Gegen Qinliantang is a representative prescription for dual releasing of exterior and interior and treating diarrhea with fever in the Treatise on Cold Damage and Miscellaneous Diseases （《伤寒杂病论》）. This prescription consists of Puerariae Lobatae Radix， Scutellariae Radix， Coptidis Rhizoma， and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle. The combination of the four herbal medicines has the ability to clear both the exterior and the interior， thereby halting diarrhea and clearing heat. According to the idea of treating different diseases with the same method， Gegen Qinliantang is used in clinical practice to treat type 2 diabetes mellitus （T2DM）， which demonstrates positive outcomes. T2DM is a chronic metabolic disease characterized by elevated blood glucose levels. The etiology and pathogenesis of T2DM are complex， mainly related to heredity， lifestyle， environment， diet and other factors. Clinical observations and experimental studies have shown that Gegen Qinliantang and its effective ingredients have significant effects of preventing and treating T2DM. Clinically， Gegen Qinliantang is often applied with modification， or in combination with Western drugs， demonstrating better therapeutic effects than Western drugs alone. Clinical practice has confirmed that Gegen Qinliantang can effectively alleviate the clinical symptoms， reduce the occurrence of complications， and alleviate gastrointestinal adverse reactions in T2DM patients. Experimental studies have demonstrated that Gegen Qinliantang can ameliorate insulin resistance and boost pancreatic function by regulating the insulin and inflammation signaling pathways， alleviating oxidative stress， and modulating gut microbiota to treat T2DM. Nevertheless， more thorough studies remain to be carried out to decipher the mechanism of Gegen Qinliantang in ameliorating insulin resistance in T2DM. To provide theoretical and data references for the subsequent in-depth research on the mechanism of Gegen Qinliantang in treating T2DM and the prevention and treatment of this disease， this article systematically reviews the clinical and experimental research progress of Gegen Qinliantang in ameliorating insulin resistance in T2DM.

Objectives:To investigate the effect of cardiac rehabilitation exercise guided by cardiopulmonary exercise test on cardiopulmonary function, cardiopulmonary endurance and activities of daily living in patients who had coronary heart disease after percutaneous coronary intervention (PCI).Methods:Seventy patients who had coronary heart disease after PCI treated in the Wenzhou Central Hospital from July 2022 to May 2023 were enrolled perspectively (3 cases eventually dropped out of the study), and they were divided into the control group (33 cases) and the rehabilitation group (34 cases) by random number table method. The control group was given conventional medication after PCI, while the rehabilitation group was additionally provided with exercise rehabilitation for 12 weeks on the basis of the control group. The patient′s cardiopulmonary function indicators, cardiopulmonary endurance indicators and ability of daily living(ADL) score of the two groups were compared before and after treatment.Results:After treatment for 12 weeks, the cardiopulmonary function indicators left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left atrial inner diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), forced expiratory volume in the first second (FEV 1), ratio of FEV 1 to forced expiratory volume (FVC) (FEV 1/FVC), maximum ventilation quantity (MVV) in the rehabilitation group were obviously improved compared with the control group: (102.8 ± 14.4) ml vs. (114.8 ± 20.4) ml, (39.9 ± 13.7) ml vs. (48.4 ± 16.9) ml, (37.1 ± 3.4) mm vs. (38.9 ± 3.6) mm, (50.3 ± 3.6) mm vs. (52.5 ± 4.7) mm, (64.0 ± 6.8)% vs. (59.6 ± 6.5)%, (2.39 ± 0.38) L vs. (2.10 ± 0.26) L, (77.7 ± 4.0)% vs. (73.8 ± 4.3)%, (101.6 ± 18.7) L/min vs. (89.6 ± 11.1) L/min, there were statistical differences ( P<0.05). After treatment for 12 weeks, the cardiopulmonary endurance indicators peak oxygen uptake (VO 2peak), peak oxygen uptake per kilogram of body weight (VO 2peak/kg), anaerobic threshold (AT), peak metabolic equivalent (METspeak), maximum working load (MWL) in the rehabilitation group were obviously improved compared with the control group: (1 441.8 ± 251.9) ml/min vs. (1 272.5 ± 207.0) ml/min, (20.7 ± 3.6) ml/(min·kg) vs. (18.2 ± 2.5) ml/(min·kg), (1 346.8 ± 201.3) ml/min vs. (1 075.4 ± 176.7) ml/min, (5.9 ± 1.1) Met vs. (5.2 ± 0.7) Met, (107.3 ± 29.1) Watt vs. (88.4 ± 17.8)Watt, there were statistical differences ( P<0.05). After treatment for 12 weeks, the ADL scores in the rehabilitation group was higher than that in the control group: (90.9 ± 8.1) scores vs. (85.6 ± 11.6) scores, there was statistical difference ( P<0.05). Conclusions:Carrying out cardiac rehabilitation exercise guided by cardiopulmonary exercise test can significantly enhance the cardiopulmonary function, cardiopulmonary endurance and self-care ability in patients who had accepted PCI for coronary heart disease.

