ObjectiveGastric cancer (GC) seriously affects human health and life, and research has shown that it is closely related to the serine/glycine metabolism. The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine. The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells. MethodsIn this work, a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems. Based on the regulation of the model, a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells. We introduced random noise to the kinetic equations of the general metabolic network, and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space. A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations. ResultsDespite the unavailability of a large number of dynamic parameters, we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells. When extracellular serine is available, the model preferentially consumes serine. In addition, when the conversion rate of glycine to serine increases, the model significantly upregulates the steady-state fluxes of S-adenosylmethionine (SAM) and S-adenosyl homocysteine (SAH). ConclusionIn this paper, we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation, which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process. This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.

Objective To compare the effects of 20 mg qd and 10 mg bidadministration of iprrazole enteric-coated tablets on the control of gastric acid in healthy subjects.Methods A randomized,single-center,parallel controlled trial was designed to include 8 healthy subjects.Randomly divided into 2 groups,20 mg qd administration group:20 mg enteric-coated tablets of iprrazole in the morning;10 mg bid administration group:10 mg enteric-coated tablets of iprrazole in the morning and 10 mg in the evening.The pH values in the stomach of the subjects before and 24 h after administration were monitored by pH meter.The plasma concentration of iprazole after administration was determined by HPLC-MS/MS.The main pharmacokinetic parameters were calculated by Phoenix WinNonlin(V8.0)software.Results The PK parameters of iprrazole enteric-coated tablets and reference preparations in fasting group were as follows:The Cmax of 20 mg qd group and 10 mg bid group were(595.75±131.15)and(283.50±96.98)ng·mL-1;AUC0-t were(5 531.94±784.35)and(4 686.67±898.23)h·ng·mL-1;AUC0-∞ were(6 003.19±538.59)and(7 361.48±1 816.77)h·ng·mL-1,respectively.The mean time percentage of gastric pH＞3 after 20 mg qd and 10 mg bid were 82.64％and 61.92％,and the median gastric pH within 24 h were 6.25±1.49 and 3.53±2.05,respectively.The mean gastric pH values within 24 h were 5.71±1.36 and 4.23±1.45,respectively.The correlation analysis of pharmacokinetic/pharmacodynamics showed that there was no significant correlation between the peak concentration of drug in plasma and the inhibitory effect of acid.Conclusion Compared with the 20 mg qd group and the 10 mg bid group,the acid inhibition effect is better,the administration times are less,and the safety of the two administration regimes is good.

Objective To investigate the effect of Jichuan decoction on defecation in rats with slow transit constipation(STC).Methods A total of 36 SD rats were divided into model group,experimental group and control group.Except the control group,STC rat models were established in the other two groups by gavage of 2％rhein acid suspension.The experimental group was given 170％Jichuan decoction of 10 mL·kg-1 by gavage,while the control group and model group were given with 0.9％NaCl by gavage,once a day for 30 days.Fecal dry-wet weight ratio and colon transport time were observed by fecal weighing and recording of first fecal discharge time;substance P(SP)and vasoactive peptide(VIP)contents in plasma were detected by kit;changes in intestinal flora were detected by real-time fluorescent quantitative polymerase chain reaction(qRT-PCR).Results The dry-wet ratio of feces in control group,model group and experimental group were(44.86±4.40)％,(53.44±3.52)％and(44.28±4.33)％,respectively;the colon transport time were(340.17±34.91),(424.67±37.26)and(377.36±38.87)min,respectively;plasma SP were(79.86±7.56),(60.30±2.41)and(78.84±5.83)pg·mL-1,respectively;plasma VIP were(30.56±2.87),(23.38±6.62)and(28.39±2.37)pg·mL-1,respectively;the numbers of Bifidobacterium were 7.77±0.04,5.19±0.09 and 7.45±0.03,respectively;the numbers of Lactobacillus were 6.40±0.07,4.10±0.05 and 6.36±0.08,respectively.There were statistically significant differences in the above indexes between model group and control group,and between experimental group and model group(P＜0.01,P＜0.05).Conclusion Jichuan decoction can improve the defecation of rats with slow transit constipation.

