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.

Objective To investigate the ameliorating effect of salidroside(SAL)on cisplatin(CIS)-induced damages of cochlear hair cells(CHC)and spiral ganglion neurons(SGNs)and its relationship with cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)/cAMP response element binding protein(CREB)pathway.Methods The cochlear basilar membranes of newborn C 57BL/6 mice were isolated and separated into control(C)group,CIS group,SAL group,SAL+SQ22536(cAMP inhibitor)group and SAL+H-89(PKA inhibitor)group,20 per group.Immunofluorescence staining was applied to observe the damages of CHC and SGNs.The kits were applied to detect the contents of ROS and cAMP in the basement membrane of the cochlea.Western blot was applied to detect the protein levels of PKA,p-CREB,CREB,Bcl-2,BDNF,and NF-M.Results CHC in CIS group were disorderly arranged and enlarged in size,SGNs had fragmented nuclei and lost neurites.SAL alleviated the damages of CHC and SGNs.Compared with the C group,the numbers of CHC and SGNs in the CIS group were less(P＜0.05),the contents of ROS and cAMP,and the levels of PKA,BDNF,NF-M,Bcl-2 proteins and p-CREB/CREB were higher(P＜0.05).Compared with the CIS group,the numbers of CHC and SGNs in the SAL group were higher(P＜0.05),the content of ROS was lower(P＜0.05),the content of cAMP,and the levels of PKA,BD-NF,NF-M,Bcl-2 proteins and p-CREB/CREB were higher(P＜0.05).Both SQ22536 and H-89 reversed the pro-tective effects of SAL on CHC and SGNs.Conclusion SAL may promote the expression of anti-apoptotic proteins and neuroprotective factors by activating the cAMP/PKA/CREB pathway to alleviate the damages of CHC and SGNs caused by CIS.

Abstract Childhood obesity is one of the major global public health challenges and has a profound impact on the physical and mental health of children and adolescents. The article summarizes the establishment of gut microbiota in early life and the influences of early nutritional status and feeding patterns, maternal and infant microbiota transmission, delivery methods and the use of antibiotics on gut microbiota and childhood obesity. The paper focuses on the possibility of using the structural characteristics of gut microbiota (gene richness and evenness, relative abundance ratio and key indicator bacteria) as potential interventional targets and predictors of intervention effects in childhood obesity, and introduces the application of probiotics and other biological agents, as well as fecal microbiota transfer for the childhood obesity intervention, and briefly describes the latest progress in the mechanism of gut microbiota and childhood obesity, so as to provide the reference for the precise prevention and control of childhood obesity.

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 investigate the use of endoscopic retrograde cholangiopancreatography(ERCP)combined with laparoscopic cholecystectomy(LC)one-stage approach in the treatment of gallstones complicated with calculus of common bile duct in a hybrid operating room.Methods 21 patients with gallstones complicated with calculus of common bile duct were selected to undergoing ERCP bile duct stone removal under total intravenous anesthesia or combined intravenous and inhalation anesthesia,followed by LC.Results 18 successfully completed the one-stage surgery of ERCP combined with LC,3 were changed to laparoscopic common bile duct exploration(LCBDE),there was no laparotomy,8 cases were complicated by hyperamylemia after surgery,and there were no serious complications such as pancreatitis,gastrointestinal bleeding and perforation.Conclusion It is safe and feasible to use ERCP combined with LC one-stage approach to treat gallstones complicated with calculus of common bile duct in the hybrid operating room,which simplifies the surgical process.

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis caused by nonalcoholic factors, and its pathogenesis, progression, treatment, and prevention have attracted more and more attention. At present, an increasing number of studies have been conducted on the association of intestinal microecology with various metabolic diseases such as obesity, diabetes, and cardiovascular diseases. Recent studies have found that butyrate, a metabolite of intestinal flora, is closely associated with NAFLD and can affect the development and progression of NAFLD through various mechanisms, such as alleviating inflammatory response, inhibiting insulin resistance, and reducing oxidative stress of liver mitochondria. Exploration of the association between butyrate and NAFLD is expected to provide a new approach for the prevention and treatment of NAFLD.

As one of the stimulus-response polymeric intelligent materials, shape memory polymers have been widely applied in biomedicine due to their better biocompatibility, higher controllability, stronger deformation restorability and biodegradability compared with shape memory alloys and shape memory ceramics. This review will introduce the structural principles of shape memory polymers and summarize their applications in the treatment of vascular diseases, especially in endovascular therapy. At the same time, the related technical problems and the future of shape memory polymers are prospected. With the continuous development of processing technology and materials, it can be predicted that shape memory polymers will be more widely used in the medical field.

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