OBJECTIVE To study the pharmacokinetic characteristics of antidepressant active components from Jiaotai pills in healthy subjects. METHODS Eight healthy subjects （3 males and 5 females） were recruited and given a single oral dose of 8.55 g of Jiaotai pills. Venous blood samples were collected before administration （0 h） and at intervals from 0.25 to 36.0 hours post- administration. After treating the plasma samples with protein precipitation， the blood concentrations of the antidepressant active ingredients （coptisine， berberine， magnoflorine， and palmatine） in Jiaotai pills were determined using liquid chromatography- tandem mass spectrometry （LC-MS/MS） method. DAS 2.0 software was employed to calculate the pharmacokinetic parameters of healthy subjects [half-life （t1/2）， peak concentration （cmax）， time to peak concentration （tmax）， area under the concentration-time curve （AUC）， and mean residence time （MRT）] using a non-compartmental model. RESULTS After healthy subjects took Jiaotai pills， the drug-time curve of the four antidepressant active ingredients conforms to a two-compartment model and tmax values were similar， with all reaching peak blood concentrations within 2.00 to 4.00 hours post-administration. However， the t1/2 and MRT of coptisine and berberine were significantly longer than that of magnoflorine and palmatine. There were also significant differences in the AUC and cmax among the four antidepressant active ingredients， with magnoflorine exhibiting markedly higher AUC0-t and cmax compared to the other three components. CONCLUSIONS In this study，LC-MS/MS is used to analyze the pharmacokinetic characteristics of the antidepressant active ingredients from Jiaotai pills in healthy subjects， can provide valuable references for the clinical application of Jiaotai pills.

Objective To construct 5 machine-learning models and compare their performance in predicting the associations between pre-pregnancy socio-psycho-behavioral exposures of both spouses and preconception outcomes.Methods Based on Chongqing Preconception Reproductive Health and Birth Outcome Cohort of volunteers recruited from Chongqing Health Center for Women and Children during January 2019 and March 2022,5 447 couples were recruited and surveyed through interviewer-interview for the demographic and social-psychological-behavioral data of both spouses(221 variables).According to the inclusion and exclusion criteria,4 097 couples were finally included,and randomly assigned into a training set(n=2 867 spouses)and a validation set(n=1 230 spouses)at a ratio of 7∶3.Feature analysis and collinear screening were applied to select the potential exposure factors.In consideration of difficulty to carry out semen parameters analysis in primary healthcare institutions,feature Set 1 including sperm parameters and feature Set 2 excluding semen parameters were constructed by including or excluding sperm quality simultaneously in the training set and the validation set.Five algorithms,that is,Logistic Regression,Naive Bayes,Random Forest,Gradient Boosting Machine,and Support Vector Machine,were used to construct preconception outcome prediction models,and the parameters of each model were optimized using random search combined with grid search.The predictive performance of each model was compared using precision,recall,F1 score,area under the receiver operating characteristic curve(AUC),and calibration curve.The optimal model was then selected by comparing the changes in the predictive ability of the questionnaire data for fertility outcomes with or without semen parameters.Results There were 24 variables screened out in feature Set 1,and 16 variables in feature Set 2.In feature Set 1,the gradient boosting machine performed better,with a relatively higher AUC value(0.651)and better F1 score(0.61).The logistic regression model performed stably(AUC value=0.647)and was suitable as the reference model.The random forest(AUC value=0.641),Naive Bayes(AUC value=0.641),and support vector machine(AUC value=0.634)performed second-best.By utilizing the gradient boosting machine,comparable results were found between the predictions from feature sets with or without semen parameters,as in feature Set 1,the AUC value of its validation set was 0.651(95%CI:0.629～0.681),the prediction accuracy was 0.63,the recall rate was 0.65,and the average precision value F1 was 0.61;and in feature Set 2,the AUC value of its validation set was 0.649(95%CI:0.624～0.663),and both the calibration curves were close to the ideal curve.The prediction results indicated that in feature Set 1,the features highly negatively correlated with preconception outcomes were female age,male age,and no pregnancy within 1 year without contraception,while the features highly positively correlated with preconception outcomes were female pregnancy history,total sperm vitality,and use of contraceptive measures before enrollment.Conclusion Among the 5 machine-learning algorithms performed in this cohort data,the gradient boosting machine shows slightly better performance.There are 24 factors being associated with preconception outcomes in both spouses,and the performance of the simplified model excluding semen parameters is not significantly declined.It is feasible to use machine-learning methods to predict human preconception outcomes through social-psychological-behavioral questionnaires.

