ObjectiveTo investigate the material basis of homologous and heterogeneous effect of Aurantii Fructus Immaturus（AFI） and Aurantii Fructus（AF） based on the total statistical moment analysis and molecular connectivity index（MCI）. MethodRelevant literature at home and abroad and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP） were consulted to establish the chemical composition database of AFI and AF， and set up their fingerprints by ultra-high performance liquid chromatography（UPLC）， and the total statistical moments and similarity parameters of the fingerprint were calculated. According to MCI， all components of AFI and AF were divided into different component groups， the average values of 0-8^th order（⁰χ-⁸χ） MCI of the common component groups of AFI and AF were calculated. ResultThe values of total zero-order moment（AUC_T） of AFI and AF were （10.57±2.45）×10⁶， （5.09±0.89）×10⁶ μV·s， the values of total first-order moment（MCRT_T） were （11.57±1.58）， （12.10±1.29） min， the values of total second-order moments（VCRT_T） were（24.49±2.30）， （26.49±2.54） min²， respectively. It showed that qualitative and quantitative parameters of AFI and AF were significantly different. The components with high similarity such as neohesperidin， hesperidin and narirutin were screened as the common potential pharmacodynamic components of AFI and AF. The non-common components of AFI， such as alysifolinone and imperatorin， and the non-common components of AF， such as neoeriocitrin and isosakuranin， with high similarity were screened out as potential heterogeneous components of AFI and AF. The composition groups of AFI and AF were classified into six categories， and the similarities between the composition groups of AFI and AF and the total constituents were 0.872-0.979 and 0.918-0.997， the average values of ⁰χ-⁸χ MCI of alkaloids in AFI and AF were 3.65 and 3.14， the average values of ⁰χ-⁸χ MCI of flavonoids were 8.47 and 8.47， the average values of ⁰χ-⁸χ MCI of volatile oils were 2.71 and 3.48， respectively. It showed that there were some differences in MCI of chemical constituents（groups） between AFI and AF. ConclusionThe chemical constituents（groups） of AFI and AF not only differ in content and species， but also in structural characteristics and structure-activity relationship， which can provide a basis for further explaining the scientific connotation of homologous and heterogeneous effect of AFI and AF.

