Search

Longjun Sun,1,* Wenjuan Chen,2,* Peixi Zhao,3 Bin Zhao,4 Guangyan Lei,1 Le Han,1,* Yili Zhang2,* 1Department of Thoracic Surgery, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 2Department of Oncology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 3Department of Department of Pharmacy, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 4Department of Epidemiology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Le Han, Department of Thoracic Surgery, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China, Email millyhan1@sohu.com Yili Zhang, Department of Oncology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China, Email doctor_z2023@stu.xjtu.edu.cnIntroduction: Hepatocellular carcinoma (HCC) is a common and deadly malignancy. Traditional Chinese medicine, such as the compound Astragalus (wild Baicalin), has shown promise in improving outcomes for HCC patients. This study aimed to investigate the effects of wild Baicalin on the human hepatoma cell line HepG2 and elucidate the underlying mechanisms, particularly the role of the AKR1B10 and PI3K/AKT signaling pathways.Methods: HepG2 cells were treated with varying concentrations of wild Baicalin. Cell proliferation, apoptosis, migration, invasion, and cell cycle were evaluated using CCK-8, flow cytometry, scratch, Transwell, and clonogenic assays, respectively. Transcriptome sequencing was performed to analyze gene expression changes induced by wild Baicalin. Differentially expressed genes were identified and analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The expression of AKR1B10 and PI3K was validated by qPCR.Results: Wild Baicalin inhibited HepG2 cell proliferation, induced apoptosis, suppressed migration and invasion, and caused cell cycle arrest in a dose-dependent manner. Transcriptome sequencing revealed 1202 differentially expressed genes, including 486 upregulated and 716 downregulated genes. GO analysis indicated that biological processes were pivotal in the anticancer mechanism of wild Baicalin, while KEGG analysis identified metabolic pathways as the most significantly regulated. AKR1B10 and PI3K, key genes in metabolic pathways, were downregulated by wild Baicalin, which was confirmed by qPCR.Discussion: The findings suggest that wild Baicalin exhibits potent anticancer effects against HepG2 cells by inducing apoptosis, inhibiting proliferation, migration, and invasion, and causing cell cycle arrest. The regulatory effects of wild Baicalin on the AKR1B10 and PI3K/AKT signaling pathways appear to be critical for its inhibitory effects on HCC cell proliferation. These results provide new insights into the mechanism of action of wild Baicalin and support its potential as a therapeutic approach for HCC treatment. Keywords: hepatocellular carcinoma, wild baicalin, transcriptome sequencing, apoptosis

Hao Yang,1– 3,* Guanglin Lei,2,* Zhuoya Deng,1 Fang Sun,1 Yuying Tian,1 Jinxia Cheng,1 Hongyu Yu,1 Cong Li,1 Changqing Bai,4 Shaogeng Zhang,2 Guangwen An,5 Penghui Yang1 1Faculty of Hepato-Pancreato-Biliary Surgery, Institute of Hepatobiliary Surgery, the First Medical Center, Chinese PLA General Hospital, Beijing, People’s Republic of China; 2Department of Hepatological Surgery, the Fifth Medical Center of Chinese PLA General Hospital, Beijing, People’s Republic of China; 3Department of Surgery, Taian City Central Hospital, Taian, People’s Republic of China; 4Department of Respiratory, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Guangdong, People’s Republic of China; 5Department of Pharmacy, No. 984 Hospital of the PLA, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Penghui Yang; Guangwen An, Email ypenghuiamms@hotmail.com; anchen337722@163.comBackground: Oncolytic virus (OV) therapy has emerged as a promising novel form of immunotherapy. Moreover, an increasing number of studies have shown that the therapeutic efficacy of OV can be further improved by arming OVs with immune-stimulating molecules.Methods: In this study, we used reverse genetics to produce a novel influenza A virus, termed IAV-OX40L, which contained the immune-stimulating molecule OX40L gene in the influenza virus nonstructural (NS1) protein gene. The oncolytic effect of IAV-OX40L was explored on hepatocellular carcinoma (HCC)HCC cells in vitro and in vivo.Results: Hemagglutination titers of the IAV-OX40L virus were stably 27– 28 in specific-pathogen-free chicken embryos. The morphology and size distribution of IAV-OX40L are similar to those of the wild-type influenza. Expression of OX40L protein was confirmed by Western blot and immunofluorescence. MTS assays showed that the cytotoxicity of IAV-OX40L was higher in HCC cells (HepG2 and Huh7) than in normal liver cells (MIHA) in a time- and dose-dependent manner in vitro. We found that intratumoral injection of IAV-OX40L reduced tumor growth and increased the survival rate of mice compared with PR8-treated controls in vivo. In addition, the pathological results showed that IAV-OX40L selectively destroyed tumor tissues without harming liver and lung tissues. CD4+ and CD8+ T cells of the IAV-OX40L group were significantly increased in the splenic lymphocytes of mice. Further validation confirmed that IAV-OX40L enhanced the immune response mainly by activating Th1-dominant immune cells, releasing interferon-γ and interleukin-2.Conclusion: Taken together, our findings demonstrate the novel chimeric influenza OV could provide a potential therapeutic strategy for combating HCC and improve the effectiveness of virotherapy for cancer therapy.Keywords: OVs, OX40L, IAV, HCC