Chemical cleaning and disinfection are crucial steps for eliminating infection in root canal treatment.However,irrigant selection or irrigation procedures are far from clear.The vapor lock effect in the apical region has yet to be solved,impeding irrigation efficacy and resulting in residual infections and compromised treatment outcomes.Additionally,ambiguous clinical indications for root canal medication and non-standardized dressing protocols must be clarified.Inappropriate intracanal medication may present side effects and jeopardize the therapeutic outcomes.Indeed,clinicians have been aware of these concerns for years.Based on the current evidence of studies,this article reviews the properties of various irrigants and intracanal medicaments and elucidates their effectiveness and interactions.The evolution of different kinetic irrigation methods,their effects,limitations,the paradigm shift,current indications,and effective operational procedures regarding intracanal medication are also discussed.This expert consensus aims to establish the clinical operation guidelines for root canal irrigation and a position statement on intracanal medication,thus facilitating a better understanding of infection control,standardizing clinical practice,and ultimately improving the success of endodontic therapy.

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Objective:To evaluate the safety and efficiency of China-made Toumai Robot-assisted laparoscopic radical prosta-tectomy(LRP).Methods:This study included 40 cases of PCa treated from January 2023 to May 2023 by robot-assisted LRP with preservation of the bladder neck and maximal functional urethral length,15 cases with the assistance of Toumai Robot(the TMR group)and the other 25 with the assistance of da Vinci Robot as controls(the DVR group).We recorded the docking time,laparo-scopic surgery time,vesico-urethral anastomosis time,intraoperative blood loss and postoperative urinary continence,and compared them between the two groups.Results:Operations were successfully completed in all the cases.No statistically significant differ-ences were observed between the TMR and DVR groups in the docking time(6 min vs 5 min,P＞0.05)or intraoperative blood loss(200 ml vs 150 ml,P＞0.05).The TMR group,compared with the DVR group,showed a significantly longer median laparoscopic surgery time(146 min vs 130 min,P＜0.05)and median vesico-urethral anastomosis time(19 min vs 16 min,P＜0.05).There were no statistically significant differences between the TMR and DVR groups in the rates of urinary continence recovery immediately af-ter surgery(60.0％[9/15]vs 64.0％[16/25],P＞0.05)or at 1 month(80.0％[12/15])vs(76.0％[19/25],P＞0.05),3 months(93.3％[14/15])vs(92.0％[23/25],P＞0.05)and 6 months postoperatively(100％[15/15])vs(96％[24/25],P＞0.05).Conclusion:China-made Toumai? Robot surgical system is safe and reliable for laparoscopic radical prosta-tectomy,with satisfactory postoperative recovery of urinary continence.

Objective: To investigate the association between chronic lung diseases and the risk of lung cancer. Methods: Using UK Biobank (UKB) survey data, 472 397 participants who had not previously been diagnosed with cancer and whose self-reported sex was consistent with their genetic sex were studied. Information on the prevalence of previous chronic lung diseases, general demographic characteristics and the prevalence of lung cancer was collected using baseline questionnaires and national health system data. The multivariate Cox proportional risk regression model was used to analyze the association between four previous chronic lung diseases (asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and interstitial pulmonary disease) and the risk of lung cancer. A total of 458 526 participants with genotype data in the observational study were selected as research objects, and the closely related and independent genetic loci with four chronic lung diseases were selected as instrumental variables, and the association between four chronic lung diseases and the risk of lung cancer was analyzed by Mendelian randomization (MR). The dose-response relationship between genetic risk score and the risk of lung cancer in different chronic lung diseases was evaluated using a restricted cubic spline function. Results: The age [M (Q₁, Q₃)] of the subjects was 57 (50, 63) years old, and there were 3 516 new cases of lung cancer (0.74%) during follow-up. The multivariate Cox proportional hazard regression model analysis showed that previous chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, about 1.61 (1.49-1.75) and 2.61 (1.24-5.49), respectively. MR Studies showed that genetically predicted chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis were associated with the risk of lung cancer, with HR (95%CI) of 1.10 (1.03-1.19) and 1.04 (1.01-1.08), respectively. The results of restricted cubic spline function analysis showed that the risk of lung cancer increased linearly with the increase of genetic risk scores for chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (P<0.05). Neither observational studies nor Mendelian randomization analysis found an association between previous asthma or interstitial lung disease and the risk of lung cancer (both P values>0.05). Conclusion: Chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis are potential risk factors for lung cancer.
Humans ; Middle Aged ; Mendelian Randomization Analysis ; Biological Specimen Banks ; Lung Neoplasms/genetics* ; Pulmonary Disease, Chronic Obstructive/genetics* ; Asthma/genetics* ; Idiopathic Pulmonary Fibrosis/genetics* ; United Kingdom/epidemiology* ; Genome-Wide Association Study

