Aim To explore the new mechanism of triptolide (TRI) inhibiting the progression of hepatocellular carcinoma (HCC) . Methods Different concentrations (0, 0 . 5, 2, and 8 jjunol • L~) of TRI were administered to act on liver cancer cells, and then the cell phenotypes and possible mechanisms were explored using experimental methods such as CCK-8, cell cloning, Transwell, and protein immunoblotting; siRNA was used to interfere with the target gene GSDME and its role was determined. Finally, the mechanism of TRI inhibiting the growth of HCC cells in vivo was validated using a transplanted tumor model. Results TRI could inhibit the proliferation, cloning, and invasion of HCC cells, and promote cell apoptosis. Immunoblotting results showed that the expression of GSDME was significantly upregulated in HepG2 or He-pal-6 hepatocellular carcinoma after TRI treatment, while the expression of cleaved caspase-3 and PARP also significantly increased. Knocking out GSDME could partially reverse TRI-induced cell apoptosis. At the same time, cells knocked down by GSDME had stronger cloning and migration abilities, and the apoptosis rate was reduced compared to the TRI treatment group alone. In vivo experiments showed that TRI inhibited HCC tumor growth, and the TRI + siGSDME group had a faster tumor growth rate than the TRI treatment group alone did. In addition, after TRI stimulation, p-eIF2a and ATF4 in HepG2 and Hepal-6 cells significantly increased. The immunofluorescence results showed a dose-dependent increase in the number of ATF4 positive cells in HepG2 and Hepal-6 cells after TRI stimulation. Conclusion The inhibitory effect of TRI on the growth and invasion of liver cancer cells may be related to its regulation of the ATF4/caspase-3/GSDME signaling pathway and promotion of liver cancer cell apoptosis.

ObjectiveBased on knowledge mapping， the studies on prediction models in the field of traditional Chinese medicine （TCM） were visually analyzed， which provided a reference basis for the excavation and evolution of the future research direction by combing the development process and summarizing the research hotspots and dynamic trends. MethodChina National Knowledge Infrastructure and Web of Science Core Collection databases were searched to obtain studies on prediction models in the field of TCM from inception to February 28， 2023. Endnote X20 software was used for document management. Knowledge mapping generated by CiteSpace software and VOSviewer software was used to visually analyze the characteristics of publication， institutional cooperation relationship， author cooperation network， co-citation， and keywords. ResultA total of 264 pieces of Chinese literature and 266 pieces of English literature were included， and the overall number of research publications showed an increasing trend year by year. The cooperation relationship between the issuing institutions showed obvious regional characteristics， with the closest cooperation relationship between the universities of TCM and their affiliated hospitals， as well as secondary units subordinate to scientific research institutions. The number of research teams and team members publishing papers in English was higher， and cooperation between different teams was more frequent. Groundbreaking and/or referential studies were widely cited and referred to. The highly cited literature was mainly published in complementary and alternative medicine journals and pharmaceutical journals. Research hotspots mainly focused on clinical prediction models of TCM， quantitative models of TCM， and specific modeling methods. The application of artificial intelligence technologies such as machine learning and deep learning in the field of TCM will be the most cutting-edge research direction in the future. ConclusionThe field of TCM is paying more and more attention to the studies on prediction models， while the research cooperation mode involving multiple organizations and teams has increasingly become the mainstream. With the continuous development of multi-disciplinary integration， studies on prediction models are closely related to the development and rise of innovative techniques and methods， and any breakthrough in theory or application will induce and guide a new round of research upsurge. Systematic reviews of topic-specific prediction models should be carried out in the future to provide evidence-based evidence.

