BACKGROUND: Oral squamous cell carcinoma (OSCC) is a prevalent type of cancer with a high mortality rate in its late stages. One of the major challenges in OSCC treatment is the resistance to epidermal growth factor receptor (EGFR) inhibitors. Therefore, it is imperative to elucidate the mechanism underlying drug resistance and develop appropriate precision therapy strategies to enhance clinical efficacy. METHODS: To evaluate the efficacy of the combination of the Ca 2+ /calmodulin-dependent protein kinase II (CAMK2) inhibitor KN93 and EGFR inhibitors, we performed in vitro and in vivo experiments using two FAT atypical cadherin 1 ( FAT1 )-deficient (SCC9 and SCC25) and two FAT1 wild-type (SCC47 and HN12) OSCC cell lines. We assessed the effects of EGFR inhibitors (afatinib or cetuximab), KN93, or their combination on the malignant phenotype of OSCC in vivo and in vitro . The alterations in protein expression levels of members of the EGFR signaling pathway and SRY-box transcription factor 2 (SOX2) were analyzed. Changes in the yes-associated protein 1 (YAP1) protein were characterized. Moreover, we analyzed mitochondrial dysfunction. Besides, the effects of combination therapy on mitochondrial dynamics were also evaluated. RESULTS: OSCC with FAT1 mutations exhibited resistance to EGFR inhibitors treatment. The combination of KN93 and EGFR inhibitors significantly inhibited the proliferation, survival, and migration of FAT1 -mutated OSCC cells and suppressed tumor growth in vivo . Mechanistically, combination therapy enhanced the therapeutic sensitivity of FAT1 -mutated OSCC cells to EGFR inhibitors by modulating the EGFR pathway and downregulated tumor stemness-related proteins. Furthermore, combination therapy induced reactive oxygen species (ROS)-mediated mitochondrial dysfunction and disrupted mitochondrial dynamics, ultimately resulting in tumor suppression. CONCLUSION Combination therapy with EGFR inhibitors and KN93 could be a novel precision therapeutic strategy and a potential clinical solution for EGFR-resistant OSCC patients with FAT1 mutations.
Humans ; ErbB Receptors/metabolism* ; Mouth Neoplasms/metabolism* ; Cell Line, Tumor ; Animals ; Drug Resistance, Neoplasm/genetics* ; Cadherins/metabolism* ; Carcinoma, Squamous Cell/metabolism* ; Mice ; Mutation/genetics* ; Mice, Nude ; Protein Kinase Inhibitors/therapeutic use* ; Cetuximab/pharmacology* ; Afatinib/therapeutic use* ; Cell Proliferation/drug effects* ; Signal Transduction/drug effects*

CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

BACKGROUND: Modern acupuncture anesthesia is a combination of Chinese and Western medicine that integrates the theories of acupuncture with anesthesia. However, some clinical studies of acupuncture anesthesia lack specific descriptions of randomization, allocation concealment, and blinding processes, with subsequent systematic reviews indicating a risk of bias. OBJECTIVE: Clinical trial registration is essential for the enhancement of the quality of clinical trials. This study aims to summarize the status of clinical trial registrations for acupuncture anesthesia listed on the World Health Organization International Clinical Trials Registry Platform (ICTRP). SEARCH STRATEGY: We searched the ICTRP for clinical trials related to acupuncture anesthesia registered between January 1, 2001 and May 31, 2023. Additionally, related publications were retrieved from PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, and Wanfang Data. Registrations and publications were analyzed for consistency in trial design characteristics. INCLUSION CRITERIA: Clinical trials that utilized one of several acupuncture-related therapies in combination with pharmacological anesthesia during the perioperative period were eligible for this review. DATA EXTRACTION AND ANALYSIS: Data extracted from articles included type of surgical procedure, perioperative symptoms, study methodology, type of intervention, trial recruitment information, and publication information related to clinical enrollment. RESULTS: A total of 166 trials related to acupuncture anesthesia from 21 countries were included in the analysis. The commonly reported symptoms in the included studies were postoperative nausea and vomiting (19.9%) and postoperative pain (13.3%). The concordance between the publications and the trial protocols in the clinical registry records was poor, with only 31.7% of the studies being fully compatible. Inconsistency rates were high for sample size (39.0%, 16/41), blinding (36.6%, 15/41), and secondary outcome indicators (24.4%, 10/41). CONCLUSION The volume of acupuncture anesthesia clinical trials registered in international trial registries over the last 20 years is low, with insufficient disclosure of results. Postoperative nausea and vomiting as well as postoperative pain, are the most investigated for acupuncture intervention. Please cite this article as: Li Y, Liu YN, Guo Z, Gu ME, Wang WJ, Zhu Y, Zhuang XJ, Chen LM, Zhou J, Li J. Current situation of clinical trial registration in acupuncture anesthesia: A scoping review. J Integr Med. 2025; 23(3): 256-263.
Humans ; Acupuncture Analgesia ; Acupuncture Therapy ; Anesthesia ; Clinical Trials as Topic ; Registries

