ObjectiveThis study aims to enhance of the farnesyl pyrophosphate（FPP） pool in Saccharomyces cerevisiae by heterologously expressing different farnesyl diphosphate synthases（FPSs） from various plants， thereby increasing the production of terpenoid compounds by the engineered yeast. MethodsRNA from mixed samples of roots， stems， and leaves of seven plants including Arabidopsis thaliana， Rosa rugosa， Artemisia annua， Centella asiatica， Humulus lupulus， Medicago sativa， and Panax ginseng was extracted by column chromatography and reverse transcribed into the first strand of complementary DNA（cDNA）， and based on the transcriptome data of the seven species of plants， sequence-specific primers were designed for CaFPS， RrFPS， MsFPS， HiFPS， PgFPS， AtFPS， and AaFPS， the full-length of the genes was cloned， and the genes were analyzed for bioinformatics in order to construct a pESC yeast shuttle vector. These seven plant-derived FPSs were further heterologously expressed in the previous constructed β-elemene-producing yeast， and the yield of β-elemene was indicated for their catalytic acivities. ResultsThe coding sequences of CaFPS， RrFPS， MsFPS， HiFPS， PgFPS， AtFPS， and AaFPS were all of 1 021 bp in length and encoding 301 amino acids， all of which were similarly related to the endogenous FPS-encoding gene（ERG20） in S. cerevisiae. After heterologous expression， RrFPS was identified as the most effective in catalyzing the synthesis of FPP from isopentenyl pyrophosphate（IPP） and dimethylallyl pyrophosphate（DMAPP）. Compared to the control strains， the RrFPS overexpressed yeast strains YB-1-Rr and YB-3-Rr increased the production of β-elemene by 231.25% and 189.3%， respectively. ConclusionBy comparing the functions of FPS-encoding genes from seven different plant sources， it is determined that the protein encoded by the RrFPS from R. rugosa has the best catalytic ability， which can provide key genetic elements for the construction of engineered yeast strain constructs with high terpenoid production.

ObjectiveThe research focuses on developing modeling and evaluation methodologies for an animal model exhibiting spleen deficiency and dampness excess syndrome， with the aim of standardizing such animal models for future reference. MethodsBy conducting a literature search on animal models of spleen deficiency and dampness excess syndrome， relevant publications meeting inclusion and exclusion criteria will be identified based on publication date， data source， types of diseases involved， animal characteristics， modeling methods， modeling duration， macroscopic syndrome assessment indicators， macroscopic quantification indicators， laboratory testing parameters， intervention approaches， positive controls and application context. A database will be established to facilitate the extraction of this information for quantitative analysis， statistical evaluation， and visual representation. ResultsA total of 137 literature articles meeting the standards have been included in the research. The primary animal species used in animal models of spleen deficiency and dampness excess are SD rats. Modeling methods include single-factor， dual-factor composite， and triple-factor composite methods， with various models widely applied in validation of pharmacological effects and mechanistic explorations. Evaluation indices of animal models for spleen deficiency and dampness excess primarily consist of macroscopic syndrome evaluation indicators and macroscopic quantitative indicators. Laboratory testing indicators are mostly related to research areas such as fluid metabolism and gastrointestinal function. The most commonly studied herbal formulas currently include Shenling Baizhu San and Pingwei San， with natural recovery and the use of the western medicine metronidazole as the most frequently used positive controls. ConclusionThe application of animal models for spleen deficiency and dampness excess is gradually increasing， with various modeling methods already simulating the typical characteristics of this syndrome pattern. However， there are still many areas that are worth contemplating and improving. This study aims to provide reference and ideas for the standardization of symptom names in animal models of spleen deficiency and dampness excess， as well as for the improvement of model construction and evaluation systems.