OBJECTIVE To investigate the effects of Tongxie yaofang （TXYF） on the symptoms of rats with irritable bowel syndrome with diarrhea （IBS-D） by regulating colonic tryptophan hydroxylase 1 （TPH1）， serotonin transporter （SERT） and intestinal flora. METHODS Forty-two SD rats were randomly divided into control group （7 rats） and modeling group （35 rats）. In modeling group， rat model of IBS-D was established by intragastrical administration of 0.45 g/L senna leaf solution [10 mL/（kg·d）] combined with chronic unpredictable stimulation. Thirty-five successfully modeled rats were randomly divided into model group， pinaverium bromide group [15 mg/（kg·d）] and TXYF low-dose， medium-dose and high-dose groups [3.75、7.5、15 g/（kg·d）， calculated by crude drug]， with 7 rats in each group. Each administration group was orally administered the corresponding drug， once a day， for 10 consecutive days. The general condition and weight changes of each group of rats were compared before modeling， after modeling and before administration， after the last drug intervention； the diarrhea index and visceral sensitivity were detected， and pathological changes of colon tissue were observed after modeling and before administration， after the last drug intervention. The level and expression of 5-hydroxytryptamine （5-HT）， protein and mRNA expressions of TPH1 and SERT were determined in colon tissue. The diversity and structural changes of fecal intestinal flora of rats were analyzed. RESULTS There was no significant change in colon histopathology in each group. Compared with model group， the general condition of rats in each medication group improved. The daily body weight gain of rats was significantly increased， while diarrhea index， visceral sensitivity， the expressions of 5-HT and TPH1 in colon tissue were significantly decreased； SERT expression of colon tissue was significantly increased in TXYF medium-dose and high-dose groups （P＜0.05 or P＜0.01）. The diarrhea index， colon TPH1 protein expression and colon 5-HT protein positive rate in the TXYF low-dose group decreased while the mRNA expression of SERT increased significantly （P＜0.05）. There was a dose- dependent trend in the effect of TXYF. Compared with model group， Chao1 index and Shannon index of the rats in TXYF high- dose group were significantly decreased （P＜0.05 or P＜0.01）， the beneficial bacteria such as Firmicutes and Lactobacillus increased significantly， while the pathogenic bacteria such as Proteobacteria， Escherichia-Shigella and Rikenellaceae_RC9_gut_ group decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS TXYF can decrease the level of 5-HT and improve intestinal flora disorder by inhibiting the expression of TPH1 and up-regulating the expression of SERT in colon tissue， thus promoting the symptoms of IBS-D rats.

Attention deficit hyperactivity disorder （ADHD）， also known as hyperactivity disorder in children， is a behavioral disorder commonly found in children， particularly preschool-aged children. This disorder can lead to cognitive impairment， learning difficulties， conduct disorders， and other mental health issues， severely impacting the quality of life for affected children. Moreover， the global prevalence of ADHD continues to rise. Establishing an animal model that closely aligns with clinical symptoms and the pathogenesis of the disease is crucial for advancing research on the prevention and treatment of ADHD. In recent years， research on animal models of ADHD has rapidly developed. Researchers have developed nearly 20 animal models from genetic and environmental perspectives. However， most of these models are still in the exploratory stage， and there is insufficient research to thoroughly investigate their pathogenesis， core characteristics， and drug effects. The spontaneously hypertensive rat （SHR） is currently the most commonly used animal model for ADHD because of its excellent face validity and developmental stage that better corresponds to childhood. In addition， dopamine transporter （DAT） knockout mice， LPHN3 knockout rats， and neonatal rat hypoxia models have also shown good face validity. Some researchers have injected SHRs with daily doses of levothyroxine sodium， which not only induces typical ADHD symptoms in the rats but also exhibits signs of Yin deficiency and Yang hyperactivity， which successfully simulates the Yin deficiency and Yang hyperactivity syndrome type of ADHD， providing a new approach for constructing and evaluating ADHD animal models that combine both traditional Chinese and western medicine. This article reviewed ADHD animal models reported in China and abroad over the past decade， summarized rodent models of ADHD into three major categories： genetic models， chemically induced models， and environmentally induced models， and analyzed each category to provide a reference for selecting and exploring appropriate models for experimental ADHD research.

