P = 0.0169) in septic non-AKI patients was higher than that in septic AKI patients. Compared with S-AKI patients who died within 28 days, the relative abundance of the genus Flavonifractor id.2059 in surviving patients was higher ( P = 0.0281). Phylogenetic analysis showed that OTU68 and HQ455040.1334-739 (genus Flavonifractor, Genetic similarity: 100%), as well as OTU2271 and LT598575.1365-770 (genus Pseudoflavonifractor, Genetic similarity: 100%), have closest genetic ties. Correlation analysis showed that the genus Flavonifractor id.2059 was related to the creatinine value (Spearman correlation: -0.379, P = 0.013). The present study demonstrates that the genus Flavonifractor id.2059 is associated with a reduced risk of AKI, revealing potential implications for the prevention and treatment of acute kidney injury.

[Clinicopathological analysis of gastric adenocarcinoma with elevated serum alpha-fetoprotein and enteroblastic differentiation].

Objective: To investigate the immunophenotypic and molecular biological characteristics of patients with elevated serum alpha-fetoprotein (AFP) and enteroblastic differentiated gastric adenocarcinoma (GAED). Methods: The clinicopathological data of 13 patients with elevated serum AFP and GAED admitted to Shanxi Cancer Hospital from 2018 to 2020 were collected. Immunohistochemistry (IHC) and next-generation sequencing (NGS) were used to analyze the immune markers and molecular biological characteristics of the pathological tissues of the patients. Kaplan-Meier method and log rank test were used for survival analysis. Results: Among the 13 patients with GAED, 12 were male and 1 was female, aged 41-70 years, with a median age of 64 years. The lesions were mainly located in the gastric antrum (5 cases) and gastric body (4 cases). IHC results showed that the tumor embryonic protein (AFP, SALL4, GPC3), intestinal epithelial differentiation protein (CDX-2, CD10), and some original intestinal epithelial phenotype markers (OCT3/4, Claudin6) were expressed in the tumor tissues. Combined application of multiple markers can reduce the rate of missed diagnosis. Among the 13 patients, 12 had at least one mutation (1 mutation: 1 case, 2-5 mutations: 3 cases, 6-15 mutations: 8 cases), and 1 case was not detected. The gene with the highest mutation frequency was TP53 (10 cases), and other mutant genes included EPHB1 (3 cases), ATRX (2 cases), EPHA5 (2 cases), GATA3 (2 cases), LRP1B (2 cases) and MAP2K4 (2 cases) were also detected. Three of the 13 patients had structural variations, which were C14orf177-GNAS, AIM1-FGFR3, and EPHA6-ROS1 gene rearrangements. All 13 patients had copy number variation, and 11 patients had copy number variation of more than 2 genes. The common amplification genes were IRS2 (5 cases), PTEN (5 cases), GNAS (4 cases), CCNE1 (3 cases), CEBPA (3 cases), PCK1 (3 cases) and ERBB2 (2 cases). The common deletion genes were SOX2 (5 cases) and MYC (5 cases). Among the 13 patients, 4 died, and 2 of the dead patients had liver metastasis. There were 4 patients with disease-free survival and 5 patients with disease progression, including 3 cases of abdominal metastasis and 2 cases of liver metastasis. The 3-year survival rate of patients was 65.9 %, and the 3-year progression-free survival rate was 30.7 %. Gene LRP1B point mutation was associated with poor prognosis (P＜0.001). There was no significant improvement in the prognosis of patients treated with immunotherapy compared with those treated with chemotherapy alone (P=0.595), but the prognosis of patients treated with postoperative chemotherapy or postoperative chemotherapy plus immunotherapy was better than that of patients treated with surgery alone (P＜0.05). Conclusions: Elevated serum AFP with GAED is a highly invasive tumor with unique molecular characteristics, often accompanied by multiple molecular events. TP53 mutation is the most common type of gene mutation. In addition, some cases are accompanied by HER2 amplification and gene rearrangement.

[Detection of PIK3CA gene mutation and its related prognosis in colorectal cancer based on next-generation sequencing].

