ObjectiveTo investigate the mechanisms of Tongmai Yangxin pills （TMYX） and Tongxinluo capsules （TXL） in treating no-reflow （NR） after myocardial ischemia and reperfusion following the concept of treating the same disease with different methods， based on integrative pharmacology and experimental validation. MethodsEighty 8-week-old SPF-grade SD rats were randomly assigned into four groups （n=20）： sham operation， NR， TMYX （4 g·kg^-1）， and TXL （2 mg·kg^-1）. A rat model of myocardial ischemia-reperfusion no-reflow was established by in-situ ligation of the left anterior descending coronary artery. Gastric gavage was first performed 4 h after the operation， and samples were collected on day 7. Thioflavin S staining was used to observe the NR area in rat myocardium. Echocardiography was performed to examine the cardiac function. Hematoxylin-eosin （HE） staining was conducted to observe the pathological changes of the myocardial tissue. An automatic biochemical analyzer was adopted to measure myocardial enzyme activity. Then， integrated pharmacology was applied for Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. Finally， Western blot was employed to quantify the protein levels of key targets in the myocardial tissue， including soluble guanylyl cyclase （sGC）， cyclic guanosine monophosphate （cGMP）/dependent protein kinase （PKG）， phosphorylated phosphatidylinositol 3-kinase （p-PI3K）， phosphorylated protein kinase B （p-Akt）， and hypoxia-inducible factor-1α （HIF-1α）. ResultsCompared with the sham operation group， the NR group showed increased NR area of myocardium， decreased left ventricular ejection fraction （EF）， left ventricular fractional shortening （FS）， left ventricular outflow tract peak velocity （LVOT Peak）， and left ventricular stroke volume （LVSV） （P<0.01）， fractured and disordered myocardial fibers as well as inflammatory cell infiltration in the myocardial tissue， enhanced activities of creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in the myocardial tissue （P<0.01）， and downregulated protein levels of sGC， PKG， phosphorylated （p）-PI3K （Tyr458）， and p-Akt （Tyr315） in the myocardial tissue （P<0.05， P<0.01）. The expression level of HIF-1α protein showed a downward trend. Compared with the NR group， the TMYX group and TXL group exhibited a decreasing trend in myocardial NR area， EF， FS， and LVOT Peak significantly increased （P<0.05， P<0.01）， LVSV showed an upward trend， ameliorated myocardial pathological morphology and inflammatory infiltration， reductions in CK， CK-MB， and LDH activities （P<0.05， P<0.01）， and upregulated protein levels of sGC， PKG， p-PI3K （Tyr458） in myocardial tissue （P<0.05， P<0.01）， the protein expressions of p-Akt （Tyr315） and HIF-1α showed an upward trend. A comparison of the therapeutic effects between the two compound prescriptions showed that TMYX tended to exert a better effect in restoring cardiac function and protecting cardiac structure in NR rats， whereas TXL was more effective in reducing myocardial NR area and lowering myocardial enzyme activities in NR rats. Integrative pharmacology analysis combined with experimental verification demonstrated that both TMYX and TXL could alleviate NR through the following mechanisms： activating the cyclic cGMP/PKG signaling pathway to regulate vascular tone， activating the PI3K/Akt signaling pathway to dilate blood vessels， and activating the HIF-1 signaling pathway to inhibit oxidative stress. However， TMYX had an advantage in activating the cGMP/PKG pathway， while TXL was superior in activating the PI3K/Akt pathway. The two compound prescriptions exerted comparable effects on the HIF-1 signaling pathway， which might serve as their common therapeutic pathway. ConclusionBoth TMYX and TXL could alleviate NR damage. TMYX exerts its protective effect against NR mainly by activating the cGMP/PKG signaling pathway， while TXL exerts its effect mainly through the PI3K/Akt pathway. The HIF-1α signaling pathway may be a common pathway for the two compound prescriptions to exert their protective effects against NR. This study reveals the similarities and differences between TMYX and TXL in the treatment effect and mechanism for NR， providing an experimental basis and a theoretical basis for better clinical application of the two compound prescriptions.

