Objective: To explore the association between CDKAL1 rs35261542, FAIM2 rs 3205718, and VGLL4 rs 2574704 polymorphisms with childhood obesity and related metabolic phenotypes to provide evidence for personalized prevention and management strategies. Methods: Based on the 2023 Long term Nutritional Health Effects of Early Childhood Nutrition Package Intervention project, the study enrolled 1 078 children aged 5-7 years from four counties in Henan (Songxian and Ruyang countries) and Guizhou (Guiding and Fuquan countries) provinces. Using BMI Z scores, 87 overweight and obese(OVOB) children were selected and matched by sex, age, and BMI Z score with 117 normal weight controls. Participants were further stratified into four metabolic phenotype groups: metabolically healthy normal weight (MHNW, n =51), metabolically unhealthy normal weight (MUNW, n =66), metabolically healthy obesity (MHO, n =31) and metabolically unhealthy obesity (MUO, n =56) based on four conventional cardiometabolic risk factor (CR) criteria. Data were collected through questionnaires, anthropometric measurements, serum biochemical tests, and KASP genotyping. The distribution of three genetic polymorphisms ( CDKAL1 rs35261542, FAIM2 rs3205718, VGLL4 rs 2574704) across metabolic subgroups was analyzed. Multivariate Logistic regression models assessed associations between these polymorphisms and obesity/metabolic phenotypes. Results: Multivariate Logistic regression analysis showed that Homozygous mutant AA genotype of CDKAL1 rs 35261542 was positively associated with OVOB( OR =3.63), MHO ( OR =11.04), MUO ( OR = 4.88 ) ( P <0.05). Homozygous TT genotype of FAIM2 rs 3205718 increased OVOB risk ( OR =4.44, P <0.05) but showed no association with metabolic phenotypes ( P >0.05). Homozygous mutant TT of VGLL4 rs 2574704 reduced the risks of MHO and MUO ( OR = 0.30, 0.24， P <0.05). Cumulative genetic effects analysis demonstrated carriers of 1 or 2 risk genotypes of rs 35261542 and rs 3205718 had progressively higher OVOB risk ( OR =2.53, 20.79), and the combination of rs 35261542 and rs 2574704 increased risks for both MHO ( OR =8.50) and MUO ( OR =5.00) ( P <0.05). Conclusions The AA genotype of rs 35261542 ( CDKAL1 ) positively correlates with childhood obesity and metabolic abnormalities. The TT genotype of rs 3205718 ( FAIM 2) increases obesity risk but not metabolic phenotypes. The TT genotype of rs 2574704 ( VGLL 4) shows protective effects against metabolic dysfunction. Risk genotypes exhibit dosedependent cumulative effects on obesity and metabolic outcomes.

Sepsis is a life-threatening organ dysfunction,which is caused by the body's uncontrolled immune response to infection.Tissue masts cells(MC),derived from blood mast cell progenitors,are one of the classical effector cells in inflammatory response.MC plays an important role in sepsis via secreting a variety of inflammatory mediators and cytokines.Here,we summarized the potential roles of MC in sepsis,which is expected to provide novel ideas for the future research on the novel mechanisms of MC in sepsis.

Objective: To determine the active components of Eupolyphaga sinensis Walker (Tu Bie Chong) and explore the mechanisms underlying its fracture-healing ability. Methods: A modified Einhorn method was used to develop a rat tibial fracture model. Progression of bone healing was assessed using radiological methods. Safranin O/fast green and CD31 immunohistochemical staining were performed to evaluate the growth of bone cells and angiogenesis at the fracture site. Methylthiazoletetrazolium blue and wound healing assays were used to analyze cell viability and migration. The Transwell assay was used to explore the invasion capacity of the cells. Tubule formation assays were used to assess the angiogenesis capacity of human vascular endothelial cells (HUVECs). qRT-PCR was used to evaluate the changes in gene transcription levels. Results: Tu Bie Chong fraction 3 (TF3) significantly shortened the fracture healing time in model rats. X-ray results showed that on day 14, fracture healing in the TF3 treatment group was significantly better than that in the control group (P = .0086). Tissue staining showed that cartilage growth and the number of H-shaped blood vessels at the fracture site of the TF3 treatment group were better than those of the control group. In vitro, TF3 significantly promoted the proliferation and wound healing of MC3T3-E1s and HUVECs (all P < .01). Transwell assays showed that TF3 promoted the migration of HUVECs, but inhibited the migration of MC3T3-E1 cells. Tubule formation experiments confirmed that TF3 markedly promoted the ability of vascular endothelial cells to form microtubules. Gene expression analysis revealed that TF3 significantly promoted the expression of VEGFA, SPOCD1, NGF, and NGFR in HUVECs. In MC3T3-E1 cells, the transcript levels of RUNX2 and COL2A1 were significantly elevated following TF3 treatment. Conclusion TF3 promotes fracture healing by promoting bone regeneration associated with the RUNX2 pathway and angiogenesis associated with the VEGFA pathway.

