ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

A close relationship between fatty acid metabolism and cancer development is well-established.The hydroxyacyl-coenzyme a dehydrogenase(HADH),a key enzyme in fatty acid beta-oxidation,has recently been identified as an anti-oncogenic factor in various cancers and an oncogenic factor in conditions like acute myeloid leukemia.In cancer cells,HADH not only directly catalyzes fatty acid beta-oxidation but also indirectly influences multiple signaling pathways such as PPAR,TNF-α,JAK-STAT3,PI3K/Akt,IFN-γ,MAPK,and non-canonical Wnt signaling pathways,affecting cancer cell proliferation and migration.HADH shows promise as a potential tumor biomarker for diagnosis,treatment,and prognosis in different cancer types,holding significant clinical value.

Objective:To quantitatively evaluate the guidelines for hypertensive disorders of pregnancy (HDP) at home and abroad, and to provide a reference for the development of related guidelines in the future.Methods:Guidelines related to HDP published at home and abroad from 1 January 2018 to 31 December 2022 were retrieved from several databases, including CNKI, Wanfang Database, Yiigle, VIP Database, PubMed, Embase, and Web of Science with the terms of "hypertension in pregnancy", "hypertensive disorders of pregnancy", "pre-eclampsia", "eclampsia", and "guidelines". The retrieved guidelines were evaluated with the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) and Scientific, Transparent and Applicable Rankings (STAR) tool. According to the manual of AGREE Ⅱ two researchers graded the retrieved guidelines from six domains: scope and purpose, participants, rigor, clarity, applicability, and independence. Mean standardized score of each domain and the overall score were obtained. STAR tool was used to grade the guidelines by two researchers and one methodologist from 11 domains: registration, protocol, funding, working groups, conflicts of interest, clinical issues, evidence, consensus methods, recommendations, accessibility, and others.Results:A total of 19 related guidelines were included, covering six countries on three continents. The mean standardized scores of the 19 guidelines in the six domains of scope and purpose, participants, rigor, clarity, applicability, and independence using the AGREE II instrument were 73.98%, 63.16%, 59.98%, 66.37%, 56.36%, and 71.93%, respectively. Scores in the 11 domains of registration, protocol, funding, working groups, conflicts of interest, clinical issues, evidence, consensus methods, recommendations, accessibility, and others using the STAR tool were 0.00%, 0.00%, 76.15%, 39.87%, 58.92%, 65.19%, 60.80%, 49.78%, 78.95%, 30.89%, and 42.11%, respectively. According to the overall evaluation results, 12 guidelines were recommended and seven needed further modifications. It was found that most guidelines were unanimous in their recommendations on the prevention of preeclampsia with aspirin, medications for patients with severe hypertension, and the timing of pregnancy termination in preeclampsia patients, with the consensus rates of 10/13, 9/13, and 9/13, respectively. Besides, these recommendations were supported by substantial evidence.Conclusions:The overall quality of guidelines related to HDP at home and abroad is high, but there is still room for improvement. When developing relevant guidelines in the future, statisticians and methodologists should be included in the working groups to improve the evidence-based quality, and much attention should be paid to the disclosure of conflicts of interest guidelines. Registration and protocol are needed before publishing a guideline. The development of multiple versions for different users will conduce to improving the management of HDP.