Objective To investigate whether 3D-guided cone-shaped segmentectomy can achieve comparable long-term outcomes with lobectomy for deep early-stage lung cancer with diameter≤2 cm. Methods We retrospectively screened patients with deep early-stage non-small cell lung cancer (NSCLC) with diameter≤2 cm who underwent lobectomy or segmentectomy in the First Affiliated Hospital of Nanjing Medical University from 2012 to 2018. All pulmonary segmentectomy was performed using 3D-guided cone-shaped segmentectomy with segment or subsegment as the resection unit. Univariate and multivariate regression analyses were performed by Cox proportional hazard regression model. The patients who underwent segmentectomy and lobectomy were matched 1∶1 by propensity-score matching analysis. The oncological outcomes of two groups were compared. Results Our cohort was divided into a segmentectomy group (n=222) and a lobectomy group (n=127). The age, total nodule size, solid component size and proportion of pure solid nodule in the lobectomy group were significantly higher than those in the segmentectomy group. The median follow-up time was 49 months. Surgical margins were negative in all patients. The local recurrence rate of segmentectomy was 0.45%. The disease-free survival (DFS) rate and overall survival (OS) rate of patients in the segmentectomy group were significantly better than those in the lobectomy group (5-year DFS rate: 98.64% vs. 89.77%, P<0.001; 5-year OS rate: 99.55% vs. 92.10%, P<0.001). Multivariate regression analysis showed that the differences between two groups were not significant [DFS rate: HR=0.52. 95%CI (0.11, 2.59), P=0.427; OS rate: HR=0.08. 95%CI (0.00, 3.24), P=0.179] after adjusting for other factors. After propensity score matching, 77 patients were preserved in both segmentectomy group and lobectomy group, with the mean nodule size of 1.44 cm and 1.49 cm and the mean consolidation tumor ratio (CTR) of 0.46 and 0.52, respectively. There was no statistical difference in DFS rate (P=0.640) or OS rate (P=0.310) between the two groups. Conclusion 3D-guided cone-shaped segmentectomy can be an acceptable treatment for low-grade malignant NSCLC deep in lung parenchyma with diameter≤2 cm, and its oncology effect is not inferior to lobectomy.

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 accuracy of magnetic resonance imaging (MRI) cine sequences in determining the range of tumor motion in radiotherapy, providing a basis for the precise delineation of the target volume in motion for radiation therapy.Methods:A modified chest motion phantom was placed in a MRI scanner, and a water-filled sphere was used to simulate a tumor. True fast imaging with steady precession (TrueFISP) MRI cine sequences from Siemens were used to capture the two-dimensional motion images of the simulated tumor. The phantom experiments were divided into three modes: head-foot motion mode, rotation motion mode, and actual respiratory waveform mode. In the head-foot motion mode, respiratory motion period (3, 4, 5, 6, 7 and 8 s), amplitude (5, 10 and 15 mm), and respiratory waveform of the simulated tumor (sin and cos4) were set, resulting in a total of 36 motion combinations. In the rotation motion mode, a cos4 waveform was used for respiration, with respiratory periods of 3, 4, 5, 6, 7 and 8 s, head-foot motion set amplitudes of 5, 10 and 15 mm, and anterior-posterior (AP) and left-right (LR) motion set amplitudes in three combinations ([2.5, 2.5] mm, [2.5, 5.0] mm, [5.0, 5.0] mm), resulting in a total of 54 motion combinations. In the actual respiratory waveform mode, respiratory waveforms of 5 randomly selected patients from Affiliated Cancer Hospital of Zhengzhou University were obtained. Under each motion combination, TrueFISP cine images (30 frames, with an acquisition time of 11 s per frame) were obtained. The code was used to automatically identify the two-dimensional coordinates of the center of the simulated tumor in each image, and sin and cos4 functions were separately employed to fit the tumor position in the motion direction, thereby obtaining the fitted motion period and amplitude. The difference between the maximum and minimum values of the tumor's center coordinates in the head-to-foot direction is taken as the range of movement, referred to as the calculated amplitude. For the actual respiratory waveform, the distance between the measured maximum and minimum positions is used to calculate the amplitude.Results:In the head-foot motion mode, the fitted amplitudes of both sin and cos4 waveforms deviated from the set amplitudes by 0-0.51 mm, with relative deviations of 0%-4.2%. The deviation range between the calculated amplitudes and the set amplitudes of the two waveforms were 0.08-0.94 mm, with relative deviations of 1.1%-6.3%. In the rotation motion mode, the fitted amplitudes deviated from the set amplitudes by 0-0.61 mm, with relative deviations of 0%-6.2%. And the deviation range between the calculated amplitudes and the set amplitudes were 0.16-0.94 mm, with relative deviations of 0%-6.3%. In the actual respiratory waveform motion mode, the deviation range between the calculated amplitudes and the set amplitudes were 0.10-0.48 mm, with relative deviations of 2.2%-8.6%.Conclusion:TrueFISP cine sequences show minimal deviations in determining the range of tumor head-foot motion and effectively captures the tumor's movement state, thereby providing important support for the precise definition of the tumor movement target area during radiotherapy .

