ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

BACKGROUND:Zinc-based alloy medical implant materials have excellent mechanical properties,complete degradability and good biocompatibility,and are mainly used in orthopedic implants,cardiovascular stents,bile duct stents,tracheal stents,nerve catheters,etc. OBJECTIVE:To review the research progress of biodegradable zinc-based alloys in bone defect repair and prospect the promising research direction and achievements of zinc-based materials. METHODS:After searching PubMed,Web of Science,WanFang Data,and CNKI databases from the establishment of the database to June 2023,various relevant articles on biodegradable zinc-based alloys for bone implant material research were collected.The basic characteristics of biodegradable zinc based alloys were summarized,and the role of zinc-based alloys in promoting bone tissue repair was sorted and summarized.The current research hotspots and shortcomings were discussed. RESULTS AND CONCLUSION:(1)Zinc-based alloys have good biocompatibility.Using zinc-based alloys as the matrix material,with the help of scaffold structure construction technology and coating optimization process,the bone conductivity of zinc-based alloys will be effectively improved,and their degradation products will have efficient bone induction to regulate the gene expression of osteoblasts and osteoclasts,thereby promoting the repair and reconstruction of bone defects.(2)However,in the research on optimizing zinc-based alloys,the coating process is relatively insufficient,and additive loading technology is still lacking.(3)Zinc-based alloys have excellent mechanical and biological properties.Through special processes,their bone conductivity and osteoinductivity can be increased to effectively improve their ability to promote bone repair and reconstruction,and it is expected to further achieve the development of personalized transplant materials.Further research and development are needed to optimize the integration of coating and additive loading technologies into zinc-based alloys.

ObjectiveTo find out whether there is any difference in the monitoring results of mosq-ovitraps placed in different orientations in multi-storey residential areas, so as to provide a scientific basis for routine and emergency monitoring of Aedes albopictus with mosq-ovitraps in residential areas. MethodsFrom July 6th to October 26th 2023, one mosquito ovitrap was set up in each of the 4 orientations of east, south, west and north around the buildings in a multi-storey residential area in Jinhui Town, Fengxian District, Shanghai. Data was collected and recorded 72 hours after placement. The chi-square test was used to compare the mosquito ovitrap indices (MOIs) of two independent samples, and the Kruskal⁃Wallis H test was used to compare the MOIs of multiple independent samples. ResultsAfter 16 weeks of surveillance, 997 mosquito ovitraps were recovered, of which 211 were positive, with the mosquito ovitrap index (MOI) of 21.16% and the Aedes albopictus density index of 1.03 mosquitoes·ovitrap^-1. The MOIs were higher in September (24.22%) and October (23.96%), and the MOIs in the west, south and north within the two months were all above 20.00%. From July to October, the MOIs in the east, west, south and north were 20.70%, 22.20%, 25.50% and 16.20%, respectively, and the difference in MOIs among the 4 orientations was not statistically significant (χ²=6.647, P=0.084). Stratified analysis by month showed that in August, the south side of the multi-storey residential areas had the highest MOI (31.30%), the north side had the lowest MOI (1.30%), and there was a statistically significant difference in MOI in the east, west, south and north (χ²=25.986, P<0.001). In October, the MOI in the west was the highest (33.30%) and the MOI in the east was the lowest (6.30%), the difference in MOIs of the 4 orientations was statistically significant (χ²=12.007, P=0.007). The MOIs in the south side of the building in the outskirts of the residential area from the 1st week in July to the 4th week in October was lower (19.20%) than that in the south side of the inner building (31.70%), and the difference in MOI was statistically significant (χ²=5.118, P=0.024). ConclusionThe study of MOI in different orientations in a multi-storey residential area is a preliminary exploration based on field work, and the results show that there is a difference in MOIs in different orientations during the peak breeding period of mosquitoes. Further indicators such as temperature, humidity and wind speed in different orientations can be collected to explore the influencing factors of MOIs.

