Metabolomics covers a wide range of applications in life sciences, biomedicine, and phytology. Data acquisition (to achieve high coverage and efficiency) and analysis (to pursue good classification) are two key segments involved in metabolomics workflows. Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups. However, insufficient feature extraction, inappropriate feature selection, overfitting, or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused. Using two ginseng varieties, namely Panax japonicus (PJ) and Panax japonicus var. major (PJvm), containing the similar ginsenosides, we integrated pseudo-targeted metabolomics and deep neural network (DNN) modeling to achieve accurate species differentiation. A pseudo-targeted metabolomics approach was optimized through data acquisition mode, ion pairs generation, comparison between multiple reaction monitoring (MRM) and scheduled MRM (sMRM), and chromatographic elution gradient. In total, 1980 ion pairs were monitored within 23 min, allowing for the most comprehensive ginseng metabolome analysis. The established DNN model demonstrated excellent classification performance (in terms of accuracy, precision, recall, F1 score, area under the curve, and receiver operating characteristic (ROC)) using the entire metabolome data and feature-selection dataset, exhibiting superior advantages over random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and multilayer perceptron (MLP). Moreover, DNNs were advantageous for automated feature learning, nonlinear modeling, adaptability, and generalization. This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples. This established approach holds promise for plant metabolomics and is not limited to ginseng.

Purpose To study the association between ultrasonography signs of midurethral sling(MUS)and postoperative bladder neck mobility,and urethral segmental mobility,to explore ultrasound parameters that measure the biomechanical effects of MUS and to analyze the relationship between them and the clinical outcomes.Materials and Methods This was a retrospective analysis of the clinical material and ultrasound imaging data of the patients who underwent MUS surgery and had postoperative clinic follow-up in the Second Xiangya Hospital,Central South University,from September 2017 to July 2022.According to the surgical outcome,all patients were divided into three groups:stress urinary incontinence(SUI)cure group,SUI recurrence group and postoperative voiding dysfunction(VD)group.Bladder neck mobility,urethral segmental mobility,MUS position,and sling-pubic gap(SPG)during maximal Valsalva manoeuvre were measured by pelvic floor ultrasound.Ultrasound results among the three groups were compared,respectively.The relationships between ultrasound signs of the sling(MUS position and SPG),bladder neck and urethral mobility,and the surgical outcomes were analyzed,respectively.Results A total of 117 women had valid data.The median follow-up interval was 10(6,18)months.On clinical examination and diagnosis,44 women(37.6％)had cured SUI,46(39.3％)had recurrence SUI,and 27(23.1％)had postoperative VD.The mean SPG of the 117 slings was(12.0±3.5)mm(range 4.7 to 23.0 mm),and the mean position of the MUS was the 53％(range 33％-75％).There was no significant difference in MUS position and SPG between the SUI cured group and the postoperative VD group(P＞0.05).The SUI recurrence group had farther MUS position[(56±11)％vs.(49±10)％,P=0.003]relative to the bladder neck and wider SPG[(13.9±3.7)mm vs.(11.2±2.7)mm,P＜0.001]than SUI cure group.No significant correlation was found between the ultrasound signs of MUS(MUS position and SPG)and bladder neck mobility(r=-0.138-0.205,all P≥0.05).MUS position and SPG were correlated with midurethral mobility(MUS position vs.point 2 and 3,r=0.322,0.322,both P＜0.01;SPG vss.point 3 to 6,r=0.288-0.434,all P＜0.01):the closer the MUS position was relative to the distal urethra,the higher the midurethral mobility.The wider the SPG,the higher the midurethral mobility.Logistic regression showed a positive correlation between SPG and SUI recurrence with an odds ratio(OR)of 1.401(95％CI 1.189-1.652,P＜0.001),and a negative correlation with postoperative VD with an OR of 0.755(95％CI 0.627-0.909,P=0.003).Conclusion SPG during the Valsalva manoeuvre can be used to measure the tightness of MUS.The larger the measured value of SPG,with the looser the MUS,the greater the likelihood of postoperative SUI recurrence,and the lower the risk of postoperative VD.

