ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

Cough variant asthma is a distinct subtype of asthma characterized by chronic irritant dry cough as the sole or predominant clinical manifestation. It is one of the primary causes of chronic cough in children. In traditional Chinese medicine, it belongs to the category of " spasmodic cough", " wind-induced cough", " chronic cough", and " asthmatic cough". At present, Western medicine treatment approaches mainly focus on symptomatic treatment, but fail to fully deal with its complex systemic mechanisms, and have limitations such as poor control of clinical symptoms and rebound exacerbation upon treatment cessation. Based on the theory of " systemic qi stagnation", this paper proposes that the core pathogenesis of cough variant asthma in children is qi stagnation, intermingling of phlegm and blood stasis, and obstruction of collaterals. Disease progression is fundamentally driven by exogenous pathogen activation of endogenous predispositions, particularly dysregulation of sanjiao qi movement, which serves as the primary disease-inducing factor. During the acute phase, the treatment principle focuses on dispelling wind and ventilating lung to restore physiological qi. As the disease progresses to the progressive phase, the focus shifts toward smoothing liver and purging lung to resolve qi counterflow. In the chronic phase, therapeutic strategy prioritizes dissipating phlegm and eliminating blood stasis to smooth collaterals. Finally, during the remission phase, treatment emphasizes strengthening spleen and kidney to consolidate the foundation and cultivate the vitality. This integrative approach synergizes the external elimination of latent pathogens, internal harmonization of qi movement, and dredging collaterals by dispelling blood stasis. It also incorporates the theory of " gentle dispersion to expel pathogens and moistening dryness to harmonize collaterals", aiming to provide a theoretical basis and effective prescriptions for the integrated traditional Chinese and Western medicine treatment of cough variant asthma in children.

Objective: To investigate the value of the Chinese visceral adiposity index (CVAI) in predicting hypertension risk, so as to provide a tool for the early assessment of hypertension risk. Methods: Health examination individuals aged ≥18 years were selected from four medical institutes in Jinhua City, Zhejiang Province in 2022. Data on basic information, lifestyle, disease history, body mass index, waist circumference, blood pressure, and blood biochemical indicators were collected through questionnaire surveys and physical examinations. CVAI was calculated to assess levels of visceral fat accumulation, divided by quartiles into Q1, Q2, Q3, and Q4 groups. The relationship between CVAI and hypertension was analyzed using a multivariable logistic regression model, and their dose-response relationship was examined using a restricted cubic spline model. The value of CVAI in predicting hypertension risk was evaluated using receiver operating characteristic (ROC) curve. Results: A total of 23 791 individuals were enrolled, with a median age of 68.00 (interquartile range, 14.00) years. Among them, 10 178 (42.78%) were males and 13 613 (57.22%) were females. The median CVAI was 111.40 (interquartile range, 48.23). Hypertension was identified in 15 563 cases, with a prevalence of 65.42%. After adjusting for lifestyle, disease history, and blood biochemical indicators, the multivariable logistic regression analysis revealed that hypertension risk in the CVAI Q2, Q3, and Q4 groups were 2.012 (95%CI: 1.865-2.170), 3.059 (95%CI: 2.826-3.311), and 5.099 (95%CI: 4.672-5.565) times that of the Q1 group, respectively. The restricted cubic spline model revealed a non-linear relationship between CVAI and hypertension risk (Pnon linearity<0.05). Hypertension risk increased more rapidly when the CVAI was ≥81.03. The area under the ROC curve for CVAI in predicting hypertension risk was 0.691, with an optimal cutoff value of 106.01, which falls within the Q2 group. Conclusions There was a nonlinear dose-response relationship between CVAI and hypertension. CVAI can predict the risk of hypertension, and 106.01 can serve as an early warning threshold for risk screening.

OBJECTIVE: To observe the clinical efficacy of Qihuang needle therapy for autism spectrum disorder (ASD) children with sleep disorder. METHODS: A total of 60 ASD children with sleep disorder were randomly divided into an observation group and a control group, 30 cases in each group. Both groups were treated with structured education intervention, 60 min each time, once a day, 6 times a week. Qihuang needle therapy was applied at Yintang (GV24⁺), Baihui (GV20) and bilateral Jueyinshu (BL14), Xinshu (BL15) in the observation group, multi-direction needling was delivered and without needle retaining. The treatment was given 2 times a week, each treatment was delivered at interval of 2 days at least. Behavioral intervention was adopted in the control group. Treatment for consecutive 12 weeks was required in both groups. Before and after treatment, the scores of children's sleep habits questionnaire (CSHQ), the autism behavior checklist (ABC), the childhood autism rating scale (CARS), and the childhood autism behavior scale (CABS) were observed in the two groups. RESULTS: After treatment, the scores of CSHQ, ABC, CARS and CABS were decreased compared with those before treatment (P<0.01), and the above scores in the observation group were lower than those in the control group (P<0.05). CONCLUSION Qihuang needle therapy can effectively treat ASD with sleep disorder, improve the core symptoms of ASD and the sleep quality.
Humans ; Autism Spectrum Disorder/physiopathology* ; Male ; Female ; Child ; Sleep Wake Disorders/physiopathology* ; Child, Preschool ; Acupuncture Therapy ; Acupuncture Points ; Treatment Outcome ; Sleep ; Needles

