1.Effects of loganin on inflammatory response and intestinal barrier damage in septic rats
Can WANG ; Yantao LI ; Zheng ZHOU ; Lupeng WANG ; Yuanyuan GAO ; Shaoxi FAN
China Pharmacy 2025;36(5):574-578
OBJECTIVE To investigate the effects of loganin on inflammatory response and intestinal barrier damage in septic rats by regulating the Ras homolog gene family member A (RhoA)/Rho-associated coiled-coil forming protein kinase 1 (ROCK1) signaling pathway. METHODS A sepsis rat model was established by cecal ligation and puncture, and randomly divided into sepsis group, loganin low-dose group (50 mg/kg loganin, gavage), loganin high-dose group (200 mg/kg loganin, gavage), positive control group (0.2 mg/kg atorvastatin, intraperitoneal injection), and loganin high-dose + lysophosphatidic acid (LPA) group (200 mg/kg loganin gavage and intraperitoneal injection of 10 mg/kg RohA activator LPA). An additional sham surgery group was established. Each group consisted of 10 rats, and medications were administered once every 6 hours for 4 times. After 24 hours of the last intervention, the levels of serum inflammatory factors interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β were detected. The pathological changes of ileal tissue were observed and Chiu’s intestinal mucosal injury score was also performed. The levels of intestinal function-lactate dehydrogenase (D-lactate), D-amino acid oxidase (DAO) and endotoxin, the percentages of zonula occludens-1 protein (ZO-1) and Occludin positive staining area, as well as protein expressions of RhoA, and ROCK1 were all detected. com RESULTS Compared with the sepsis group, the percentages of ZO-1 and Occludin positive areas increased significantly in loganin low-dose and high-dose groups; while the levels of IL-6, TNF-α, IL-1β, DAO, D-lactate and endotoxin, Chiu’s intestinal mucosal injury score as well as protein expressions of RhoA and ROCK1 decreased significantly (P<0.05); the destruction of rat ileal tissue was alleviated, and tissue edema and inflammatory infiltration were significantly reduced; moreover, the improvement effect in loganin high-dose group was superior to that in loganin low-dose group (P<0.05). Compared with loganin high-dose group, RhoA activator LPA reversed the trend of changes in the above indicators (P<0.05). CONCLUSIONS Loganin can alleviate inflammatory response and intestinal barrier damage in septic rats, the mechanism of which may be associated with inhibiting RhoA/ROCK1 signaling pathway.
2.Molecular characteristics of Japanese encephalitis virus carried by Culex tritaeniorhynchus in Dongchuan District, Kunming City, Yunnan Province
Yangyang GU ; Yuwen HE ; Yiju CHEN ; Zhenxing YANG ; Nan LI ; Shunyan LÜ ; Yantao ZHU ; Fangchao RUAN ; Jiali WANG ; Jinglin WANG
Chinese Journal of Schistosomiasis Control 2024;36(4):361-369
Objective To isolate the Japanese encephalitis virus carried by Culex tritaeniorhynchus in Dongchuan District of Yunnan Province and analyze its molecular characteristics, so as to provide insights into the prevention and control of Japanese encephalitis in Yunnan Province. Methods Mosquito specimens were collected using mosquito-trapping lamps from pig farms in Batang Village and Xiaoxin Village, Dongchuan District, Kunming City, Yunnan Province in July 2016, and the mosquito species was identified according to the mosquito morphology. Then, 60 to 100 mosquitoes of each species served as a group and were ground. Baby hamster kidney-21 (BHK-21) cells and Aedes albopictus clone C6/36 cells were used for virus isolation, and positive isolates were identified using flavivirus primers. The positive isolates were amplified using reverse transcription polymerase chain reaction (RT-PCR) assay with 15 pairs of specific primers covering the full length of the genotype I Japanese encephalitis virus, and DNA sequence assembly was performed using the software SeqMan in the DNASTAR package. The obtained sequences were aligned with the complete sequences of 38 Japanese encephalitis virus downloaded from the GenBank with the software MegAlign, and the nucleotide and amino acid homology analyses of the obtained sequences were performed. The difference in amino acid sites was analyzed with the software GeneDoc, and phylogenetic trees were created based on the sequences of the coding region and E protein of the isolated Japanese encephalitis virus with the software Mega X. In addition, the secondary