ObjectiveTo assess the prognostic value of ¹⁸F-FDG PET/CT parameters for predicting therapeutic response in diffuse large B-cell lymphoma （DLBCL）. MethodsWe retrospectively analyzed the clinical data and ¹⁸F-FDG PET/CT radiomics features of 81 DLBCL patients enrolled between June 2015 and October 2020. Multivariate logistic regression analysis was used to identify the predictive factors for therapeutic response of DLBCL， based on which a predictive model was developed accordingly. The performance of the model was evaluated by receiver operating characteristic （ROC） curves and calibration plots. ResultsDuring the two years after first chemotherapy， 23 patients （28.3%） developed relapse and 58 patients （71.7%） had progression-free survival （PFS）. The analysis for the predictive capability of the binary logistic regression model incorporating the PET/CT features revealed that the imaging features of ¹⁸F-FDG PET/CT after chemotherapy were independent prognostic factors for PFS. Among them， SUV_THR-mean2 was the most important factor for predicting therapeutic response in DLBCL patients after chemotherapy， with a cutoff value of 2.00 （AUC=0.81）. Conclusions¹⁸F-FDG PET/CT showed a valuable prognostic performance for PFS in DLBCL patients after chemotherapy， with the imaging feature after chemotherapy SUV_TLR-mean2 being the optimal independent predictor. Our predictive model of imaging features might have an important prognostic value in assessing the risk of disease progression， guiding the treatment and follow-up protocol， improving therapeutic efficiency and cutting down the medical cost.

This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.
Rats ; Animals ; Rats, Sprague-Dawley ; Depression/drug therapy* ; AMP-Activated Protein Kinases/metabolism* ; Proteomics ; Hippocampus ; Stress, Psychological/metabolism* ; Sphingolipids/metabolism* ; Disease Models, Animal ; Drugs, Chinese Herbal

Objective: To examine the short-term curative effect with minimally invasive right infra-axillary thoracotomy for transaortic modified Morrow procedure. Methods: The clinical data of 60 patients who underwent video-assisted thoracoscopic transaortic modified Morrow procedure from August 2021 to August 2022 at Department of Cardiovascular Surgery, Zhejiang Provincial People's Hospital were retrospectively analyzed. There were 31 males and 29 females, with the age (M (IQR)) of 54.0(22.3) years (range: 15 to 71 years). The echocardiography confirmed the diagnosis of moderate mitral regurgitation in 30 patients, and severe mitral regurgitation in 13 patients. Systolic anterior motion (SAM) was present preoperatively in 54 patients. All 60 patients underwent transaortic modified Morrow procedure through a right infra-axillary thoracotomy using femorofemoral cardiopulmonary bypass. Surgical procedures mainly included transverse aortic incision, exposure of left ventricular outflow tract (LVOT), septal myectomy, and correction of the abnormal mitral valve and subvalvular structures. Results: All 60 patients underwent the programmatic procedures successfully without conversion to full sternotomy. The cardiopulmonary bypass time was (142.0±32.1) minutes (range: 89 to 240 minutes), while the cross-clamp time was (95.0±23.5) minutes (range: 50 to 162 minutes). The patients had a postoperative peak LVOT gradient of 7.0 (5.0) mmHg (range: 0 to 38 mmHg) (1 mmHg=0.133 kPa). A total of 57 patients were extubated on the operating table. The drainage volume in the first 24 h was (175.9±57.0) ml (range: 60 to 327 ml). The length of intensive care unit stay was 21.0 (5.8)h (range: 8 to 120 h) and postoperative hospital stay was 8 (5) days (range: 5 to 19 days). The postoperative septal thickness was 11 (2) mm (range: 8 to 14 mm). All patients had no iatrogenic ventricular septal perforation or postoperative residual SAM. The patients were followed up for 4 (9) months (range: 1 to 15 months), and none of them needed cardiac surgery again due to valve dysfunction or increased peak LVOT gradient during follow-up. Conclusion: Using a video-assisted thoracoscopic transaortic modified Morrow procedure through a right infra-axillary minithoracotomy can provide good visualization of the LVOT and hypertrophic ventricular septum, ensure optimal exposure of the mitral valve in the presence of complex mitral subvalvular structures, so that allows satisfactory short-term surgical results.
Male ; Female ; Humans ; Mitral Valve Insufficiency/surgery* ; Thoracotomy ; Retrospective Studies ; Cardiomyopathy, Hypertrophic/surgery* ; Ventricular Septum/surgery* ; Treatment Outcome ; Minimally Invasive Surgical Procedures/methods*