Objectives: To investigate the mutation of PIK3CA in colorectal cancer and to analyze their clinicopathological features, and evaluate their role in clinical treatment and prognostication. Methods: A total of 128 paraffin-embbeded tissue samples of colorectal cancer from Shanxi Cancer Hospital from 2018 to 2021 were collected. DNA was extracted from the samples, and next-generation sequencing (NGS) was used to detect PIK3CA mutation. The relationship between PIK3CA mutation, their clinicopathological features, and prognosis were analyzed. Results: Among the 128 colorectal cancer samples, there were 75 males and 53 females; with aged range 32-86 years, median 61.5 years, 27 (21.09%) had PIK3CA mutations. Colorectal cancer with PIK3CA mutation was more likely to occur in male patients (P=0.007), which was related to tumor site (P=0.032), tumor size (P=0.029) and TP53 wild-type (P=0.001). The common site mutations of PIK3CA mostly occurred in tumors with tumor mutation burden≥10 Muts/Mb (P=0.031).PIK3CA mutation had no significant effect on the survival prognosis of patients, but the efficacy of anti-angiogenic therapy was poor in these patients. Conclusions: PIK3CA mutation is a common mutation in colorectal cancer and plays an important role in the occurrence and development of colorectal cancer. PIK3CA mutation may lead to resistance to anti-angiogenic drugs in colorectal cancer, but its impact on survival and prognosis to patients needs further study.

[Selection of postoperative adjuvant therapy for patients with stage IB lung adenocarcinoma: analysis of 653 cases].

OBJECTIVE: To explore the optimal postoperative adjuvant regimens for patients with stage IB lung adenocarcinoma. METHODS: We respectively analyzed the data of 653 patients undergoing surgery for stage IB lung adenocarcinoma in our hospital from January, 2013 to December, 2021. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared among the patients receiving postoperative adjuvant therapy with epidermal growth factor-tyrosine kinase inhibitors (EGFR-TKIs group, n=111), chemotherapy (CT group, n=108) and clinical observation (CO group, n=434). RESULTS: In TKIs, CT, and CO groups, the 5-year DFS rates were 92.8%, 80.7%, and 81.7%, respectively, significantly higher in TKIs group than in CO group (P < 0.01). The 3-year OS rates of the 3 groups were 96.8%, 97.1%, and 91.7%, respectively. Subgroup analysis showed that in TKIs, CT, and CO groups, the 5-year DFS rates of patients with with T3-4 cmN0M0 were 92.6%, 84.0%, and 81.4%, respectively, significantly higher in TKIs group than in CO group (P < 0.05); the 5-year DFS rates of T2ViscPlN0M0 patients were 95.1%, 71.4%, and 83.5%, respectively. Multivariate COX regression analysis showed that age (P < 0.05; HR=0.631, 95% CI: 0.401-0.993), solid nodules (P < 0.01; HR=7.620, 95% CI: 3.037-19.121), micropapillary or solid component (P < 0.05; HR= 1.776, 95% CI: 1.010-3.122), lymphovascular invasion (P < 0.05; HR=2.981, 95% CI: 1.198-7.419), and adjuvant therapy (P < 0.01) were independent predictors of DFS. The most common adverse effects included rashes, paronychia, and diarrhea for TKIs and hematological suppression and gastrointestinal reactions for chemotherapy, and TKIs were associated with a higher incidence of grade 3 or above adverse effects (44.4% vs 9.0%). CONCLUSION: Adjuvant therapy with TKIs helps improve DFS in patients with stage IB (T3-4cmN0M0) lung adenocarcinoma but not in patients with T2ViscPlN0M0. Adjuvant chemotherapy does not improve DFS or OS in patients with stage IB lung adenocarcinoma.

[Upregulating KLF11 ameliorates intestinal inflammation in mice with 2, 4, 6-trinitrobenesulfonic acid-induced colitis by inhibiting the JAK2/STAT3 signaling pathway].

