In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.

AIM:To investigate the impact of platycodin D(PD)on the viability,migration,invasion,apop-tosis and cell cycle of osteosarcoma cells in vitro,along with its underlying mechanisms.METHODS:Human osteosarco-ma cells MG63 and U2OS were divided into control group(0 μmol/L)and PD treatment group(6.25,12.5,25,50 and 100 μmol/L,respectively).Human osteosarcoma cells MG63 and U2OS were categorized into control groups(0 μmol/L PD)and PD treatment groups(6.25,12.5,25,50 and 100 μmol/L).The CCK-8 assay determined cell viability and identified effective treatment concentrations.MG63(15 μmol/L PD)and U2OS(25 μmol/L PD)were specifically ana-lyzed.Cell scratch and Transwell assays assessed migration and invasion.Hoechst 33342 staining examined nuclear mor-phological changes.Flow cytometry analyzed cell cycle distribution and apoptosis rate.Western blot measured protein ex-pression levels:cleaved caspase-3,cleaved PARP,c-Jun N-terminal kinase(JNK),p-JNK,B-cell lymphoma-2(Bcl-2),Bcl-2-ssociated X protein(BAX),matrix metalloproteinase 2(MMP-2),MMP-9,cyclin-dependent kinase 4(CDK4),cyclin D1,CDK1,cyclin B1,extracellular signal-regulated kinase(ERK)and p-ERK.Proteome sequencing of MG63 cells was performed.RESULTS:PD treatment significantly decreased cell survival,scratch healing rate,and invasive cell numbers,while increasing apoptosis rates(P<0.05).Morphological changes such as nuclear hyperchroma-tism and fragmentation were observed in PD-treated cells.PD induced G2/M phase arrest in MG63 and G0/G1 phase arrest in U2OS cells.PD treatment upregulated BAX,cleaved caspase-3,cleaved PARP,and p-JNK/JNK,while downregulat-ing Bcl-2,MMP-2,MMP-9,CDK4,cyclin D1,CDK1,cyclin B1,and p-ERK/ERK(P<0.05).Proteome sequencing re-vealed PD's involvement in cell division,cell cycle regulation,focal adhesion,apoptosis,and the MAPK signaling path-way.CONCLUSION:PD inhibits cell viability,migration,and invasion of osteosarcoma cells in vitro,while promoting apoptosis and inducing cell cycle arrest.These effects are likely mediated through modulation of the MAPK signaling path-way.

Objective:To investigate the clinical effect of composite surgery in the treatment of chronic common carotid artery occlusion(CCAO).Methods:A retrospective descriptive study was conducted. The clinical data of 7 patients with CCAO admitted to Xuanwu Hospital, Capital Medical University from October 2020 to December 2023 were collected retrospectively. There were 6 males and 1 female. The age was (66.7±10.9) years, ranging from 52 to 83 years. Outpatient or telephone follow-up were conducted after surgery, carotid artery ultrasound or computed tomography angiography were performed at 3 months, 6 months, and 1 year postoperatively to determine vascular patency. The selection of surgical methods and clinical effect were analyzed. Normally distributed measurement data were expressed as mean±standard deviation ( ± s). The measurement data of skewed distribution were expressed by M ( Q1, Q3). Count data were expressed as frequency. Results:All 7 patients were diagnosed with chronic CCAO before operation, 6 on the left and 1 on the right. 3 cases affected the middle and distal segments of the common carotid artery, 1 case affected the proximal segment, and 1 case each affected the middle and distal segments, the remaining case involves the entire common carotid artery. All the procedures were successfully performed, among which 4 cases underwent carotid endarterectomy combined with stent placement, and 3 cases did not receive stent placement after carotid endarterectomy. 1 patient developed neck hematoma after surgery and the remaining patients recovered well after surgery without any complications or deaths. The follow-up time was 13.5(4.0, 20.5) months; 1 patient was lost to follow-up, and 6 patients received effective follow-up. the common carotid artery remained unobstructed in all 6 patients, and there were no transient ischemic attacks or strokes during the follow-up period.Conclusion:Composite surgery is a safe and feasible method that can be used to treat chronic CCAO lesions, and has satisfactory short-term results.