Yanhong Yan,1 Jiao Geng,2 Xu Cui,1 Guiyu Lei,1 Lili Wu,1 Guyan Wang1 1Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Anesthesiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Guyan Wang, Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomingxiang, Beijing, 100730, People’s Republic of China, Tel +86-13910985139, Fax +86-10-58268017, Email guyanwang2006@163.comPurpose: Thoracic paravertebral block (TPVB) may be highly beneficial for thoracoscopic lobectomy patients, but it may increase the risk of hypothermia. Apart from its anesthetic-reducing effects, this randomized controlled trial aimed to investigate the hypothermic effect of TPVB, and thus optimize its clinical use.Patients and methods: Adult patients were randomly allocated to two groups: TPVB + general anesthesia (GA) group or GA group. In the TPVB+GA group, the block was performed after GA induction by an experienced but unrelated anesthesiologist. Both the lower esophageal and axillary temperature were recorded at the beginning of surgery (T0) and every 15 min thereafter (T1-T8), and the end of surgery (Tp). The primary outcome was the lower esophageal temperature at Tp. The secondary outcomes included lower esophageal temperature from T0-T8 and axillary temperature from T0-Tp. The total propofol, analgesics, and norepinephrine consumption and the incidence of adverse events were also recorded.Results: Forty-eight patients were randomly allocated to the TPVB+GA (n=24) and GA (n=24) groups. The core temperature at the end of the surgery was lower in the TPVB+GA group than the GA group (35.90± 0.30°C vs 36.35± 0.33°C, P< 0.001), with a significant difference from 45 min after the surgery began until the end of the surgery (P< 0.05). In contrast, the peripheral temperature showed a significant difference at 60 min after the surgery began till the end (P< 0.05). TPVB+GA exhibited excellent analgesic and sedative-sparing effects compared to GA alone (P< 0.001), though it increased norepinephrine consumption due to hypotension (P< 0.001).Conclusion: Although thorough warming strategies were used, TPVB combined with GA remarkably reduced the body temperature, which is an easily neglected side effect. Further studies on the most effective precautions are needed to optimize the clinical use of TPVB.Keywords: core temperature, peripheral temperature, general anesthesia, warming strategy

Lili Wu,1 Guiyu Lei,1 Ying Liu,2 Zheng Wei,1 Yue Yin,1 Yanru Li,3 Guyan Wang1 1Department of Anesthesiology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Operating Room, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Key Laboratory of Otolaryngology, Head and Neck Surgery (Ministry of Education of China), Beijing, People’s Republic of ChinaCorrespondence: Guyan WangDepartment of Anesthesiology, Beijng Tongren Hospital, Capital Medical University, Beijing, People’s Republic of ChinaTel +8613910985139Email guyanwang2006@163.comPurpose: Current data on the occurrence of EFBs in relation to different time periods are scant. The purpose of this study was to compare the occurrence, type and location of EFBs in people who presented at our center on weekdays, weekends and holidays.Patients and Methods: A retrospective analysis of patients (n=1353) received rigid esophagoscopy for foreign body extraction under general anesthesia from January 2018 to 2020 December.Results: The occurrence of EFB ingestion was significantly higher (p< 0.05) on holidays (2.75/day) than on weekdays (0.91/day) and weekends (1.46/day). Patients were much older on holidays, with a mean age of 58.18 ± 17.34 years, than patients on weekdays (54.71 ± 16.71 years) and weekends (55.05 ± 17.36 years).Conclusion: Our findings demonstrate that EFB ingestion is most likely to occur on weekends and holidays, and elderly patients should be advised to chewing slowly and eating non-nuclear jujube, especially during holidays, to minimize their risk.Keywords: esophageal foreign body, weekday, weekend, holiday

Min Peng,1 Xing Li,2 Gu Lei,3 Yi Ming Weng,1 Meng Xue Hu,1 Qi Bin Song1 1Department of Oncology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, Hubei Province, China; 2Department of Urology, Renmin Hospital of Wuhan University, Wuhan University, Wuhan 430060, Hubei Province, China; 3Department of Pathology, Huangshi Central Hospital of Edong Healthcare Group, Huangshi 435000, Hubei Province, China Abstract: The value of immune checkpoint inhibitor (ICI) combination therapy for patients with lung cancer remains unclear. We conducted a meta-analysis using PubMed, Embase, and ClinicalTrials.gov databases to identify eligible randomized controlled trials (RCTs) that might provide a reference for clinical practice. The selection criteria were defined according to the population, intervention, comparison, outcome and study design (PICOS) framework. In all, 12 RCTs with 5,989 patients were included in this meta-analysis. Our results showed that ICI combination therapy was significantly associated with the improvement of overall response rate (ORR) (RR =1.44 [95% CI 1.19, 1.74], P=0.0002), progression-free survival (PFS) (HR =0.67 [95% CI 0.59, 0.77], P