Objective To explore the efficacy of T-cell spot test of tuberculosis infection(T-SPOT.TB)in the differential diagnosis of spinal tuberculosis(STB),and optimize diagnostic efficacy through the optimal cut-off value of receiver operating characteristic(ROC)curve.Methods Clinical data of patients with spinal infection in a hospi-tal from January 2010 to May 2019 were collected,including preoperative T-SPOT.TB test results,white blood cell count,C-reactive protein,erythrocyte sedimentation rate,procalcitonin,and tuberculosis antibodies,etal.Clinical diagnosis was conducted based on diagnostic criteria.The sensitivity and specificity of T-SPOT.TB in preoperative diagnosis of STB and other spinal infection was analyzed,and the diagnostic efficacy of the optimized T-SPOT.TB indicators was evaluated.Results A total of 132 patients were included in this study,out of whom 78 patients(59.09％)were diagnosed with STB,and 54(40.91％)were diagnosed with non-tuberculosis(non-TB)spinal in-fection.The sensitivity and specificity of T-SPOT.TB in differential diagnosis of STB were 67.68％and 66.67％,respectively.Univariate logistic regression analysis showed that compared with non-TB spinal infection,the OR va-lue of T-SPOT.TB test in diagnosing STB was 4.188(95％CI:1.847-9.974,P＜0.001).The optimized T-SPOT.TB evaluation index through ROC curve to determine the optimal cut-off values of ESAT-6,CFP-10,and CFP-10+ESAT-6 for differential diagnosis of STB and non-TB spinal infection were 12.5,19.5,and 36,respec-tively,and area under curve(AUC)values were 0.765 6,0.741 5,and 0.778 6,respectively,all with good diag-nostic efficacy.CFP-10+ESAT-6 had the highest AUC.CFP-10+ESAT-6 specific spot count had higher efficacy in the diagnosis of STB,with a diagnostic accuracy of 75.56％,higher than 67.42％of pre-optimized T-SPOT.TB.Conclusion T-SPOT.TB test has high diagnostic efficacy in differentiating STB from non-TB spinal infection.Posi-tivity in T-SPOT.TB test,especially with spot count of CFP-10+ESAT-6 over 36,indicates a higher likelihood of STB.

Objective To explore the effects of different concentrations of lidocaine infiltration and analgesia in pleural cavity after lung cancer surgery on rehabilitation of patients.Methods A total of 86 patients with lung cancer were selected and divided into the high concentration group(43 cases)and low concentration group(43 cases)by random number table method.Patients in the high concentration group received injection of 2.0%lidocaine hydrochloride in pleural cavity through the epidural catheter 1st day after surgery,and patients in the low concentration group received injection of 1.5%lidocaine hydrochloride in pleural cavity.In addition,patients in the two groups were treated with patient-controlled intravenous analgesia after surgery.The first time of getting out of bed,first time of exhaustion,first time of defecation and hospital stay after surgery of the two groups were compared.The visual analogue scale(VAS)scores 6 hours,12 hours,24 hours and 48 hours after surgery,the occurrence of agitation during the postoperative awakening period,and the number of analgesic pump compressions and the dosage of analgesic drugs within 24 hours after surgery were compared.The incidence of adverse drug reactions 24 hours after surgery were recorded and the quality of recovery of patients 24 hours after surgery was evaluated by 40-item quality of recovery score(QoR-40).Results The first time of getting out of bed,first time of exhaustion,first time of defecation and hospital stay after operation of patients in the high concentration group were shorter than those in the low concentration group(P<0.05).The VAS scores of the two groups 12 hours and 24 hours after surgery were higher than those 6 hours after surgery(P<0.05),the VAS scores 24 hours and 48 hours after surgery were lower than those 12 hours after surgery(P<0.05),and the VAS scores 48 hours after surgery were lower than those 24 hours after surgery(P<0.05).The VAS scores 6 hours,12 hours,24 hours,and 48 hours after surgery of patients in the high concentration group were lower than those in the low concentration group(P<0.05).The occurrence of agitation during the postoperative awakening period,and the number of analgesic pump compressions and the dosage of analgesic drugs within 24 hours after surgery for patients in the high concentration group were lower/less than those in the low concentration group(P<0.05).There was no significant difference in the total incidence of adverse drug reactions between the two groups(P>0.05).The total QoR-40 score of patients in the high concentration group were higher than those in the low concentration group(P<0.05).Conclusion The use of 2.0%lidocaine infiltration and analgesia in pleural cavity for patients after lung cancer surgery can reduce the agitation during the awakening period,alleviate the postoperative pain,improve the quality of postoperative recovery,and promote the postoperative recovery of the patients,with certain safety.