and tertiary structures of the E protein of the Japanese encephalitis virus were predicted using the online tool SOPMA and the software Swiss-Model. Results A total of 5 820 mosquitoes were collected and 3 843 Cx. tritaeniorhynchus (66.03%) were identified according to the mosquito morphology. A positive virus isolate, termed YNDC55-33, was isolated from Cx. tritaeniorhynchoides following batches of virus isolation from mosquito specimens, and cytopathic effect was observed following inoculation into BHK-21 and C6/36 cells. The YNDC55-33 virus isolate was successfully amplified with the flavivirus primes, and a long sequence containing 300 nucleotides was obtained. Following sequence alignment using the BLAST tool, the sequence of the YNDC55-33 virus isolate had high homology with that of the genotype I Japanese encephalitis virus. A long sequence with 10 845 nucleotides in length, which encoded 3 432 amino acids, was obtained by splicing the full sequence of the YNDC55-33 virus isolate. Phylogenetic analysis based on the whole-genome sequence and E gene sequence of the YNDC55-33 virus isolate showed that the new YNDC55-33 virus isolate was most closely related to the genotype I Guizhou isolate (GenBank accession number: HM366552), with nucleotide homology of 98.5% and amino acid homology of 99.4%, and the YNDC55-33 virus isolate shared 97.96% ± 0.33% nucleotide homology and 99.35% ± 0.08% amino acid homology with other genotype I Japanese encephalitis virus isolates, and < 90% nucleotide homology and < 98% amino acid homology with other genotypes of Japanese encephalitis virus. The YNDC55-33 virus isolate and the live attenuated virus vaccine candidate SA14-14-2 isolate differed at 16 amino acid sites on E gene, and 7 out of 8 key amino acid sites related to neurovirulence. The secondary and tertiary structures of the E protein of the YNDC55-33 virus isolate were predicted to be characterized by random coils. Conclusions A genotype I Japanese encephalitis virus was isolated from Cx. tritaeniorhynchus in Dongchuan District, Kunming City. This virus isolate and the live attenuated virus vaccine candidate SA14-14-2 isolate does not differ at antigenic epitopes-related key amino acid sites, and the major protein structure of the virus isolate is random coils. This study adds new data for the epidemiological distribution of Japanese encephalitis virus in Yunnan Province, which may provide insights into the prevention and control of Japanese encephalitis in the province.
3.Analysis of blood testing indicators in HIV patients co-infected with different genotypes of HCV in Kunming area of Yunnan Province
LIU Junyi ; KANG Lijuan ; WANG Shimin ; ZHU Yantao ; ZHANG Mi ; ZHANG Nian ; XIE Qi ; LIU Shifang ; YANG Jiantao ; LI Xiao ; HE Quanying ; WANG Jiali
China Tropical Medicine 2024;24(3):252-
Objective To understand the genotyping of human immunodeficiency virus (HIV) co-infected hepatitis C virus (HCV) patients in Yunnan Province, and to analyze the differences in viral load, biochemical indicators, and blood routine indicators among different genotypes, in order to provide a laboratory basis for the diagnosis and clinical treatment of HIV/HCV co-infected patients. Methods From November 2022 to June 2023, the serum samples and basic information of patients diagnosed with HIV/HCV co-infection were collected in the antiviral outpatient clinic of Yunnan Provincial Hospital of Infectious Diseases. The HCV viral load was detected by one-step qRT-PCR amplification, the positive samples were sequenced, and genotyping was determined based on NS5 gene sequence. The differences in biochemical and blood routine indexes between HIV patients co-infected with different HCV genotypes and low/high viral loads were analyzed. Results A total of 126 HIV/HCV co-infected patients were collected, including 20 HCV genotype 1 (15.9%), 91 HCV genotype 3 (72.2%), and 15 HCV genotype 6 (11.9%). The maximum and minimum viral load of the three HCV genotypes were as follows: HCV type 1 (1.0×108, 4.8×104 IU/mL), HCV type 3 (2.2×108, 2.9×102 IU/mL), and HCV type 6 (8.1×107, 6.8×104 IU/mL). The results showed that there was no significant difference between HIV co-infection with different genotypes of HCV and three HIV treatment schemes, including nucleoside reverse transcriptase inhibitors+integrase strand transfer inhibitors (NRTIs+INSTIs), nucleoside reverse transcriptase inhibitors+non-nucleoside reverse