ObjectiveTo compare the Children's Hepatic tumors International Collaboration （CHIC） and the new Chinese Children's Cancer Group （CCCG） hepatoblastoma （HB） risk stratification systems in terms of their prognostic prediction efficacy and chemotherapy guidance value for Chinese children with HB， aiming to identify the risk stratification system more suitable for Chinese HB patients. MethodsThis retrospective study analyzed the clinical data of 403 pediatric patients with HB aged ＜ 18 years who were initially diagnosed at The First Affiliated Hospital of Sun Yat-sen University between February 2010 and September 2023. The prognostic predictive efficacy and chemotherapy-guided value of the CHIC and CCCG risk stratification systems was compared. Statistical analysis was performed using SPSS 27.0. Results①Using the new CCCG risk stratification， the 5-year event-free survival （EFS） rates for children who received versus did not receive risk-stratified chemotherapy according to the CCCG-HB-2016 protocol were 82.5% and 67.7% （P=0.002）， respectively， and the 5-year overall survival （OS） rates were 91.5% and 85.1% （P=0.038）. Using CHIC risk stratification， the corresponding 5-year EFS rates for children who received versus did not receive risk-stratified chemotherapy according to the CCCG-HB-2016 protocol were 80.3% and 68.5% （P=0.030）， and the 5-year OS rates were 90.9% and 85.8% （P=0.151）. ②Among children treated with the CCCG-HB-2016 protocol stratified by the new CCCG system， the 5-year EFS rates for the very low-risk （6 cases）， low-risk （20 cases）， intermediate-risk （61 cases）， and high-risk （69 cases） groups were 100%， 94.1%， 94.7%， and 66.2% （P＜0.001）， respectively， and the 5-year OS rates were 100%， 100%， 96.5%， and 82.0% （P=0.017）. Among children treated with the CCCG-HB-2016 protocol stratified by the CHIC system， the 5-year EFS rates for the very low-risk （32 cases）， low-risk （22 cases）， intermediate-risk （37 cases）， and high-risk （54 cases） groups were 93.8%， 95.2%， 76.1%， and 66.8% （P=0.003）， respectively， and the 5-year OS rates were 93.1%， 100%， 89.5%， and 85.6% （P=0.190）. ③For patients receiving CCCG-HB-2016 risk-stratified chemotherapy， the P-values for EFS comparisons between the CHIC and new CCCG systems within the very low-risk， low-risk， intermediate-risk， and high-risk groups were 0.537， 0.879， 0.023， and 0.934， respectively. Among patients who received stratified chemotherapy according to the CCCG-HB-2016 regimen， the intermediate-risk group in the new CCCG risk stratification system exhibited a significant advantage in 5-year event-free survival （EFS） compared with the intermediate-risk group in the CHIC risk stratification system （94.7% vs. 76.1%）. ConclusionCompared to the CHIC risk stratification， the new CCCG stratification may offer better prognostic prediction and guidance value for chemotherapy in Chinese HB patients， with the intermediate-risk group showing superior outcomes.

Head and neck squamous cell carcinoma （HNSCC） is one of the ten most common cancers worldwide and is one of the refractory cancers with a poor prognosis in otorhinolaryngology-head and neck surgery. Cetuximab is widely used in the clinical treatment of HNSCC and has been approved by the FDA as a first-line chemotherapeutic agent. However, its efficacy varies significantly among different individuals. Therefore, exploring the resistance mechanisms of cetuximab in the treatment of HNSCC and screening for sensitive populations are essential for the precision treatment of head and neck cancer. This article summarizes the research progress on cetuximab resistance mechanisms in HNSCC, and the main aspects include: alterations in epidermal growth factor receptor （EGFR） and its ligands, changes in downstream effectors of EGFR, bypass activation and crosstalk, epithelial-mesenchymal transition, epigenetic modifications, and immunosuppression in the tumor microenvironment.