Objective:To explore the inhibitory mechanism of herb cake-partitioned moxibustion on tumor growth in colitis-associated colorectal cancer(CAC)based on histone lysine demethylase 4D(KDM4D). Methods:Inbred male Sprague-Dawley rats were randomly divided into a normal group,a CAC group,a herb cake-partitioned moxibustion group,and an inhibitor group.Except the normal group,rats in the other three groups were treated with azoxymethane(AOM)combined with dextran sulfate sodium(DSS)to make CAC rat models.Rats in the normal group and the CAC group did not receive interventions;rats in the herb cake-partitioned moxibustion group received moxibustion at Qihai(CV6)and bilateral Tianshu(ST25),2 cones for one point each time,once a day for 30 d with 1-day rest every week;rats in the inhibitor group received intraperitoneal injection of KDM4D inhibitor,5-chloro-8-hydroxyquinoline(5-c-8HQ),once a day for 30 d.After intervention,the general condition,colon length,tumor number and volume,and histopathological colon changes were observed.The expression of adenomatous polyposis coli(APC),axis inhibitor(Axin),cyclin D1,matrix metalloproteinase(MMP)-7 and MMP-9 mRNAs were detected by real-time quantitative polymerase chain reaction.The proliferating cell nuclear antigen(PCNA),cleaved caspase3,KDM4D,APC,and Axin proteins were detected by immunohistochemistry. Results:Compared with the normal group,the general condition was poor,the colon length was significantly shortened(P<0.01),the number and volume of colonic tumors were increased(P<0.01),the structure of glandular duct was obviously disordered with"back-to-back"and cowall phenomenon,and also high-grade adenocarcinoma formed;the protein expression levels of PCNA and KDM4D were significantly increased(P<0.01),while cleaved caspase3,APC,and Axin were significantly reduced(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were significantly increased(P<0.01),while APC and Axin were significantly reduced(P<0.01)in the CAC group.Compared with the CAC group,the general condition was improved,the length of colon was significantly increased(P<0.01),the number and volume of the colonic tumors were reduced(P<0.05),and the colon tissues showed epithelial cell proliferation with enlarged and deep staining nuclei,dysplasia and inflammatory cell infiltration;the protein expression levels of PCNA and KDM4D were significantly reduced(P<0.01),while the cleaved caspase3,APC,and Axin were significantly increased(P<0.01);the mRNA expression levels of cyclin D1,MMP-7,and MMP-9 were reduced(P<0.05),while the APC and Axin were increased(P<0.05)in the colon tissues of rats in the herb cake-partitioned moxibustion group and the inhibitor group. Conclusion:Herb cake-partitioned moxibustion regulated abnormally expressed KDM4D in CAC rats,activated APC and Axin,the upstream molecules of Wnt/β-catenin pathway,inhibited abnormally activated downstream molecules of Wnt/β-catenin pathway.This may be a key mechanism of herb cake-partitioned moxibustion in inhibiting CAC tumor growth.

ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide（LPS）-induced depression， as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group， model group， fluoxetine group（10 mg·kg^-1） and total alkaloids of C. saxicola group（210 mg·kg^-1）， with 6 rats in each group. In addition to the normal group， the rats were injected intraperitoneally with LPS to establish the inflammation model of depression， and the drug administration was started 1 week after modeling， and the administration groups were gavaged according to the corresponding dose， and the normal and model groups were intragastric administration with equal volume of distilled water， and the administration was performed along with the modeling. After two weeks of continuous administration， the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference， forced swimming and open field experiments， the levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of rat hippocampus were observed by hematoxylin-eosin（HE） staining. After the last administration， blood was collected from orbit according to the set time， and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS） was established to simultaneously detect the concentrations of dehydrocavidine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in plasma， and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group， the model group exhibited a decrease in sucrose preference rate， total distance traveled in the open field， as well as an increase in swimming immobility time and serum inflammatory factor expression（P<0.01）. In contrast， compared with the model group， rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field， a decrease in swimming immobility time， and a reduction in serum inflammatory factor expression（P<0.05， P<0.01）. Additionally， HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss， disorganization and residual vacuoles， whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak（t_max） and half-life（t_1/2） of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them， the area under the curve（AUC_0-∞） of tetrahydropalmatine was the highest and the t_1/2 was the shortest， and the AUC_0-∞ of coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine were low. The curves of dehydrocavidine， coptisine， palmatine， berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats， inhibit the expression of inflammatory factors in serum， improve the pathological injury of hippocampus， and has the antidepressant effect. Meanwhile， the effective site is absorbed quickly and eliminated slowly in the depressed model rats， and the efficacy is maintained for a long time.