transcriptase inhibitors (NRTIs+NNRTIs) and nucleoside reverse transcriptase inhibitors+protease inhibitor (NRTIs+PLs), and the viral load of patients (P>0.05). The analysis of biochemical indexes such as total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CREA), and blood routine indexes such as white blood cell (WBC), red blood cell (RBC), hemoglobin (HGB), platelet (PLT), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) among different HCV genotypes and low/high viral loads showed that there was no significant difference in biochemical indexes and blood routine indexes between low/high viral loads of HIV co-infected HCV patients (P>0.05); however, the biochemical indicators TBIL, IBIL and MCHC were significantly different statistically between patients with genotype 3 HCV infection and those with genotype 1 HCV infection (P<0.05), while other biochemical and blood routine indexes were not statistically different among different HCV genotypes (P>0.05). Conclusions There are six subtypes of HCV co-infection in HIV patients in Kunming, Yunnan Province, including three genes of genotype 1, 3, and 6. Among them, genotype 3 HCV is the main prevalent genetic virus among HIV co-infected populations. The TBIL, IBIL and MCHC values of HIV patients co-infected with HCV type 3 are different from those infected with HCV type 1.
4.Fabrication of a coral-like barium titanate nano-piezoelectric coating and its effect on promoting osteogenic differentiation of rat bone marrow mesenchymal stem cells in vitro
Luying LI ; Ying LI ; Meng LI ; Wei ZHANG ; Lingzhou ZHAO ; Xiantong HU ; Yantao ZHAO ; Chufan MA
Chinese Journal of Stomatology 2024;59(6):578-585
Objective:To investigate the biocompatibility of coral-like barium titanate nano-piezoelectric coatings and the influence of ultrasound-excited piezoelectric effect on the early osteogenic differentiation.Methods:The barium titanate nano-piezoelectric coating (the coating group) was prepared on the surface of titanium metal by anodic oxidation, hydrothermal reaction and high-temperature annealing, and polished titanium specimens were used as control group. The surface morphology, composition, and crystal phase and hydrophilicity of the two groups of titanium specimens were characterized using scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy and contact angle meter. The piezoelectric properties of the materials were characterized by piezoresponse force microscopy. Rat bone marrow mesenchymal stem cells (BMSC) were cultured and identified and seeded the surface of titanium specimens in two groups. The cells seeded on blank culture plates were used as blank group. After low intensity pulsed ultrasound intervention, cell proliferation and live/dead staining were detected to evaluate cytocompatibility of the coatings. Alkaline phosphatase (ALP) activity of each group was detected by ALP staining kit, and the expression of osteogenesis-related genes [integrin, bone morphogenetic protein 2 (BMP-2), Runt-related transcription factor 2 (RUNX2)] was detected by real-time fluorescent quantitative PCR (RT-qPCR) to evaluate the effect of the coating on promoting the early osteogenic differentiation of BMSC.Results:The surface of titanium specimens in the coating group showed a uniform coral-like morphology, and the diameter of the coral tentacles was 70-100 nm. The main component was tetragonal barium titanate. The surface hydrophilicity of the coating group (water contact angle 10.12°± 0.93°) was significantly better than that of the control group (water contact angle 78.32°±0.71°) ( F= 10 165.91, P<0.001). The coating has a stable piezoelectric property with a piezoelectric constant of about 5 pC/N. Cell experiments showed that, with or without ultrasound, the cell proliferation activity of the coating group was significantly lower than that of the blank group and the control group on the third day ( P<0.05). On the fifth day, with or without ultrasound, there was no significant difference in cell proliferation activity between the three groups ( P>0.05). After 7 days of culture, the ALP activity of the coating group was significantly higher than that of the blank group and the control group ( P<0.05). The results of RT-qPCR showed that the mRNA expression of integrin and BMP-2 in the coating group with ultrasound was significantly higher than that in the other groups with ultrasound, and was higher than that of the coating group without ultrasound ( P<0.05). The expression of integrin mRNA in the control group with ultrasound was significantly higher than that in the control group without ultrasound ( P<0.05). The expression of RUNX2 mRNA in the coating group with ultrasound was significantly higher than that in the coating group without ultrasound ( P<0.05). Conclusions:The coral-like barium titanate nano-piezoelectric coating exhibits favorable biocompatibility and stable piezoelectric property, and facilitates the early osteogenic differentiation of BMSC under the excitation of low-intensity pulsed ultrasound.