Viral myocarditis(VMC)is the leading cause of dilated cardiomyopathy,which can lead to heart failure and sudden cardiac death.With the development of high-throughput sequencing technology,non-coding RNA(ncRNA)plays an important role in the occurrence and development of VMC.ncRNA promotes the occurrence and development of VMC by regulating viral replication,immune cell function,myocardial cell death,myocardial interstitial fibrosis,and other pathological processes.This article reviews the research progress of ncRNA in VMC and provides new ideas for the pathogenesis,diagnosis,and treatment of VMC.

Objective:To investigate the effects of aloperine(ALO)on cell behavior of colorectal cancer(CRC)cells through IL-6/tyrosine kinase 1(JAK1)/signal transducer and activator of transcription 3(STAT3)pathway.Methods:SW480 cells were grouped into CK group(normal culture of SW480 cells),ALO low-dose group(ALO-L group,0.2 mmol/L),ALO medium-dose group(ALO-M group,0.4 mmol/L),ALO high-dose group(ALO-H group,0.8 mmol/L)and ALO-H+activator(IL-6 activator recombinant human IL-6 protein)group(0.8 mmol/L+100 ng/ml).Proliferation of SW480 cells was detected by CCK-8 and plate cloning experi-ments;apoptosis of SW480 cells was detected by flow cytometry;Western blot was used to detect expressions of proliferating cell nu-clear antigen(PCNA),Bcl-2-associated X protein(Bax),IL-6,p-JAK1,p-STAT3 proteins in cells.After the above five groups of cells were co-cultured with natural killer cells NK-92MI,respectively,they were named as CK co-culture group,ALO-L co-culture group,ALO-M co-culture group,ALO-H co-culture group,and ALO-H+activator co-culture group,respectively.Levels of TNF-α and IFN-γ in supernatant and immune killing rate of NK-92MI in the co-culture system were detected.Results:Compared with CK group,OD450 value,clone formation rate,protein expressions of PCNA,IL-6,p-JAK1,p-STAT3 in SW480 cells in ALO-L group,ALO-M group and ALO-H group were decreased,while apoptosis rate and protein expression of Bax were increased,in a dose-dependent manner(P<0.05);compared with ALO-H group,OD450 value,clone formation rate,protein expressions of PCNA,IL-6,p-JAK1,p-STAT3 in SW480 cells in ALO-H+activator were increased,while apoptosis rate and protein expression of Bax were decreased(P<0.05);compared with CK co-culture group,levels of TNF-α and IFN-γ in supernatant of cells,and the immune killing rate of NK-92MI cells in ALO-L co-culture group,ALO-M co-culture group and ALO-H co-culture group were increased,and in a dose-dependent manner(P<0.05);compared with ALO-H co-culture group,levels of TNF-α and IFN-γ in supernatant of cells,and immune killing rate of NK-92MI cells in ALO-H+activator co-culture group were decreased(P<0.05).Conclusion:ALO may inhibit the proliferation,immune escape and promote apoptosis of SW480 cells by inhibiting IL-6/JAK1/STAT3 signaling pathway.