ObjectiveTo investigate the differences in clinical efficacy of different medication regimens of Wangbi Tablets （尪痹片） for knee osteoarthritis （KOA） in a real-world setting， providing a basis for rational clinical use of Wangbi Tablets. MethodsA prospective registry study was conducted， involving 2，999 KOA patients registered in 30 hospitals nationwide from January 26th， 2019， to December 17th， 2021. Based on the use of Wangbi Tablets during the observation period， patients were divided into a monotherapy group （1，507 cases） and a combination therapy group （1，492 cases）， and the combination group can be further divided into Wangbi Tablets plus Chinese medicine （CM）， Wangbi Tablets plus western medicine （WM）， and Wangbi Tablets plus Chinese and western medicine （CM+WM） subgroups. The baseline data of patients in the monotherapy group and the combination group were compared， including age， gender， body weight， medication time， clinical stage， K-L grade， and others. Efficacy indicators included the Visual Analog Scale （VAS） score， Western Ontario and McMaster Universities Osteoarthritis Index （WOMAC） score， and EuroQol five-dimensional （EQ-5D） health index， which were evaluated before and after 4-， 8- and 12-week treatment， and the difference before and after treatment was calculated after 4， 8 and 12 weeks of treatment. The difference between the baseline and 12 weeks of treatment of all the above indicators was used as the dependent variables， and gender， age， body mass index （BMI）， course of disease， K-L grade， and clinical stage were used as independent variables， when multiple linear regression was taken to explore the influencing factors of the efficacy. At the same time， the occurrence of major symptoms （including morning stiffness， joint swelling， soreness of waist and knees， fear of wind， and fear of cold） was counted， and the disappearance of symptoms at each time point was counted after 4， 8， and 12 weeks of treatment. ResultsAt baseline， there were no statistically significant differences in gender and age distribution between the monotherapy and combination therapy groups （P＞0.05）； the proportion of patients in the acute stage and recovery stage was higher in the monotherapy group than in the combination therapy group， while the proportion in the remission stage was lower （P＜0.05）； the VAS score was higher in the monotherapy group， and the EQ-5D index was lower （P＜0.01）， with no statistically significant difference in total WOMAC score between the two groups （P＞0.05）. Compared to those measured before treatment and at previous timepoint， the VAS score and WOMAC total score significantly decreased in both groups， while EQ-5D value increased （P＜0.05）. The difference in VAS score between baseline and after 12-week treatment was higher in the monotherapy group than the combination group， while the differences in WOMAC total score and EQ-5D value between baseline and after 4-， 8- and 12-week treatment were higher in the combination group （P＜0.05）. Multiple linear regression showed that VAS score before treatment had greatest impact on pain improvement （P＜0.01）， and compared to Wangbi Tablets monotherapy， the combination of Wangbi tablets with WM or CM had larger associations with pain improvement （P＜0.05）； and Wangbi Tablets had better efficacy when the course of treatment was ＞28 days （P＜0.01）. Wangbi Tablets plus WM had a better effect on improving the overall function of the knee joint than Wangbi Tablets alone （P＜0.01）； and the efficacy of Wangbi Tablets with a course of treatment ＞28 days was better （P＜0.05）. The improvement of quality of life of patients in the attack and remission stages was more obvious than that in the recovery stage （P＜0.01）； Wangbi Tablets plus WM or CM had a better effect on improving quality of life than Wangbi Tablets alone （P＜0.05）. Before treatment， the proportion of patients with morning stiffness， soreness of waist and knees， fear of wind and chills in the monotherapy group was higher than that in the combination group （P＜0.01）. The proportion of main symptoms in both groups decreased after 4， 8 and 12 weeks of treatment （P＜0.05）. After 4 weeks of treatment， the disappearance rate of each main symptom in the combination group was higher than that in the monotherapy group， and after 12 weeks of treatment， the disappearance rate of fear of wind in the monotherapy group was higher than that in the combination group， while the disappearance rate of joint swelling and soreness of waist and knees was lower （P＜0.05）. ConclusionWangbi Tablets， whether used alone or in combination with other medications， is effective throughout the course of KOA， with greater benefits in improving joint function and quality of life during the acute and remission stages compared to the recovery stage. Combination therapy had a faster onset of effect， but began to converge with monotherapy after 8 weeks. The best efficacy was observed with the combination of Wangbi Tablets with WM， followed by combination with CM.

Objective:To investigate the predictive value of infiltrating zone contrast-enhanced ultrasound(CEUS) gradient features in Nottingham grading and pathologically true infiltration of invasive ductal carcinoma(IDC).Methods:A retrospective analysis was performed on 78 female breast cancer patients (95 masses) confirmed by surgical and pathology in the Affiliated Hospital of Jiangsu University from July 2019 to June 2022, which were divided into Grade-Ⅰ (22 masses), Grade-Ⅱ (28 masses), and Grade-Ⅲ (45 masses) according to the Nottingham histological grading system. The differences in the maximum diameter of the infiltration zone and the characteristic parameters of the gradient of the inner and outer edges of the infiltration zone among the three groups of masses were compared, and the differential gradient features among them were analyzed by multivariate ordered Logistic regression and ROC curves. The relationship between the differential gradient characteristics of the infiltration zone and the pathologically true infiltration of the mass was further explored.Results:The univariate analysis showed statistically significant differences among the three groups for peak-arrival time gradient (ΔTTP), ascending branch slope gradient (ΔRS), peak intensity gradient (ΔPI) and area gradient under the curve (ΔAUC) (all P<0.05). Multiple ordered logistic regression analysis showed that ΔTTP, ΔPI and ΔAUC had independent influences on the histologic grading of IDC (all P<0.05), and the area under the curve for the combination of the three in predicting IDC histology grades Ⅰ, Ⅱ and Ⅲ was 0.692, 0.705 and 0.765, respectively. In addition, the maximum diameter of pathologically true infiltration of the mass was positively correlated with ΔTTP ( r=0.621, P<0.05) and negatively correlated with ΔPI ( r=-0.605, P<0.05) and ΔAUC ( r=-0.719, P<0.05). Conclusions:Infiltration zone CEUS gradient features are effective in predicting the histologic grade of IDC and strongly correlate with the degree of pathologically true infiltration of the mass.