5.Clinical study of 980 nm semiconductor laser preablation of urethra mucosa in prostatic tip in small volume benign prostatic hyperplasia laser vaporization
Binbin ZHANG ; Lingling DU ; Xiaolong HE ; Yantao DANG ; Wenshuai YAN ; Jixue GAO ; Yi LI ; Lijun MA ; Hongxiong SONG
International Journal of Surgery 2024;51(11):752-758
Objective:To investigate the effect of 980 nm semiconductor laser preablation of urethra mucosa at the prostatic tip in small volume benign prostatic hyperplasia (BPH).Methods:The case data of 120 patients diagnosed with small volume BPH in the Yan′an University Affiliated Hospital from June 2020 to June 2022 were retrospectively analyzed, and they were divided into improved group and conventional group according to different treatment methods, with 60 cases in each group. Patients in the improved group were treated with 980 nm semiconductor laser preablation of urethra mucosa at the prostatic tip, and patients in the conventional group were treated with 980 nm semiconductor laser vaporization of prostate. The sexual function of the patients was evaluated by the international erectile function index-5(IIEF-5) score, erectile hardness score (EHS) and retrograde ejaculation before surgery and 1, 3, 6, and 12 months after surgery. International prostate symptom scale (IPSS), quality of life (QOL) score, the maximum urine flow rate (Qmax) and postvoid residual urine (PVR) were used to evaluate urinary control function. The incidence of urinary incontinence, bladder neck contracture and other complications were compared between the two groups. Measurement data were expressed as mean±standard deviation ( ± s), and t-test was used for comparison between groups. The count data were expressed as cases and percentage, and Chi-square test was used for comparison between groups. Results:There was no significant difference in PVR, Qmax, IPSS score, QOL score, IIEF-5 score and EHS score between two groups ( P>0.05). In terms of PVR, Qmax, IPSS score, QOL score, IIEF-5 score and EHS score at 1, 3, 6 and 12 months after surgery, all these parameters were significantly improved compared with the preoperative, the differences were statistically significant ( P< 0.05). However, there was no significant difference between the two groups ( P> 0.05). There was no significant difference in IIEF-5 score and EHS score between the two groups during postoperative follow-up and before and after operation ( P> 0.05). The incidence of retrograde ejaculation rate in the improved group was lower than that in the conventional group during the follow-up 1, 3, 6 months after surgery, and the difference was statistically significant ( P<0.05). In the follow-up 1, 3 months after surgery, the incidence of stress urinary incontinence in the improved group was lower than that in the conventional group, the differences were statistically significant ( P< 0.05). At follow-up 6, 12 months after surgery, the rates of stress urinary incontinence were similar between the two groups, and the difference was not statistically significant ( P> 0.05). In the follow-up 12 months after surgery, there were 2 cases (3.33%) of bladder and neck contracture in the improved group, and 8 cases (13.33%) in the conventional group, the difference was statistically significant ( P<0.05). Conclusions:The effect of 980 nm semiconductor laser preablation of urethra mucosa at the prostatic tip in small volume BPH patients is similar to that of conventional vaporization, and the operation time is short. At the same time, the proximal 1 cm tissue of the verticulae and the integrity of the bladder neck are preserved, and the internal and external sphincter of the urethra are protected, thus improving the immediate postoperative urinary control rate and the incidence of retrograde ejaculation in small volume BPH patients.