OBJECTIVE To optimize the simmering technology of Rheum palmatum from Menghe Medical School and compare the difference of chemical components before and after processing. METHODS Using appearance score， the contents of gallic acid， 5-hydroxymethylfurfural （5-HMF）， sennoside A+sennoside B， combined anthraquinone and free anthraquinone as indexes， analytic hierarchy process （AHP）-entropy weight method was used to calculate the comprehensive score of evaluation indicators； the orthogonal experiment was designed to optimize the processing technology of simmering R. palmatum with fire temperature， simmering time， paper layer number and paper wrapping time as factors； validation test was conducted. The changes in the contents of five anthraquinones （aloe-emodin， rhein， emodin， chrysophanol， physcion）， five anthraquinone glycosides （barbaloin， rheinoside， rhubarb glycoside， emodin glycoside， and emodin methyl ether glycoside）， two sennosides （sennoside A， sennoside B）， gallic acid and 5-HMF were compared between simmered R. palmatum prepared by optimized technology and R. palmatum. RESULTS The optimal processing conditions of R. palmatum was as follows: each 80 g R. palmatum was wrapped with a layer of wet paper for 0.5 h， simmered on high heat for 20 min and then simmered at 140 ℃， the total simmering time was 2.5 h. The average comprehensive score of 3 validation tests was 94.10 （RSD＜1.0%）. After simmering， the contents of five anthraquinones and two sennosides were decreased significantly， while those of 5 free anthraquinones and gallic acid were increased to different extents； a new component 5-HMF was formed. CONCLUSIONS This study successfully optimizes the simmering technology of R. palmatum. There is a significant difference in the chemical components before and after processing， which can explain that simmering technology slows down the relase of R. palmatum and beneficiate it.

OBJECTIVE To explore the effect and potential mechanism of the compatibility of Astragali Radix-Puerariae Lobatae Radix on ferroptosis of liver cells in type 2 diabetes mellitus （T2DM） insulin resistance （IR） rats. METHODS Sixty male SD rats were randomly divided into control group （12 rats） and modeling group （48 rats）. The modeling group was fed with a high- fat diet for 4 consecutive weeks and then given a one-time tail vein injection of 1% streptozotocin to establish T2DM IR model. The model rats were randomly divided into model group， the compatibility of Astragali Radix-Puerariae Lobatae Radix group [QG group， 4.05 g/（kg·d）， intragastric administration]， ferroptosis inhibitor ferrostatin-1 group [Fer-1 group， 5 mg/kg by intraperitoneal injection， once every other day]， the compatibility of Astragali Radix-Puerariae Lobatae Radix+ferroptosis inducer erastin group [QG+erastin group， 4.05 g/（kg·d） by intragastric administration+erastin 10 mg/（kg·d）， intraperitoneal injection]. After 4 weeks of intervention， serum fasting blood glucose （FBG） and fasting insulin （FINS） were measured in each group of rats， and homeostasis model assessment of insulin resistance （HOMA-IR） and the natural logarithm of insulin action index（IAI） were calculated； the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）， aspartate transaminase （AST） and alanine transaminase （ALT）， Fe2+ and Fe content， glutathione （GSH）， malondialdehyde （MDA） and superoxide dismutase （SOD） levels， NADP+/NADPH ratio and reactive oxygen species （ROS） were determined. The pathological morphology of its liver tissue was observed； the protein expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， long-chain acyl-CoA synthetase 3 （ACSL3）， ACSL4， ferritin mitochondrial （FTMT）， and cystine/glutamate anti-porter （xCT） in the liver tissue of rats were detected. RESULTS Compared with control group， the liver cells in the model group of rats showed disordered arrangement， swelling， deepened nuclear staining， and more infiltration of inflammatory cells， as well as a large number of hepatocyte vacuoles and steatosis； FBG （after medication）， the levels of TC， TG， LDL-C， AST， ALT， FINS， MDA and ROS， HOMA-IR， Fe2+ and Fe content， NADP+/NADPH ratio and protein expression of ACSL4 were significantly increased or up-regulated， while the levels of HDL-C， GSH and SOD， IAI， protein expressions of GPX4， FTH1， ACSL3， FTMT and xCT were significantly reduced or down-regulated （P＜0.01）. Compared with the model group， both QG group and Fer-1 group showed varying degrees of improvement in pathological damage of liver tissue and the levels of the above indicators， the differences in the changes of most indicators were statistically significant （P＜0.01 or P＜0.05）. Compared with QG group， the improvement of the above indexes of QG+erastin group had been reversed significantly （P＜0.01）. CONCLUSIONS The compatibility decoction of Astragali Radix-Puerariae Lobatae Radix can reduce the level of FBG in T2DM IR rats， and alleviate IR degree， ion overload and pathological damage of liver tissue. The above effects are related to the inhibition of ferroptosis.