ObjectivesThere is still a large unmet need for novel osteoarthritis (OA) treatments that could provide clinically important effects on long-term pain relief (≥12 months). We examined the relation of bariatric surgery along with weight loss to analgesic prescription and all-cause mortality among individuals with OA.MethodsWe conducted a cohort study among individuals with OA using The Health Improvement Network. We compared the rate of no analgesic prescription ≥12 consecutive months and the risk of all-cause mortality using inverse probability weighting Cox-proportional hazard models and the difference in number of analgesic prescriptions (non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in the 50th, 75th and 90th percentiles using quantile regression model between bariatric and non-bariatric cohorts.ResultsIncluded were 588,494 individuals (694 had bariatric surgery). Compared with non-bariatric group, the rate of no analgesic prescription ≥12 consecutive months was higher (HR = 1.23, 95% CI: 1.08-1.38) in bariatric surgery group, and the number of analgesic prescriptions was lower in the 75th (44 vs 58) and 90th (74 vs 106) percentiles during a mean follow-up of 4.3 years. All-cause mortality in bariatric surgery group was lower than comparison group (HR = 0.46, 95% CI: 0.41-0.51).ConclusionThis study presents the first evidence that bariatric surgery was associated with decreased long-term analgesic prescription and decreased all-cause mortality among individuals with OA. However, our findings may be overestimated owing to intractable confounding by indication for bariatric surgery; thus, future studies (e.g., clinical trials) are warranted.

OBJECTIVE:A recent randomized clinical trial reported that repeated intra-articular corticosteroids (IACs) were associated with a greater cartilage loss. This study aimed to examine the relation of IACs to knee radiographic osteoarthritis (ROA) progression in a real-world setting. DESIGN:A cohort that initiated IACs and a comparison cohort without IACs from participants with mild to moderate knee ROA in the Osteoarthritis Initiative (OAI) were assembled (from 0-month to 48-month). Two measures of knee ROA progression were assessed during the follow-up period: (1) an increase in Kellgren and Lawrence (KL) grade by ≥1 grade or having a knee replacement (i.e., KL grade worsening); and (2) a decrease in joint space width (JSW) by ≥0.7 mm or having a knee replacement (i.e., JSW worsening). The associations of IACs initiation using a propensity-score matched cohort study and continuous IACs using marginal structural models with the risk of knee ROA progression were examined. RESULTS:Among 684 propensity-score matched participants at baseline (148 IACs initiators, 536 comparators), 65 knees (21.7/100 person-years) in the IACs initiation cohort and 90 knees (7.1/100 person-years) in the comparison cohort experienced KL worsening. The hazard ratios (HRs) of KL worsening from IACs initiation and continuous IACs were 3.02 (95% confidence interval [CI], 2.19-4.16) and 4.67 (95% CI, 2.92-7.47), respectively. The corresponding HRs of JSW worsening were 2.93 (95% CI, 2.13-4.02) and 3.26 (95% CI, 1.78-5.96), respectively. All HRs for continuous use of IACs were further away from the null. CONCLUSIONS:IACs, especially continuous IACs, may be associated with an increased risk of knee ROA progression.

ObjectiveTo evaluate the etiologic heterogeneity between medial and lateral tibiofemoral radiographic osteoarthritis (ROA).MethodsKnees without medial or lateral tibiofemoral ROA at baseline were followed for 60-month in Multicenter Osteoarthritis Study (MOST) and for 48-month in Osteoarthritis Initiative (OAI). We examined the relation of previously reported risk factors to incident medial and lateral tibiofemoral ROA separately and determined the etiology heterogeneity with a ratio of rate ratios (RRs) (i.e., the RR for medial tibiofemoral ROA divided by the RR for lateral tibiofemoral ROA) using a duplication method for Cox proportional hazard regression.ResultsOf 2,016 participants in MOST, 436 and 162 knees developed medial or lateral tibiofemoral ROA, respectively. Obesity and varus malalignment were 95% and 466% more strongly associated with incident medial tibiofemoral ROA than with lateral tibiofemoral ROA, respectively (ratios of RRs, 1.95 [95% confidence interval (CI):1.05-3.62] and 5.66 [95% CI:3.20-10.0]). In contrast, the associations of female sex and valgus malalignment with incident medial tibiofemoral ROA were weaker or in an opposite direction compared with lateral tibiofemoral Osteoarthritis (OA) (ratios of RRs, 0.40 [95% CI:0.26-0.63] and 0.20 [95% CI:0.12-0.34], respectively). Older age tended to show a weaker association with incident medial tibiofemoral ROA than with incident lateral tibiofemoral ROA. No heterogeneity was observed for the relation of race, knee injury, or contralateral knee ROA. These findings were closely replicated in OAI.ConclusionRisk factor profiles for medial and lateral tibiofemoral ROA are different. These results can provide a framework for the development of targeted prevention and potential treatment strategies for specific knee OA subtypes.