Objective To explore the safety and efficacy of neoadjuvant chemotherapy(NAC)combined with immunotherapy before radical cystectomy plus pelvic lymph nodes dissection(RC-PLND)for muscle-invasive bladder cancer(MIBC).Methods The clinical data of 101 patients with MIBC who underwent neoadjuvant therapy followed by RC-PLND in the Department of Urology,the First Affiliated Hospital of Xi'an Jiaotong University during Jan.2019 and Dec.2023 were retrospectively analyzed,including 71 patients(70.3％)who received NAC(NAC group)and 30(29.7％)who received NAC combined with immunotherapy(NAC combine immunotherapy group).The clinical and pathological data and adverse events during neoadjuvant therapy were compared.Logistic regression analysis was used to explore the independent predictors of pathological complete response(pCR)and pathological partial response(pPR).Results There were no significant differences in the baseline data between the two groups(P＞0.05).However,the proportion of multiple tumors in patients receiving NAC before surgery was significantly higher than that in the NAC combined immunotherapy group(69.0％vs.46.7％,P=0.034).Compared with NAC group,NAC combined with immunotherapy group had significantly improved rate of pathological downstaging and pPR(60.6％vs.83.3％,P=0.026;45.1％vs.70.0％,P=0.022).Furthermore,the rate of pCR in patients undergoing NAC combined immunotherapy was higher than those undergoing NAC,but the difference was not significant(53.3％vs.33.8％,P=0.067).Logistic regression analysis revealed that clinical T-stage and tumor diameter were independent predictors of pCR and pPR(P＜0.05).In addition,the most common adverse events during neoadjuvant therapy were anemia,decreased white blood cells,nausea,and vomiting,but most of them were grade 1-2 and could be relieved through symptomatic treatment.Conclusion NAC combined with immunotherapy is safe and effective,which can improve the rate of pathological downstaging,pPR and pCR,without increasing the incidence of adverse reactions.

Objective:To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities.Methods:This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results:A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged ( M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95% CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95% CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion:The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.

Objective:To compare the application effect of domestic and imported intravenous radiofrequency closure system in the treatment of primary varicose veins of lower extremities.Methods:This single-center prospective, non-inferiority randomized controlled trial was performed in the Department of Vascular Surgery, the Fourth Affiliated Hospital, Zhejiang University School of Medicine from January 2021 to January 2022. Patients with primary varicose veins of lower extremities who met the ataxation criteria were randomly assigned to the experimental group(domestic novel venous radiofrequency closure system) or the control group(imported venous radiofrequency closure system) in a ratio of 1∶1. The two groups of subjects were compared in terms of target vein closure rate, technical success rate, system operation performance, incidence of adverse events and incidence of serious adverse events(SAE) within 6 months after surgery. Quantitative data were compared by Mann-Whitney U test, and categorical data were compared by χ2 test and non-inferiority test. Results:A total of 80 subjects were included in the trial (41 in the experimental group and 39 in the control group), including 27 males and 53 females, aged ( M(IQR)) 55(23) years (range:40 to 78 years). There were 48 cases of left lower limb and 32 cases of right lower limb. The technical success rate and system control performance between the groups were 100%.The incidence of adverse events (58.5% (24/41) vs. 61.5% (24/39), χ2=0.075, P=0.784), and the incidence of SAE (7.3% (3/41) vs. 5.1% (2/39), χ2=0.163, P=0.686) within 6 months after surgery in experimental group and control group had no statistical significance. There was one device-related adverse event in each of the two groups. In the experimental group, one patient developed endovenous heat-induced thrombosis after surgery and recovered after taking rivaroxaban tablets. One patient in the control group had pain in the upper right thigh for more than 1 day after operation, which was cured after using analgesic cream. No device-related SAE occurred. The venous closure rate of the experimental group was 100% (38/38) at 6 months after surgery, and that of the control group was 97.4% (37/38). The difference between the two groups was 2.63% (95% CI:-3.19 to 8.45, Z=4.865, P<0.01), and the 95% CI lower limit of the difference in target venous closure rate between two groups was greater than the non-inferiority threshold of -10.00%. Conclusion:The early application effect of the new domestic intravenous radiofrequency closure system in patients with primary varicose veins of lower extremities is in line with expectations, it is not inferior to the imported system.