6.The cutoff value of small airway dysfunction in children with bronchial asthma
Wei CHEN ; Zhe YANG ; Chuanhe LIU ; Xinyu JIA ; Yantao ZHANG ; Xin SONG ; Shuo LI
Chinese Journal of Pediatrics 2024;62(3):245-249
Objective:To explore the cutoff value for assessing small airway dysfunction in children with asthma.Methods:A total of 364 asthmatic children aged 5 to 14 years, with normal ventilatory function, followed up at the Asthma Clinic of the Children′s Hospital of Capital Institute of Pediatrics from January 2017 to January 2018, were selected as the case group. Concurrently, 403 healthy children of the same age range and without any symptoms in the community were chosen as the control group, and pulmonary function tests were conducted. The values of forced expiratory volume in 1 second (FEV 1), forced vital capacity (FVC), forced expiratory flow at 50% of FVC (FEF 50), forced expiratory flow at 75% of FVC (FEF 75) and maximum mid-expiratory flow (MMEF) were compared between case group and control group. Statistical tests such as t-test, χ2 test, or Mann-Whitney U test were used to analyze the differences between the groups. Receiver operating characteristic (ROC) curves were constructed, and the maximum Youden Index was utilized to determine the optimal cutoff values and thresholds for identifying small airway dysfunction in asthmatic children. Results:This study comprised 364 children in the case group (220 boys and 144 girls) and 403 children in the control group (198 boys and 205 girls). The small airway parameters (FEF 50%pred, FEF 75%pred, MMEF%pred) in the asthmatic group were significantly lower than in the control group (77% (69%, 91%) vs. 95% (83%, 109%), 67% (54%, 82%) vs. 84% (70%, 102%), 76% (66%, 90%) vs. 97% (86%, 113%), Z=12.03, 11.35, 13.66, all P<0.001). The ROC curve area under the curve for FEF 50%pred, FEF 75%pred, MMEF%pred was 0.75, 0.74, and 0.79, respectively. Using a cutoff value of 80% for FEF 50%pred achieved a sensitivity of 56.9% and specificity of 81.4%. A cutoff value of 74% for FEF 75%pred resulted in a sensitivity of 67.3% and specificity of 69.2%. Finally, using a cutoff value of 84% for MMEF%pred achieved a sensitivity of 67.9% and specificity of 77.2%. Conclusion:In the presence of normal ventilatory function, utilizing FEF 50<80% predicted or MMEF<84% predicted can accurately serve as criteria for identifying small airway dysfunction in children with controlled asthma.