Objective To investigate the clinicopathological and prognostic characteristics of intestinal inflammatory myofibroblastic tumours(IMT)in middle-aged and elderly patients.Methods The clinical,pathologi-cal morphology,immunophenotype and follow-up results of 5 cases of intestinal IMT in middle-aged and elderly patients were retrospectively analyzed.Results 4 cases of IMT occurred in the right half colon and 1 in the ileum.Most patients(3/5)had a history of intestinal injury,starting the digestive tract symptoms and increased leukocytes.The tumor tissue was composed of fusiform myofibroblasts and fibroblasts arranged in storiform pattern,with an infiltrative growth pattern,accompanied by a large number of lymphocytes and plasma cells infiltration,collagen formation and myxedema.One case was atypically large and deformed.Immunophenotype:vimentin(5cases),SMA(5 cases),desmin(3 cases),ALK(3 cases),CK(2 cases)were positive.Caldesmon,CD34,β-catenin,MC,CD117,DOG1,S-100,BCL-2,CD99,CD68 were negative,and Ki-67 proliferation index was 1.28%to 10.01%.All the 5 cases underwent complete tumor resection and were followed up for 48.5 to 133 months.Among them,1 patient aged 83 was considered to have tumor recurrence 27 months after surgery.The other patient survived 122 months without tumor and died of other causes.All the others survived without tumor and were in good condition.Conclusion(1)Intestinal IMT in the middle-aged and elderly people in this group was more common in the right half colon,and most of them had a history of intestinal injury,first gastrointestinal symptoms and elevated white blood cells;(2)Vimentin and SMA were positive at the same time,and ALK was more positive;(3)4/5 patients had good surgical resection,and 1/5 patients could relapse 2～3 years after surgery;old age,ALK-positive,Ki67 up to 10%,atypia may be an important risk factor for intestinal IMT recurrence in the elderly,of which ALK-positive patients may have a recurrence risk of 1/3.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Objective:To investigate the efficacy and safety of recombinant human endostatin(Endostar)combined with platium-contained chemotherapeutic agents in advanced non-small cell lung cancer(NSCLC)patients over 60 years old.Methods:93 advanced NSCLC patients from January 2019 to June 2021 were selected as the research objects.The patients received three days of continuous intravenous infusion of Endostar(210 mg for 72 hours)combined with platinum-containing chemotherapy.The efficacy and toxicities were evaluated according to Response Evaluation Criteria in Solid Tumors(RECIST)version1.1 and National Cancer Institute Common Terminology Criteria for Adverse Events(NCI-CTCAE version 4.0), respectively.Follow-up data were obtained to perform the Kaplan-Meier survival analysis.Results:In our study, the objective remission rate(ORR)and disease control rate(DCR)were 38.7% and 78.5%, respectively.The median progression-free survival(PFS)and overall survival(OS)were 6.8 months and 16.5 months, respectively.A Multivariate analysis showed that tumor staging and TP53 mutation were independent prognostic factors related to PFS and OS in advanced NSCLC patients.Adverse reactions related to Endostar during treatment included arrhythmia in 2 cases(2.2%), myocardial ischemia in 1 case(1.07%)and bloody sputum in 1 case(1.07%), all of which were Grade 1 or Grade 2.Conclusions:The application of three days continuous intravenous infusion of Endostar combined with platium-contained chemotherapeutic agents is worthy to be recommended for clinical application in elderly patients with advanced NSCLC due to its high effective rate and survival advantage, as well as good safety.

Objective To determine the causal relationship between acromegaly and colon cancer by using two-sample Mendelian randomization. Methods Genetic loci closely related to acromegaly in the whole genome-wide association study (GWAS) were selected as tool variables, and the genetic data of colon cancer from different GWASs were analyzed by two-sample Mendelian randomization (MR).The inverse variance weighting method (IVW) of the random effect model was used for analysis, and MR-weighted median and MR-Egger methods were used to supplement the analysis. Results were presented as OR values. Results Four SNPs closely related to acromegaly were obtained as tool variables, and the multiplicity test of tool variables showed that P=0.59.Three methods were used to estimate causal effects.The IVW analysis were OR=1.00(0.99-1.001) and P=0.42;the MR-Egger analysis results were OR=1.00(0.99-1.001) and P=0.42;and the Weighted median analysis results were OR=1.00(1.00-1.001) and P=0.03.The sensitivity test showed that the confidence interval of the tool variable SNP passed through 0, indicating the robustness of the MR results. Conclusion Acromegaly is not an independent risk factor for colon cancer.