Objective To analyze the mechanism that Hcp1 protein in type Ⅵ secretion system of Burkholderia pseudomallei(B.pseudomallei)mediates the formation of multinucleated giant cells(MNGCs)when host cells are infected by the bacterium.Methods The mutant strain(BPC006 Δhcp1)and complementation strain(BPC006 Δhcp1::hcp1)were constructed by homologous recombination and plasmid complement technology,respectively.After RAW264.7 cells were infected with B.pseudomallei,the localization of Hcp1 in host cells was analyzed by immunofluorescence staining.The localization was further verified by cytoplasmic-membrane isolation in 293T cells after transfecting pCDNA4.1-Hcp1.The biological significance and effect of Hcp1 were explored by the anti-Hcp1 polyclonal antibody blocking and the formation of MNGC was detected by Giemsa staining.Results Western blotting showed that BPC006 Δhcp1 could not express Hcp1,while BPC006 Δhcp1::hcp1 restored Hcp1 expression.The above results proved that the mutant and complement strains were successfully constructed.Both cellular immunofluorescence co-localization and cytoplasmic-membrane isolation experiments showed that Hcp1 localized to host cell membranes.Last but not least,compared with the control group,anti-Hcp1 polyclonal antibodies inhibited the formation of MNGC(P＜0.01).Conclusion Hcp1 protein in type Ⅵ secretion system of B.pseudomallei is able to translocate to the RAW264.7 cell membranes and plays an important role in the formation of MNGCs.

To investigate the evaluation and management of gastrointestinal fistula after upper gastrointestinal tunnel endoscopic surgery, a retrospective analysis was performed on 15 patients with gastrointestinal fistula after upper gastrointestinal tunnel endoscopic surgery, who were treated at the Endoscopy Center of Zhongshan Hospital, Fudan University from January 2012 to October 2022. All patients were treated successfully after comprehensive treatment. Three patients received metal clipping and gastric tube drainage; 10 patients received gastric tube drainage combined with jejunal nutritional tube placement, and 7 of them had gastric tube directly put into the fistula cavity; 2 patients received covered esophageal stent placement combined with jejunal nutritional tube placement. Five patients received wound tissue glue spraying; 2 patients underwent purse-string suture with nylon loops and metal clips after reduced fistula burned by hot biopsy forcep or argon plasma coagulation. The gastrointestinal fistula after tunnel endoscopic surgery is a complex postoperative complication, which needs early detection, careful evaluation and comprehensive treatment.

Objective:To investigate the effect of total anatomical reconstruction (TAR) during robot-assisted radical prostatectomy (RARP) .Methods:The clinical data of 99 patients with RARP performed by a single doctor in our hospital from January 2018 to January 2021 were analyzed retrospectively.There were 38 patients in the TAR+ vesicourethral anastomosis (VUA) group and 61 patients in the VUA group. There were no significant differences between the two groups in the age of patients [ 65.5 (60.8, 71.0) years vs. 66.0 (61.5, 69.0) years], body mass index[ (24.92±2.65) kg/m 2 vs. (25.51±2.80) kg/m 2], prostate volume [28.13 (25.21, 36.53) ml vs. 26.33 (19.75, 47.84) ml], PSA [15.67 (9.02, 31.49) ng/ml vs. 14.58 (9.23, 30.06) ng/ml], neoadjuvant therapy [50.0% (19/38) vs. 63.9% (39/61)], Gleason score (6/7/8/9-10 scores: 8/16/5/9 cases vs. 16/25/9/11 cases) and clinical T stage (T 1/T 2/T 3 stage: 4/29/5 cases vs. 3/53/5 cases)(all P>0.05). The TAR technique was performed as follows. ①The two layers of posterior reconstruction involved the residual Denonvilliers fascia, the striated sphincter and medial dorsal raphe (MDR), and the vesicoprostatic muscle (VPM), the fascia which was 1-2 cm from the cranial side of the bladder neck and MDR. ②The one layer of anterior reconstruction involved detrusor apron, tissues around the urethra and the visceral and parietal layers of the endoplevic fascia. The VUA technique was suturing the bladder neck and urethra consecutively. Perioperative indexes were compared between the two groups. Results:All 99 operations were successfully completed. There were no statistically significant differences between the TAR+ VUA and VUA groups in operation time [ (174.16±47.21) min vs. (188.70±45.39) min], blood loss [ 50 (50, 100) ml vs. 100 (50, 100) ml], incidence of postoperative complications [10.5% (4/38) vs. 14.8% (9/61)], phathological T stage [pT 2/pT 3~4 stage: 25/12 cases vs. 42/19 cases, P=0.895], and the time of indwelling catheter [ 21.0 (19.0, 21.0) d vs. 21.0 (21.0, 21.0) d] (all P>0.05). The difference in postoperative length of stay between the two groups was statistically significant[6.0 (5.0, 6.0) d vs. 7.0 (6.0, 7.5)d, P<0.001]. Follow-up was performed for 1 year after surgery. The recovery rate of urinary continence 3 months after surgery in TAR+ VUA and VUA groups were 86.8% (33/38) vs. 65.6% (40/61), which were statistically significant( P=0.019). There were no significant differences between TAR+ VUA and VUA groups in recovery rate of urinary continence 1 months after surgery [47.4% (18/38) vs. 45.9% (28/61)], 6 months after surgery [94.7% (36/38) vs. 85.2% (52/61)], and 12 months after surgery [94.7% (36/38) vs. 93.4% (57/61)] (all P>0.05). Conclusions:TAR technique has good surgical safety, and can promote recovery of early urinary continence after RARP.