Humans ; Cetuximab/therapeutic use* ; Drug Resistance, Neoplasm ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Head and Neck Neoplasms/drug therapy* ; ErbB Receptors/metabolism* ; Tumor Microenvironment ; Epithelial-Mesenchymal Transition ; Molecular Targeted Therapy ; Antineoplastic Agents, Immunological/therapeutic use*

OBJECTIVE To investigate the result of human immunodeficiency virus(HIV)screening for the people visiting to a three-A hospital of Sichuan Province and analyze the prevalence of complications with hepatitis B virus(HBV)infection,hepatitis C virus(HCV)infection and Treponema pallidum(TP)infection in the emerging HIV infection patients.METHODS The result of HIV screening for the people who visited to Ziyang Central Hos-pital from Jan.1,2020 to Dec.31,2024 and the test results of HBV,HCV and TP for the emerging HIV infec-tion patients were collected and were summarized and statistically analyzed by SPSS.0 software.RESULTS Totally 289 891 case-times were tested for HIV,1529 cases were previously diagnosed with HIV,465 of whom were tested posi-tive for the first time,there was significant difference in the positive rate of test for the first time among the 5 years(x2=15.998,P=0.003).Totally 353 cases were confirmed positive among the 465 primary positive screening cases.Among the emerging HIV infection patients,the positive rate was higher in the male than in the female(x2=141.141,P＜0.001),and the positive rate was high among the population aged more than 40 year old(x2=11.448,P＜0.001),mi-grant workers(x2=270.110,P＜0.001)and low education level population(x2=25.911,P＜0.001).The detection rate of gp41 was up to 100.00％in strip type testing.The analysis of the ratio of relative light unit(RLU)to Cutoff val-ue(COI)in the initial screening experiment showed that when COI was greater than 50,all of the confirmed tests were positive,when COI ranged between 1 and 5,the false positive rate was 97.06％.The incidence of complica-tion with HBV infection in the emerging HIV infection patients was increased year by year(x2=20.355,P＜0.001),and the incidence of complication with HCV infection was increased in recent two years(x2=10.690,P=0.030).CONCLUSIONS There is no obvious rise of positive rate of HIV screening among the people visiting to the hospital in recent 5 years.The sensitivity of the primary screening of clinical laboratory is high without posi-tive missing test.The positive rates of HBV and HCV are increased among the emerging HIV infection patients.

The master protocol design encompasses a comprehensive clinical trial protocol containing multiple sub-protocols, which can be used to evaluate the clinical intervention effects of various drugs or vaccines on various diseases. Particularly, this design strategy represents an efficient and innovative approach to trial design in the context of precision medicine. The master protocol design can be used for emerging infectious diseases and urgent vaccine development in complex situations. This review aims to outline the types and concepts of master protocol design, analyze the key points and details, and discuss its application scenarios in vaccine clinical evaluations. Additionally, it will explore potential challenges that may arise during implementation to provide references for optimizing emergency clinical trial designs of infectious disease vaccines in China.

Objective: To investigate the relationship of metabolic score for insulin resistance (METS-IR) with bone mineral content (BMC) and bone metabolic markers levels among adolescents, so as to provide a scientific foundation for the early identification and prevention of bone related diseases. Methods: From 2017 to 2019 and 2023, a total of 1 414 adolescents aged 12-18 years from Yinchuan were selected using a method combining convenient sampling with stratified cluster random sampling. The data of basic information, body mass index, BMC, serum osteocalcin (OC), type I collagen cross linked C-terminal peptide (CTX) and calcium (Ca), METS-IR among adolescents were obtained by questionnaire survey, physical measurement and laboratory examination,and METS-IR was divided into four groups Q1-Q 4 according to P 25 , P 50 and P 75 . Logistic regression models combined with restricted cubic splines were employed to analyze the relationship between METS-IR and low BMC as well as low bone metabolic markers. The receiver operating characteristic (ROC) curve was used to evaluate METS-IR effectiveness in diagnosing low BMC. Results: The levels of BMC, OC, CTX, Ca and METS-IR in the surveyed adolescents were (2.66±0.52)kg, (20.49±13.77) ng/mL , (2 460.89±1 818.96)pg/mL, (2.47±0.67)mmol/L, 30.63±7.58. After adjusting for gender, age and physical activity level, METS-IR in Q 4 group had a reduced risk of low BMC and low CTX [ OR (95% CI )=0.03(0.01-0.07), 0.45(0.32-0.65)] and an elevated risk of low OC [ OR (95%CI )=1.85(1.28-2.67)], compared with the Q 1 group (all P <0.05). Gender stratified analyses revealed similar trends for both males and females (all P <0.05). Non linear dose response relationships were observed between METS-IR and low BMC ( P total trend <0.01, P non linearity =0.01), as well as low OC ( P total trend <0.01, P non linearity =0.01), while a linear relationship was detected with low CTX ( P total trend <0.01, P non linearity =0.72). ROC curves revealed that METS-IR had the best diagnostic performance for low BMC (AUC=0.85, 95% CI=0.82-0.88, P <0.01). Conclusions Higher METS-IR score is linked to reduced risk of low BMC and CTX but increase risk of low OC among adolescents. These findings suggest METS-IR is a reliable indicator for assessing BMC and early predicting bone health risk among adolescents.