OBJECTIVE: To investigate the expression level of Kruppel-like transcription factor family member KLF11 in intestinal mucosal tissues of Crohn's disease (CD) and its regulatory effect on intestinal inflammation in CD-like colitis. METHODS: We examined KLF11 expression levels in diseased and normal colon mucosal tissues from 12 CD patients and 12 patients with colorectal cancer using immunofluorescence staining. KLF11 expression was also detected in the colon mucosal tissues of a mouse model of 2, 4, 6-trinitrobenesulfonic acid (TNBS)-induced colitis. A recombinant adenoviral vector was used to upregulate KLF11 expression in the mouse models and the changes in intestinal inflammation was observed. A Caco-2 cell model with stable KLF11 overexpression was constructed by lentiviral infection. The effect of KLF11 overexpression on expressions of JAK2/STAT3 signaling pathway proteins was investigated using immunoblotting in both the mouse and cell models. The mouse models were treated with coumermycin A1, a JAK2/STAT3 signaling pathway agonist, and the changes in intestinal inflammatory responses were observed. RESULTS: The expression level of KLF11 was significantly lowered in both the clinical specimens of diseased colon mucosal tissues and the colon tissues of mice with TNBS-induced colitis (P < 0.05). Adenovirus-mediated upregulation of KLF11 significantly improved intestinal inflammation and reduced the expression levels of inflammatory factors in the intestinal mucosa of the colitis mouse models (P < 0.05). Overexpression of KLF11 significantly inhibited the expression levels of p-JAK2 and p-STAT3 in intestinal mucosal tissues of the mouse models and in Caco-2 cells (P < 0.05). Treatment with coumermycin A1 obviously inhibited the effect of KLF11 upregulation for improving colitis and significantly increased the expression levels of inflammatory factors in the intestinal mucosa of the mouse models (P < 0.05). CONCLUSION: KLF11 is downregulated in the intestinal mucosa in CD, and upregulation of KLF11 can improve intestinal inflammation and reduce the production of inflammatory factors probably by inhibiting the JAK2/STAT3 signaling pathway.

Spatial-temporal trends in leprosy burden and its associations with socioeconomic and physical geographic factors: results from the Global Burden of Disease Study 2019.

OBJECTIVES: The purpose of our study was to assess the multiscalar changes in leprosy burden and its associated risk factors over the last three decades. STUDY DESIGN: We conducted an in-depth examination of leprosy's spatial-temporal trends at multiple geographical scale (global, regional, and national), utilizing information from Global Burden of Disease, Injuries, and Risk Factors Study (GBD 2019). METHODS: Incidence and the estimated annual percentage change (EAPC) in age-standardized incidence rate (ASIR) of leprosy were determined, with countries categorized based on leprosy incidence changes. We examined socioeconomic and physical geography influences on leprosy incidence via Spearman correlation analysis, using ternary phase diagrams to reveal the synergetic effects on leprosy occurrence. RESULTS: Globally, incident cases of leprosy decreased by 27.86% from 1990 to 2019, with a reduction in ASIR (EAPC = -2.53), yet trends were not homogeneous across regions. ASIR and EAPC correlated positively with sociodemographic index (SDI), and an ASIR growth appeared in high SDI region (EAPC = 3.07). Leprosy burden was chiefly distributed in Tropical Latin America, Oceania, Central Sub-Saharan Africa, and South Asia. Negative correlations were detected between the incidence of leprosy and factors of SDI, GDP per capita, urban population to total population, and precipitation, whereas the number of refugee population, temperature, and elevation showed opposite positive results. CONCLUSIONS: Despite a global decline in leprosy over the past three decades, the disparities of disease occurrence at regional and national scales still persisted. Socioeconomic and physical geographic factors posed an obvious influence on the transmission risk of leprosy. The persistence and regional fluctuations of leprosy incidence necessitate the ongoing dynamic and multilayered control strategies worldwide in combating this ancient disease.

[Ophthalmic surgical robot-assisted retinal puncture and injection for submacular hemorrhage caused by polypoid choroidal vasculopathy: a case report].

A 65-year-old man presented with decreased visual acuity in the left eye for 1 month. The diagnosis of hemorrhagic retinal detachment (submacular hemorrhage), which was caused by idiopathic polypoid choroidal vasculopathy, was confirmed by the ultra-wide-angle fundus examination, optical coherence tomography, and B-ultrasound. A vitrectomy combined with an ophthalmic surgical robot-assisted retinal puncture and injection was performed. The recombinant tissue plasminogen activator was injected accurately by the ophthalmic surgical robot between the retinal nerve epithelium and retinal pigment epithelium through a micro-injection needle. During the 2-month follow-up, the subretinal hemorrhage was significantly regressive, the visual acuity of the left eye was improved from hand movement to 0.1, and no other complications were observed. (This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on March 15, 2024).

[The application of full-length urethral preservation without anastomosis in single-port laparoscopic radical prostate cancer].