Objective:To study the effect of treadmill training on myelin regeneration in rats with controlled cortical impact(CCI).Methods:The rat CCI model of was prepared by impinging method,and the rat model was trained by running on the treadmill for 8 weeks.The neural function deficit was detected by the modified neurological function se-verity scoring method,the motor function of the rats was detected by the balance beam test,and the expression of BDNF was detected by enzyme-linked immunosorbent assay(ELISA)and RT-qPCR.The expressions of myelin basic protein(MBP),myelin oligodendrocyte glycating protein(MOG)and myelin protein lipoprotein(PLP)in corpus callosum were detected by Western Blot.Results:Treadmill training improved the neural function score and motor function of CCI injured rats,increased the expression of BDNF in cortex,and upregulated the expression of MBP,MOG,and PLP.Conclusion:Treadmill training promotes myelin repair by upregating BDNF,thereby improving the neural function defi-cit caused by CCI injury.

Background/Aims: Previous studies have shown that diet and physical activity can influence constipation. However, the combined effect of diet and physical activity on constipation remains unclear. Methods: Constipation was defined based on stool consistency and frequency, while overall diet quality was assessed using Healthy Eating Index (HEI)-2015 scores. Participants were categorized into low (metabolic equivalent [MET]-min/wk < 500) and high physical activitygroups (MET-min/wk ≥ 500). The association between diet and constipation across physical activity groups was analyzed using surveylogistic regression and restricted cubic splines. Results: Higher HEI-2015 scores were associated with reduced constipation risk in the high physical activity group when constipation was defined by stool consistency (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.97-0.99). However, in the low physical activity group, increased HEI-2015 scores did not significantly affect constipation risk (OR, 1.01; 95% CI, 0.97-1.05). Similar results were found when constipation was defined based on stool frequency. In the high physical activity group, increased HEI-2015 scores were significantly associated with a reduced constipation risk (OR, 0.96; 95% CI, 0.94-0.98). Conversely, in the low physical activity group, increased HEI-2015 scores did not affect the risk of constipation (OR, 0.96; 95% CI, 0.90-1.03). Conclusions Our findings suggest that a higher HEI-2015 score is negatively associated with constipation among individuals with high physical activity levels but not among those with low physical activity levels. This association was consistent when different definitions of constipation were used. These results highlight the importance of combining healthy diet with regular physical activity to alleviate constipation.

Objective:To analyze the results of the joint screening of newborn hearing and deafness genes in Dalian to provide a reference for the prevention and control of hereditary deafness.Methods:Eight hundred and forty-two neonates born in Dalian Women and Children′s Medical Group from January 1, 2022 to May 30, 2022 were screened retrospectively, using AABR (automatic brainstem evoked potential). And 20 mutation sites of common genetic deafness 4 genes , including GJB2, GJB3, SLC26A4 (PDS) and mitochondrial genes associated with drug-induced deafness (MT-RNRI)(12SrRNA), were detected by high-throughput sequencing.Results:Among the 842 newborns, 840 passed hearing screening (99.8%); 36 cases (4.3%) passed the hearing screening but not the hearing loss gene screening; 804 cases passed through the both screening (95.5%); 2 cases (0.24%) failed in the both screening. 38 cases of deafness gene mutations were detected, with a total carrying rate of 4.51% (38/842). Among them, the carrying rates of heterozygous mutations in GJB2, GJB3, SLC26A4 (PDS), MT-RNRI (12SrRNA) were 1.90%, 0.24%, 1.30%, and 0.95%, respectively. The carrying rates of GJB2/GJB3 composite heterozygous mutations were 0.12%.Conclusions:The combined screening of neonatal hearing and deafness genes can reduce the missed rate of hearing screening. The carrier rate of neonatal deafness gene in Dalian is 4.51%, with the highest GJB 2 carrier rate, followed by SLC26A4 (PDS) carrier rate.

