Objective:To construct an explainable artificial intelligence(AI) model of risk characteristics of papillary thyroid carcinoma(PTC), and to explore its value of it combined with clinical features in predicting cervical lymph node metastasis(CLNM) in PTC patients.Methods:From January 2021 to September 2022, 422 patients(422 nodules) with pathologically confirmed PTC underwent thyroidectomy and neck lymph node dissection in the Second Affiliated Hospital of Xi′an Jiaotong University were retrospectively collected, the patients were randomly divided into training set and test set according to the ratio of 7∶3. Ultrasonographic features highly correlated with PTC risk characteristics were extracted by traditional machine learning method, and an intelligent prediction model with optimal probability of risk characteristics was established. Then, a risk model for predicting CLNM of PTC patients was constructed in combination with clinical features. The diagnostic effectiveness of the model was evaluated by drawing a ROC curve and calculating the area under curve (AUC).Results:In the AI explaineable model of PTC risk characteristics in the test set, the intelligent diagnosis model of calcification based on logistic regression classification showed the highest diagnostic efficiency, with an AUC of 0.87 ( P<0.05). Compared with the probability model of risk characteristic of PTC alone, the comprehensive model combined with clinical characteristics showed higher diagnostic efficiency in predicting CLNM of PTC patients, with AUC of 0.97, diagnostic critical value of 0.15, corresponding accuracy, sensitivity and specificity of 92.65%, 92.76% and 92.54%, respectively (all P<0.05). Conclusions:The explaineble risk characteristics of PTC AI model combined with clinical features can effectively predict the cervical lymph node metastasis of PTC, and then provide effective information for clinical decision-making of PTC patients.

Gegen Qinlian decoction has a wide range of clinical applications. However, there is a lack of systematic quality evaluation methods to ensure the safety and effectiveness of Gegen Qinlian decoction in clinical use. The UHPLC fingerprint and multi-component determination method of Gegen Qinlian decoction were established to provide scientific basis for the quality control and evaluation of Gegen Qinlian decoction. The chromatography was performed on a ZORBAX Eclipse Plus-C₁₈ column (150 mm × 4.6 mm, 3.5 μm) with mobile phase consisted of acetonitrile (A) - 20 mmol·L^-1 ammonium acetate (containing 0.8% acetic acid and 0.5% triethylamine) (B) and gradient elution at a flow rate of 1.0 mL·min^-1. The column temperature was 25 ℃, the detection wavelength was 260 nm, the fingerprint of 10 batches of Gegen Qinlian decoction was determined, and the similarity evaluation system of TCM chromatographic fingerprint was used for comprehensive analysis, and 9 components were quantitatively analyzed. In the fingerprint study of Gegen Qinlian decoction, a total of 18 peaks were obtained, 12 of which were identified by reference substances. Moreover, the similarity of 10 batches of Gegen Qinlian decoction was good, and all of them were greater than 0.99. In the multi-component quantitative analysis, the linear relationship between the nine components and the peak area was good (r ≥ 0.999) in the corresponding mass concentration range. The average recovery rate was 94.4%-100.3%, and the RSD was 0.1%-1.4%. The fingerprint of Gegen Qinlian decoction was studied under the same wavelength, and the content of 9 main components were determined by our established method. The method has high sensitivity and strong specificity, which provided a comprehensive scientific basis for the comprehensive evaluation of the quality of Gegen Qinlian decoction.