Objective To investigate the clinical prognosis value of serum microRNA(miR)-138-5p and miR-212-5p levels in prostate cancer.Methods A total of 95 cases of prostate cancer patients admitted to the First Hospital of Handan from July 2020 to June 2021 were collected.Based on follow-up records for two years after surgery,these patients were separated into a poor prognosis group(n=52)and a good prognosis group(n=43),and 48 healthy volunteers who underwent a physical examination at the hospital were collected as the healthy control group.In addition,quantitative real-time fluorescence-PCR(qRT-PCR)was applied to detect the relative expression levels of miR-138-5p and miR-212-5p in the serum of study subjects,and the clinical data of the patients were collected and analyzed.Multivariate COX regression was applied to analyze factors that affected the prognosis of prostate cancer patients.The predictive value of serum miR-138-5p and miR-212-5p for the prognosis of prostate patients was tested,and receiver operating characteristic(ROC)curves were plotted.Pearson method was applied to analyze the correlation between the expression of serum miR-138-5p and miR-212-5p and the Gleason score.Results Compared to the healthy control group,the serum levels of miR-138-5p(0.88±0.10,0.83±0.09 vs 1.01±0.10),and miR-212-5p(0.75±0.09,0.71±0.08 vs 1.02±0.11)were lower in the good prostate cancer prognosis group and poor prostate cancer prognosis group,and the differences were significant(t=14.021,22.275;9.825,18.063,all P＜0.05).The prognosis of prostate cancer patients was related to TNM staging,bone metastasis,tissue differentiation degree,preoperative PSA level,and Gleason score(x2=4.417～7.187,t=14.235,all P＜0.05).Serum miR-138-5p[HR(95％CI):0.871(0.785～0.966)],and miR-212-5p[HR(95％CI):0.822(0.725～0.932)]were protective factors for poor prognosis(all P＜0.05).While Gleason score[HR(95％CI):1.253(1.026～1.530)],TNM stage[HR(95％CI):1.224(1.024～1.463)],bone metastasis[HR(95％CI):1.398(1.036～1.887)],tissue differentiation degree[HR(95％CI):1.520(1.146～2.016)]and PSA level[HR(95％CI):1.426(1.094～1.858)]were all risk factors for poor prognosis(all P＜0.05).The AUC(95％CI)of serum miR-138-5p and miR-212-5p were 0.883(95％CI:0.801～0.940)and 0.863(95％CI:0.777～0.925),respectively.Serum miR-138-5p and miR-212-5p were negatively correlated with the Gleason score(r=-0.610,-0.420,all P＜0.05).Conclusion Serum miR-138-5p and miR-212-5p levels are elevated in patients with poor prostate cancer prognosis and may have a certain auxiliary predictive value for prostate cancer patient prognosis.

Objective To investigate the readmission of male schizophrenia patients in a hospital of Zhoushan and its influencing factors,and to build a nomogram model.Methods A total of 183 male schizophrenics patients admitted to the Second People's Hospital of Zhoushan from January to December 2022 were analyzed retrospectively.Patients were divided into readmission group (hospitalization frequency ≥ 2 times) and non-readmission group (hospitalization was once) based on the number of hospitalization.Perform univariate analysis on the data of two groups of patients using t test or x2 test.Multivariate Logistic regression model was used to investigate the influencing factors of readmission in schizophrenia patients within one year,and a nomogram prediction model was established.Results The rate of readmission was 49.18％ in 183 schizophrenic patients.Course of disease,duration of first hospitalization,and history of tobacco and alcohol consumption were independent risk factors for readmission (P<0.05).The area under the curve (AUC) of the receiver operating characteristic curve in the column chart model is 76.53.Conclusion The readmission rate of male schizophrenia patients in the Second People's Hospital of Zhoushan is high,and the course of disease,duration of first hospitalization,and history of tobacco and alcohol consumption are independent risk factors for the readmission of schizophrenia patients within one year.The establishment of the nomogram prediction model is expected to evaluate the high risk factors for the readmission of schizophrenia patients and implement targeted interventions to improve the quality of life of patients.