Objective: To preliminarily examine the feasibility and outcome of single-port laparoscopic radical prostatectomy with full-length urethral preservation (FLUP-SPRP). Method: This study was a prospective case series study. A total of 25 patients with prostate cancer who met the enrollment criteria and agreed to this surgical procedure from March 2022 to December 2022 were collected at the Department of Urology, the Second Affiliated Hospital of Nanjing Medical University. The age of the patients was (67.2±7.6) years (range: 61 to 76 years). This novel procedure was performed by an experienced surgeon who performed single hole radical prostatectomy skillfully. Patient urinary control, tumor control, and related surgical complications after surgery were regularly monitored. Postoperative urinary control was evaluated using the daily amount of urine pad, 0 to 1 piece of urine pad was to restore urinary control, and 0 to 1 piece of pad within 24 hours after catheter removal was immediate urinary control. Result: All prodecures were successfully completed without transit to open surgery. The surgical time was (128.4±22.4) minutes (range: 100 to 145 minutes), the intraoperative blood loss was (68.2±13.7) ml (range: 50 to 120 ml). The urethral injury occurred in 4 cases during surgery and was repaired by sutures. The urinary control recovery rates within 24 hours, 1 week, 4 weeks, and 7 weeks after surgery were 80.0%, 84.0%, 92.0% and 100%, respectively. Postoperative large section pathology revealed 1 case with a positive basal margin of the prostate and negative margins of all prostate glands around the urethra. Postoperative complications included urinary tract infection in 3 cases, urodynia in 2 cases, and acute urinary retention in 1 case. MRI follow-up 3 months after surgery showed normal anatomy of the bladder and urethra. The follow-up values of prostate specific antigen at 3 and 6 months after surgery were less than 0.1 µg/L. Conclusions: The preliminary results of this study indicate that the FLUP-SPRP procedure is safe and feasible. The early results of postoperative urinary control and oncology are as expected.

[Prevalence of Helicobacter pylori infection and risk factors among family members in Qinghai Province, China].

Objective: To investigate the prevalence of Helicobacter pylori infection among family members, and analyze associated risk factors. Methods: The current investigation was a cross-sectional study. The Qinghai region was stratified into urban areas, agricultural areas, and pastoral areas. The urban areas of Xining City, the agricultural areas of Haidong City, and the pastoral areas of Haibei Tibetan Autonomous Prefecture were selected. A total of 396 resident families (1 131 people) who underwent health checkups from 2021 to 2022 in the above areas were included in the survey study. Questionnaires were administered and H. pylori infection was detected using the 13C-urea breath test. Numerical data were expressed as cases and percentages, and the Chi-square test was used to compare differences in H. pylori infection rates in the populations and families in each group. Multifactorial logistic regression was used to analyze risk factors for H. pylori infection, and P<0.05 was considered statistically significant. Results: The prevalence of H. pylori infection in Qinghai province was 52.8% (597/1 131) and the prevalence of H. pylori infection in households was 80.6% (319/396). In H. pylori-positive households with at least 1 infected spouse, 40.4% (36/89) had only 1 infected spouse, and in 59.6% (53/89) both spouses were infected. In analysis of children infected by parents with H. pylori, 20.0% (9/45) of households had fathers and children infected, 48.9% (22/45) had mothers and children infected, and 31.1% (14/45) had both parents and children infected. In univariate analysis there was a statistically significant difference in the overall comparison of H. pylori infection rates among families with different numbers of people living together (χ2=11.12, P=0.004), and between-group comparisons suggested that H. pylori infection rates were higher in families with 4 or 5 people and more than 5 people living together than in families with 2 or 3 people living together. The H. pylori infection rate was higher in families that did not use serving chopsticks and spoons during family meals than in families that did use serving chopsticks and spoons (χ2=6.12, P=0.013). In multifactorial logistic regression analyses the number of people living together in a family and whether or not serving chopsticks and spoons were used at family meals were associated with H. pylori infection (P<0.05). Conclusion: The H. pylori infection rate in families in Qinghai Province is high, and there is a clear association with family aggregation. It is more common for both members of a couple to be infected, and H. pylori infection of a mother has a greater effect on the children's infection status than H. pylori infection of a father. The infection rate of H. pylori was lower in families that used serving chopsticks and spoons during dinner gatherings, and the fewer the number of people living together in the family, the lower the H. pylori infection rate.

[Research progress on scleral perforating vessels in the formation of myopic choroidal neovascularization].