Objective:To evaluate the radiological and functional outcomes of moderate to severe hallux valgus patients with enlarged distal metatarsal articular angle (DMAA) underwent modified Chevron osteotomy.Methods:The clinical data of patients with moderate and severe hallux valgus with increased distal metatarsal joint angle who accepted surgery operation in the Department of Foot and Ankle Surgery of Yantaishan Hospital from October 2020 to December 2022 were retrospectively analyzed. All patients underwent modified Chevron osteotomy. Taking the proximal end of the metatarsal head centre as the osteotomy apex, the vertical arm osteotomy line in the sagittal plane made an angle of ≤80° with the metatarsal stem, the horizontal plane was inclined to the lateral distal end of the metatarsal head by about 10°, and the sagittal plane metatarsal arm osteotomy line made an angle of ≥90° with the vertical arm osteotomy line; at the proximal osteotomy surface, another cuneiform bone with its base on the medial and its apex on the lateral was resected. The deformity correction was insufficient and Akin osteotomy was performed in combination. Weil osteotomy was performed in combination with metatarsalgia. Radiological assessment including the hallux valgus angle (HVA), intermetatarsal angle (IMA), DMAA, the joint congruity angle (JCA), forefoot bone width and soft tissue width was performed preoperatively and at last follow-up postoperatively. American Orthopedic Foot and Ankle Society/hallux metatarsophalangeal-interphalangeal scale (AOFAS/HMIS) was used for clinical and functional evaluation, total score from 0 to 100, with higher scores indicating better function.Visual analogue scale (VAS) was used for pain valuation, total score from 0 to 10, with higher scores indicating more pain. A questionnaire survey on patient satisfaction was conducted at the last follow-up. Shapiro-Wilk test was used for normal distribution test, and measurement data following normal distribution were represented as Mean±SD. Paired t-test was used for comparison before and after operation. Other indicators conformed to non-normal distribution were denoted by M( Q1, Q3) and were tested by Wilcoxon signed-rank test. P<0.05 was considered statistically significant. Results:Fifty-two feet of 48 patients (5 males, 43 females; mean age (52.4±14.9) years; range, 24 to 78 years) were enrolled. Before the operation, 8 feet combined with metatarsalgia, among them, 7 feet underwent modified Chevron+ Akin+ Weil osteotomy, and 1 foot underwent modified Chevron+ Weil osteotomy. Among the 44 feet without metatarsalgia, 11 feet underwent modified Chevron osteotomy and 33 feet underwent modified Chevron+ Akin osteotomy. The mean follow-up time was 17.8 months (12-24 months). The HVA angle decreased from 38.30°±7.59° before surgery to 10.00°±5.73° at the last follow-up; the IMA angle decreased from 16.08°(12.89°, 18.24°) to 4.81°(3.62°, 7.57°); the DMAA angle decreased from 18.35°(13.03°, 27.47°) to 4.52°(2.68°, 7.09°); JCA decreased significantly from 15.93°(10.25°, 23.06°) to 3.56°(1.71°, 6.98°); forefoot bone width decreased from (90.05±6.12) mm to (82.75±5.01) mm; forefoot soft tissue width decrease from 102.25(96.77, 107.15) mm to 98.08(91.01, 100.60) mm; the VAS decreased from 6(5.5, 7) points to 0(0, 0) points; the score according to the AOFAS/HMIS forefoot was increased from 49(42, 52.5) points to 90(83.5, 95) points; which were statistically significant compared with that before the operation (all P<0.01). There was no statistically significant difference in the first metatarsal length before the operation and at the last follow-up [54.60(52.86, 56.42) mm vs. 54.29(51.85, 56.35) mm, P>0.05]. In the post-operative period, there were 8 feet had limited metatarsophalangeal joint movement, 3 feet had