Objective:To build an evaluation index system for linac stability and establish a scientific, systematic and objective evaluation standard for the stability of linac equipment.Methods:Based on the Delphi and AHP methods, a three-level index system for the stability of linac equipment was established, and the correlation coefficients and weights were calculated using Microsoft Excel 2007 and SPSS 16.0.Results:The enthusiasm of experts in two rounds was 85%(17/20) and 92%(23/25), the authority coefficients were 0.79 and 0.87, and the expert Kendall coordination coefficients were 0.957(first-level index, P<0.05), 0.637(second-level index, P<0.05) and 0.527(third-level index, P<0.05), respectively. Finally, a three-level index system covering 2 first-level indicators of mechanical treatment system and accessory system, 9 second-level indicators and 32 third-level indicators was established. The CVs of all levels of indicators were less than 0.25 and passed the consistency test. Conclusion:The evaluation index system for linac equipment stability has good scientificity, operability and versatility, which can provide theoretical and quantitative reference for linac stability evaluation and equipment purchase.

Objective:To compare the clinical efficacy between 3D printing-assisted percutaneous balloon dilatation calcaneal plasty (3D-PCP) and conventional open reduction and internal fixation (ORIF) via the extended lateral L-shaped approach in the treatment of osteoporotic calcaneal fractures of Sanders type Ⅱ or Ⅲ in the elderly patients.Methods:Retrospectively analyzed were the data of 36 elderly patients with osteoporotic calcaneal fracture of Sanders type Ⅱ or Ⅲ who had been surgically treated at Department of Orthopaedics, Yixing People's Hospital from June 2012 to June 2018. According to their treatment methods, the patients were divided into a 3D-PCP group [16 cases, 9 males and 7 females with an age of (73.0 ± 3.4) years] and an ORIF group [20 cases, 8 females and 12 females with an age of (71.4 ± 2.6) years]. The 2 groups were compared in terms of hospital stay, operation time, intraoperative fluoroscopy frequency, suture removal time, weight bearing time, fracture healing time, visual analogue scale (VAS) for the surgical site 2 days and one year after surgery, American Foot and Ankle Surgery Association (AOFAS) ankle-hindfoot score, calcaneal imaging parameters (B?hler angle, Gissane angle, and length, width and height of the calcaneus axis) at 2 days and one year after surgery, and postoperative complications.Results:There was no significant difference in the preoperative general data between the 2 groups, showing comparability ( P > 0.05). All patients were followed up for 14 to 18 months (mean, 15.6 months). Compared with the ORIF group, the 3D-PCP group had significantly shorter hospital stay, significantly shorter operation time, significantly earlier suture removal, significantly earlier weight-bearing, significantly lower VAS scores at 2 days after surgery, significantly higher AOFAS ankle-hindfoot scores at one month after surgery, but significantly more times of intraoperative fluoroscopy (all P < 0.05). In all patients, the VAS scores at 2 days after surgery were significantly lower than those before surgery, and those at one year after surgery significantly lower than those at 2 days after surgery ( P < 0.05). In all patients, the AOFAS ankle-hindfoot scores at one month after surgery were significantly higher than those before surgery ( P < 0.001). In the ORIF group, the AOFAS ankle-hindfoot scores at one year after surgery were significantly higher than those at one month after surgery ( P < 0.05), but in the 3D-PCP group there was no such a significant difference between one year and one month after surgery ( P > 0.05). There was no significant difference in VAS score, AOFAS score, fracture healing time or postoperative imaging parameters between the 2 groups at one year after surgery ( P > 0.05). There was no significant difference either in the incidence of complications between the 2 groups ( P > 0.05). Conclusion:In the treatment of osteoporotic calcaneal fractures of Sanders type Ⅱ or Ⅲ in the elderly patients, compared with conventional ORIF, 3D-PCP shows advantages of shorter operation time, minimal invasion, quicker incision healing, shorter hospital stay, earlier weight-bearing exercise, and better functional recovery but a disadvantage of increased times of intraoperative fluoroscopy.