OBJECTIVE: To retrospectively analyze the clinical efficacy of anterior cruciate ligament (ACL) reconstruction combined with anterolateral complex repair and ACL reconstruction combined with ALL reconstruction in the treatment of anterior cruciate ligament injuries with high-grade pivot shift. METHODS: From January 2018 to June 2022, 49 patients combined ACL and ALL injuries with high-grade pivot shift were retrospectively studied from three hospitals, 29 of them underwent ACL reconstruction with anterolateral complex repair (repair group), including 23 males and 6 females with an average age of (27.5±4.8) years old, ranged from 20 to 37 years old;the injured sides were 13 on the left and 16 on the right, and 11 patients were suffered with meniscus injury. The other 20 patients underwent ACL and ALL reconstruction (reconstruction group) including 17 males and 3 females with the mean age of (27.1±4.5) years old, ranged from 20 to 38 years old;the injured sides were 8 on the left and 12 on the right, and 6 patients were suffered with meniscus injury. Knee stability (pivot shift test, KT-2000), range of motion, knee function (Lysholm scoring scale, Cincinnati sports activity scale (CSAS) scoring scale, and Tegner activity level score between two groups were compared. RESULTS: A total of 49 patients were followed up, the repair group receiving 13 to 20(15.3±1.8) months and the reconstruction group receiving 12 to 21(16.0±2.2) months. There was no statistically significant difference in the preoperative pivot shift test grading distribution between two groups (P>0.05). At the last postoperative follow-up, there were 24 patients with grade 0 and 5 patients with grade 1 in the repair group, and there were 18 patients with grade 0 and 2 patients with grade 1 in the reconstruction group, there is no significant difference in the distribution of axial shift test grading between two groups(P>0.05). The preoperative KT-2000 tibial displacement of two groups were (9.39±0.77) mm (repair group) and (9.14±0.78) mm (reconstruction group) respectively, with no statistically significant difference (P>0.05). At the final postoperative follow-up, there were 24 patients with KT-2000 tibial displacement <3 mm and 5 patients with 3 to 5 mm in the repair group, while 18 patients with <3 mm and 2 patients with 3 to 5 mm in the reconstruction group, KT-2000 tibial displacement distribution of two groups was no significant difference (P>0.05), but the KT-2000 tibial displacement in the reconstruction group (1.30±0.86) mm was significantly smaller than that in the repair group (1.99±1.11) mm (P<0.05). The final postoperative follow-up range of motion of the contralateral side knee between two groups was no significant difference (P>0.05). The range of motion of the suffering knee in the repair group was less than that in the reconstruction group (P<0.05). There was no significant difference in preoperative Lysholm and CSAS scores between two groups (P>0.05). At the final postoperative follow-up, both groups showed significant improvement in Lysholm and CSAS scores, while the Lysholm and CSAS scores of the reconstruction group were better than those of the repair group, and the difference was statistically significant (P<0.05). Significant differences was found in Tegner scores between two groups, which 16 patients in the repair group returned to their pre-injury activity level, and 17 patients in the reconstruction group returned to their pre-injury level (P<0.05). CONCLUSION Compared to anterolateral complex repair, combined ACL and ALL reconstruction in the treatment of ACL injuries with high-grade pivot shift results in better knee joint function and stability. This is advantageous in reducing the risk of ACL reconstruction failure.
Humans ; Male ; Female ; Adult ; Anterior Cruciate Ligament Reconstruction/methods* ; Anterior Cruciate Ligament Injuries/surgery* ; Young Adult ; Retrospective Studies ; Anterior Cruciate Ligament/surgery* ; Range of Motion, Articular

OBJECTIVES: To investigate the prevalence rate of non-alcoholic fatty liver disease (NAFLD) in overweight/obese children who visit a hospital, and to explore the influencing factors of NAFLD, in order to provide a basis for the prevention of NAFLD in overweight/obese children. METHODS: Overweight/obese children who visited Hunan Children's Hospital from June 2019 to September 2021 were recruited. The prevalence rate of NAFLD was examined. Logistic regression analysis was used to explore the factors influencing the development of NAFLD [non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)]. Receiver operating characteristic curve analysis was used to evaluate the predictive value of the influencing factors for NAFL and NASH. RESULTS: A total of 844 overweight/obese children aged 6-17 years were enrolled. The prevalence rate of NAFLD in overweight/obese children was 38.2% (322/844), among which the prevalence rates of NAFL and NASH were 28.8% (243/844) and 9.4% (79/844), respectively. Multivariate logistic regression analysis showed that the increase of waist-to-hip ratio (WHR) and low high-density lipoprotein cholesterol (HDL-C) were associated with the development of NAFL and NASH (P<0.05). The receiver operating characteristic curve analysis showed that the combined measurement of WHR and HDL-C had a predictive value for NAFL (area under the curve: 0.653, 95%CI: 0.613-0.694), and for NASH (area under the curve: 0.771, 95%CI: 0.723-0.819). CONCLUSIONS The prevalence rate of NAFLD in overweight/obese children who visit a hospital is high. WHR and HDL-C are associated with the development of NAFLD and the combined measurement of WHR and HDL-C has a certain value for predicating the development of NAFLD.
Child ; Humans ; Cholesterol, HDL ; Cross-Sectional Studies ; Non-alcoholic Fatty Liver Disease/complications* ; Overweight/complications* ; Pediatric Obesity/epidemiology* ; Prevalence ; Adolescent