Myopic choroidal neovascularization (mCNV) is a severe complication of pathological myopia. Currently, the primary treatment involves anti-vascular endothelial growth factor (VEGF) therapy, which significantly improves visual acuity in mCNV patients. However, challenges such as high recurrence rates and inconsistent therapeutic outcomes persist. Previous studies attributed mCNV to choroidal thinning and ischemia. Recent research suggests that, in addition to choroidal factors, perforating scleral vessels (PSV) are closely associated with the occurrence and therapeutic efficacy of mCNV. This review comprehensively explores the definition of PSVs, their imaging classifications and features, as well as their intricate connections with the occurrence and clinical outcomes of mCNV. By delving into the role and potential mechanisms of PSVs in mCNV, this review aims to deepen our understanding of their involvement in this condition.

Tislelizumab versus chemotherapy as second-line treatment for European and North American patients with advanced or metastatic esophageal squamous cell carcinoma: a subgroup analysis of the randomized phase III RATIONALE-302 study.

BACKGROUND: The phase III RATIONALE-302 study evaluated tislelizumab, an anti-programmed cell death protein 1 antibody, as second-line (2L) treatment for advanced/metastatic esophageal squamous cell carcinoma (ESCC). This prespecified exploratory analysis investigated outcomes in patients from Europe and North America (Europe/North America subgroup). PATIENTS AND METHODS: Patients with tumor progression during/after first-line systemic treatment were randomized 1 : 1 to open-label tislelizumab or investigator's choice of chemotherapy (paclitaxel, docetaxel, or irinotecan). RESULTS: The Europe/North America subgroup comprised 108 patients (tislelizumab: n = 55; chemotherapy: n = 53). Overall survival (OS) was prolonged with tislelizumab versus chemotherapy (median: 11.2 versus 6.3 months), with a hazard ratio (HR) of 0.55 [95% confidence interval (CI) 0.35-0.87]; HR was similar irrespective of programmed death-ligand 1 score [≥10%: 0.47 (95% CI 0.18-1.21); <10%: 0.55 (95% CI 0.30-1.01)]. Median progression-free survival was 2.3 versus 2.7 months with tislelizumab versus chemotherapy [HR: 0.97 (95% CI 0.64-1.47)]. Overall response rate was greater with tislelizumab (20.0%) versus chemotherapy (11.3%), with more durable response (median duration of response: 5.1 versus 2.1 months). Tislelizumab had a favorable safety profile versus chemotherapy, with fewer patients experiencing ≥grade 3 treatment-related adverse events (13.0% versus 51.0%). Those on tislelizumab experienced less deterioration in health-related quality of life, physical functioning, and/or disease- and treatment-related symptoms (i.e. fatigue, pain, and eating problems) as compared to those on chemotherapy, per the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30) and QLQ-OES18 scores. CONCLUSIONS: As a 2L therapy for advanced/metastatic ESCC, tislelizumab improved OS and had a favorable safety profile as compared to chemotherapy in European/North American ESCC patients in the randomized phase III RATIONALE-302 study.

[Two cases of acute methyl acetate poisoning].

This article analyzed the clinical data and on-site occupational health survey results of a patient with occupational acute methyl acetate poisoning in Zhejiang. Based on the pathways of methyl acetate poisoning and the characteristics of target organ damage, diagnosis and treatment experience were summarized, providing reference for the diagnosis and treatment of occupational acute methyl acetate poisoning and occupational health monitoring of methyl acetate.

[Incidence and related factors of chronic neuropathic pain in elderly patients after video-assisted thoracoscopic surgery].

Objective: To investigate the incidence and related factors of chronic neuropathic pain (CNP) in elderly patients after thoracoscopic surgery. Methods: A total of 463 elderly patients (aged≥60 years) who underwent elective video-assisted thoracoscopic surgery from November 2020 to May 2021 at Peking Union Medical College Hospital were prospectively recruited. Among them, 283 were males and 180 were females, with an average age of (66.6±4.8) years. Chronic postsurgical pain (CPSP) was assessed by telephone at 6 months after surgery, and then the patients with CNP were screened using the ID-pain scale. Multivariable logistic regression was used to analyze the related factors for CNP in elderly patients after thoracoscopic surgery. Results: The incidence of CPSP was 41.9% (194/463), and the incidence of CNP was 18.8% (87/463). Multivariable logistic regression analysis showed that incision number<3 (OR=0.385, 95%CI: 0.156-0.949, P=0.038) and intraoperative N2O inhalation (OR=0.506, 95%CI: 0.304-0.842, P=0.009) were protective factors for CNP in elderly patients after thoracoscopic surgery, but high numeric rating scale (NRS) score on the first day after surgery (OR=1.180, 95%CI: 1.056-1.318, P=0.003) was a risk factor. Conclusions: The incidence of CNP in elderly patients after thoracoscopic surgery is 18.8%. Incision number<3 and intraoperative N2O inhalation are protective factors for CNP, but high NRS score on the first day after surgery is a risk factor.

