Objective:To investigate the value of machine learning models based on CT radiomics for predicting the outcome of neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC).Methods:A retrospective case series study was conducted. A total of 279 LAGC patients receiving NAC before surgery in Shanxi Province Cancer Hospital from January 2018 to November 2020 were included. According to a ratio of 7∶3, all patients were randomly divided into the training set (196 cases) and the validation set (83 cases). According to the tumor regression grade (TRG), the pathological grade was divided into the good response of NAC (GR) group (TRG 0-1, 55 cases) and the poor response of NAC (PR) group (TRG 2-3, 224 cases). The clinicopathological data of patients were collected, such as age, gender, differentiation degree, clinical T and N staging, carcinoembryonic antigen (CEA), and carbohydrate antigen 199 (CA199) level. Radiomics features were extracted from the enhanced CT images in the vein phase, and the features were screened by 3-step dimensionality reduction. And then 5 machine learning algorithms including logistic regression (LR), naive bayes (NB), random forest (RF), support vector machine (SVM) and extreme gradient boosting (XGB) were applied to build prediction models based on the CT radiomics. The receiver operating characteristic (ROC) curve and the decision analysis (DCA) curve were drawn to evaluate the predictive performance and clinical benefit of each model on the outcome of NAC in patients with LAGC.Results:Among 196 patients in the training set, there were 39 cases in GR group and 157 cases in PR group; among 83 patients in the validation set, there were 16 cases in GR group and 67 cases in PR group. There were no statistically significant differences in clinicopathological data of patients between the training and validation sets, or between GR and PR groups in the training and validation sets (all P > 0.05). A total of 102 radiomics features were extracted from region of interest of CT images in the vein phase, and 6 key features were finally selected including original_firstorder_10Percentile, original_firstorder_RoubustMeanAbsoluteDeviation, original_glcm_Idmn, original_glcm_MCC, original_ngtdm_Busyness, original_ngtdm_Contrast; and there were statistically significant differences in 6 features between the GR and PR groups (all P < 0.05). LR, NB, RF, SVM and XGB machine learning algorithms were used to construct 5 prediction models based on the CT radiomics. The area under ROC curve for NAC prediction in the training set was 0.553, 0.709, 0.668, 0.772 and 0.790, respectively; in the validation set was 0.662, 0.622, 0.683, 0.752 and 0.784, respectively. The model constructed by XGB showed the best comprehensive performance, and its accuracy, sensitivity and specificity was 0.771, 0.562 and 0.821, respectively. In the DCA of 5 machine learning models in the training set, XGB-based model provided a higher net benefit. Conclusions:Machine learning models based on enhanced CT radiomics in the vein phase have a high predictive efficacy in the outcome of NAC in LAGC patients before surgery and it helps make clinical personalized treatment decisions.

Objective:To investigate the value of machine learning models based on CT radiomics for predicting the outcome of neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC).Methods:A retrospective case series study was conducted. A total of 279 LAGC patients receiving NAC before surgery in Shanxi Province Cancer Hospital from January 2018 to November 2020 were included. According to a ratio of 7∶3, all patients were randomly divided into the training set (196 cases) and the validation set (83 cases). According to the tumor regression grade (TRG), the pathological grade was divided into the good response of NAC (GR) group (TRG 0-1, 55 cases) and the poor response of NAC (PR) group (TRG 2-3, 224 cases). The clinicopathological data of patients were collected, such as age, gender, differentiation degree, clinical T and N staging, carcinoembryonic antigen (CEA), and carbohydrate antigen 199 (CA199) level. Radiomics features were extracted from the enhanced CT images in the vein phase, and the features were screened by 3-step dimensionality reduction. And then 5 machine learning algorithms including logistic regression (LR), naive bayes (NB), random forest (RF), support vector machine (SVM) and extreme gradient boosting (XGB) were applied to build prediction models based on the CT radiomics. The receiver operating characteristic (ROC) curve and the decision analysis (DCA) curve were drawn to evaluate the predictive performance and clinical benefit of each model on the outcome of NAC in patients with LAGC.Results:Among 196 patients in the training set, there were 39 cases in GR group and 157 cases in PR group; among 83 patients in the validation set, there were 16 cases in GR group and 67 cases in PR group. There were no statistically significant differences in clinicopathological data of patients between the training and validation sets, or between GR and PR groups in the training and validation sets (all P > 0.05). A total of 102 radiomics features were extracted from region of interest of CT images in the vein phase, and 6 key features were finally selected including original_firstorder_10Percentile, original_firstorder_RoubustMeanAbsoluteDeviation, original_glcm_Idmn, original_glcm_MCC, original_ngtdm_Busyness, original_ngtdm_Contrast; and there were statistically significant differences in 6 features between the GR and PR groups (all P < 0.05). LR, NB, RF, SVM and XGB machine learning algorithms were used to construct 5 prediction models based on the CT radiomics. The area under ROC curve for NAC prediction in the training set was 0.553, 0.709, 0.668, 0.772 and 0.790, respectively; in the validation set was 0.662, 0.622, 0.683, 0.752 and 0.784, respectively. The model constructed by XGB showed the best comprehensive performance, and its accuracy, sensitivity and specificity was 0.771, 0.562 and 0.821, respectively. In the DCA of 5 machine learning models in the training set, XGB-based model provided a higher net benefit. Conclusions:Machine learning models based on enhanced CT radiomics in the vein phase have a high predictive efficacy in the outcome of NAC in LAGC patients before surgery and it helps make clinical personalized treatment decisions.

