OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

Objective:To identify the relevant factors for the first-course remission of acute myeloid leukemia (AML) and to develop a predictive model as well as assess its predictive capability.Methods:Clinical data of 749 patients newly diagnosed with AML admitted to the Department of Hematology, the First Affiliated Hospital, Zhejiang University, School of Medicine from January 1, 2019, to April 30, 2023, were collected and randomly divided into training and validation sets. Multivariate logistic regression analysis was conducted to determine variables associated with complete remission in the first course of induction therapy, and a predictive model was established based on these variables. The receiver operating characteristic (ROC) curve of the predictive model was plotted, and the area under the curve (AUC) was calculated.Results:The indicators predicting the first remission course included peripheral blood white blood cell count during onset, CBF::MYH11 fusion gene, CEBPA bZIP region mutation, myelodysplastic syndrome-related gene mutation, and induction chemotherapy regimen selection as independent factors for the first remission course. The model’s area under the training and validation curves was 0.738 (95% CI: 0.696-0.780) and 0.726 (95% CI: 0.650-0.801), respectively. The Hosmer-Lemeshow test results yielded P-values of 0.993 and 0.335, respectively. Conclusion:In this study, the developed model demonstrates a strong predictive capability for the efficacy of the first course of patients with AML, providing valuable guidance to clinicians in assessing patient prognosis and selecting appropriate treatment strategies.

OBJECTIVE To investigate the mechanism of Pangshi antai zhixue decoction in the improvement of spontaneous abortion with heat syndrome by regulating the NOD-like receptor protein 3 (NLRP3) inflammasome.METHODS The binding activities of 13 main components in Pangshi antai zhixue decoction with NLRP3,apoptosis-associated speck-like protein containing a CARD (ASC),and caspase-1 precursor (pro-caspase-1) were predicted by molecular docking.Sixty 1-day-old pregnant rats were randomly divided into normal group,model group,dexamethasone group (0.002 g/kg),and Pangshi antai zhixue decoction low-,medium-,and high-dose groups (11.025,22.05,44.10 g/kg),with 10 rats in each group.Each group was given distilled water/corresponding medicinal solution intragastrically,once a day,for 12 consecutive days.Except for normal group,other groups were given traditional Chinese medicine for warming yang and mifepristone to establish a model of spontaneous abortion with heat syndrome.24 h after the last medication,serum levels of triiodothyronine (T3),thyroxine (T4),interleukin-2 (IL-2),IL-4,IL-6,IL-10,and interferon-γ (IFN-γ) were all detected;the abortion rate and uterine coefficient were calculated;the pathological morphology of the pregnant uterus was observed;protein expressions of NLRP3,ASC and caspase-1 were detected.RESULTS The molecular docking results showed that the binding energies of 13 main components of Pangshi antai zhixue decoction with NLRP3,ASC,and pro-caspase-1 were all less than-5 kJ/moL.The animal experiment results showed that compared with normal group,the uterine coefficient and serum levels of IL-4,IL-6 and IL-10 were decreased significantly in model group (P<0.05);the abortion rate and serum levels of T3,T4,IL-2 and IFN-γ as well as protein expressions of NLRP3,ASC and caspase-1 were increased significantly (P<0.05);there were abortion lesions in the pregnant endometrium.Compared with the model group,most of the quantitative indicators mentioned above were significantly reversed in Pangshi antai zhixue decoction groups (P<0.05),and the endometrial miscarriage lesions in pregnancy were improved to varying degrees.CONCLUSIONS Pangshi antai zhixue decoction influences the immune balance between mother and fetus by regulating the formation of NLRP3 inflammasome,down-regulating pro-inflammatory cytokines such as IFN-γ and IL-2,and up-regulating anti-inflammatory cytokines such as IL-4,IL-6 and IL-10,thereby improving spontaneous abortion with heat syndrome.

OBJECTIVE To provide a reference for improving the relevant standard operating procedures （SOP） and biological sample management in drug clinical trials. METHODS According to Good Clinical Practice， Data On-site Verification Points of Drugs Clinical Trials， Human Genetic Resources Management Regulations Implementation Rules， Qualification Examination Rules of Drug Clinical Trials Institution， based on the experience of managing clinical trials programs， the irregularities in biological samples management were analyzed by using statistical quality control tables and protocol deviation （PD） reported by sponsors， in the context of the quality control of drug clinical trials projects managed by the author from July 2016 to May 2023. The precautions in various aspects of sample management were put forward. RESULTS & CONCLUSIONS A total of 101 biospecimen- related irregularities were found in the 60 drug clinical trials projects. Biological sample collection， preservation， and handling were the aspects with the highest incidence of irregular operations in biological sample management， accounting for 37.62%， 25.74%， and 21.78%， respectively. Regulating the management of biospecimens requires multiple efforts. The institutional office and the ethics committee carefully reviewed the consistency of the protocols， informed consent， and genetic office application involving biospecimen collection and handling when the project was initiated. Institutional office quality controllers should pay attention to the attendance and training of authorized personnel at project initiation. The principal investigator， research nurse， collector， handler， transporter， relevant personnel of the central laboratory， and institutional office quality controller have their roles during the project implementation phase. On this basis， all parties involved in the management of biological samples should do a good job of effective communication， find problems and report them in time， and conduct special studies on key aspects.