7.Effect of the setting of control point of Monaco radiotherapy planning system on dosimetry of dIMRT plan for esophageal cancer of middle and lower segment
Hao WANG ; Yunyi YANG ; Yi LI ; Qi DING ; Feng GUO ; Yantao GONG ; Genxiang CHEN ; Ya CHE ; Yinghong REN
China Medical Equipment 2024;21(9):1-6
Objective:To study the dosimetry effects of differently selected values of control point(CP)in Monaco radiotherapy planning system on dynamic intensity modulated radiation therapy(dIMRT)for esophageal cancer of middle and lower segment.Methods:Thirteen patients with esophageal cancer at middle and lower segment who received dIMRT in Shangluo Central Hospital from January to June 2023 were selected.In the Monaco radiotherapy planning system,nine groups of dIMRT plans were designed for each patient according to the 9 kinds of CP limit values(10,20,30,40,50,60,70,80 and 90).There were not changes in other optimized parameters except CP parameter.The differences of the dosimetry between target region and organs at risk(OAR)included lung,heart and spinal cord were analyzed.Results:With the increase of the CP limit value,the maximum dose of the target region which was radiation dose(D2%)of 2%volume of target region,the mean dose,which was radiation dose(D50%)of 50%volume of target region,and the homogeneity index(HI)appeared a trend of gradual stability after reduction,and the radiation dose(D98%)of 98%volume of target region which was the minimum dose of target region and the conformance index(CI)appeared a trend of gradual stability after increase.There was not significant in each dose indicator of OAR(P>0.05).The variation ranges of lung at 5,10,20,30 Gy dose(V5,V10,V20 and V30)were respectively 1.13%,0.75%,0.29%and 0.19%,and the maximum deviation of mean dose(Vmean)of lung was 18.7 cGy.The variation ranges of V10,V20,V30 and V40 in the heart were respectively 2.2%,1.23%,1.39%and 1.12%,and the maximum deviation of Vmean in the heart was 63.85 cGy,and the maximum deviation of Dmax in the spinal-cord was 70.78 cGy.There were statistically significant differences in the actual CP number(CPs),execution time(DT)of plan,and ratio value of machine unit(MU)of the complexity of plan to CPs(MU/CPs)among the plans of 9 groups(F=2.857,25.145,135.467,P<0.05),respectively.Conclusion:In the dIMRT plan of esophageal cancer of middle and lower segment,the maximum CP value is set at between 40-50,which can reduce the optimization time of the plan,the number of subfields and the treatment time of patients under the premise of meeting the dose of the target region and the OAR.
8.Analysis of prognostic risk factors for patients with locally advanced gastric cancer in the stage ypT0~2N0M0 after neoadjuvant chemotherapy
Xinxin SHAO ; Weikun LI ; Haitao HU ; Yiming LU ; Yantao TIAN
Chinese Journal of Oncology 2024;46(12):1187-1194
Objectives:To analyze the long-term prognosis of patients with locally advanced gastric cancer in the stage of ypT0~2N0M0 after neoadjuvant chemotherapy.Methods:The clinical data of 78 patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy and radical resection at ypT0~2N0M0 stage from January 2012 to December 2019 in the Department of Abdominal Surgery/Pancreatic and Gastric Surgery of the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Kaplan-Meier method was used to calculate the overall survival and disease-free survival, and the survival difference between patients with postoperative ypT0N0M0 and ypT1~2N0M0 was compared. Multivariate Cox proportional hazards regression analysis was performed on clinical, pathologic and treatment measures that may affect survival.Results:Among the 78 patients, there were 18 cases (23.1%) with ypT0N0M0, 14 cases (17.9%) with ypT1aN0M0, 17 cases (21.8%) with ypT1bN0M0, and 29 cases (37.2%) with ypT2N0M0. Median follow-up time was 74.1 (19.8~132.5) months. Fourteen patients (17.9%) had tumor recurrence and metastasis, and 9 patients died from tumor recurrence and metastasis. The 5-year disease-free survival and overall survival rates were 84.4% and 87.8%, respectively. There was no statistically significant difference in 5-year overall survival (86.9% vs 87.8%) or 5-year disease-free survival (88.9% vs 83.2%) between patients with ypT0N0M0 and ypT1~2N0M0. Analysis of factors that may affect prognosis revealed that signet ring cell carcinoma, nerve invasion, and lymph node dissection of fewer than 16 were significantly associated with prognosis ( P<0.05). Multivariate Cox analysis including these three factors showed that only lymph node dissection of fewer than 16 was an independent risk factor affecting prognosis (OS: HR=10.44 ,95% CI: 2.15-50.72, P=0.004; DFS: HR=11.47, 95% CI: 2.85-46.20, P=0.001). Conclusions:The long-term prognosis of patients with locally advanced gastric cancer at ypT0~2N0M0 stage after neoadjuvant chemotherapy is relatively good, and the long-term survival time of patients with ypT1~2N0M0 and ypT0N0M0 is similar. Lymph node dissection of less than 16 nodes may be an independent risk factor affecting prognosis. During surgery, efforts should be made to increase the number of lymph node dissections. For patients with less than 16 nodes dissected, postoperative treatment and follow-up should be strengthened.