ObjectiveTo compare the similarities and differences of material basis for improving insulin resistance （IR） in different parts of Morus alba based on liquid-mass combination combined with network pharmacology and molecular docking technology. MethodUltra-high performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was used to analyze the composition differences in different parts of M. alba. Sybyl-X2.1 was used to connect components with IR core targets， and the selection criterion was Total Score≥5. The "component-target-disease" network map was drawn. The total statistical moment standard similarity （TQSMSS） between the single target-component docking score data set and the total target-component docking score data set was calculated. The targets with higher TQSMSS were screened out， and the protein-protein interaction （PPI） network was constructed. The Gene Ontology （GO） functional analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed using R language. ResultForty-one active components were obtained by UPLC-Q-TOF-MS. According to the total statistical moment （similarity） method， there were 20， 23， 30， and 27 targets with TQSMSS≥0.75 in Mori Ramulus， Mori Cortex， Mori Fructus， and Mori Folium， respectively. In the four M. alba medicinal sources， the functional order of the targets by GO enrichment analysis was Mori Fructus>Mori Folium>Mori Cortex>Mori Ramulus， which were involved in biological processes such as blood glucose homeostasis， glucose metabolism， and glucose transmembrane transport. The order of the four M. alba medicinal sources by KEGG pathway enrichment analysis was Mori Fructus>Mori Ramulus>Mori Folium>Mori Cortex， which were involved in the adenosine monophosphate-activated protein kinase （AMPK） energy metabolism signaling pathway， the insulin regulation-related signaling pathway， the anti-inflammatory and anti-oxidative stress signaling pathway， and so on. ConclusionThis research demonstrates that there are differences in the material basis for improving IR by different parts of M. alba， which provides references for the development of different parts of M. alba.

ObjectiveBased on the supramolecular "imprinting template" theory， the autonomous action law of the component groups of Shentong Zhuyutang in the preparation process of medicinal materials-decoction pieces-formulas was studied to clarify the quantitative transfer law of its quality attributes. MethodUltra performance liquid chromatography（UPLC） fingerprint of Shentong Zhuyutang was established with mobile phase of 0.4% phosphoric acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-2.5 min， 100%A； 2.5-6 min， 100%-96%A； 6-15 min， 96%-92%A； 15-25 min， 92%-88%A； 25-35 min， 88%-75%A； 35-50 min， 75%-65%A； 50-60 min， 65%-50%A； 60-65 min， 50%-30%A； 65-70 min， 100%A） and detection wavelength of 235 nm， and the total statistical moments， information entropy and primary feeding amount of fingerprint of medicinal materials， decoction pieces and benchmark samples were calculated. Dry extract rate of the benchmark samples， the transfer rates and the addition parameters of medicinal materials-decoction pieces-formulas were calculated. ResultSimilarities of the total statistical moments of UPLC fingerprint of 15 batches of medicinal materials and decoction pieces were>0.89， the relative standard deviations（RSDs） of information entropy of UPLC fingerprint of 12 medicinal materials and decoction pieces were<10%. RSDs of total first-order moment（MCRT_T） and information entropy of Shentong Zhuyutang（medicinal materials） were 5.5% and 2.3%， while the RSDs of MCRT_T and information entropy of Shentong Zhuyutang（decoction pieces） were 4.8% and 2.6%， respectively. The dry extract rate of 45 batches of Shentong Zhuyutang was 17.2%-20.2%. The transfer rate of medicinal materials to decoction pieces was within the range of data fluctuation， which was 70%-130% of the average value. The overall transfer rates of medicinal materials to decoction pieces and decoction pieces to benchmark samples were 101.8% and 83.0%， respectively. ConclusionThe quality properties of Shentong Zhuyutang benchmark samples can be studied by total statistical moment analysis and primary feeding amount analysis， which can confirm the supramolecular "imprinting template" theory to a certain extent.