Identifying the compound formulae-related xenobiotics in bio-samples is full of challenges.Conventional strategies always exhibit the insufficiencies in overall coverage,analytical efficiency,and degree of automation,and the results highly rely on the personal knowledge and experience.The goal of this work was to establish a software-aided approach,by integrating ultra-high performance liquid chromatography/ion-mobility quadrupole time-of-flight mass spectrometry(UHPLC/IM-QTOF-MS)and in-house high-definition MS2 library,to enhance the identification of prototypes and metabolites of the compound formulae in vivo,taking Sishen formula(SSF)as a template.Seven different MS2 acquisition methods were compared,which demonstrated the potency of a hybrid scan approach(namely high-definition data-independent/data-dependent acquisition(HDDIDDA))in the identification precision,MS1 coverage,and MS2 spectra quality.The HDDIDDA data for 55 reference compounds,four component drugs,and SSF,together with the rat bio-samples(e.g.,plasma,urine,feces,liver,and kidney),were acquired.Based on the UNIFI? platform(Waters),the efficient data processing workflows were estab-lished by combining mass defect filtering(MDF)-induced classification,diagnostic product ions(DPIs),and neutral loss filtering(NLF)-dominated structural confirmation.The high-definition MS2 spectral li-braries,dubbed in vitro-SSF and in vivo-SSF,were elaborated,enabling the efficient and automatic identification of SSF-associated xenobiotics in diverse rat bio-samples.Consequently,118 prototypes and 206 metabolites of SSF were identified,with the identification rate reaching 80.51％and 79.61％,respectively.The metabolic pathways mainly involved the oxidation,reduction,hydrolysis,sulfation,methylation,demethylation,acetylation,glucuronidation,and the combined reactions.Conclusively,the proposed strategy can drive the identification of compound formulae-related xenobiotics in vivo in an intelligent manner.

Objective:To study the agreements between transperineal ultrasound (TPUS) and endoanal ultrasound in assessing obstetrics anal sphincter injury (OASI), and to analyse the diagnostic efficacy of OASI in predicting AI relationship between OASI and anal incontinence (AI).Methods:A total of 217 women were prospectively recruited from the clinic in the Second Xiangya Hospital of Central South University from January 2021 to May 2022. Symptoms of AI were determined using the St Mark′s Incontinence Score (SMIS). TPUS and EAUS were performed by the same operator with the same machine on every participant for detecting OASI: OASI grades 3a, 3b, 3c, and 4 were performed according to the extent of the injuries in the anal sphincter complex. The angle of the defect in the external anal sphincter (EAS) was measured. A "significant EAS defect" was diagnosed as a defect affecting at least 2/3 of the length of the EAS with a defect angle of ≥30° in each slice.Ultrasound findings were compared between the two methods. The diagnostic efficacy of "ultrasound OASI" in predicting AI was analysed by logistic regression.Results:Of 217 women, twenty-eight (12.9%) suffered from AI with SMIS ranging from 5~20(11.9±4.5). On TPUS, 79 (36.4%) cases were suspected of OASI, that was 50 OASI 3a, 13 OASI 3b, and 16 OASI 3c/4. On EAUS, 78 (35.9%) cases were suspected of OASI that was 23 OASI 3a, 22 OASI 3b, 15 OASI 3c, and 18 OASI 4. Twenty-four "significant EAS defects" were diagnosed by TPUS and twenty-eight by EAUS, TPUS had excellent agreement with EAUS (weighted Kappa=0.91, P<0.001). Logistic regression analysis showed that "ultrasound OASI" was associated with AI symptoms. ROC curve analysis showed that the area under the curve (AUC) was 0.92, 0.87, 0.89, 0.92 for TPUS OASI 3b+ , EAUS OASI 3b+ , TPUS "Significant EAS defect" , and EAUS "Significant EAS defect" for predicting AI, respectively. Conclusions:TPUS has good agreement with EAUS in detecting OASI. OASI 3b+ and "significant EAS defect" on TPUS and EAUS had good performance in predicting AI symptoms.