Background and purpose:Esophageal carcinoma(ESCA)is one of the malignant tumors with high mortality rate,and the underlying mechanism of its development is largely unknown.CDC20 plays an important role in tumorigenesis,and its dysregulated expression is closely related to tumor occurrence and development.The expression of CDC20 is increased in a variety of tumors,and knocking down CDC20 can inhibit tumor cell proliferation.NLRP3 is the main component of the inflammasome,and inflammasome is also closely related to tumor occurrence and development.Here,our study aimed to investigate whether CDC20 promotes the proliferation of ESCA cells through NLRP3 and its regulatory mechanism.Methods:The expression levels of CDC20 and NLRP3 genes in ESCA patients were analyzed using The Cancer Genome Atlas(TCGA)detabase and GTEx public database.We collected clinical and pathological data and tissues from 80 ESCA patients at the First Affiliated Hospital of Xinxiang Medical College,and detected the protein expression of NLRP3 in ESCA patients through immunohistochemistry staining.This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College(Number:EC-021-137).We studied the effects of knocking down CDC20 and NLRP3 gene on the proliferation ability of esophageal squamous cell carcinoma cells EC9706 and KYSE150 using short hairpin RNA(shRNA)technology.Co-immunoprecipitation(Co-IP),proteasome inhibitors and ubiquitination experiments were used to detect whether CDC20 interacts with NLRP3,and to elucidate whether CDC20 regulates NLRP3 expression through the ubiquitination pathway.This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College(Number:EC-021-137).Results:The TCGA database analysis showed that the expression levels of CDC20 and NLRP3 mRNA were significantly higher in the cancer tissues of ESCA patients than in the adjacent tissues.The immunohistochemistry results further showed that compared with adjacent tissues,the protein expression levels of CDC20 and NLRP3 were increased in ESCA tissues.Knocking down CDC20 and NLRP3 genes inhibited the proliferation of ESCA cells.Co-IP,proteasome inhibitors and ubiquitination experiments confirmed that CDC20 interacted with NLRP3 through its leucine-rich repeat(LRR),and CDC20 stabilized its expression by promoting NLRP3 ubiquitination.Conclusion:CDC20 and NLRP3 are upregulated in ESCA tissues,and CDC20 stabilizes their expression through ubiquitination of NLRP3,promoting ESCA cell proliferation.This suggests that CDC20 and NLRP3 may be potential diagnostic targets for ESCA.

