Objective To evaluate the safety and efficacy of simultaneous resection for initially resectable rectal cancer with synchronous liver metastases. Methods A retrospective analysis was conducted on 305 patients with initially resectable rectal cancer with synchronous liver metastases. These patients were diagnosed at Zhongshan Hospital, Fudan University from January 2016 to June 2020. Among them, 191 underwent simultaneous rectum and liver resection and 114 underwent staged resection. Propensity score matching (PSM) was performed at a 1∶1 ratio. Clinical data were compared and Kaplan-Meier survival curves were plotted. Results After PSM, 85 patients were included in each group. General data showed no significant differences. Except for liver metastasis resection method, no statistical differences were found in primary tumor surgery approach, intraoperative blood loss, intraoperative complications, time to first flatus and defecation, 30-day mortality, and postoperative hospital stay between the simultaneous resection group and the staged resection group. The overall complication rate was higher in the simultaneous resection group (48.2% vs 29.4%, P＝0.04). Specifically, the grade Ⅱ complications were significantly higher (29.4% vs 14.1%, P＝0.016), but there’s no differences in severe complications (grade Ⅲ-Ⅴ). No statistically differences were observed in median progression-free survival (HR＝0.70, 95%CI 0.50-0.97, P＝0.103) and 5-year overall survival (HR＝0.95, 95%CI 0.63-1.44, P＝0.259). Conclusions Simultaneous resection demonstrates comparable safety and efficacy to staged resection for initially resectable rectal cancer with synchronous liver metastases.

This study constructed a LHCGR-CRE-luc-HEK293 transgenic cell line according to the activation of the cAMP signaling pathway after recombinant human chorionic gonadotropin binding to the receptor. The biological activity of recombinant human chorionic gonadotropin was assayed using a luciferase assay system. The relative potency of the samples was calculated using four-parameter model. And the method conditions were optimized to validate the specificity, relative accuracy, precision and linearity of the method. The results showed that there was a quantitative potency relationship of human chorinonic gonadotropin (hCG) in the method and it was in accordance with the four-parameter curve. After optimization, the conditions were determined as hCG dilution concentration of 2.5 μg·mL^-1, dilution ratio of 1∶4, cell number of 10 000-15 000 cells/well, and induction time of 6 h. The method had good specificity, relative accuracy with relative bias ranging from -8.9% to 3.4%, linear regression equation correlation coefficient of 0.996, intermediate precision geometric coefficient of variation ranging from 3.3% to 15.0%, and linearity range of 50% to 200%. This study successfully established and validated a reporter gene method to detect hCG biological activity, which can be used for hCG biological activity assay and quality control.

AIM:To study whether glycyrrhizic acid(GL)can resist the ototoxicity of cisplatin(CDDP)in mice and its molecular mechanism.METHODS:Male C57BL/6J mice were divided into 5 groups:control group,DMSO(5%)group,CDDP(4 mg/kg)group,CDDP+low-dose(50 mg/kg)GL group,and CDDP+high-dose(100 mg/kg)GL group(n=14).Auditory brainstem response(ABR)was used to detect hearing changes of mice.HE staining was used to observe the morphological change of cochlear stria vascular in mice.Evans blue(EB)staining was used to observe the per-meability change of the blood-labyrinth barrier(BLB).Immunohistochemical technique was used to detect the expression and distribution of adhesion protein VE-cadherin and tight junction protein ZO-1 on the cochlear stria.ELISA assay and immunofluorescence technology were employed to detect the expression of tumor necrosis factor-α(TNF-α)and interleu-kin-1β(1L-1β).RESULTS:In CDDP group,ABR waveforms of all frequencies were disturbed,the hearing threshold was significantly increased,and I wave latency was prolonged(P＜0.05).In CDDP+GL group,ABR waveforms of various frequencies were well differentiated,the hearing threshold was significantly decreased,and the latency of I-wave was shortened(P＜0.01).The disordered morphology and more vacuoles in the stria vascularis were observed by HE staining in CDDP group.The GL alleviated CDDP-induced damage in the stria vascularis.In EB staining,CDDP caused an increase in per-meability of BLB(P＜0.01),which was improved by GL treatment(P＜0.01).Immunohistochemical results showed that the expression of VE-cadherin and ZO-1 in CDDP group were decreased(P＜0.01),which was restored in CDDP+GL group(P＜0.01).The ELISA and immunofluorescence results showed that the expression of IL-1β and TNF-α was in-creased after CDDP treatment(P＜0.01),which was restored in CDDP+GL group(P＜0.01).CONCLUSION:The GL alleviates CDDP-induced hearing loss in mice by inhibiting CDDP-induced inflammation and reducing the permeability of BLB.

italic>Salmonella has emerged as a promising tumor-targeting strategy in recent years due to its good tumor targeting ability and certain safety. In order to further optimize its therapeutic effect, scientists have tried to modify Salmonella, including its attenuation and drug loading. This paper summarizes the mechanism and research progress of Salmonella-mediated targeted tumor therapy, and introduces the strategies and related progress of its modification and optimization. At the same time, the advantages, current challenges and future development directions of Salmonella-mediated tumor therapy are summarized.