Objective To investigate the factors influencing the pregnancy outcomes during frozen-thawed embryo transfer(FET)cycles in patients with polycystic ovary syndrome(PCOS).Methods A retrospective analysis was conducted on patients'data from 882 FET cycles.According to the pregnancy outcome,the patients were divided into non-implantation group(Group A),abortion group(Group B1)and live birth group(Group B2).Clinical data and laboratory parameters were compared among the three groups,and ordered Logistic regression analysis was used to study the factors influencing pregnancy outcomes after FET.Patients were also divided into four groups(C1-C4)based on the number of high-quality embryos obtained(0-3,4-6,7-10,≥11),and their clinical data and laboratory parameters were compared.Results The clinical pregnancy rate,live birth rate,and miscar-riage rate in the 882 treatment cycles were 71.09%(627/882),61.68%(544/882),and 13.24%(83/627),respectively.Single-factor analysis showed significant differences in body mass index(BMI),infertility type,hu-man chorionic gonadotropin(hCG)day estradiol(E2)level,number of retrieved oocytes,and number of high-quality embryos among Groups A,B1,and B2(P<0.05).Further multiple Logistic regression analysis revealed that BMI(OR=1.046,95%CI:1.001-1.093,P=0.044)and a history of previous pregnancy(OR=1.417,95%CI:1.030-1.950,P=0.032)were independent risk factors for successful FET in PCOS patients,while an in-creased number of high-quality embryos was an independent protective factor for successful pregnancy.Based on the results of Group B2,compared to Group A,OR=0.920,95%CI:0.880-0.962,P=0.000;compared to Group B1,OR=0.923,95%CI:0.862-0.988,P=0.022.Compared with the other three groups(C1-C3),the total amount of gonadotropin(Gn)in the C4 group was the lowest and the number of oocytes obtained was the high-est(P<0.05).Multiple comparisons showed that Group C4 had lower BMI,follicle-stimulating hormone(FSH),very low-density lipoprotein(vLDL)levels,a higher luteinizing hormone and follicle-stimulating hormone(LH/FSH)ratio compared to Group C1(P<0.05).Group C4 had lower fasting insulin(FINS)and homeostasis model assessment of insulin resistance(HOMA-IR)levels compared to Group C3,and higher high-density lipoprotein-cholesterol(HDL-C)and apolipoprotein A1(Apo A1)levels compared to Groups C2 and C3(P<0.05).Con-clusion BMI,the history of previous pregnancy and the number of high-quality embryos were both independent factors for predicting pregnancy outcomes in PCOS patients undergoing FET cycles.Patients with a higher number of high-quality embryos have a higher clinical pregnancy rate during FET cycles.

Objective To investigate the role of squalene epoxidase(SQLE)knockout in anti-tumor effect vial im-proving CD8+T cell infiltration in melanoma tumor microenvironment.Methods Both immunodeficient and immu-nocompetent mice were inoculated with SQLE knockout B16F10 cells to determine the cell-autonomous and non-au-tonomous regulation of malignancy.Antibody blockade,Luminex multiplex assays,and flow cytometry were em-ployed to explore the impact of SQLE gene knockout on the secretion of cytokines/chemokines and immune cell in-filtration.Bioinformatics analysis was conducted to validate the correlation between SQLE expression and immune infiltration as well as clinical prognosis in melanoma patients.Results Compared with immunodeficient mice,SQLE knockout significantly inhibited melanoma proliferation in immunocompetent mice and prolonged their surviv-al.SQLE knockout induced the secretion of cytokines and chemokines from tumor cells,improved CD8+T cell in-filtration in the tumor microenvironment,thereby potentiating anti-tumor immunity.Bioinformatics analysis sugges-ted a significant correlation between SQLE and its corresponding immune infiltration markers with the prognosis of melanoma patients.Conclusion SQLE regulates anti-tumor immunity by controlling cytokines and chemokines re-leasing in tumor microenvironment,thus holding promise as a novel tumor immunotherapy target and efficacy predic-tion molecular indicator.