Objective:This study aims to explore the prevalence of hepatitis E virus (HEV) infection in patients and the screening value of serological indicators for HEV infection patients.Methods:Retrospective analysis was conducted on 97 440 cases of anti-HEV IgM and IgG simultaneously tested in two Beijing hospitals from January 1, 2018 to August 31, 2023. Among them, there were 61 005 males and 36 435 females, with an average age of 51.65±13.05 years old. According to the positivity of anti HEV specific antibodies, they were divided into anti-HEV IgM positive group (3 588 cases), anti-HEV IgG positive group (18 083 cases), and anti-HEV antibody negative group (78 892 cases). Results of HEV RNA, liver function, AFP, PIVKA-Ⅱ and PT were collected, and their basic clinical information were recorded. The prevalence of HEV infection in patients, as well as the relationship between the positivity of anti-HEV specific antibodies and the patient′s age group, HEV RNA, and clinical characteristics were analyzed.Results:Among 97 440 patients who tested anti-HEV IgM and IgG simultaneously, the positivity rate of anti-HEV IgM was 3.68% (3 588/97 440), and was 18.56% for anti-HEV IgG (18 083/97 440). The overall positivity rates of anti-HEV IgM in two Beijing hospitals from 2018 to 2023 were 2.51%, 2.53%, 3.02%, 4.59%, 5.72%, and 4.26% ( χ2=1 401.73, P<0.001), while the positivity rates of anti-HEV IgG were 12.56%, 12.32%, 12.85%, 22.65%, 27.42%, and 26.66% ( χ2=1 058.29, P<0.001). These rates showed a gradual increase until 2023 when a decline was observed. The positivity rates of anti-HEV IgM (2.28%, 3.60%, 4.47%) ( χ2=89.62, P<0.001) and IgG (4.71%, 17.86%, 25.94%) ( χ2=2 017.32, P<0.001) increased with age in patients who aged 1-30, >30-60, and over 60 years old. The age and ALB values of patients in the anti-HEV IgM positive group were lower than the IgG-positive group, while the proportion of males, TBIL, ALT, AFP and PT values were higher than the IgG-positive group, and the differences were statistically significance ( P<0.05). Furthermore, patients in both the anti-HEV IgM and IgG positive groups had higher age, male proportion, TBIL, ALT, AFP, PIVKA-Ⅱ, and PT values than the anti-HEV negative group. Additionally, both groups had lower ALB values than the anti-HEV negative group, all of which were statistically significant ( P<0.05). 2 162 HEV infected patients were grouped based on HEV RNA positivity. The proportion of anti-HEV IgM single positive, IgG single positive, IgM+IgG double positive, and antibody negative patients in the HEV RNA positive group were 5.42% (18/332), 3.62% (12/332), 90.36% (300/332), and 0.60% (2/332), respectively. Among them, the proportion of anti-HEV IgM+IgG double positive patients in the HEV RNA positive group was higher than that in the HEV RNA negative group ( χ2=302.87, P<0.001), while the proportion of anti-HEV IgG single positive ( χ2=174.36, P<0.001) and anti-HEV antibody negative patients ( χ2=59.28, P<0.001) were lower than that in the HEV RNA negative group, both of which were statistically significant ( P<0.001). In addition, the positive rates of HEV RNA in anti-HEV IgM positive, IgG positive, and antibody negative patients were 29.23% (318/1 088), 17.59% (312/1 774), and 0.65% (2/306), respectively. Conclusion:The HEV infection rate among patients declined in 2023. HEV infection is age-related, with older individuals being more susceptible. Abnormal liver function and jaundice were commonly observed during HEV infection. It is crucial to note that the absence of anti-HEV specific antibodies cannot rule out HEV infection; therefore, additional testing for HEV RNA and/or HEV Ag is necessary for accurate diagnosis.