OBJECTIVE To investigate the current situation of clinical trial institutions in Chongqing after the recording system of clinical trial institutions, and to put forward suggestions. METHODS A total of 34 clinical trial institutions in Chongqing were selected as the research objects. The research contents mainly included the basic situation of the institutions, staffing, hardware and software construction, project operation and work difficulties, etc. Combined with the research results, suggestions were put forward for the difficulties of the new and old institutions in the operation of clinical trial institutions. RESULTS A total of 29 questionnaires were collected and 29 were valid. The release of clinical trial resources in Chongqing were not sufficient and uniform, there were problems such as insufficient incentive policies, lack of information platform construction, and the number and professional degrees of practitioners need to be improved. The new institutions had certain advantages in project load, office space and willingness to undertake, but it was restricted by principle investigator qualification, project experience and institutional reputation. CONCLUSION It is suggested to clarify the incentive mechanism, enhance the enthusiasm of clinical trials and establish a standardized training mechanism for clinical trial professionals. Make full use of the information platform to improve the efficiency of clinical trials, build a regional information platform to share information and resources, and accelerate the development of regional clinical trials.

Objective To investigate the therapeutic effect and mechanisms of live combined bifidobacterium and lactobacillus tablets on slow transit constipation(STC)rats.Methods A total of 30 SPF grade Wistar adult female rats were blinded and divided into control group,model group,live combined bifidobacterium and lactobacillus tablets low-dose(0.270g/kg),live combined bifidobacterium and lactobacillus tablets medium dose group(0.540g/kg),live combined bifidobacterium and lactobacillus tablets high-dose group(1.080g/kg),and positive drug group(prucalopride succinate tablet)(0.180mg/kg),with 5 rats in each group.A rat model of STC was established by gavage of loperamide hydrochloride.After successful modeling,medication was administered by gavage for 14 consecutive days on the basis of continued modeling.Observe the changes in general physical signs,fecal water content,and calculate intestinal motility in each group of rats.Using HE staining to observe pathological changes in colon tissue,immunohistochemical methods were used to detect the protein expression of receptor tyrosine kinase(c-Kit),5-hydroxytryptamine(5-HT),5-hydroxytryptamine 3 receptor(5-HT3R),and 5-hydroxytryptamine 4 receptor(5-HT4R)in rat colon tissue.Results Compared with control group,frequency of defecation,fecal water content and intestinal propulsion speed of STC model rats were significantly decreased.The expression levels of proteins such as c-Kit,5-HT,5-HT3R,and 5-HT4R in intestinal tissues were significantly reduced in STC model rats.Compared with STC model group,rats treated with low,medium and high doses of live combined bifidobacterium and lactobacillus tablets and positive drug groups showed a significant increase in bowel frequency,fecal water content,and intestinal motility after intervention.Compared with STC model group,frequency of defecation,fecal water content,intestinal propulsion rate and protein expression of c-Kit,5-HT,5-HT3R and 5-HT4R in rat intestinal tissues were significantly increased after intervention of live combined bifidobacterium and lactobacillus tablets low,medium and high dose groups.Conclusion This study confirms that probiotic preparation live combined bifidobacterium and lactobacillus tablets effectively improves slow transit constipation by promoting the proliferation of Cajal interstitial cells in the colon,increasing the expression of 5-HT,5-HT3R,and 5-HT4R,enhancing intestinal peristalsis,and achieving the therapeutic effect on STC rats.