Objective To investigate the effects of allergens on the expressions of IL-18,IL-18BPa and IL-18Rα protein in peripheral blood CD4+Th1 cells of healthy control subjects(HC)and patients with allergic rhi-nitis(AR),and on the expressions of IL-18,IL-18BPa and IL-18Rα mRNA in the peripheral blood CD4+T cells.Methods Blood samples were collected from patients with rhinitis for negative skin prick test(AR-),rhinitis for positive skin prick test(AR+)and HC.Flow cytometry was used to evaluate the effects of allergens on the expres-sions of IL-18,IL-18BPa and IL-18Rα protein in CD4+Th1 cells.The expressions of IL-18,IL-18BPa and IL-18Rα mRNA in CD4+T cells were determined by qPCR.Results Compared with HC,increased IL-18 while de-creased IL-18BPa expressions in Th1 cells of AR-and AR+patients were observed,increased IL-18Rα expression in Th1 cells of AR+patients was also found.Additionally,allergens induced elevated expression of IL-18Rα pro-tein in Th1 cells of HC,and induced elevated mRNA expressions of IL-18,IL-18BPa and IL-18Rα in isolated blood CD4+T cells of AR+patients and HC.Conclusion Allergens may be involved in the pathogenesis of AR by inducing the expressions of IL-18 and IL-18Rα in blood CD4+Th1 cells.

Objective: To explore the intervention effect of improved nursing measures in the treatment of patients with dystonia with deep brain stimulation in MRI localization. Methods: Twenty patients with dystonia treated with deep brain stimulation from January 2013 to December 2015 were selected as the control group. Twenty patients with dystonia treated by deep brain stimulation surgery with improved nursing from January 2016 to December 2018 were in the experimental group. The primary success rate of MRI localization, examination time related indexes and incidence of adverse reactions after intravenous anesthesia were observed in the 2 groups. Results: The primary success rate of MRI localization in the experimental group (95.00%,19/20) was higher than that in the control group (55.00%,11/20), and the difference was statistically significant (χ²=8.533, P<0.01).The total examination time of the experimental group (33.60±8.27) min was significantly shorter than that of the control group (44.30±13.43) min, and the difference was statistically significant (t=-3.663, P<0.05).The incidence of total adverse reactions to MRI localization after intravenous anesthesia was lower in the experimental group (5%, 1/20) than in the control group (30%, 6/20), and the difference was statistically significant (χ² =4.329, P < 0.05). Conclusions Improved nursing measures can effectively improve the success rate of MRI stereotactic brain target location in patients with dystonia, providing a guarantee for accurate calculation of surgical targets, enabling the operation to achieve the best results, early detection of changes in vital signs during examination, and the close cooperation of the medical team is the guarantee for the smooth completion of MRI examination.

