In this study, araucarene diterpenes, characterized by a pimarene skeleton with a variably oxidized side chain at C-13, were investigated. A total of 16 araucarene diterpenoids and their derivatives were isolated from the woods of Agathis dammara, including 11 previously unreported compounds: dammaradione (1), dammarones D-G (2, 5, 14, 15), dammaric acids B-F (8-12), and dammarol (16). The structures of these new compounds were elucidated using high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) and one-dimensional/two-dimensional (1D/2D) nuclear magnetic resonance (NMR), while their absolute configurations were determined through the electronic circular dichroism (ECD) exciton chirality method and Snatzke's method. The hypoglycemic activity of all isolated compounds was evaluated using a transgenic zebrafish model, and a structure-activity relationship (SAR) analysis was conducted. Araucarone (3) and dammaric acid C (9), serving as representative compounds, demonstrated significant hypoglycemic effects on zebrafish. The primary mechanism involves the promotion of pancreatic β cell regeneration and glucose uptake. Specifically, these compounds enhance the differentiation of pancreatic endocrine precursor cells (PEP cells) into β cells in zebrafish.
Zebrafish ; Animals ; Diterpenes/isolation & purification* ; Insulin-Secreting Cells/cytology* ; Glucose/metabolism* ; Hypoglycemic Agents/isolation & purification* ; Molecular Structure ; Structure-Activity Relationship ; Plant Extracts/pharmacology* ; Regeneration/drug effects*

Objective To establish a nomogram model for predicting clinical pregnancy rate in patients with endometriosis undergoing fresh embryo transfer.Methods We retrospectively collected the data of 464 endometriosis patients undergoing fresh embryo transfer,who were randomly divided into a training dataset(60%)and a testing dataset(40%).Using univariate analysis,multiple logistic regression analysis,and LASSO regression analysis,we identified the factors associated with the fresh transplantation pregnancy rate in these patients and developed a nomogram model for predicting the clinical pregnancy rate following fresh embryo transfer.We employed an integrated learning approach that combined GBM,XGBOOST,and MLP algorithms for optimization of the model performance through parameter adjustments.Results The clinical pregnancy rate following fresh embryo transfer was significantly influenced by female age,Gn initiation dose,number of assisted reproduction cycles,and number of embryos transferred.The variables included in the LASSO model selection included female age,FSH levels,duration and initial dose of Gn usage,number of assisted reproduction cycles,retrieved oocytes,embryos transferred,endometrial thickness on HCG day,and progesterone level on HCG day.The nomogram demonstrated an accuracy of 0.642(95%CI:0.605-0.679)in the training dataset and 0.652(95%CI:0.600-0.704)in the validation dataset.The predictive ability of the model was further improved using ensemble learning methods and achieved predicative accuracies of 0.725(95%CI:0.680-0.770)in the training dataset and 0.718(95%CI:0.675-0.761)in the validation dataset.Conclusions The established prediction model in this study can help in prediction of clinical pregnancy rates following fresh embryo transfer in patients with endometriosis.

  Objective  To promote the development of high-quality health standards in China and summarize the characteristics of global health standards management systems and development processes.  Methods  We conducted a systematic search of relevant databases and the websites of standardization institutions. A descriptive method was used to analyze the basic characteristics of the standard management systems and development processes.  Results  The majority of the investigated countries and organizations primarily implement voluntary standards, with the exception of Chinese and the European Committee for Standardization that enforce compulsory standards. All countries and organizations have health standards at the national, group, and enterprise levels. In China and Japan, standards authorities are subordinate to the government, while in other countries or organizations, they operate as independent civil societies. The development process for health standards generally involves five stages: "Project/Proposal → Draft → Enquiry → Review → Publication". However, the specific steps in the development of health standards vary across different countries and organizations. Furthermore, China ranks high in the number of both standards and health standards issued, but the proportion of health standards is only 2.06%.  Conclusions  There are significant differences between China and other countries in terms of the management system and development process of health standards. To promote the management and development of high-quality health standards in China, we recommend promoting the coordination mechanism for standard development, increasing efforts to publicize standards and evaluate the implementation effect, strengthening the construction of personnel for the development of health standards, optimizing the efficiency of standard development and improving the internationalization level of health standards.

Objective To investigate the expression of LncRNA HOXA-AS2 in gastric cancer tissues and its effect on the malig-nant biology of gastric cancer.Methods The expression levels of lncRNA HOXA-AS2 in gastric cancer tissues and gastric cancer cell lines were detected by qPCR;the effect of lncRNA HOXA-AS2 on the prognosis of gastric cancer patients was analyzed by Kaplan-Meier Plotter,an online website for bioinformatics analysis;the correlation between the expression levels of lncRNA HOXA-AS2 and the clinical and pathological characteristics of gastric cancer patients;cell lines interfering with the expression of lncRNA HOXA-AS2 were constructed,and the effects of down-regulation of lncRNA HOXA-AS2 on the proliferation ability,migration ability and invasion ability of gastric cancer cells were analyzed using CCK8,clone formation assay,scratch assay and Transwell assay.Results The expression lev-el of lncRNA HOXA-AS2 was significantly upregulated in gastric cancer tissues compared with paraneoplastic tissues;the expression lev-el of lncRNA HOXA-AS2 was significantly higher in gastric cancer cell lines compared with human normal gastric mucosal cells GES(P＜0.05);survival analysis showed that high expression of lncRNA HOXA-AS2 was associated with poor prognosis of gastric cancer patients;lncRNA HOXA-AS2 expression level correlated with gastric cancer stage,lymph node metastasis and differentiation(P＜0.05);the expression level of lncRNA HOXA-AS2 was significantly decreased in gastric cancer cells transfected with SiRNA(P＜0.05),and their cell proliferation,migration,and invasion ability were also significantly decreased(P＜0.05).Conclusion lncRNA HOXA-AS2 plays an oncogene role in gastric cancer and is associated with prognosis.Down-regulation of lncRNA HOXA-AS2 ex-pression can inhibit the proliferation,migration,and invasion ability of gastric cancer cells.