In this study, a new in situ film of compound iodine oral spray was prepared by in situ gel technology, which was used to exert sustained-release effect for promoting the repair of oral ulcer wounds. Firstly, the formulation and process of the spray solution were optimized according to the spray state and film-forming time. The drug-liquid mixing ratio was evaluated by film-forming time and drug film adhesion. The drug content, stability, pH, and spraying effect of compound iodine oral spray prepared by the optimal formulation were investigated; and the physicochemical properties, including film formation time, solubility, hygroscopicity, moisture retention and in vitro release of drug film were evaluated. In addition, the biocompatibility of the film-forming materials and proliferation ability of drug film were investigated by cell experiment. Through the rabbit oral ulcer model, the in vivo film-forming and repair-promoting effects of compound iodine oral spray were evaluated. The results showed that the pH of liquid A and liquid B prepared were 6.21±0.02 and 6.42±0.03, respectively, which were in line with the normal pH range of oral mucosa; liquid A and liquid B had good stability and spray state; the iodine content in solution B was (1.96±0.01) mg/mL; the in situ membrane formation time in vitro and in the oral cavity were (118.3±3.6) s and (133.3±4.6) s, respectively; the 24-hour dissolution rate was (87.31±1.74)%, the moisture absorption rate was (124.17±7.13)%, and the moisture retention rate was (26.85±2.50)%; the iodine content in the oral spray was (47.42±0.39) mg/g, with good flexibility and adhesion, as well as some slow-release effect. In cell experiment, the film-forming materials showed good biocompatibility and growth promotion ability. The results of the rabbit oral ulcer experiment showed that the compound iodine oral spray could rapidly form a film in vivo and significantly promote the repair of oral ulcer. In conclusion, the compound iodine oral spray in situ film with a stable preparation process can effectively promote the repair of oral ulcer wounds, which provides a new idea for the research of novel oral mucosa formulations, with a good prospect of transfer.

Objective To analyze and summarize the clinical presentation of spontaneous and secondary intracranial hypotension syndrome(IHS).Methods Patients diagnosed with spontaneous or secondary IHS from September 2022 to May 2023 were retrospectively analyzed.The clinical data,imaging features,treatment methods and prognosis were collected.The correlation between intracranial pressure values and clinical characteristics of the patients was statistically analyzed.Results A total of 30 patients were enrolled,and the proportion of spontaneous and secondary IHS was 63%(19 cases)and 37%(11 cases),respectively.In terms of clinical features,orthostatic headache was the most common type(29 cases,96.7%)and most commonly involved occipital region(12 cases,40.0%),followed by frontoparietal region(9 cases,30.0%).Among the brain imaging features,dural enhancement was the most common(17 cases,56.7%).According to CT angiography of spinal cord findings,cerebrospinal fluid leakage is one of the most common location of cervical spine segments(10 cases),and on the thoracic segments(9 cases),followed by the thoracic segments(4 cases)and lumbar segments(4 cases).After conservative treatment and surgical treatment,the total effective rate was 90%.Conclusion Orthostatic headache and cranial MRI"dural enhancement"have strong indication on the definitive diagnosis of IHS.CT myelography is helpful to precisely localize the site of cerebrospinal fluid leakage.Targeted epidural blood patch therapy is an effective method to cure IHS when conservative treatment is ineffective.

Tetraacetyl phytosphingosine (TAPS) is an excellent raw material for natural skin care products. Its deacetylation leads to the production of phytosphingosine, which can be further used for synthesizing the moisturizing skin care product ceramide. For this reason, TAPS is widely used in the skin care oriented cosmetics industry. The unconventional yeast Wickerhamomyces ciferrii is the only known microorganism that can naturally secrete TAPS, and it has become the host for the industrial production of TAPS. This review firstly introduces the discovery, functions of TAPS, and the metabolic pathway for TAPS biosynthesis is further introduced. Subsequently, the strategies for increasing the TAPS yield of W. ciferrii, including haploid screening, mutagenesis breeding and metabolic engineering, are summarized. In addition, the prospects of TAPS biomanufacturing by W. ciferrii are discussed in light of the current progresses, challenges, and trends in this field. Finally, guidelines for engineering W. ciferrii cell factory using synthetic biology tools for TAPS production are also presented.
Sphingosine ; Ceramides ; Metabolic Engineering ; Synthetic Biology

Information technology has become an important driver to facilitate higher education developments in the context of new medical sciences. A new “virtual-real combination” experimental teaching model was designed and created through integrating information technology with experimental teaching by Experimental Teaching Center of Basic Medical Sciences and Department of Pathogen Biology, Nanjing Medical University and was applied in Human Parasitology teaching, which achieved satisfactory teaching effectiveness. This new model showed effective to deepen the understanding of the basic human parasitology knowledge, improve the operative skills, and cultivate the moral literacy and comprehensive capability among medical students. This report presents the teaching protocols and implementation, teaching effectiveness and evaluation, and experiences of comprehensive schistosome experiments.