Objective:To investigate the effect of different spray-coagulation time of argon plasma coagulation (APC) injury on the Glisson system primary branche(G1) in the hepatic portal of pigs.Methods:Fifty clean healthy domestic pigs (27 females and 23 males, aged 7 to 14 months) were selected, with the body weighted (100.0±9.5) kg. They were randomly divided into five groups (A, B, C, D, and E), with 10 pigs in each group. G1 models were made and sprayed by APC for 1, 2, 3, 4, and 5 seconds. The damage, maximum damage area, maximum damage depth, and damage of the three branches of the Glisson system (the first branches of the portal vein, intrahepatic bile duct, and hepatic artery) were compared among the groups. The pigs were divided into two groups based on whether the three branches were damaged or not: the three-branch damage group ( n=23) and the control group ( n=27). The maximum damage area and maximum damage depth were compared between the two groups. Results:After the APC spraying, circular or elliptical damage appeared on the surface of the G1, with changes such as yellow-brown color, brown color, charred appearance, and defects. Under the microscope, G1 capsule was found to be deficient, the fibrous tissue beneath the capsule was ruptured, and the structures of small blood vessels and small bile ducts were incomplete. " Burn marks" and damage to the three branches of the Glisson system in G1 were also observed, and the damage was more severe at the center of the spray-coagulation. As the spray-coagulation time increased, the maximum damage area of the G1 model also increased, and the two were positively correlated ( r=0.90, P<0.001). The maximum damage depth was also positively correlated with spray-coagulation time ( r=0.97, P<0.001). The numbers of pigs with damage to the three branches of the Glisson system in Groups A-E were 0, 2, 5, 6, and 10, respectively, and the number of pigs with damage increased with the spray-coagulation time. In the three-branch damage group, the spray-coagulation time, maximum damage area, and maximum damage depth were all higher than those in the control group (without three-branch damage), and the differences were statistically significant (all P<0.05). Conclusion:The degree of damage to G1 caused by APC is positively correlated with the spray-coagulation time, and damage to the three branches of the Glisson system in G1 is related to the maximum damage area, maximum damage depth, and APC spray-coagulation time.

Objective:To evaluate the effects of pegylated interferon (Peg-IFN) alfa-2b combined with nucleotide analogues (NAs) on the recurrence of hepatitis B-related liver cancer after resection, and to explore the changes of HBsAg and HBV DNA in patients with chronic hepatitis B liver cancer during postoperative treatment.Methods:The prospective study was conducted. Clinical data of 43 patients with hepatitis B-related liver cancer who underwent radical resection treated in 900th Hospital of People′s Liberation Army were prospectively analyzed from January 2020 to December 2021. Among 43 patients, there were 39 males and 4 females, the age was 30-76 years. According to different treatment methods they were divided into two groups, the patients treated by Peg-IFN alfa-2b combined with NAs were devided into the IFN group( n=10), and those treated by NAs alone into the NAs group( n=33). Two-pair semi-quantitative were collected every 3 months after operation. The recurrence-free survival rate, recurrence time after 2 years in the two groups, the clearance rate and the negative rate of HBsAg and HBV DNA in the two groups. Peg-IFN alfa-2b was evaluated in improving the prognosis of hepatitis B-related liver cancer. The measurement data of normal distribution were expressed by mean±standard deviation ( ± s), and t-test was used for comparison between the two groups. Chi-square test was used for comparison between the two groups of count data. Repeated analysis of measurement variance was used for analysis HBsAg and HBV DNA changes of the interferon group overall survival time and recurrence-free surrival time of patients was estimated using Kaplan-Meier method and the difference between groups was assessed using Log-rank test. Results:HBsAg and HBV DNA: The HBsAg clearance rate at 24 weeks and that at 48 weeks in the IFN group were 24.6% and 59.0% respectively. The HBsAg negative rate at 48 weeks was 16.7%. The HBV DNA clearance rate at 24 weeks and that at 48 weeks were 33.9% and 53.8% respectively. The HBV DNA negative rate was 0 at 48 weeks. The levels of HBsAg and HBV DNA in the IFN group decreased gradually with time. There were statistically differences between the levels of HBsAg and HBV DNA at 0 weeks, 24 weeks and 48 weeks( P<0.05). The 2-year overall survival rates of IFN group and NAs group were 100% and 90.9% respectively. The 2-year recurrence-free survival rates were 90.0% and 63.6% respectively. There were no significant statistical differences in the overall survival rate and recurrence-free survival rate between the groups ( P>0.05). The postoperative recurrence time of the IFN group and the NAs group were (15.00±7.07) months and (5.78±3.39) months respectively. The difference between the two groups was statistically significant ( t=3.160, P<0.01). Conclusion:Long-term antiviral therapy of Peg-IFN alfa-2b combined with NAs can prolong the recurrence time of liver cancer, reduce the levels of HBsAg and HBV DNA in serum, and potentially improve the survival rate of the patients compared with therapy of NAs alone.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