Objective To evaluate the molluscicidal effects and costs of spraying 20% suspension concentrate of pyricloben-zuron sulphate (SCPS) with drones against Pomacea canaliculata in paddy environments, so as to provide insights into the extensive applications of pyriclobenzuron against P. canaliculata. Methods On July 2022, a paddy field was selected from Nanchang City, Jiangxi Province as the study area, and 72 independent rectangular plots measuring 2 m × 1 m were allocated in the study area, with 1 m interval between each plot, and 20 P. canaliculata snails gently placed in each plot. The activity of 25% wettable powder of pyriclobenzuron sulphate (WPPS) by manual spraying at doses of 0.50, 1.00, 2.00 g/m² and 4.00 g/m² against P. canaliculata was tested in 54 plots, and manual spraying of 50% wettable powder of niclosamide ethanolamine salt (WPNES) at a dose of 0.10 g/m² served as a chemical control, while manual spraying of the same volume of clean water served as a blank control, with 9 plots in each group. The activity of SCPS against P. canaliculata was tested in the remaining 18 plots. Based on the molluscicidal tests of WPPS, the molluscicidal effect of SCPS by manual spraying at doses of 0.20, 0.30, 0.40 g/m² and 0.50 g/m² against P. canaliculata was evaluated, and manual spraying of WPNES at a dose of 0.10 g/m² served as a chemical control, while manual spraying of the same volume of clean water served as a blank control, with three plots in each group. On July 2023, 14 paddy fields with a mean living P. canaliculata density of > 5 snails/m² were selected from Yujiang District, Yingtan City, Jiangxi Province for molluscicidal tests. Based on the molluscicidal effect of pyriclobenzuron against P. canaliculata in plots, the molluscicidal effects of WPPS by manual spraying at doses of 0.25, 0.50 g/m² and 1.00 g/m² and manual applications of WPPS at dose of 0.25, 0.50, 1.00 g/m² and 2.00 g/m² mixed with soil were tested, and manual spraying of 0.10 g/m² WPNES served as a chemical control group, while manual spraying of the same volume of clean water served as a blank control, with one paddy field in each group. Based on the effect of pyriclobenzuron against P. canaliculata in plots, the activity of SCPS sprayed with drones at doses of 0.25 g/m² and 0.50 g/m² mixed in water at 2 kg/667 m² and 4 kg/667 m² was tested against P. canaliculata, and spraying of the same volume of clean water with drones served as a blank control. All P. canaliculata snails were captured 3 days and 7 days following chemical treatment in plots and paddy fields and identified for survival, and the mortality and corrected mortality of P. canaliculata snails were estimated. In addition, the areas of chemical treatment, amount of molluscicide use and labor costs of chemical treatment were estimated in molluscicidal tests in paddy fields, and the costs of chemical treatment for an area covering 667 m² by drones and manual applications were calculated. Results The mortality of P. canaliculata snails was all 100% in plots 3 days and 7 days following spraying WPPS at doses of 0.50, 1.00, 2.00 g/m² and 4.00 g/m², and the mortality rates of P. canaliculata snails were 66.67% to 100.00% 3 days post-treatment with SCPS at various doses (χ² = 277.897, P < 0.05) and 76.67% to 100.00% 7 days post-treatment (χ² = 274.206, P < 0.05). The mortality rates of P. canaliculata snails were 98.19% to 100.00% 3 days post-treatment with WPPS at various doses in paddy fields. There was a significant difference in the mortality of P. canaliculata snails among WPPS treatment groups and controls (χ² = 270.778, P < 0.05), and there were no significant differences between WPPS treatment groups and the chemical control group (all P values > 0.05), while there were significant differences in the mortality of P. canaliculata snails between WPPS treatment groups and the blank control group (all P values < 0.05). The mortality rates of P. canaliculata snails were 89.83% to 95.31% 3 days post-treatment with SCPS at various doses sprayed with drones, and there was a significant difference in the mortality of P. canaliculata snails among SCPS treatment groups and the blank control group (χ² = 1 132.892, P < 0.05). There were no significant differences in the mortality of P. canaliculata snails among SCPS treatment groups or water mixture groups (all P values > 0.05), and there were significant differences in the mortality of P. canaliculata snails between SCPS treatment groups and the blank control group (all P values < 0.05). The mortality rates of P. canaliculata snails were 94.62% to 100.00% 7 days post-treatment with SCPS at various doses sprayed with drones, and there was a significant difference in the mortality of P. canaliculata snails among SCPS treatment groups and the blank control group (χ² = 1 266.932, P < 0.05), with the highest mortality found following spraying 0.50 g/m² SCPS mixed in 2 kg/667 m² water with drones (P < 0.05). The costs of P. canaliculata snail control by drones and manually were 35.85 Yuan/667 m² and 43.33 Yuan/667 m²; however, the snail control efficiency was 6.67 times higher by drones than by manual applications. Conclusions SCPS sprayed with drones is highly active against P. canaliculata snails in paddy fields. SCPS sprayed with drones is highly efficient and low in cost for P. canaliculata snail control in paddy fields, beaches and river courses.

Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.

Background:Gastric cancer is a malignant tumor originating from the gastric mucosal epithelium.OLGA/OLGIM staging systems are scoring systems for gastric mucosal atrophy and intestinal metaplasia based on gastroscopic pathology.Serum pepsinogen(PG)and PG Ⅰ/PG Ⅱ ratio(PGR)can reflect the gastric mucosal function and status.Studying the relationship between PG and OLGA/OLGIM stages and the changing trends is of great value for early screening of gastric cancer.Aims:To explore the relationship between serum PG and OLGA/OLGIM stages,and its application value in screening of early gastric cancer.Methods:A total of 188 healthy individuals underwent gastroscopy from June 2021 to June 2023 at Shanghai Health and Medical Center were selected.The serum PG level was measured,and the status of Helicobacter pylori(Hp)infection was evaluated.OLGA/OLGIM stages were assessed according to the findings of gastroscopic pathology,and correlated with the serum PG level.After two years of follow-up,changes of PG and PGR in subjects with different baseline OLGA/OLGIM stages were analyzed.Results:There were significant differences in PG Ⅰand PGR among subjects with various baseline OLGA/OLGIM stages(P＜0.05).OLGA/OLGIM stages were correlated with Hp infection,family history of malignant gastrointestinal tumors and spicy diet(P＜0.05).The incidences of gastric mucosal atrophy in PG Ⅰ ≤70 μg/L group and PGR≤3.0 group were significantly higher than those in PG Ⅰ＞70 μg/L group and PGR＞3.0 group,respectively(P＜0.05).The follow-up results showed that for baseline OLGA/OLGIM stage 0,PG Ⅰ showed a decreasing trend over time,while no significant change of PG Ⅰ was found in other OLGA/OLGIM stages;PG Ⅱ showed a decreasing trend while PGR showed an increasing trend over time in all stages.But all these trends were not statistically significant(P＞0.05).Conclusions:The combined detection of PG and Hp infection has important value in evaluating the severity of chronic atrophic gastritis and the risk of gastric cancer.It can be applied as an early screening project for gastric cancer in individuals undergoing physical examination.

Objective To explore the occurrence and influencing factors of delayed cerebral ischemia(DCI)after clipping surgery in patients with anterior circulation aneurysms.Methods A retrospective analysis was conducted on 248 patients with anterior circulation aneurysms who underwent clipping surgery in our hospital from May 2018 to May 2023.The patients were divided into the DCI group and the non-DCI group based on the occurrence of DCI after surgery.A1∶1 propensity score matching method was used to match 54 patients in the DCI group with 54 patients in the non-DCI group.The random forest algorithm was employed to rank the importance of factors influencing DCI.Multivariable Logistic regression analysis was performed to identify independent risk factors for DCI,and the E-value method was used to assess the sensitivity of model parameters.A DCI risk prediction model was constructed,and the discriminative ability and accuracy of the model were evaluated using ROC curve and Hosmer-Lemeshow test.Results After matching,no statistically significant differences were observed between the two groups in terms of gender,age,body mass index(BMI),smoking history,alcohol consumption,history of cerebral infarction,history of subarachnoid hemorrhage,aneurysm location,and maximum aneurysm diameter(all P＞0.05).Compared to the non-DCI group,the DCI group had a higher proportion of modified Fisher grade 3-4 and Hunt-Hess grade IV patients,higher levels of D-dimer(D-D),total bilirubin(TBIL),TNF-α,high-sensitivity C-reactive protein(hs-CRP),IL-6,and glutamate,and lower levels of immunoglobulin(Ig)G,IgM,and IgA(all P＜0.05).The random forest analysis showed that including Hunt-Hess grade,modified Fisher grade,D-D,glutamate,TB1L,IgA,and IL-6 in the multivariable regression analysis achieved the lowest out-of-bag error rate.Multivariable analysis revealed that Hunt-Hess grade Ⅳ,modified Fisher grade 3-4,D-D,glutamate,TBIL were independent risk factors for DCI,while IgA was a protective factor(all P＜0.05).The risk prediction equation was as follows:P=1/[1+e(3.142+1.307 Hunt-Hess grade+1.086 modified Fisher grade+0.976 D-D+0.748 glutamate+0.552 TBIL-0.524 IgA+0.487 IL-6)].A patient with a risk probability P＞0.65 was considered to have a postoperative occurrence of DCI.The ROC curve results showed that after internal validation,the AUC of the model was 0.869(95％CI:0.836-0.897),with sensitivity and specificity of 81.08％and 97.34％,respectively,indicating good discrimination of the model.The Hosmer-Lemeshow test results showed that after internal validation,the goodness of fit of the model wasx2=4.219,P=0.561,indicating good fit of the model.Conclusions Hunt-Hess grade Ⅳ,modified Fisher grade 3-4,D-D,glutamate,TBIL,and IL-6 are identified as independent risk factors for DCI,while IgA is a protective factor.The predictive model constructed using these factors demonstrates high accuracy and discriminative ability.A risk probability P＞0.65 indicates a postoperative occurrence of DCI in patients.