Objective To investigate the therapeutic effect and mechanisms of live combined bifidobacterium and lactobacillus tablets on slow transit constipation(STC)rats.Methods A total of 30 SPF grade Wistar adult female rats were blinded and divided into control group,model group,live combined bifidobacterium and lactobacillus tablets low-dose(0.270g/kg),live combined bifidobacterium and lactobacillus tablets medium dose group(0.540g/kg),live combined bifidobacterium and lactobacillus tablets high-dose group(1.080g/kg),and positive drug group(prucalopride succinate tablet)(0.180mg/kg),with 5 rats in each group.A rat model of STC was established by gavage of loperamide hydrochloride.After successful modeling,medication was administered by gavage for 14 consecutive days on the basis of continued modeling.Observe the changes in general physical signs,fecal water content,and calculate intestinal motility in each group of rats.Using HE staining to observe pathological changes in colon tissue,immunohistochemical methods were used to detect the protein expression of receptor tyrosine kinase(c-Kit),5-hydroxytryptamine(5-HT),5-hydroxytryptamine 3 receptor(5-HT3R),and 5-hydroxytryptamine 4 receptor(5-HT4R)in rat colon tissue.Results Compared with control group,frequency of defecation,fecal water content and intestinal propulsion speed of STC model rats were significantly decreased.The expression levels of proteins such as c-Kit,5-HT,5-HT3R,and 5-HT4R in intestinal tissues were significantly reduced in STC model rats.Compared with STC model group,rats treated with low,medium and high doses of live combined bifidobacterium and lactobacillus tablets and positive drug groups showed a significant increase in bowel frequency,fecal water content,and intestinal motility after intervention.Compared with STC model group,frequency of defecation,fecal water content,intestinal propulsion rate and protein expression of c-Kit,5-HT,5-HT3R and 5-HT4R in rat intestinal tissues were significantly increased after intervention of live combined bifidobacterium and lactobacillus tablets low,medium and high dose groups.Conclusion This study confirms that probiotic preparation live combined bifidobacterium and lactobacillus tablets effectively improves slow transit constipation by promoting the proliferation of Cajal interstitial cells in the colon,increasing the expression of 5-HT,5-HT3R,and 5-HT4R,enhancing intestinal peristalsis,and achieving the therapeutic effect on STC rats.

Objective To investigate the value of pancreatitis activity scoring system (PASS) score, Bedside Index for Severity in Acute Pancreatitis (BISAP) score, Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE-Ⅱ) score, harmless acute pancreatitis score (HAPS), and Ranson score in evaluating the severity and prognosis of hypertriglyceridemia acute pancreatitis (HTGAP). Methods A retrospective analysis was performed for the clinical data of 300 patients with HTGAP who were admitted to General Hospital of Ningxia Medical University from January 2016 to January 2022, and according to the disease severity, these patients were divided into mild acute pancreatitis (MAP) group, moderate-severe acute pancreatitis (MSAP) group, and severe acute pancreatitis (SAP) group. Clinical data and the above scores were compared between the three groups. The chi-square test was used for comparison of categorical data between groups; an analysis of variance was used for continuous data with homogeneity of variance, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic (ROC) curve was plotted according to disease severity, and related indicators were compared in terms of the area under the ROC curve (AUC). Results There were significant differences between the three groups in PASS score ( F =219.351, P < 0.01), Ranson score ( χ 2 =83.084, P < 0.01), APACHE-Ⅱ score ( χ 2 =43.388, P < 0.01), and BISAP score ( χ 2 = 50.785, P < 0.01). Compared with the other four scoring systems in evaluating and predicting disease severity, PASS score had the highest sensitivity of 0.945 and the largest AUC of 0.963, followed by Ranson score with a sensitivity of 0.655 and an AUC of 0.819. Conclusion For patients with HTGAP, PASS score can more accurately assess the severity and prognosis of HTGAP patients and thus holds promise for clinical application.

OBJECTIVE To learn the common proto col deviation （PD）in the process of drug clinical trials and discuss the methods and precautions for preventing and reducing PD so as to provide reference for the standardization of drug clinical trials. METHODS According to Good Clinical Practice ，Notice on Issuing Guidelines for Planning and Reporting of Data Management and Statistical Analysis of Drug Clinical Trials ，Guidelines for Ethical Review of Drug Clinical Trials ，ICH E 3，ICH E 6（R2）and other regulations ，the PD reported in the relevant projects managed by the author from March 2017 to February 2022，as well as the PD found in the submission materials and project quality control ，were sorted out and statistically analyzed. RESULTS & CONCLUSIONS A total of 39 drug clinical trials were included ，and 212 subjects were selected. In all projects ，258 PDs were reported，including 28 major PD （accounting for 10.85％）and 230 ordinary PD （accounting for 89.15％）. The report of PD mainly included missed inspections/tests （93 reports，accounting for 36.05％），lack of visits （36 reports，accounting for 13.95％）， inspection/testing out-of-window （29 reports，accounting for 11.24％），dosage and usage of test drugs （28 reports，accounting for 10.85％），drug over-temperature/missing temperature （21 reports，accounting for 8.14％），etc. Avoiding and reducing the occurrence of PD requires the efforts of multiple parties ：the sponsor designs a reasonable protocol with appropriate interview rate and window period after listening to the opinions of multiple parties ；the investigators and clinical research coordinator should strengthen their own learning and training ，and be familiar with the protocol ，Good Clinical Practice and corresponding regulations；the compliance education of the subjects should be strengthened ；the institutional offices and ethics committees should conduct multi-angle and whole-process supervision and management when a drug clinical trial is approved ，in progress ，and jsyj- concluded，to ensure the safety rights and interests of the zdcxX0079） subjects and the quality of clinical trials. On this basis ，all parties should communicate effectively and timely ，report PD in time ，and conduct special studies on major PD that have com occurred and key links that are prone to PD.