The Kirsten rat sarcoma viral oncogene homolog ( KRAS ) mutation is one of the most prevalent activating alterations in cancer. It indicates a poor overall prognosis due to its highly invasive nature. Although several KRAS inhibitors have been developed in recent years, a significant clinical challenge has emerged as a substantial proportion of patients eventually develop resistance to these therapies. Therefore, identifying determinants of drug resistance is critical for guiding treatment strategies. This review provides a comprehensive overview of the mutation landscape and molecular mechanisms of KRAS activity in various cancers. Meanwhile, it summaries the progress and prospects of small molecule KRAS inhibitors undergoing clinical trials. Furthemore, this review explores potential strategies to overcome drug resistance, with the ultimate goal of steering toward patient-centric precision oncology in the foreseeable future.
Humans ; Drug Resistance, Neoplasm/drug effects* ; Proto-Oncogene Proteins p21(ras)/metabolism* ; Mutation/genetics* ; Neoplasms/genetics* ; Antineoplastic Agents/therapeutic use*

ObjectiveTo investigate the effect of Tangbikang granules on oxidative stress of sciatic nerve in diabetic rats by regulating adenylate activated protein kinase/peroxisome proliferator-activated receptor γ coactivator-1α/mitochondrial Sirtuins 3 （AMPK/PGC-1α/SIRT3） signaling pathway. MethodThe spontaneous obesity type 2 diabetes model was established using ZDF rats. After modeling， they were randomly divided into high， medium， and low dose Tangbikang granule groups （2.5， 1.25， 0.625 g·kg^-1·d^-1） and lipoic acid group （0.026 8 g·kg^-1·d^-1）， and the normal group was set up. The rats were administered continuously for 12 weeks after modeling. The blood glucose of rats was detected before intervention and at 4， 8， 12 weeks after intervention. At the 12^th week， motor nerve conduction velocity （MNCV）， sensory nerve conduction velocity （SNCV）， nerve blood flow velocity， mechanical pain threshold， and thermal pain threshold were detected. The sciatic nerve was taken for hematoxylin-eosin （HE） staining to observe the tissue morphology. The ultrastructure of the sciatic nerve was observed by transmission electron microscope. The expression levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in sciatic nerve were determined by enzyme-related immunosorbent assay （ELISA）. The mRNA expressions of AMPKα， AMPKβ， PGC-1α， and SIRT3 in sciatic nerve were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， fasting blood glucose in the model group was increased at each time point （P<0.01）. The mechanical pain threshold was decreased （P<0.05）， and the incubation time of the hot plate was extended （P<0.01）. MNCV， SNCV， and nerve blood flow velocity decreased （P<0.05）. The expression level of SOD was decreased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were increased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were decreased （P<0.01）. The structure of sciatic nerve fibers in the model group was loose， and the arrangement was disordered. The demyelination change was obvious. Compared with the model group， the fasting blood glucose of rats in the high dose Tangbikang granule group was decreased after the intervention of eight weeks and 12 weeks （P<0.01）. The mechanical pain threshold increased （P<0.05）. The incubation time of the hot plate was shortened （P<0.01）. MNCV， SNCV， and Flux increased （P<0.05）. The expression level of SOD was increased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were decreased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were increased （P<0.01）. The sciatic nerve fibers in the high-dose Tangbikang granule group were tighter and more neatly arranged， with only a few demyelinating changes. The high， medium， and low dose Tangbikang granule groups showed a significant dose-effect trend. ConclusionTangbikang granules may improve sciatic nerve function in diabetic rats by regulating AMPK/PGC-1α/SIRT3 signaling pathway partly to inhibit oxidative stress.