Background::With an increasing proportion of multiparas, proper interpregnancy intervals (IPIs) are urgently needed. However, the association between IPIs and adverse perinatal outcomes has always been debated. This study aimed to explore the association between IPIs and adverse outcomes in different fertility policy periods and for different previous gestational ages.Methods::We used individual data from China’s National Maternal Near Miss Surveillance System between 2014 and 2019. Multivariable Poisson models with restricted cubic splines were used. Each adverse outcome was analyzed separately in the overall model and stratified models. The stratified models included different categories of fertility policy periods (2014–2015, 2016–2017, and 2018–2019) and infant gestational age in previous pregnancy (<28 weeks, 28–36 weeks, and ≥37 weeks).Results::There were 781,731 pregnancies enrolled in this study. A short IPI (≤6 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.63 [1.55, 1.71] for vaginal delivery [VD] and 1.10 [1.03, 1.19] for cesarean section [CS]), low Apgar scores and small for gestational age (SGA), and a decreased risk of diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. A long IPI (≥60 months) was associated with an increased risk of preterm birth (OR [95% CI]: 1.18 [1.11, 1.26] for VD and 1.39 [1.32, 1.47] for CS), placenta previa, postpartum hemorrhage, diabetes mellitus in pregnancy, preeclampsia or eclampsia, and gestational hypertension. Fertility policy changes had little effect on the association of IPIs and adverse maternal and neonatal outcomes. The estimated risk of preterm birth, low Apgar scores, SGA, diabetes mellitus in pregnancy, and gestational hypertension was more profound among women with previous term births than among those with preterm births or pregnancy loss.Conclusion::For pregnant women with shorter or longer IPIs, more targeted health care measures during pregnancy should be formulated according to infant gestational age in previous pregnancy.

Objective To elucidate the bidirectional causal relationship between lipid profiles and colorectal cancer(CRC)by using the two-sample and two-step Mendelian randomization(MR)methods,and to explore the mediating role and proportion of immune cells as intermediary factors.Methods The pooled statistical data related to the study were screened,and 179 lipids and CRC were analyzed using two-sample and two-step MR with the inverse variance weighted method.Simultaneously,the causal effect was verified via Bayesian weighted MR.Two-step MR analysis was conducted to determine whether a mediated effect was exerted on immune cell traits.Sensitivity,heterogeneity,and pleiotropy analyses were performed to verify the reliability of the study results.Results The causal relationship between nine lipid traits and CRC was preliminarily identified,and no reverse causal effect was found(P>0.05).The validity of the results was verified via Bayesian weighted MR(P<0.05).Twenty-seven types of immune cells were suggested to exert a causal effect on CRC.The causal effect of phosphatidylcholine(O-18:2_20:4)on CRC was determined via mediation analysis(OR:0.8579,95% CI=0.7395-0.9952,P=0.0429).The CD127-mediated proportion on CD45RA+CD4+T cells was 9.14% (β=-0.1052,P=0.0155).Conclusion A causal relationship exists between lipid traits and CRC,and the intervention of CD127 on CD45RA+CD4+T cell helps phosph-atidylcholine reduce the risk of CRC.

Objective To observe the effect of remifentanil-based fast-track anesthesia on the quality of anesthesia recovery in children with congenital heart disease underwent transcatheter closure.Methods Children with congenital heart disease who underwent transcatheter closure were divided into treatment group and control group according to the anesthesia plan.The anesthesia plan of the control group was as follows:anesthesia induction(intramuscular injection of ketamine at 4 mg·kg-1,intravenous injection of propofol at 2.5 mg·kg-1,fentanyl at 10 μg·kg-1and cisatracurium at 0.1 mg·kg-1)and anesthesia maintenance(fentanyl at0.4μg·kg-1·min-1 and propofol at 8 μg·kg-1·min-1).The anesthesia plan of the treatment group was as follows:anesthesia induction(intramuscular injection of ketamine at 5 mg·kg-,intravenous injection of midazolam at 0.1 mg·kg-1,sufentanil at 1.0 μg·kg-1 and cisatracurium at 0.1 mg·kg-1)and anesthesia maintenance(remifentanil at 0.5 μg·kg-1·min-1 and propofol at 8 μg·kg-1·min-1).Anesthesia recovery,facial expression,leg posture,activity,crying and comfortability(FLACC)of 5 pain scores,Ramsay score,hemodynamics,myocardial injury indexes,and adverse drug reactions were compared between the two groups.Results There were 64 cases in treatment group and 56 cases in control group.The spontaneous respiration recovery time,call time and extubation time of the treatment group were(4.87±1.22),(10.16±2.58)and(12.55±3.19)min,shorter than those in control group,which were(5.49±1.35),(13.34±3.27)and(15.67±3.62)min(all P＜0.05).At 1 h and 2 h after operation,Ramsay scores of treatment group were 2.58±0.35 and 3.69±0.42,were lower than 3.02±0.47 and 4.24±0.39 in control group(all P＜0.05).At 1 h and 2 h after operation,the FLACC scores of the treatment group were 3.03±0.81 and 3.75±0.84,lower than 3.78±0.62 and 4.36±0.51 in control group(all P＜0.05).Mean arterial pressure(MAP)of treatment group at the insertion of laryngeal mask,the insertion of occluder and the end of the operation were(102.45±10.26),(94.18±8.37)and(91.46±10.15)mmHg,lower than those in control group,which were(107.84±10.11),(100.57±9.84)and(97.33±8.53)mmHg(all P＜0.05).On day 1 and day 3 after operation,serum creatine kinase isoenzyme(CK-MB)levels in the treatment group were(10.03±2.58)and(8.65±2.16)U·L-1,lower than those in control group,which were(12.44±3.07)and(10.16±2.35)U·L-1(all P＜0.05).On day 1 and day 3 after operation,serum cardiac troponin Ⅰ(cTn Ⅰ)levels in treatment group[(0.07±0.02)and(0.04±0.01)μg·L-1]were lower than those in control group[(0.09±0.03)and(0.06±0.02)μg·L-1](all P＜0.05).The incidence of adverse anesthesia reactions in treatment group was 6.25％(4 cases/64 cases),lower than 17.86％(10 cases/56 cases)in control group(P＜0.05).Conclusion Remifentanil-based fast-track anesthesia can improve the quality of anesthesia recovery in children with congenital heart disease undergoing transcatheter closure,with good sedative and analgesic effects,stable hemodynamics during operation,and low incidence of adverse drug reactions.