From January 2019 to December 2021, overweight and obese children who visited in health outpatient Center of Hunan Children's Hospital were studied to explore and analyze the rate, related factors and patterns of multimorbidity of overweight and obesity-related diseases in children in Hunan Province. Univariate and multivariate logistic regression models were used to analyze the multimorbidity-related factors of overweight and obesity-related diseases in children. Association rules (apriori algorithm) were used to explore the multimorbidity patterns of overweight and obesity-related diseases in children. A total of 725 overweight and obese children were included in this study. The multimorbidity rate of overweight and obesity-related diseases in children was 46.07% (334/725). Age, waist circumference, the frequency of food consumption such as hamburgers and fries and adding meals before bedtime were multimorbidity-related factors of overweight and obesity-related diseases in children. The multimorbidity associated with nonalcoholic fatty liver disease (NAFLD) was relatively common. The patterns with the top three support degrees were "NAFLD+dyslipidemia","NAFLD+hypertension" and "NAFLD+hyperuricemia". The patterns with the top three confidence and elevation degrees were "Hypertension+dyslipidemia => NAFLD","Hyperuricemia => NAFLD" and "NAFLD+hypertension => dyslipidemia".
Child ; Humans ; Overweight/complications* ; Non-alcoholic Fatty Liver Disease ; Pediatric Obesity/epidemiology* ; Hyperuricemia ; Multimorbidity ; Hypertension/epidemiology* ; Dyslipidemias ; Body Mass Index ; Risk Factors

Objective: To analyze mortality and its trend of chronic respiratory diseases (CRD) in China from 1990 to 2019. Methods: Based on the provincial results of China from the 2019 Global Burden of Disease (GBD) study, the average annual percent change (AAPC) of standardized mortality rates of different CRDs were analyzed by using Joinpoint 4.8.0.1, and the age-standardized mortality rate of CRD was calculated by using the GBD 2019 world standard population. Based on the comparative risk assessment theory of GBD, the attributable deaths due to 12 CRD risk factors were estimated, including smoking, indoor air pollution, occupational gas exposure, particulates and smog exposure, environmental particulate pollution, low temperature, passive smoking, ozone pollution, occupational exposure to silica, occupational asthma, high body mass index, high temperature and occupational exposure to asbestos. Results: From 1990 to 2019, the number of deaths and standardized mortality of chronic obstructive pulmonary disease (COPD) showed a downward trend (P<0.001). The number of COPD deaths decreased from 1 244 000 (912 000 - 1 395 000) in 1990 to 1 037 000 (889 000 - 1 266 000) in 2019. AAPC=-0.9% (95%CI: -1.5% - -0.3%), P<0.001; The standardized mortality rate decreased from 217.9/100 000 (163.3/100 000 - 242.0/100 000) in 1990 to 65.2/100 000 (55.5/100 000 - 80.1/100 000) in 2019. AAPC= -4.2% (95%CI:-5.2% - -3.2%), P<0.001. The number of deaths from asthma decreased from 40 000 (30 000 - 58 000) in 1990 to 25 000 (20 000 - 31 000) in 2019. AAPC=-2.0% (95%CI: -2.6% - -1.4%), P<0.001; The standardized mortality rate of asthma decreased from 6.4/100 000 (4.7/100 000 - 9.5/100 000) in 1990 to 1.5/100 000 (1.2/100 000 - 1.9/100 000) in 2019. AAPC=-5.1% (95%CI: -5.8% - -4.4%), P<0.001. The number of pneumoconiosis deaths decreased from 11 000 (8 000 - 14 000) in 1990 to 10 000 (8 000 - 14 000) in 2019, AAPC=-0.2%(95%CI:-0.4% - 0.1%), P=0.200; The standardized mortality rate of pneumoconiosis decreased from 1.4/100 000 (1.0/100 000 - 1.7/100 000) in 1990 to 0.5/100 000 (0.4/100 000 - 0.7/100 000) in 2019. AAPC=-3.1% (95%CI: -3.4% - -2.8%), P<0.001. The number of deaths from pulmonary interstitial diseases and pulmonary sarcoidosis increased from 3 000 (3 000 - 6 000) in 1990 to 8 000 (6 000 - 10 000) in 2019, AAPC=3.5% (95%CI: 2.7% - 4.2%), P<0.001; The corresponding standardized mortality rate changed little from 1990 to 2019, and AAPC was not statistically significant.The age-standardized mortality rates of different CRDs were higher in men than those in women. In 1990 and 2019, the mortality rates of COPD, asthma, pneumoconiosis and interstitial pulmonary disease and pulmonary sarcoidosis increased with age. In 2019, the population attributable fractions (PAFs) for smoking, environmental particulate pollution, occupational gas exposure, particulate and smog exposure, low temperature exposure and passive smoking were 71.1% (68.0% - 74.3%), 24.7% (20.1% - 30.0%), 19.3% (13.0% - 25.4%), 15.7% (13.6% - 18.3%) and 8.8% (4.5% - 13.1%) respectively in men, and the PAFs for environmental particulate pollution, smoking, low temperature exposure, occupational gas exposure, particulate and smog exposure, and passive smoking were 24.1% (19.6% - 29.3%), 21.9% (18.7% - 25.2%), 16.4% (14.0% - 19.2%), 15.6% (10.2% - 21.1%) and 14.7% (7.9% - 21.3%) respectively in women. Conclusions: During 1990-2019, the overall death level of CRD decreased significantly in China, but it is still at high level in the world. Active prevention and control measures should be taken to reduce the death level caused by CRD.
Asthma ; China/epidemiology* ; Female ; Global Burden of Disease ; Humans ; Male ; Mortality ; Pulmonary Disease, Chronic Obstructive ; Quality-Adjusted Life Years