Objective·To explore the association between gene-gene interaction of glutamate pathway and anhedonia.Methods·A total of 279 patients with schizophrenia(SZ)and 236 patients with major depression disorder(MDD)recruited in the outpatient department and ward of Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,and 236 healthy controls(HC)recruited in the community from January 2017 to August 2020 were included in the study.General demographic data and clinical characteristics of the three groups were collected and compared.The Chinese version of Temporal Experience of Pleasure Scale(TEPS)was used to evaluate the pleasure experience ability of the three groups.Generalized multifactor dimensionality reduction(GMDR)method was used to establish the interaction model of the single nucleotide polymorphism(SNP)in glutamate pathway genes(NOS1AP,GSK3β,DAOA,DISC1 and GRIN2A).According to the interaction model,SZ and MDD patients were divided into high-risk group and low-risk group,and the differences in pleasure experience ability were compared between the two groups,so as to analyze the effect of gene-gene interaction on anhedonia.Results·There were significant differences in age and years of education among the three groups,and in age of onset and duration of illness between SZ and MDD groups(all P=0.000).There were significant differences among the three groups of participants in terms of overall pleasure experience,anticipatory pleasure experience and consummatory pleasure experience(all P=0.000);the overall pleasure experience,anticipatory pleasure experience and consummatory pleasure experience in the SZ and MDD group were lower than those in the HC group(all Pcorr=0.000),and there was marginal statistical difference in anticipatory pleasure experience between the SZ and MDD groups(Pcorr=0.051).Through GMDR modeling,it was found that the 2-loci interaction model composed of DAOA-rs3916965 and DISC1-rs821577 had a predictive effect on the overall pleasure experience ability of SZ patients(P=0.003),and the 2-loci interaction model composed of NOS1AP-rs1858232 and GRIN2A-rs1014531 had a predictive effect on the anticipatory pleasure experience ability of MDD patients(P=0.037);moreover,the overall pleasure experience ability of patients in the SZ high-risk group and anticipatory pleasure experience ability of patients in MDD high-risk groups were lower than those in their low-risk groups(t=3.443,P=0.000;t=3.471,P=0.001).Conclusion·The interaction of glutamate pathway gene polymorphisms may be involved in the occurrence of anhedonia.

Objective To minimize variations in treatment outcomes of L5/S1 percutaneous intervertebral radiofrequency thermocoagulation(PIRFT)arising from physician proficiency and achieve precise quantitative risk assessment of the puncture paths.Methods We used a self-developed deep neural network DWT-UNet for automatic segmentation of the magnetic resonance(MR)images of the L5/S1 segments into 7 key structures:L5,S1,Ilium,Disc,N5,Dura mater,and Skin,based on which a needle insertion path planning environment was modeled.Six hard constraints and 6 soft constraints were proposed based on clinical criteria for needle insertion,and the physician's experience was quantified into weights using the analytic hierarchy process and incorporated into the risk function for needle insertion paths to enhance individual case adaptability.By leveraging the proposed skin entry point sampling sub-algorithm and Kambin's triangle projection area sub-algorithm in conjunction with the analytic hierarchy process,and employing various technologies such as ray tracing,CPU multi-threading,and GPU parallel computing,a puncture path was calculated that not only met clinical hard constraints but also optimized the overall soft constraints.Results A surgical team conducted a subjective evaluation of the 21 needle puncture paths planned by the algorithm,and all the paths met the clinical requirements,with 95.24%of them rated excellent or good.Compared with the physician's planning results,the plans generated by the algorithm showed inferior DIlium,DS1,and Depth(P<0.05)but much better DDura,DL5,DN5,and AKambin(P<0.05).In the 21 cases,the planning time of the algorithm averaged 7.97±3.73 s,much shorter than that by the physicians(typically beyond 10 min).Conclusion The multi-constraint optimal puncture path planning algorithm offers an efficient automated solution for PIRFT of the L5/S1 segments with great potentials for clinical application.