Objective To study the feasibility of laparoscopic pancreaticoduodenectomy ( LPD) in the treatment of pancreatic head cancer, and to analyze the short-term postoperative outcomes. Methods The clinical data of 57 patients with pancreatic head cancer who underwent laparoscopic pancreaticoduode-nectomy from April 2015 to November 2017 in the Second Hospital of Hebei Medical University were retro-spectively analyzed. Results Of the 57 patients, conversion to open surgery was required in 2 patients, and major venous resection and reconstruction were performed in 9 patients, including 8 end-to-end anastomosis, and 1 synthetic graft interposition. Total pancreatectomy was carried out in 4 patients. For the remaining 53 patients, pancreaticojejunal mucosal anastomoses were carried out in 50 patients, and sleeve pancreaticojeju-nostomy in 3 patients. The mean operative time and operative blood loss were 497 (240～720) min and 435 (50～3 000 ) ml, respectively. The mean postoperative hospital stay was 17. 7 ( 6. 0 ～59. 0 ) days. Postoperative complications were detected in 26. 3% (15/57) of patients, which included delayed gastric emptying (DGE) in 4 patients, Grade B pancreatic fistula (PF) in 4 patients, biliary fistula ( BF) in 2 patients, postpancreatectomy hemorrhage ( PPH) in 2 patients, intraabdominal infection in 1 patient and pulmonary infection in 2 patients. All the patients with DGE recovered with conservative treatment and they were discharged home. Reoperation was only required in the two patients with PPH. One patient died after the operation. The postoperative pathological results revealed pancreatic duct adenocarcinoma in 53 patients, adenosscale carcinoma in 1 patient and neuroendocrine carcinoma in 3 patients. The maximum and minimum tumor sizes were 7. 0 cm×5. 0 cm×3. 5 cm and 2. 5 cm×1. 5 ×1. 0 cm, respectively. The mean lymph nodes harvest and positive lymph node retrieval were 14(1～60) and 0. 7(0～3), respectively. Negative resection margins were obtained in 84. 2% (48/57) of patients. This study was censored on December 31, 2017. The follow-up for these patients ranged between 1 to 32 months. Mortality occurred in 21 patients, including 1 patient with a ruptured aneurysm 2 months after operation, 2 patients with GI bleeding 2 and 9 months respectively after operation, 1 patient with severe pulmonary infection and 17 patients with cancer recurrence with survival varying from 2 to 21 months. 35 patients were still alive. Conclusion Laparoscopic pancreaticoduodenectomy is a safe and feasible procedure for pancreatic head cancer.

Objective To analyze the clinical outcomes and surgical procedures of 32 patients who underwent laparoscopic radical resection of hilar cholangiocarcinoma.Methods From January 2013 to July 2018,32 patients who were diagnosed to have hilar cholangiocarcinoma underwent total laparoscopic treatment in Second Hospital of Hebei Medical University.The clinical data of these patients were recorded,including the general data,Bismuth types,AJCC types,postoperative complications,pathological findings,and follow-up results.Results This study included 20 males and 12 females with a mean age of 60.9±8.8 years and a body mass index of 22.6±3.2 kg/m2.According to the preoperative imaging studies,the Bismuth types Ⅰ,Ⅱ,Ⅲa,Ⅲb,and Ⅳ were found in 12,2,3,4 and 11 patients,respectively.Laparoscopic radical resection of hilar cholangiocarcinoma and bilioenteric anastomosis was performed in 12 patients,with radical resection and external bile drainage in 6 patients,extended hemihepatectomy with caudate lobectomy in 6 patients and concomitant portal vein resection in 2 patients.The mean operative time was 365.6± 121.9min and the median intraoperative blood loss was 300 (75,400) ml.Intraoperative red cell and plasma transfusion were 0-15 U and 400(0,625)ml,respectively.According to the Clavien-Dindo complication classification system,5 of 32 (15.6％) patients developed type Ⅱ morbidity.The postoperative pathological findings revealed bile duct adenocarcinoma in 30 patients and mucinous adenocarcinoma in 2 patients.The median size of cancer was 3.0 (1.0,3.5) cm.According to the 8th AJCC staging system,stage Ⅰ,Ⅱ,Ⅲ,and Ⅳ were found in 6,13,11,and 2 patients,respectively.A negative resection margin was achieved in 24 of 32 patients (75％).Up to August 6,30 of 32 patients (93.8％) were followed up and the overall 1-,2-,and 3-year survival rates for the patients who underwent laparoscopic radical resection for hilar cholangiocarcinoma were 80.0％,53.0％,and 53.3％.The median survival time was 21.8 months.Conclusion Total laparoscopic surgery for hilar cholangiocarcinoma was safe and feasible if performed by an experienced surgeon after accurate preoperative evaluation.