Objective To explore the effect and mechanism of hydroxysafflor yellow A(HSYA)on autophagy in bEnd.3 cells after oxygen-glucose deprivation(OGD).Methods The bEnd.3 cells were divided into normal group(conventional culture),model group(OGD model),HSYA group(OGD model+75 μmol·L-1 HSYA),3-methyladenine(3MA)group(5 mmol·L-1 3MA+OGD model)and 3 MA+HSYA group(5 mmol·L-1 3 MA+OGD model+75 μmol·L-1 HSYA).The level of apoptosis was determined by TUNEL fluorescence staining;Western blot was used to detect the expression of autophagy,blood brain barrier(BBB)related proteins;real time fluorescence quantitative polymerase chain reaction method for determining the expression of sirtuin-1(SIRT1)and forkhead box protein O3a(FOXO3A)mRNA.Results In the normal group,model group,HSYA group,3MA group and 3MA+HSYA group,the positive cells selected for TUNEL staining were 5.00±1.00,28.00±2.00,21.00±3.00,35.33±2.51 and 29.67±2.52;the expression levels of microtubule-associated protein 1 light chain 3-Ⅱ/-Ⅰ(LC3-Ⅱ/-Ⅰ)were 0.90±0.20,1.34±0.10,1.95±0.14,0.76±0.15 and 1.14±0.09;sequestosome 1(P62)were 0.99±0.02,0.60±0.02,0.38±0.01,0.67±0.04 and 0.54±0.01;occludin were 1.39±0.17,0.62±0.15,1.00±0.09,0.40±0.13 and 0.80±0.15;zonula occludens-1(ZO-1)were 1.63±0.20,0.64±0.06,0.98±0.14,0.37±0.14 and 0.87±0.04;SIRT1 mRNA were 1.00±0.00,0.75±0.07,1.69±0.09,0.31±0.02 and 0.56±0.01;FOXO3A mRNA were 1.00±0.00,0.80±0.05,1.47±0.09,0.40±0.01 and 0.62±0.09,respectively.Significant differences were found between model group and normal group,HSYA group and model group,3MA+HSYA group and 3MA group(P＜0.05,P＜0.01,P＜0.001).Conclusion HSYA may enhance autophagy levels in bEnd.3 cells after OGD through the SIRT1/FOXO3A pathway,inhibit cell apoptosis and alleviate BBB damage.

Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90％confidence interval(CI)of the geometric mean ratio(GMR)were 94.11％-118.06％,99.22％-107.74％and 99.16％-107.44％for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00％-125.00％.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90％CI of GMR were 96.99％-101.19％and 97.17％-101.41％for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00％-125.00％.The 95％upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00％-125.00％.The incidence of adverse events in fasting and fed studies was 22.86％and 22.92％,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective:The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) .Methods:This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared.Results:①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD ( P=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM ( R2=0.035, P=0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion:sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.