Objective: To compare clinical efficacy between laparoscopic radical proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic radical total gastrectomy with Roux-en-Y reconstruction (LTG-RY) in patients with early upper gastric cancer, and to provide a reference for the selection of surgical methods in early upper gastric cancer. Methods: A retrospective cohort study method was carried out. Clinical data of 80 patients with early upper gastric cancer who underwent LPG-DTR or LTG-RY by the same surgical team at the Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2021 were retrospectively analyzed. Patients were divided into the DTR group (32 cases) and R-Y group (48 cases) according to surgical procedures and digestive tract reconstruction methods. Surgical and pathological characteristics, postoperative complications (short-term complications within 30 days after surgery and long-term complications after postoperative 30 days), survival time and nutritinal status were compared between the two groups. For nutritional status, reduction rate was used to represent the changes in total protein, albumin, total cholesterol, body mass, hemoglobin and vitamin B12 levels at postoperative 1-year and 2-year. Non-normally distributed continuous data were presented as median (interquartile range), and the Mann-Whitney U test was used for comparison between groups. The χ(2) test or Fisher's exact test was used for comparison of data between groups. The Mann-Whitney U test was used to compare the ranked data between groups. The survival rate was calculated by Kaplan-Meier method categorical, and compared by using the log-rank test. Results: There were no statistically significant differences in baseline data betweeen the two groups, except that patients in the R-Y group were oldere and had larger tumor. Patients of both groups successfully completed the operation without conversion to laparotomy, combined organ resection, or perioperative death. There were no significant differences in the distance from proximal resection margin to superior margin of tumor, postoperative hospital stay, time to flatus and food-taking, hospitalization cost, short- and long-term complications between the two groups (all P>0.05). Compared with the R-Y group, the DTR group had shorter distal margins [(3.2±0.5) cm vs. (11.7±2.0) cm, t=-23.033, P<0.001], longer surgery time [232.5 (63.7) minutes vs. 185.0 (63.0) minutes, Z=-3.238, P=0.001], longer anastomosis time [62.5 (17.5) minutes vs. 40.0 (10.0) minutes, Z=-6.321, P<0.001], less intraoperative blood loss [(138.1±51.6) ml vs. (184.3±62.1) ml, t=-3.477, P=0.001], with significant differences (all P<0.05). The median follow-up of the whole group was 18 months, and the 2-year cancer-specific survival rate was 97.5%, with 100% in the DTR group and 95.8% in the R-Y group (P=0.373). Compared with R-Y group at postoperative 1 year, the reduction rate of weight, hemoglobin and vitamin B12 were lower in DTR group with significant differences (all P<0.05); at postoperative 2-year, the reduction rate of vitamin B12 was still lower with significant differences (P<0.001), but the reduction rates of total protein, albumin, total cholesterol, body weight and hemoglobin were similar between the two groups (all P>0.05). Conclusions: LPG-DTR is safe and feasible in the treatment of early upper gastric cancer. The short-term postoperative nutritional status and long-term vitamin B12 levels of patients undergoing LPG-DTR are superior to those undergoing LTG-RY.
Albumins ; Anastomosis, Roux-en-Y/adverse effects* ; Cholesterol ; Gastrectomy/methods* ; Hemoglobins ; Humans ; Laparoscopy/methods* ; Postoperative Complications/etiology* ; Retrospective Studies ; Stomach Neoplasms/pathology* ; Treatment Outcome ; Vitamin B 12