Objective To provide a simple, convenient, and safe anesthesia method for the establishment of a M1 segment of middle cerebral artery occlusion model in rhesus monkey or other large laboratory animals.Method Twenty male rhesus monkeys weighing 7-11 kg (ages 7-9 years) from Academy of Military Medical Sciences were used in this study.Sumianxin injection combined with 0.1 mg/kg ketamine was given before endotracheal intubation (ID:4.5-5.5#).The animals were then transported to an interventional operation room, where the intravenous access was established and a urinary catheter was inserted into the urinary bladder.Mechanical ventilation was used during the surgery, propofol was continuously injected in a speed of 2-4 mg/kg/h, and Sumianxin-ketamine could be given if necessary to maintain adequate anesthesia depth.The dose was adjusted according to vital signs of the rhesus such as body movements, physiological parameters, and demand of surgery.Brain MRI examination was performed before and after thrombolysis.Anesthetic injection was suspended and the animals were allowed to have a spontaneous breathing every time before the MRI text.Heart rates, temperature, non-invasive blood pressure, and SpO2 were monitored during the whole surgery.Blood samples were taken from the radial artery for blood gas analysis after anesthesia induction and during operation.Results All the 20 animals underwent the operation successfully, no animal had restlessness, respiratory depression, arrhythmia and other serious complications.At the end of the study, animals awake soon.Fifteen of them survived longer than 24 hours, only 5 died from serious cerebral hemorrhage and larger cerebral infarction.Conclusions General endotracheal anesthesia is safe for rhesus monkeys during such interventional operation and MRI examination.

OBJECTIVE: To observe the expression changes of metadherin (MTDH) and matrix metalloproteinase-9 (MMP-9) in the laryngeal squamous cell carcinoma tissues and to investigate the significance. METHOD: The expression of MTDH and MMP-9 in 54 cases of laryngeal squamous cell carcinoma tissues(observation group) and 30 cases of para-carcinoma tissues (control group) was examined by immunohistochemical method, the correlation between them and their correlations with the clinicopathological parameters were analyzed. RESULT: The positive expression rates of MTDH in the observation group and control group were 64.8% (35/54) and 6.7% (2/30), respectively; the positive expression rates of MMP-9 in the observation group and control group were 70.4% (38/ 54) and 13.3% (4/30), respectively; and there was a statistically significant difference between two groups (all P < 0.01). In the laryngeal squamous cell carcinoma tissues, the expression of MTDH protein was related with degree of differentiation, lymph-node metastasis and TNM stage (all P < 0.05); and the expression of MMP-9 protein was related lymph-node metastasis and TNM stage (all P < 0.05). The expression of MTDH was positively correlated with MMP-9 in the laryngeal squamous cell carcinoma tissues (r = 0.371, P < 0.01). CONCLUSION The high expression of MTDH and MMP-9 was closely related to the occurrence, development and metastasis of laryngeal squamous cell carcinoma, joint detection of the two proteins was valuable for early diagnosis and prognosis of laryngeal squamous cell carcinoma.
Carcinoma, Squamous Cell ; diagnosis ; metabolism ; Case-Control Studies ; Cell Adhesion Molecules ; metabolism ; Cell Differentiation ; Head and Neck Neoplasms ; diagnosis ; metabolism ; Humans ; Laryngeal Neoplasms ; diagnosis ; metabolism ; Lymphatic Metastasis ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasm Staging ; Prognosis ; Squamous Cell Carcinoma of Head and Neck

The protective effects of Da Chai Hu Granules (DCHKL) on islet cells which were incubated with 4 mmol x L(-1) alloxan (AXN) were studied. The viability of islet cells were measured with MTT. Insulin released into medium and in islets was detected by radioimmunoassay. Cell apoptosis rate was determined by flow cytometry. The expression of anti-apoptotic gene Bcl-2 and pro-apoptotic gene Bax in islet cells were measured with RT-PCR (reverse transcription polymerase chain reaction). Serum containing DCHKL can promote the activity of islet cells significantly (P < 0.01). Basal insulin secretion and high glucose-stimulated insulin secretion increased significantly (P < 0.01). Serum containing DCHKL can inhibit apoptosis of islet cells, the ratio of apoptosis was decreased. Serum containing DCHKL increased expression of Bcl-2 mRNA and decreased expression of Bax mRNA. DCHKL can significantly promote proliferation of islet cells and increase the amount of basal secretion of pancreatic islet cells and high glucose-stimulated insulin secretion. The expression of Bcl-2 increased significantly. The expression of Bax decreased significantly. DCHKL have a protective effect on the islet cells.