Objective:To investigate the clinical characteristics and surgical treatment experience of carotid body tumor (CBT).Methods:The clinical data of 12 patients with CBT admitted to the Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University from March 2013 to August 2020 were analyzed retrospectively. Among them, there were 6 males and 6 females, aged 31-83 years, with a median age of 57 years. Among the 12 patients, 2 patients were not treated surgically. The body mass index (BMI), tumor side, maximum diameter of tumor, and tumor classification, operation time, intraoperative bleeding volume, postoperative drainage volume and time, postoperative hospital stay and postoperative complications of patients undergoing surgery were recorded.Results:BMI of the 12 patients was 17.19-29.07 kg/m 2, with an average of (24.05±3.95) kg/m 2. Among the 12 patients, there were 4 tumors on the left side, 6 tumors on the right side and 2 patients had bilateral tumors. The maximum diameter of the tumor was 1.7-8.7 cm, with an average of (4.05 ± 1.89) cm. Among the 2 patients with bilateral tumors, 1 patient underwent staged resection within 9 months and 1 patient only removed the larger tumor. A total of 10 patients underwent surgical resection. All excised tumors were confirmed histopathologically to be paraganglioma. The average operation time and the amount of bleeding was(164.73 ± 74.39)min and 341.82 mL respectively. The drainage time was 1-3 d, with an average of (1.73 ± 0.65) d. The cumulative drainage volume was 22-237 mL, with an average of (77.18 ± 57.47) mL. Classification of 11 surgically resected tumors: 3 patients (3/11, 27.3%) were Shamblin Ⅰ, 7 patients (7/11, 63.6%) were Shamblin Ⅱ and 1 patient (1/11, 9.1%) were Shamblin Ⅲ. There were 1 patient of hematoma and 1 patient of acute cerebral infarction after operation. One patient with decrease in muscle strength of right limb, other surgical patients complained no complications such as stroke and cranial nerve injury when discharged. Patients undergoing surgery were hospitalized for 8-20 days, with an average of (13.36 ± 3.61) d. Conclusions:CBT is a rare paraganglioma in clinic. Surgical resection is an effective method to treat CBT. Careful operation should be carried out to avoid serious complications such as wound hematoma, cranial nerve injury and ischemic stroke.

Objective:To investigate the printability and cytocompatibility of sodium alginate-gelatin (AG) bioink containing platelet-rich plasma derived from human umbilical cord blood (HUCB-PRP), named HUCB-PRP-AG bioink, and the effect of the three-dimensionally printed tissue with the bioink on full-thickness skin defect wounds in nude mice.Methods:The method of experimental research was used. HUCB-PRP-AG bioinks with 2.5%, 5.0%, and 10.0% of HUCB-PRP by volume were prepared and named 1P-AG, 2P-AG, and 4P-AG, respectively. The appearances of AG, 1P-AG, 2P-AG, and 4P-AG at room temperature were observed, and their viscosity and storage/loss modulus were measured by a rotational rheometer. The above four bioinks were used for three-dimensional bioprinting respectively, and the appearances of the printed tissue were observed (the printed tissue was subsequently cross-linked and used). The four kinds of bioprinted tissue were respectively co-cultured with human umbilical vein endothelial cells (HUVECs) in Transwell chambers with HUVEC special medium for 24 h, and the cell proliferation level was detected by cell counting kit 8 ( n=3). The four kinds of bioprinted tissue were respectively cultured in Dulbecco's modified eagle medium for 12, 24, and 48 h, which were dried and weighed, and the degradation rate was calculated ( n=3). The expression of vascular endothelial growth factor (VEGF) in the culture supernatant of 1P-AG, 2P-AG, or 4P-AG cultured in phosphate buffer solution at 0.5, 24.0, and 48.0 h was detected by enzyme-linked immunosorbent assay ( n=5). Sixteen female BALB/c-NU nude mice aged 6-8 weeks were selected to establish a full-thickness skin defect wound model on the back and were divided into conventional control group with wounds being covered with medical hydrocolloid dressing alone, HUCB-PRP group with additional HUCB-PRP dripping to the wounds, AG group additionally covered with AG printed tissue, and 4P-AG group additionally covered with 4P-AG printed tissue, respectively (with 4 nude mice in each group). The wound healing of 3 nude mice in each group was observed on post injury day (PID) 4, 8, and 14, and the wound healing rate was calculated. The wound tissue of the remaining nude mouse in each group was collected on PID 8, the histopathological changes were observed after hematoxylin and eosin staining, and the CD31-positive new blood vessels were observed after immunohistochemical staining. Data were statistically analyzed with analysis of variance for repeated measurement, least significant difference test, and Bonferroni correction. Results:At room temperature, AG, 1P-AG, 2P-AG, and 4P-AG were semi-transparent liquid, and AG was light yellow, while 1P-AG, 2P-AG, and 4P-AG were light red but the color successively deepened. The viscosity of AG, 1P-AG, 2P-AG, and 4P-AG decreased with the increase of shear rate at the temperature of 10 ℃ and shear rate of 0.1-10.0 s -1; the storage moduli of the four bioinks were greater than the loss moduli at the temperature of 10 ℃ and angular frequency range of 1-100 rad/s. Both the resolution and morphology of the printed tissue of four bioinks were similar. The proliferation levels of HUVECs co-cultured with 