Objective:To find a method for fertility preservation through oocytes retrieval during gynecological operation and provide an experimental basis for patients who are not suitable for fertility preservation by transvaginal oocyte retrieval.Methods:The objects of the study were patients with polycystic ovary syndrome (PCOS) who underwent laparoscopic surgery in the Affiliated Reproductive Hospital of Shandong University from April to June 2020 and patients with tumors who underwent fertility preservation during gynecological surgery. This was a retrospective study. Totally 23 patients with PCOS infertility who were to undergo laparoscopy surgery underwent ovarian surface follicle puncture for oocyte retrieval, and the oocytes were obtained and sent to the assisted reproduction laboratory for in vitro culture, and mature oocytes were inseminated by intracytoplasmic sperm injection (ICSI), and high-quality embryos were obtained for cryopreservation. Gynecological surgery and ovarian surface follicle puncture were performed for oocytes retrieval in tumor patients ( n=6) with fertility preservation. The feasibility of simultaneous gynecological surgery with oocytes retrieved was evaluated according to the indexes of the number of oocytes retrieval, maturation, fertilization and embryo culture. Results:In PCOS patients, oocytes retrieved rate was 52.17% (12/23) per cycle. The number of oocytes retrieved was 2.00±1.48, among which the number of culturable oocytes was 1.50±1.00. The oocyte maturation rate was 22.22% (4/18). Two oocytes got fertilization and one zygote got cleavage. In contrast, the fertility-preserving oncology patients undergoing gynecologic surgery had a 100.00% (6/6) oocytes retrieved rate per cycle, with 3.00±1.27 oocytes retrieved. Oocyte maturation rate was 38.46% (5/13). Three oocytes got fertilization and one blastocyst formed. Three patients got oocytes or embryos cryopreservation.Conclusion:For patients who are not suitable for transvaginal oocyte retrieval for fertility preservation, follicle puncture during the gynecologic operation can yield available oocytes.

Objective:To find a method for fertility preservation through oocytes retrieval during gynecological operation and provide an experimental basis for patients who are not suitable for fertility preservation by transvaginal oocyte retrieval.Methods:The objects of the study were patients with polycystic ovary syndrome (PCOS) who underwent laparoscopic surgery in the Affiliated Reproductive Hospital of Shandong University from April to June 2020 and patients with tumors who underwent fertility preservation during gynecological surgery. This was a retrospective study. Totally 23 patients with PCOS infertility who were to undergo laparoscopy surgery underwent ovarian surface follicle puncture for oocyte retrieval, and the oocytes were obtained and sent to the assisted reproduction laboratory for in vitro culture, and mature oocytes were inseminated by intracytoplasmic sperm injection (ICSI), and high-quality embryos were obtained for cryopreservation. Gynecological surgery and ovarian surface follicle puncture were performed for oocytes retrieval in tumor patients ( n=6) with fertility preservation. The feasibility of simultaneous gynecological surgery with oocytes retrieved was evaluated according to the indexes of the number of oocytes retrieval, maturation, fertilization and embryo culture. Results:In PCOS patients, oocytes retrieved rate was 52.17% (12/23) per cycle. The number of oocytes retrieved was 2.00±1.48, among which the number of culturable oocytes was 1.50±1.00. The oocyte maturation rate was 22.22% (4/18). Two oocytes got fertilization and one zygote got cleavage. In contrast, the fertility-preserving oncology patients undergoing gynecologic surgery had a 100.00% (6/6) oocytes retrieved rate per cycle, with 3.00±1.27 oocytes retrieved. Oocyte maturation rate was 38.46% (5/13). Three oocytes got fertilization and one blastocyst formed. Three patients got oocytes or embryos cryopreservation.Conclusion:For patients who are not suitable for transvaginal oocyte retrieval for fertility preservation, follicle puncture during the gynecologic operation can yield available oocytes.

OBJECTIVE: To detect the mutation site in a pedigree affected with autosomal dominant polycystic kidney disease (ADPKD) and verify its impact on the protein function. METHODS: Peripheral blood samples were collected from the proband and his pedigree members for the extraction of genomic DNA. Mutational analysis was performed on the proband through whole-exome sequencing. Suspected variant was verified by Sanger sequencing. A series of molecular methods including PCR amplification, restriction enzyme digestion, ligation and transformation were also used to construct wild-type and mutant eukaryotic expression vectors of the PKD2 gene, which were transfected into HEK293T and HeLa cells for the observation of protein expression and cell localization. RESULTS: The proband was found to harbor a c.2051dupA (p. Tyr684Ter) frame shift mutation of the PKD2 gene, which caused repeat of the 2051st nucleotide of its cDNA sequence and a truncated protein. Immunofluorescence experiment showed that the localization of the mutant protein within the cell was altered compared with the wild-type, which may be due to deletion of the C-terminus of the PKD2 gene. CONCLUSION The c.2051dupA (p. Tyr684Ter) mutation of the PKD2 gene probably underlay the pathogenesis of ADPKD in this pedigree.
DNA Mutational Analysis ; Female ; Frameshift Mutation ; HEK293 Cells ; HeLa Cells ; Humans ; Male ; Pedigree ; Polycystic Kidney, Autosomal Dominant/physiopathology* ; Protein Kinases/genetics* ; Protein Transport/genetics* ; Whole Exome Sequencing