limited interphalangeal joint movement, 5 feet had limited movement in both joints, which did not affect walking and function; 3 feet of partial recurrence of hallux valgus, 2 feet of screw irritation pain, 1 foot of cystic degeneration of the first metatarsal head, and no complications such as metastatic metatarsalgia. The satisfaction survey showed that the satisfaction rate of patients with the orthopedic effect was 90.4% (47/52). Conclusion:The modified Chevron osteotomy is effective in the treatment of moderate to severe hallux valgus with enlarged DMAA. Careful intraoperative operation and standardized postoperative rehabilitation training can reduce complications.

Objective To establish a cell bank of extrahepatic cholangiocarcinoma (ECC)-derived organoids and investigate the key factors influencing the organoids generation. Methods The tumor samples from patients with portal cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA) were used to isolate cells, and these cells were cultured using three-dimensional (3D) technique to establish ECC organoids. Histological characteristics of the organoids were evaluated and identified through hematoxylin-eosin (HE) and immunohistochemistry stainings. The success rates of organoids generation from different tumor types were compared. And clinical characteristics of patients between successful and failure culture groups were compared. Results The success rates of organoids establishment from pCCA and dCCA were all low, with 42.4% (14/33), 51.9% (14/27), respectively. The tumor was larger in successful group than that in failure group (P＜0.001); there was no statistical difference in tumor differentiation status, microvascular invasion, and perineural invasion between the two groups. Conclusions The successful rate of ECC-derived organoids establishment is low, and larger tumor has higher successful culture rate.

Objective To investigate the expression levels of LINC02009 and LOC107984895 in peripheral lymphocytes of patients with atrial fibrillation and their clinical significance.Methods A total of 75 hospitalized patients with atrial fibrillation(50 with persistent atrial fibrillation and 25 with paroxysmal atrial fibrillation)from Kunming First People's Hospital between January 2023 and December 2023 were selected as study subjects,along with 50 normal control patients.Real-time quantitative PCR was used to detect the expression levels of LINC02009 and LOC107984895 in peripheral blood leukocytes of patients with atrial fibrillation.Logistic regression analysis was employed to assess the relationship between expression levels and risk factors for atrial fibrillation,and ROC curves were used to predict the diagnostic cut-off values for LINC02009 and LOC107984895 in diagnosing atrial fibrillation.Results There were statistically significant differences in baseline diseases such as hypertension and coronary heart disease,biochemical indicators such as Cr and BNP,and myocardial remodeling indicators such as LAd and LVEF between the AF(paroxysmal atrial fibrillation and persistent atrial fibrillation)group and the Normal group(P＜0.05).The expression levels of LINC02009 and LOC 107984895 in the plasma of the atrial fibrillation group were significantly higher than those in the control group(P＜0.05)and were negatively correlated with LVEF(P＜0.05).The areas under the curve(AUC)of LINC02009 and LOC 107984895 in predicting atrial fibrillation were 0.967(95％CI:0.938～0.995)and 0.900(95％CI:0.838～0.963),respectively.The optimal cut-off values were 1.985 and 0.915,with sensitivities of 88％and 76％,respectively,and specificities of 94％and 90％,respectively.Conclusion LINC02009 and LOC 107984895 are independent risk factors for atrial fibrillation and have certain predictive value for the occurrence of atrial fibrillation.