Whether anatomical segmentectomy can replace lobectomy in the treatment of early-stage lung cancer remains controversial. A large number of studies have been conducted for decades to explore whether pulmonary segmentectomy can treat early-stage lung cancer, which is actually to explore the indications of intentional segment-ectomy. With the development of scientific researches, it is found that many characteristics affect the malignancy of lung cancer, and the different grades of each characteristic affect the prognosis of patients. It is worth exploring whether different surgical approaches can be used for early-stage lung cancer with different characteristics and different grades. This article reviews the literature and studies to discuss the advances in indications of segmentectomy for early-stage lung in terms of tumor size, consolidation-to-tumor ratio, pathological classification and tumor location, respectively. The objective of this review is to help thoracic surgeons to objectively and scientifically select the surgical method according to the clinical characteristics of early-stage lung cancer.

Objective:To investigate the relationship between the positive surgical margin and clinical factors such as neoadjuvant hormonal therapy after robot-assisted laparoscopic radical prostatectomy (RARP) in high-risk patients with prostate cancer.Methods:The clinical data of 164 patients with high-risk prostate cancer being performed RARP by one surgeon were analyzed retrospectively in our hospital from January 2016 to January 2022. The mean patient’s age was (65.3±6.2) years old, mean body mass index (BMI) was (25.6±3.0) kg/m 2, the median value of total prostate specific antigen (tPSA) before operation was 18.6(11.3, 31.3)ng/ml, the median value of Gleason score before operation was 7 (7, 8), the median value of prostate volume was 29.3 (22.4, 40.2) ml, and the clinical stage was T 2aN 0M 0-T 4N 0M 0. 80 patients with prostate cancer were treated with neoadjuvant endocrine therapy. All of them were treated with complete androgen blockade with a median course of 3 months. Univariate analysis was used to analyze the correlation between age, BMI, prostate volume, neoadjuvant hormonal therapy, preoperative tPSA, clinical stage, Gleason score before operation and positive surgical margin. Then multivariate logistic regression was used to further analyze the independent risk factor of positive surgical margin after RARP. Results:The postoperative pathological diagnosis included pT 2 stage in 111 cases (67.7%), pT 3a stage in 15 cases (9.1%), pT 3b stage in 25 cases (15.2%), pT 4 stage in 13 cases (7.9%). No lymph node metastasis was noticed in all patients. The Gleason scores included 6 in 11 cases (6.7%), 3+ 4 in 26 cases (15.9%), 4+ 3 in 36 cases (22.0%), 8 in 17 cases (10.4%), 9-10 in 24 cases (14.6%), un-evaluation due to endocrine therapy in 50 (30.5%). The positive surgical margin of high-risk patients with prostate cancer was 44.5% (73/164). Univariate analysis showed that the neoadjuvant hormonal therapy, tPSA and clinical stage were correlated with positive surgical margin ( P<0.05). Multivariate logistic regression analysis showed that non-neoadjuvant hormonal therapy, preoperative tPSA>20ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of high-risk patients with prostate cancer. Stratified analysis showed that when the preoperative tPSA was 10-20 ng/ml(21.1% vs.55.9%, P=0.014), the clinical stage was T 2c(29.6% vs.49.1%, P=0.040), the Gleason score before operation was 7(19.4% vs.54.1%, P=0.003), the positive surgical margin of high-risk patients in the neoadjuvant hormonal therapy group was significantly lower than that in the non-neoadjuvant hormonal therapy group ( P<0.05). Conclusions:Non-neoadjuvant hormonal therapy, preoperative tPSA>20 ng/ml and clinical stage>T 2b were independent risk factors for positive surgical margin of RARP in the high-risk patients with prostate cancer. For high-risk patients with preoperative tPSA of 10-20 ng/ml, clinical stage of T 2c and Gleason score before operation of 7, neoadjuvant hormonal therapy has important clinical significance in reducing the positive surgical margin of RARP.