ObjectiveTo establish the clinical comprehensive evaluation index system for Chinese patent medicine（CPM） based on Evidence and Value：Impact on DEcisionMaking（EVIDEM） framework， so as to promote the scientific， systematic and standardized implementation of clinical comprehensive evaluation of CPM. MethodThe clinical comprehensive evaluation index system was determined through literature review， semi-structured interview and Delphi method， and the weights of each index were clarified by analytic hierarchy process（AHP）. ResultThe recovery rates of both rounds of expert consultation were 100%， and the authority coefficient of experts was 0.90 and 0.905， respectively. Kendall's coordination coefficients（W） of the second- and third-level indicators in the first-round consultation were 0.320 and 0.283（P<0.001）， and in the second round were 0.411 and 0.351， respectively（P<0.001）. The finally constructed clinical comprehensive evaluation index system for CPM included 6 first-level indicators， 13 second-level indicators and 28 third-level indicators. Among the first-level indicators， the weights of effectiveness， safety， economy， innovation， suitability and accessibility were 37.34%， 32.68%， 11.85%， 5.87%， 5.79% and 6.47%， respectively. ConclusionThis study has constructed a universal clinical comprehensive evaluation index system for CPM， and the domain and criteria are introduced and interpreted in detail， which can provide reference and information for carrying out the clinical comprehensive evaluation of CPM， but it needs to be refined and improved in combination with the clinical practice of CPM for specialized diseases.

Cation exchange chromatography, as a commonly used separation and purification technique in biopharmaceutical manufacturing, is often employed for downstream processes to separate target monoclonal antibodies from their charge variants. For samples with complex and poorly resolved charge variant profiles, the collection solely based on ultraviolet detection does not provide specific compositional information for individual charge variants, making it challenging to determine the range of pooled fractions directly. Subsequent laborious fractionation analysis is then required to guide collection according to production requirements. A mechanistic model for the cation exchange chromatography process of the target monoclonal antibody's critical components was established, and it was employed to assist in product collection. The model accurately predicted the elution peak shapes of the modeled variants, with a root mean square error between predicted and actual values below 0.009. In comparison to the online ultraviolet-based collection method, the model-assisted collection method not only visualized the chromatographic process but also increased the relative productivity by fourfold while ensuring compliance rate.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To investigate the effect of individualized psychological nursing intervention on anxiety,de-pression and sleep quality of elderly patients with coronary heart disease(CHD)during the CO VID-19 epidemic.Methods:A total of 128 elderly CHD patients who were treated in our hospital during the CO VID-19 epidemic from Jan 2020 to Feb 2021 were selected,and randomly divided into control group(n=64,routine nursing)and in-tervention group(n=64,received individualized psychological nursing intervention),both groups were treated for one month.The scores of self-rating anxiety scale(SAS),self-rating depression scale(SDS)and Pittsburgh sleep quality index(PSQI)were compared between two groups before and after intervention.Results:Compared with before intervention,after intervention,there were significant reductions in scores of SAS,SDS,all dimensional scores and total score of PSQI in two groups,P＜0.01 all;compared with control group after intervention,there were significant reductions in scores of SAS[(53.31±1.87)points vs.(32.13±1.24)points],SDS[(44.14±1.38)points vs.(33.88±1.06)points]and total score of PSQI[(8.98±2.17)points vs.(7.33±1.26)points]in intervention group,P=0.001 all.Conclusion:The application of individualized psychological nursing intervention can significantly alleviate patient's anxiety and depression,improve quality of sleep in elderly CHD patients during the CO VID-19 epidemic,which helps to improve prognosis.