OBJECTIVE: To analyze the pathogenic variant of preaxial polydactyly in a Chinese Han pedigree and identify the cause of polydactyly. METHODS: The peripheral blood DNA of the proband and her parents was extracted. The polydactyly-related genes were detected by trio whole exome sequencing, and the suspected pathogenic gene was screened out. Sanger sequencing was applied to other members of the pedigree. RESULTS: The results of gene sequencing showed that the LMBR1 gene had a heterozygous variant of c.423+4909(IVS5)C>T in 6 patients of the pedigree. The same variant was not detected in family members with normal phenotype. Based on the ACMG guidelines, c.423+4909(IVS5)C>T of the LMBR1 gene was predicted to be pathogenic (PM1+PM2+PP1-S(PS)+PP4+PP5). CONCLUSION The heterozygous C>T variant at position 4909 of intron 5 of the LMBR1 gene probably underlies the disease in this pedigree.
China ; Female ; Humans ; Mutation ; Pedigree ; Polydactyly/genetics* ; Thumb ; Whole Exome Sequencing

OBJECTIVE: To explore the genetic basis for a Chinese patient with amyotrophic lateral sclerosis (ALS). METHODS: Peripheral blood samples were collected from the patient and his parents for the extraction of genomic DNA. Genetic variant was identified by whole exome sequencing. Candidate variant was verified by Sanger sequencing of his parents and healthy controls. RESULTS: The patient was found to harbor a heterozygous c.420C>G (p.Asn140Lys) variant of the SOD1 gene. The same variant was not detected in his parents and 100 healthy controls. The variant has not been included in HGMD, dbSNP and other databases. CONCLUSION The c.420C>G variant of the SOD1 gene may underlie the ALS in this patient. Above finding has enriched the spectrum of SOD1 gene variants.
Amyotrophic Lateral Sclerosis/genetics* ; China ; Heterozygote ; Humans ; Superoxide Dismutase-1/genetics* ; Whole Exome Sequencing

OBJECTIVE:To systematically review the efficacy of ursodeoxycholic acid(UDCA)in the prevention ofulcerative colitisassociated colorectal cancer (UC-CRC) and dysplasia (UC-Dys),and provide evidence-based reference for clinic. METH-ODS:Retrieved from Cochrane Library,EMBase,PubMed,CJFD,CBM,VIP and Wanfang Database,randomized controlled tri-als(RCT)or cohort studies about UDCA(test group)versus placebo(control group)in the prevention of UC-CRC and UC-Dys were collected. Meta-analysis was performed by using Rev Man 5.3 software after quality evaluation and data extraction by Co-chrane Manual 5.1.0. RESULTS:Totally 7 studies(3 randomized controlled trials and 4 cohort studies)were included in the analy-sis,involving 672 patients. Results of Meta-analysis of 3 RCT showed that there was no significant difference in the incidence of UC-CRC and UC-Dys between 2 groups [OR=0.95,95%CI(0.17,5.12),P=0.95];results of Meta-analysis of 4 cohort studiess-howed that there was no significant difference in the incidence of UC-CRC and UC-Dys between 2 groups[OR=0.74,95%CI(0.30, 1.84),P=0.52]. Results of subgroup analysis showed,the incidence of UC-CRC and UC-Dys in test group with low-dose UDCA (<15 mg/kg) was significantly lower than control group,the difference was statistically significant [OR=0.19,95%CI(0.08, 0.49),P<0.001];there were no signifficant diferences in the incidence of UC-CRC and UC-Dys in high-dose UDCA group[OR=1.97,95%Cl(0.53,7.25),P=0.31](≥15 mg/kg). There was no significant difference in the incidence of adverse reactions(P>0.05). CONCLUSIONS:UDCA can not decease the incidence of UC-CRC and UC-Dys,it only prompts a possible trend toward decreased UC-CRC and UC-Dys risk in low-doseUDCA.