[A phase I study of subcutaneous envafolimab (KN035) monotherapy in Chinese patients with advanced solid tumors].

Objective: To evaluate the safety and antitumor activity of envafolimab monotherapy in Chinese patients with advanced solid tumors. Methods: This open-label, multicenter phase I trial included dose escalation and dose expansion phases. In the dose escalation phase, patients received subcutaneous 0.1, 0.3, 1.0, 2.5, 5.0 or 10.0 mg/kg envafolimab once weekly (QW) following a modified "3+ 3" design. The dose expansion phase was performed in the 2.5 mg/kg and 5.0 mg/kg (QW) dose cohorts. Results: At November 25, 2019, a total of 287 patients received envafolimab treatment. During the dose escalation phase, no dose-limiting toxicities (DLT) was observed. In all dose cohorts, drug-related treatment-emergent adverse events (TEAEs) for all grades occurred in 75.3% of patients, and grade 3 or 4 occurred in 20.6% of patients. The incidence of immune-related adverse reactions (irAE) was 24.0% for all grades, the most common irAEs (≥2%) included hypothyroidism, hyperthyroidism, immune-associated hepatitis and rash. The incidence of injection site reactions was low (3.8%), all of which were grades 1-2. Among the 216 efficacy evaluable patients, the objective response rate (ORR) and disease control rate (DCR) were 11.6% and 43.1%, respectively. Median duration of response was 49.1 weeks (95% CI: 24.0, 49.3). Pharmacokinetic (PK) exposure to envafolimab is proportional to dose and median time to maximum plasma concentration is 72-120 hours based on the PK results from the dose escalation phase of the study. Conclusion: Subcutaneous envafolimab has a favorable safety and promising preliminary anti-tumor activity in Chinese patients with advanced solid tumors.

[Cardiac progenitor cells-derived exosomes alleviate myocardial injury by regulating Treg cell differentiation through the mTOR pathway in mice with myocardial infarction].

OBJECTIVE: To investigate the effect of cardiac progenitor cells-derived exosomes (CPCs-Exo) on Treg differentiation in mice with myocardial infarction (MI). METHODS: Mouse models of MI established by ligation of the left anterior descending coronary artery (LAD) were treated with CPCs-Exos, and naive CD4+T cells were isolated from the spleen of the mice and divided into control group, CD4+T cell activation group (CD3+CD28), CPCs-Exos stimulation group (CD3+CD28+CPCs-Exos), mTOR activator group (CD3+CD28+CPCs-Exos+mTOR activator) and mTOR inhibitor group (CD3+CD28+CPCs-Exos+mTOR inhibitor). Western blotting was used to detect the expression levels of mTOR and p-mTOR in the treated cells. Flow cytometry was used to analyze the percentages of Treg and CD4+IL-10+T cells. The infarct size of the mice were measured with 2, 3, 5-triphenyltetrazole chloride (TTC) staining, and serum levels of LDH and CK-MB were detected using an automatic biochemical analyzer. RESULTS: Compared with the control group, the mouse models of MI showed significantly increased release of LDH (P<0.001) and CK-MB (P=0.0002) and increased percentages of Treg and CD4+IL-10+T cells. Treatment with CPC-Exos effectively reduced the MI area and lowered serum levels of LDH (P=0.003) and CK-MB (P=0.003) and the percentages of Tregs (P=0.001) and CD4+IL-10+T cells (P=0.004) in the MI mouse models. In the isolated CD4+T cells, CPCsExos treatment significantly up-regulated the percentages of Treg (P=0.01) and CD4+IL-10+ T cells (P=0.004) and increased the expression of mTOR (P=0.009) and p-mTOR (P=0.009), and these effects could be further enhanced by the mTOR activator but obviously attenuated by the mTOR inhibitor. CONCLUSION: CPCs-Exos promotes the differentiation of Treg in mice with MI by modulating the mTOR signaling pathway.