Objective:To summarize the clinical and pathological characteristics, treatment methods, and prognosis of papillary renal neoplasm with reverse polarity (PRNRP).Methods:The clinical and pathological data of six pathologically confirmed PRNRP patients admitted to Renji Hospital affiliated with Shanghai Jiaotong University School of Medicine from August 2022 to August 2023 were retrospectively analyzed. Among them, three were male and three were female, with an average age of (55.3±10.5) years old. All six cases were incidentally discovered during health examinations. Preoperative contrast-enhanced CT scans showed tumors with cortical phase manifestations of uneven enhancement, avascularity, and indistinct borders, with CT values of (85.6±18.7) HU. In the corticomedullary phase, the CT values showed mild elevation, with an average of (94.3±4.7) HU. In the delayed phase, the tumor boundaries were clear, and the enhancement degree was significantly lower than that of the surrounding renal cortex and medulla, with a tumor CT value of (86.3±11.9) HU. The pseudocapsule of the tumor was not clearly displayed on contrast-enhanced CT scans. All cases underwent partial nephrectomy, including two cases of robot-assisted laparoscopic partial nephrectomy and four cases of laparoscopic partial nephrectomy.Results:Postoperative pathological measurements revealed a maximum tumor diameter ranging from 6 to 15 mm, with an average diameter of (11.0±3.5) mm. All six cases were classified as pT 1aN 0M 0 stage. Microscopically, the tumors exhibited branching papillary structures with eosinophilic cytoplasm, and the tumor cells displayed low-grade nuclei located at the top of the cytoplasm and away from the basal membrane. Immunohistochemical analysis showed diffuse strong positivity for GATA3 and CK7, while CA-Ⅸ expression was negative. The median follow-up time after surgery was 10(9, 13) months, and no tumor recurrence or metastasis was observed. Conclusions:PRNRP is a rare, low-grade malignant papillary renal tumor. Contrast-enhanced CT scan has characteristic features of avascularity. Pathological morphological features are low-grade nuclei located at the top of the cytoplasm and far away from the basal membrane, forming a "reverse polarity". The immunophenotype shows positive expression of GATA3 and CK7. Partial nephrectomy is the recommended treatment approach, and the postoperative prognosis is favorable.

Purpose/Significance To solve the problem that regional clinical research data are difficult to integrate efficiently,and to promote"Chinese evidence"and"Chinese protocol"in the global clinical research community.Method/Process Based on the standard-ization theory,the data standardization system is proposed,and the construction and application methods of the regional clinical research data platform are explored with the integration of multi-center clinical research data as the starting point.Result/Conclusion The theo-retical framework of the regional clinical research data platform has been preliminarily established,and the clinical research capabilities of tertiary hospitals in Shanghai have been significantly improved.

Objective To evaluate the quality and authenticity of Ophiopogon japonicus in Shengmaiyin,establish ultra performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)for the determination of three characteristic components(methylophiopogonanone A,liriopeside B and liriope muscari baily saponin C),and provide technical support for drug supervision.Methods Samples were analyzed on a Phenomenex Kinetex F5 C18 column(100 mm×3.0 mm,2.6 μm)in a gradient elution mode with 0.1％formic acid water and-0.1％formic acid acetonitrile as the mobile phase at a flow rate of 0.4 mL/min,the column temperature was 30 ℃,and the injection volume was 1 μL.Mass spectrometer detector,electro spray ion source of positive and negative ions,and multi-reaction monitoring mode were used.Results The linear ranges of methylophiopogonanone A,liriopeside B and liriope muscari baily saponin C were 0.016 7-1.666 0,0.039 7-15.872 0 and 0.022 5～8.988 0 ng(r＞0.999 9),respectively.The average recovery rates of these three components were 85.16％,86.95％and 95.07％,respectively,with RSSDs of 2.65％,1.45％and 1.14％(n=6).The content of methylophiopogonanone A in thirty-eight batches was quite different.Seven batches of liriopeside B or liriope muscari baily saponin C were detected.Conclusion The method is simple and sensitive,and suitable for determining of three characteristic components in Shengmaiyin,which provides references for the quality control of Ophiopogon japonicus in Shengmaiyin.