1P-AG, 2P-AG, and 4P-AG printed tissue for 24 h were 0.885±0.030, 1.126±0.032, and 1.156±0.045, respectively, which were significantly higher than 0.712±0.019 of HUVECs co-cultured with AG printed tissue ( P<0.01). The proliferation levels of HUVECs co-cultured with 2P-AG and 4P-AG printed tissue for 24 h were significantly higher than the level of HUVECs co-cultured with 1P-AG printed tissue ( P<0.01). The degradation rates of 1P-AG, 2P-AG, and 4P-AG printed tissue were significantly higher than those of AG printed tissue at 12, 24, and 48 h of culture ( P<0.01). The degradation rates of 2P-AG and 4P-AG printed tissue at 24 and 48 h of culture were significantly higher than those of 1P-AG printed tissue ( P<0.01). The degradation rate of 4P-AG printed tissue at 12 h of culture was significantly higher than that of 1P-AG printed tissue ( P<0.01), and the degradation rates of 4P-AG printed tissue at 24 and 48 h of culture were significantly higher than those of 2P-AG printed tissue ( P<0.01). At 0.5, 24.0, and 48.0 h of culture, the expressions of VEGF in the culture supernatant of 2P-AG printed tissue were significantly higher than those of 1P-AG printed tissue ( P<0.01), and the expressions of VEGF in the culture supernatant of 1P-AG and 2P-AG printed tissue were significantly lower than those of 4P-AG printed tissue ( P<0.01). The wounds of nude mice in conventional control group and HUCB-PRP group were dry and smaller on PID 8 compared with those on PID 4, and the wounds of nude mice in HUCB-PRP group were smaller with no scabs on PID 14 compared with those in conventional control group. The printed tissue on the wound of nude mice in AG and 4P-AG groups was significantly degraded with no obvious exudation being observed on the wounds on PID 4, the wounds were significantly epithelialized and smaller on PID 8, and there was no scab on the wound on PID 14. The wounds of nude mice in 4P-AG group were completely epithelialized on PID 14. Compared with those in conventional control group, the wound healing rate of nude mice in AG group was significantly decreased on PID 4 ( P<0.05), and the wound healing rates of nude mice in HUCB-PRP group and 4P-AG group at all time points after injury and in AG group on PID 8 and 14 were significantly increased ( P<0.01). Compared with those in HUCB-PRP group, the wound healing rates of nude mice were significantly decreased on PID 4 and 8 in AG group and on PID 4 in 4P-AG group ( P<0.01), while the wound healing rates of nude mice were significantly increased on PID 14 in AG group and on PID 8 and 14 in 4P-AG group ( P<0.01). The wound healing rate of nude mice in 4P-AG group was significantly higher than that in AG group at all time points after injury ( P<0.01). On PID 8, a large number of inflammatory cells infiltration, a small amount of new microvessels, and a small amount of CD31-positive new blood vessels were observed in the wounds of nude mice in conventional control group; a large number of inflammatory cells infiltration, abundant new microvessels, and quite a lot CD31-positive new blood vessels were observed in the wounds of nude mice in HUCB-PRP group; light inflammatory inflammation, a small amount of new microvessels, and a small amount of CD31-positive new blood vessels were observed in the wounds of nude mice in AG group; light inflammatory inflammation, a large number of new microvessels, and a large number of CD31-positive new blood vessels were observed in the wounds of nude mice in 4P-AG group. Conclusions:HUCB-PRP-AG bioink has good printability and cytocompatibility, and its three-dimensionally printed tissue can promote vascularization of full-thickness skin defect wounds in nude mice and accelerate wound healing.

The positive interaction between medical treatment system and medical insurance system is of great significance to promote the reform of medical and health care system. Due to the complexity of the relationship between them, it is difficult to explain it comprehensively with a single theoretical method. The authors analyzed the relationship between medical treatment system and medical insurance system by applying system theory, game theory and synergy theory, and then put forward policy suggestions to optimize the linkage reform of medical treatment system and medical insurance system, so as to better promote the reform of " three medical linkage" and promote the construction of healthy China. The suggestions included optimizing the allocation of health resources, accelerating the construction of medical insurance legislation and health technical evaluation system, strengthening the construction of multi-level medical insurance system, promoting the inter regional information interconnection between medical care and medical insurance, improving the coordination mechanism, negotiation mechanism, incentive and constraint mechanism between medical care and medical insurance.

The construction of Health Hospital will become an important opportunity to promote the strategy of Healthy China. The authors analyzed the connotation of Health Hospital, and the feasibility of building Health Hospital from four aspects, including integrating health policy, building healthy environment, implementing health actions and optimizing health services. Then, six essential factors of building Health Hospital were put forward, namely, establishing a green environment, improving the operation mechanism, disseminating health culture, developing information technology, creating intelligent health care and strengthening top-level design.