BACKGROUND:Perinatal hypoxic-ischemic brain injury is one of the most common causes of cerebral palsy.Shujin Jiannao Prescription is an experienced formula for treating cerebral palsy and improving blood supply to the brain developed by the Dongzhimen Hospital,Beijing University of Chinese Medicine. OBJECTIVE:To explore the possible mechanism of Shujin Jiannao Prescription in treating hypoxic-ischemic cerebral palsy. METHODS:Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into six groups.There were 12 rats in each of the control and model groups as well as 10 animals in each of the minocycline group,and the low-,medium-,and high-dose groups of Shujin Jiannao Prescription.The neonatal rat ischemic-hypoxic cerebral palsy model was established in all groups except for the control group.After successful modeling,rats in each drug group were respectively gavaged with minocycline and Shujin Jiannao Prescription at a dose of 4,8,and 16 g/kg per day for 1 week.Body mass of rats was measured and behavioral changes were detected before and after drug administration.Hematoxylin-eosin staining was used to observe the histomorphology of hippocampal CA1 region of rat brain tissue,and immunohistochemistry and western blot were used to detect the expression levels of Bcl-2,Bax,and Caspase-3 in the brain tissue of rats. RESULTS AND CONCLUSION:Compared with the model group,medium-and high-dose Shujin Jiannao Prescription significantly increased the body mass of rats(P<0.05).Compared with the model group,minocycline effectively prolonged the suspension time of ischemic-hypoxic cerebral palsy rats(P<0.05),while medium-and high-dose Shujin Jiannao Prescription significantly prolonged the suspension time,shortened the inclined plane test time,and increased the Longa score of rats(P<0.05).The pathological results showed that after drug intervention,only a small number of neuronal cells in the brain tissue of rats were necrotic,the cells were more neatly arranged,the cell structure was more complete,and only part of the cell nuclei became smaller.Compared with the model group,minocycline and medium-and high-dose Shujin Jiannao Prescription reduced the expression of Bax Caspase-3(P<0.05),medium-and high-dose Shujin Jiannao Prescription increased the expression of Bcl-2(P<0.05),and Bcl-2/Bax protein expression was increased in minocycline and three Shujin Jiannao Prescription groups(P<0.05).In addition,the protein expression was increased in a dose-dependent manner after intervention with Shujin Jiannao Prescription,and there was no significant difference between the minocycline and three Shujin Jiannao Prescription groups(P>0.05).To conclude,the mechanism by which Shujin Jiannao Prescription treats ischemic-hypoxic cerebral palsy in rats may be to enhance the expression of anti-apoptotic protein Bcl-2,inhibit the expression of pro-apoptotic protein Bax,and reduce the expression of Caspase-3,ultimately inhibiting the apoptosis of hippocampal neuronal cells in rats with cerebral palsy.Within a certain range,the higher dose of Shujin Jiannao Prescription indicates the better therapeutic effect,and the high-dose Shujin Jiannao Prescription is as effective as minocycline.

Objective:To investigate the safety and effectiveness of endoscopic cold snare resection of small colorectal polyps and prophylactic hemostatic clip.Methods:A total of 260 patients diagnosed as having small colorectal polyps in Qinghai Provincial People's Hospital from January 2021 to March 2022 were randomly assigned to cold snare polypectomy (CSP) group (receiving CSP), CSP+hemostatic clip group (receiving CSP+prophylactic hemostatic clip), hot snare polypectomy (HSP) group, and HSP +hemostatic clip group (receiving HSP+prophylactic hemostatic clip). Each group had 65 cases. The treatment, incidence of bleeding, and other complications were compared.Results:There was no significant difference in the basic characteristics of patients or polyps among the four groups ( P>0.05). Immediate intraoperative bleeding occurred in 5 cases (7.69%), 4 cases (6.15%), 3 cases (4.62%), and 3 cases (4.62%) in the four groups respectively with no significant difference ( χ2=0.778, P=0.855), while only 1 delayed postoperative bleeding was observed in HSP group with no significant difference among the four groups ( χ2=3.012, P=0.390). The incidence of postoperative abdominal pain was the highest in the HSP group ( n=7, 10.77%) significantly different from those of the CSP group ( n=1, 1.54%) and the CSP+hemostatic clip group ( n=1, 1.54%) ( P<0.05). Polypectomy time of single polyp in CSP group was the shortest (2.18±1.07 min) , followed by HSP group (2.83±0.82 min), then CSP+hemostatic clip group (3.15±1.16 min), with HSP+hemostatic clip group (4.88±1.85 min) being the longest ( F=50.397, P<0.001). Conclusion:It is suggested to use CSP for small colorectal polyps. If there is no risk of bleeding or perforation during the operation, it is not necessary to use prophylactic hemostatic clips.

Objective: To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie diet-induced pneumonia through proteomics analysis. Methods: Based on the Gene Expression Omnibus (GEO) database, lung tissue samples from normal and high-fat diet (HFD) fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses. In the animal experiments, mice were randomly divided into the control (N), high-calorie diet pneumonia (M), and Yinlai decoction treatment (Y) groups. Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d. The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d. Pathological evaluation of the lung tissue was performed. Differentially expressed proteins (DEPs) in the lung tissue were identified using quantitative proteomics and bioinformatics analyses. The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory (MGL) Tools. DEPs were verified by western blot. Results: GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue. The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet. A total of 47 DEPs were identified between the Y and M groups. Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle (TCA) and oxidative phosphorylation. The protein-protein interaction network revealed that Atp5a1, Pdha1, and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction. Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide, praeruptorin B, chrysoeriol, and other components in Yinlai decoction to Atp5a1. Conclusion The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation. Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.