Objective To establish a nomogram model for predicting clinical pregnancy rate in patients with endometriosis undergoing fresh embryo transfer.Methods We retrospectively collected the data of 464 endometriosis patients undergoing fresh embryo transfer,who were randomly divided into a training dataset(60%)and a testing dataset(40%).Using univariate analysis,multiple logistic regression analysis,and LASSO regression analysis,we identified the factors associated with the fresh transplantation pregnancy rate in these patients and developed a nomogram model for predicting the clinical pregnancy rate following fresh embryo transfer.We employed an integrated learning approach that combined GBM,XGBOOST,and MLP algorithms for optimization of the model performance through parameter adjustments.Results The clinical pregnancy rate following fresh embryo transfer was significantly influenced by female age,Gn initiation dose,number of assisted reproduction cycles,and number of embryos transferred.The variables included in the LASSO model selection included female age,FSH levels,duration and initial dose of Gn usage,number of assisted reproduction cycles,retrieved oocytes,embryos transferred,endometrial thickness on HCG day,and progesterone level on HCG day.The nomogram demonstrated an accuracy of 0.642(95%CI:0.605-0.679)in the training dataset and 0.652(95%CI:0.600-0.704)in the validation dataset.The predictive ability of the model was further improved using ensemble learning methods and achieved predicative accuracies of 0.725(95%CI:0.680-0.770)in the training dataset and 0.718(95%CI:0.675-0.761)in the validation dataset.Conclusions The established prediction model in this study can help in prediction of clinical pregnancy rates following fresh embryo transfer in patients with endometriosis.

Objective:To investigate the application value of laparoscopic natural orifice specimen extraction surgery (NOSES) based on purse-string suture for sigmoid colon and upper rectal cancer.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 14 patients undergoing laparoscopic NOSES based on purse-string suture for sigmoid colon and upper rectal cancer in The First Affiliated Hospital of Sun Yat-sen University from October 2022 to June 2023 were collected. There were 8 males and 6 females, aged (56±10)years. Observation indicators: (1) surgical conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers. Results:(1) Surgical conditions. All patients underwent laparoscopic NOSES based on purse-string suture for sigmoid colon and upper rectal cancer successfully, without conversion to open surgery. The operation time of 14 patients was (162±32)minutes, and the volume of intraoperative blood loss was (22±12)mL. (2) Postoperative conditions. Time to postoperative first out-of-bed activity, time to postoperative first flatus, time to postoperative first drinking, time to postoperative initial liquid food intake, duration of postoperative hospital stay of 14 patients were (1.6±0.7)days, (2.1±0.6)days, (2.4±0.6)days, (3.8±1.0)days, (6.0±0.9)days, respectively. None of patient had perioperative complications such as postoperative anastomotic leakage and bleeding. (3) Follow-up. All 14 patients were followed up for (9.7±1.9)months. There was no postoperative recurrence, metastasis or death in 14 pati-ents.Conclusion:The laparoscopic NOSES based on purse-string suture can be used for sigmoid colon and upper rectal cancer, which is safe and feasible.

Objective To investigate the key genes associated with ferroptosis in peri-implantitis and explore the potential mecha-nisms regulating peri-implantitis.Methods Several datasets were obtained from the GEO database.Differential expressed genes were screened,and GO and KEGG analyses were performed.A PPI network was constructed using the STRING website.Key genes were val-idated using a test set,and the diagnostic value of key genes was determined.The content and proportion of 22 immune cells in peri-im-plantitis tissues were obtained through immune infiltration analysis.Key genes were validated by qRT-PCR and Western Blot(WB).Results There were 1 138 differential genes between peri-implantitis tissues and normal gingival tissues,of which 29 were related to ferroptosis.The gene expression in peri-implantitis tissues mainly involved processes such as immune response activation.Five key genes in the ferroptosis-related differential genes,namely SOX2,GJA1,IL1B,GPX2 and CHAC1,were differentially expressed in peri-implantitis tissues and had high diagnostic value.Immune infiltration analysis showed significant changes in immune cells such as memory B cells and plasma cells in peri-implantitis tissues.qRT-PCR and WB confirmed significant differential expression of mRNA and the protein transcribed by key genes.Conclusion Differential genes between peri-implantitis and ferroptosis are screened using bioinformatics analysis and biological validation,providing new insights into the study on peri-implantitis.

In recent years, artificial intelligence-related technologies have been deeply combined with many medical fields, and the intersection of medicine and engineering has become a hot topic. There are problems with heavy data and difficulty making decisions in orthopedic disease diagnosis and treatment. Machine learning is an important method of artificial intelligence. Since it can automatically analyze and predict medical big data, it is widely used in the field of orthopedics. It also assists physicians in completing disease diagnosis and treatment efficiently. In this review paper, the application and progress of machine learning in preoperative, intraoperative, and postoperative diagnosis and treatment in orthopedics are reviewed, providing new ways for exploring more rational diagnosis and treatment strategies.

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.