OBJECTIVE To explore the clinical features， diagnosis， treatment and management measures of multiple immune- related adverse event （irAE） after toripalimab treatment， in order to provide reference for the clinical management of similar cases. METHODS A retrospective analysis was conducted on a post-operative bladder cancer patient who developed various irAEs after toripalimab treatment. The patient’s medical history， laboratory tests， imaging studies， treatment course and outcomes were detailed. The Naranjo scale was used to assess the relationship between the irAEs and toripalimab. RESULTS The patient developed irAEs after receiving toripalimab， such as immune-related myocarditis， liver dysfunction， and myasthenia. According to the Naranjo scale evaluation， it was assessed that these adverse events were related to the administration of toripalimab. After high- dose corticosteroid pulse therapy and immunoglobulin immunomodulation， the patient’s symptoms were effectively relieved， with a improved trend in various physiological indicators and significant improvement in the degree of system/organ damage. CONCLUSIONS Toripalimab may lead to multiple irAEs， including immune-related myocarditis， liver injury， and myasthenia. Early recognition， timely diagnosis， and appropriate treatment of irAE are crucial for improving patient’s prognosis.

Traditional Chinese medicine （TCM） therapy has unique clinical advantages in the treatment of atrial fibrillation， mainly reflected in five aspects， improving quality of life， enabling early diagnosis and treatment， promoting cardiac rehabilitation， making up for the limitations of Western medicine， and improving the success rate of catheter ablation. However， there is insufficient evidence in current clinical research. Based on the current status of TCM research in the treatment of atrial fibrillation， it is suggested that future studies should focus on standardized research on syndrome differentiation and classification. This can be achieved through clinical epidemiological surveys， expert consensus， and other methods to establish a unified syndrome differentiation and classification standard for atrial fibrillation. Clinical efficacy evaluation indicators should be standardized， and core outcome measures for clinical research on TCM treatment of atrial fibrillation should be developed through systematic reviews， patient interviews， and other methods. Additionally， clinical research design， implementation， and data management should be improved. By leveraging modern information technologies such as artificial intelligence， the scientific and standardized nature of TCM intervention research on atrial fibrillation can be enhanced， ultimately improving the quality of research.

Objective: To analyze the trend in burden of rheumatoid arthritis (RA) in China from 1990 to 2021, so as to provide insights into reducing the RA burden in China. Methods: Data of Global Burden of Disease Study 2021 were collected, and the incidence, mortality and disability-adjusted life years (DALY) of RA in China from 1990 to 2021 were analyzed and compared with global and different Socio-demographic Index (SDI) regions. The trend in burden of RA was analyzed using average annual percent change (AAPC). Results: The crude incidence rates of RA in China increased from 10.87/105 in 1990 to 17.38/105 in 2021, the crude mortality rates increased from 0.41/105 to 0.72/105, and the crude DALY rates increased from 34.26/105 to 58.61/105, with the increases of 59.98%, 77.95% and 71.06%, respectively. From 1990 to 2021, the standardized incidence rates of RA in China showed an increasing trend (AAPC=0.545%, P<0.05), the standardized mortality rates showed a decreasing trend (AAPC=-0.783%, P<0.05), and the standardized DALY rates showed no significant trend (AAPC=-0.017%, P>0.05). In 2021, the standardized incidence rate, standardized mortality rate and standardized DALY rate of RA were higher in females than in males; from 1990 to 2021, the standardized DALY rates of RA showed a decreasing trend in females (AAPC=-0.200%, P<0.05) and an increasing trend in males (AAPC=0.316%, P<0.05). The crude incidence rates of RA first increased and then decreased with age in 2021, reaching the highest in the age group of 75-<80 years at 34.36/105. Both the crude mortality rates and the crude DALY rates increased with age, reaching the highest in the age group of 95 years and older at 26.72/105 and 285.67/105, respectively. The standardized incidence rates and standardized DALY rates of RA in China in 2021 were lower than those in high SDI regions, while the standardized mortality rate was lower than that in medium-low SDI regions. Conclusions The burden of RA in China from 1990 to 2021 showed an upward trend, and was at a high level compared to different SDI regions. Higher disease burden of RA was seen in females and the elderly.