Purpose: This study compared the diagnostic performance of the Ovarian-Adnexal Reporting and Data System (O-RADS), the Risk of Malignancy Index 4 (RMI4), the International Ovarian of Tumor Analysis Logistic Regression Model 2 (IOTA LR2), and the IOTA Simple Rules (IOTA SR) in predicting the malignancy of adnexal masses (AMs). Methods: This retrospective study included 575 women with AMs between 2017 and 2020. All clinical messages, ultrasound images, and pathological findings were collected. Two senior doctors (group I) and two junior doctors (group II) used the four systems to classify AMs. The postoperative pathological diagnosis was used as the gold standard to evaluate the diagnostic efficiency. A receiver operating characteristic curve was used to test the diagnostic performance. The interrater agreement between the two groups was tested using kappa values. Results: Of all 592 AMs, 447 (75.5%) were benign, 123 (20.8%) were malignant, and 22 (3.7%) were borderline. The intergroup consistency test yielded kappa values of 0.71, 0.92, 0.68, and 0.77 for the O-RADS, RMI4, IOTA LR2, and IOTA SR, respectively. To predict malignant lesions, the areas under the curve of the O-RADS, RMI4, IOTA LR2, and IOTA SR systems were 0.90, 0.89, 0.90, and 0.86 for group I and 0.89, 0.87, 0.88, and 0.84 for group II, respectively. The O-RADS had the highest sensitivity (91.0% in group I and 84.8% in group II). Conclusion The four diagnostic systems could compensate for junior doctors’ inexperience in predicting malignant adnexal lesions. The O-RADS performed best and showed the highest sensitivity.

Hilar cholangiocarcinoma(HCCA) is a hotpot and a difficult point in the field of hepatobiliary surgery. HCCA is the most common type of cholangiocarcinoma and is characterized by atypical early clinical manifestations, rapid progression and poor prognosis. There is no specific marker for HCCA and its preoperative diagnosis and evaluation mainly relies on imaging examination. Surgical treatment is still the main treatment, but most patients have lost the opportunity of surgical resection by the time of treatment. In recent years, a large number of studies have been conducted on the diagnosis and treatment of HCCA at home and abroad, and the efficacy of HCCA has been improved. Perioperative management, including the selection of preoperative drainage and perioperative chemoradiotherapy and others, improved postoperative survival. Among them, the application of preoperative radiotherapy and chemotherapy in the field of liver transplantation has achieved quite good results. Targeted therapy and immunotherapy have provided new treatment methods for HCCA. This paper reviews the diagnosis and multimodal treatment of HCCA.

Objective:To explore the clinical efficacy of liver transplantation for Wilson's disease(WD).Methods:From January 1999 to November 2021, clinical data were retrospectively reviewed for 16 recipients with WD undergoing liver transplantation.There were 9 males and 7 females with an age range of 29.5(14~54)years.They were followed up by telephone, outpatient services and hospitalization.The starting point of follow-up was operation date.And recipient death was an endpoint.Postoperative survival, improvement of neuropsychiatric symptom, changes of corneal K-F ring, altered levels of liver function and serum copper-protein at Month 1 post-operation were observed.The follow-up deadline was November 24, 2021.Results:15 recipients underwent classical orthotopic liver transplantation and the other one recipient underwent living-related liver transplantation.No perioperative deaths occurred.All 16 recipients were followed up for 122(6~260)months.The 1-, 5-, and 10-year survival rates were 93.8%、85.2%and 75.8%, respectively.Among 10 recipients with corneal K-F ring positive with varying degrees after operation and was disappeared in 2 recipients at 7 and 11 months.Among 5 recipients with neuropsychiatric manifestation, 4 recipients showed ameliorative neuropsychic symptoms with varying degrees after operation and 1 recipient died.All the levels of liver function and serum copper-protien of all recipients recovered obviously in 1 month and the 1-, 5-, and 10-year post-operation.Conclusions:Classical orthotopic liver transplantation and living-related liver transplantation not only effectively improves copper metabolism of patient with WD and relieves their severe neurological manifestation, but also improves their life and prolongs survival, which is worthy of clinical promotion.