Targeted therapeutic drugs for acute myeloid leukemia (AML) are showing immense development, thereby laying a solid foundation for the precise treatment of AML patients. The paper reviews four types of targeted drugs that have progressed rapidly for AML treatment (by targeting genes or signaling-pathway alterations, targeting apoptosis-related pathways, targeting cell-surface antigens, and targeting immune-related substances). We look forward to the future development directions of targeted drugs, providing references for hematologists and developers of new drugs for AML.

Background In recent years, the incidence of metabolic syndrome (MS) is increasing significantly in China. Some studies have found that temperature is related to single metabolic index, but there is a lack of research on associated mechanism and identifying path of the influence of temperature on MS. Objective Based on the data of Guangdong Province, to investigate the effect of temperature on MS and its pathway. Methods A total of 8524 residents were enrolled by multi-stage random sampling from October 2015 to January 2016 in Guangdong. Basic characteristics, behavioral characteristics, health status, and physical activity level were obtained through questionnaires and physical examinations, and meteorological data were obtained from meteorological monitoring sites. We matched individual data both with the temperature data of the physical examination day and of a lag of 14 d. A generalized additive model was used to explore the exposure-effect relationship between temperature and MS and its indexes, calculate effect values, and explore the effects of single-day lag temperature. Based on the literature and the results of generalized additive model analysis, a path analysis was conducted to explore the pathways of temperature influencing MS. Results The association between daily average temperature on the current day or lag 14 day and MS risk was not statistically significant. When daily average temperature increased by 1 ℃, the change values of fasting blood-glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), and high density lipoprotein cholesterol (HDL-C) were −0.033 (95%CI: −0.040-−0.026) mmol·L⁻¹, −0.662 (95%CI: −0.741-−0.583) mmHg, −0.277 (95%CI: −0.323-−0.230) mmHg, and −0.005 (95%CI: −0.007-−0.004) mmol·L⁻¹ respectively. The effects of average daily temperature on FBG, blood pressure, HDL-C, and waist circumference lasted until lag 14 day. The effects of daily average temperature on SBP and DBP were the largest on the current day. Daily average temperature of current day had direct and indirect effects on FBG and SBP. Temperature had an indirect effect on TG, and the intermediate variables were waist circumference and FBG, with an indirect effect value of −0.011 (95%CI: −0.020-−0.002). The indirect effects of daily average temperature on SBP, FBG, and TG were weak. Conclusion There is no significant correlation between temperature and risk of MS, and daily average temperature of current day could significantly affected blood pressure and FBG with a lag effect. Daily average temperature of current day has indirect effects on FBG and TG.

Objective To establish a druggability evaluation method for new targets of anti-tumor drugs by analyzing the mutation genes of common tumors in the digestive system. Methods We collected the mutant gene data of the five common tumors of the digestive system (esophageal cancer, gastric cancer, colorectal cancer, liver cancer and pancreatic cancer) in the Integrative Onco Genomics database, and screened out the genes with higher mutation rates in each tumor. We evaluated the druggability of these genes or their encoded proteins, and discovered the potential targets for the new anti-tumor drugs. Results A total of five tumors, 35 cohorts and 5445 tumor samples were collected in this study. The top 10 mutation genes were selected for further analysis. The canSAR database was used to analyze the druggability of unpublished mutant genes or their encoded proteins, and a total of 17 potential therapeutic drug targets were screened out. Conclusion A method for evaluating druggability of targets based on mutant genes or their encoded protein is established in this study. The application of this method can provide a reference for discovering new anti-tumor therapeutic target, saving the cost and time of target screening in new drug development.

Objective : To construct a cell-free DNA ( cfDNA) methylation model for early screening in male pa- tients with gastric cancer by using novel cfDNA methylation detection technology． Methods : Methylation informa- tion of the whole genome of gastric cancer patients were detected by cell-free methylated DNA immunoprecipitation and highthroughput sequencing ( cfMeDIP-seq ) technology and locate gastrogenic cfDNA． Then bioinformation methods were used to extract specific methylation labels which could distinguish GC patients and establish diagnosis model by random forest algorithm. Related validation clinical researches were also conducted. Results : 63 most sig- nificant DMR were selected to construct the cfDNA methylation model based on GC samples and normal control samples，the goal sensitivity was above 85 percent while the goal specificity was above 95% ．The sensitivity and specificity of the validation set were 98. 7% and 99. 0% while the area under curve(AUC) was 0. 999． Conclusion The cfDNA methylation model constructed in this study has good performance in predicting GC.