Objective: To analyze the trends in incidence and mortality of prostate cancer in Ningbo City, Zhejiang Province, so as to provide insights into the prevention and control of prostate cancer. Methods: Data of the incidence and mortality of prostate cancer in Ningbo City from 2011 to 2023 were collected through Ningbo Chronic Disease Collaborative Management System. The incidence and mortality of prostate cancer were calculated and standardized by the data from the sixth national population census in 2010 and the Segi's world standard population in 1960. The trends in incidence and mortality of prostate cancer were evaluated using average annual percent change (AAPC). Results: A total of 15 411 cases of prostate cancer were reported in Ningbo City from 2011 to 2023, and the crude incidence, Chinese-standardized incidence and world-standardized incidence were 39.62/105, 22.18/105 and 16.49/105, respectively, showing upward trends (AAPC=14.782%, 10.390% and 10.608%, all P<0.05). The Chinese-standardized incidence of prostate cancer was higher in urban areas than in rural areas, and both showed upward trends (25.14/105 vs. 19.44/105; AAPC=9.057% and 14.272%, both P<0.05). The crude incidence of prostate cancer in the groups aged 50-<60 years, 60-<70 years, 70-<80 years and ≥80 years showed upward trends (AAPC=11.657%, 14.031%, 10.734% and 5.300%, all P<0.05). A total of 3 739 deaths were reported, and the crude mortality, Chinese-standardized mortality and world-standardized mortality were 9.66/105, 5.23/105 and 3.71/105, respectively, showing upward trends (AAPC=8.458%, 3.620% and 3.602%, all P<0.05). The Chinese-standardized mortality of prostate cancer was higher in urban areas than in rural areas, and both showed upward trends (5.35/105 vs. 5.13/105; AAPC=3.183% and 3.962%, both P<0.05). The crude mortality of prostate cancer the groups ageds ≥80 years showed an upward trend (AAPC=7.482%, P<0.05). Conclusions From 2011 to 2023, the incidence and mortality of prostate cancer in Ningbo City showed upward trends. Special attention should be paid to urban residents, and prostate cancer screening should be strengthened among males aged 50 years and older.

Objective: To construct a prediction model for sleep disorders in shift workers of a chemical fiber enterprise, so as to provide the basis for early identification and prevention of sleep disorders in shift workers. Methods: Shift workers were sampled from a chemical fiber enterprise in Tongxiang City, Zhejiang Province using a cluster sampling method from August 2022 to July 2024. Demographic information, length of service and average weekly working hours were collected through questionnaire surveys. Depressive symptoms, anxiety symptoms and sleep disorders were evaluated using the Pittsburgh Sleep Quality Index, Patient Health Questionnaire and Generalized Anxiety Disorder Questionnaire, respectively. The shift workers were randomly divided into a training set and a validation set at a ratio of 7∶3. Predictive factors were selected using a multivariable logistic regression model based on the training set, and a nomograph model for prediction of sleep disorders in shift workers was established. The predictive values of the model were evaluated using the receiver operating characteristic (ROC) curve and calibration curve based on the training set and validation set. Results: Totally 673 shift workers were included, with a median age of 32 (interquartile range, 12) years. There were 493 males, accounting for 73.25%. There were 471 (69.99%) workers in the training set and 202 (30.01%) workers in the validation set. There were 274 workers with sleep disorders, accounting for 40.71%. The equation for the prediction model was ln[p/(1-p)]=-8.391+1.906×average weekly working hours+1.822×depressive symptoms+1.667×anxiety symptoms. The area under the ROC curve was 0.769 (95%CI: 0.661-0.835) for the training set and 0.655 (95%CI: 0.593-0.737) for the validation set, and Hosmer-Lemeshow test showed a good fitting effect (both P>0.05). Conclusion The nomograph model constructed by average weekly working hours, depressive symptoms and anxiety symptoms can be used to predict the risk of sleep disorders in shift workers of a chemical fiber enterprise.

The implementation of the "Regulations on Organ Donation and Transplantation" (hereinafter referred to as the new "Regulations") and supporting documents has laid a solid foundation for improving the organ donation and transplantation work system in accordance with laws and regulations. In order to better publicize, implement, and carry out the new "Regulations" and supporting documents, and in response to the problems and challenges encountered in actual work, combined with the development of the national human organ donation and transplantation work system and the national work on determination of brain death, this article analyzes and discusses the construction of hospitals' organ donation and transplantation work systems and the systematic multidisciplinary collaboration mechanism for organ donation, as well as several issues that need attention by the ethics committees for organ transplantation. The aim is to provide references for the construction of ethics committees for organ transplantation in China and to promote the continuous and healthy development of China's organ donation and transplantation cause.