9.Analysis of prognostic risk factors for patients with locally advanced gastric cancer in the stage ypT0~2N0M0 after neoadjuvant chemotherapy
Xinxin SHAO ; Weikun LI ; Haitao HU ; Yiming LU ; Yantao TIAN
Chinese Journal of Oncology 2024;46(12):1187-1194
Objectives:To analyze the long-term prognosis of patients with locally advanced gastric cancer in the stage of ypT0~2N0M0 after neoadjuvant chemotherapy.Methods:The clinical data of 78 patients with locally advanced gastric cancer who underwent neoadjuvant chemotherapy and radical resection at ypT0~2N0M0 stage from January 2012 to December 2019 in the Department of Abdominal Surgery/Pancreatic and Gastric Surgery of the Cancer Hospital of Chinese Academy of Medical Sciences were retrospectively analyzed. Kaplan-Meier method was used to calculate the overall survival and disease-free survival, and the survival difference between patients with postoperative ypT0N0M0 and ypT1~2N0M0 was compared. Multivariate Cox proportional hazards regression analysis was performed on clinical, pathologic and treatment measures that may affect survival.Results:Among the 78 patients, there were 18 cases (23.1%) with ypT0N0M0, 14 cases (17.9%) with ypT1aN0M0, 17 cases (21.8%) with ypT1bN0M0, and 29 cases (37.2%) with ypT2N0M0. Median follow-up time was 74.1 (19.8~132.5) months. Fourteen patients (17.9%) had tumor recurrence and metastasis, and 9 patients died from tumor recurrence and metastasis. The 5-year disease-free survival and overall survival rates were 84.4% and 87.8%, respectively. There was no statistically significant difference in 5-year overall survival (86.9% vs 87.8%) or 5-year disease-free survival (88.9% vs 83.2%) between patients with ypT0N0M0 and ypT1~2N0M0. Analysis of factors that may affect prognosis revealed that signet ring cell carcinoma, nerve invasion, and lymph node dissection of fewer than 16 were significantly associated with prognosis ( P<0.05). Multivariate Cox analysis including these three factors showed that only lymph node dissection of fewer than 16 was an independent risk factor affecting prognosis (OS: HR=10.44 ,95% CI: 2.15-50.72, P=0.004; DFS: HR=11.47, 95% CI: 2.85-46.20, P=0.001). Conclusions:The long-term prognosis of patients with locally advanced gastric cancer at ypT0~2N0M0 stage after neoadjuvant chemotherapy is relatively good, and the long-term survival time of patients with ypT1~2N0M0 and ypT0N0M0 is similar. Lymph node dissection of less than 16 nodes may be an independent risk factor affecting prognosis. During surgery, efforts should be made to increase the number of lymph node dissections. For patients with less than 16 nodes dissected, postoperative treatment and follow-up should be strengthened.
10.Clinicopathological characteristics of the CD8+T lymphocytes infiltration and its mechanism in distinct molecular subtype of medulloblastoma
Xiaodong CHAI ; Ziwen SUN ; Haishuang LI ; Liangyi ZHU ; Xiaodan LIU ; Yantao LIU ; Fei PEI ; Qing CHANG
Journal of Peking University(Health Sciences) 2024;56(3):512-518
Objective:To investigate the characteristics of the CD8+T cells infiltration from the 4 sub-types in medulloblastoma(MB),to analyze the relationship between CD8+T cells infiltration and prog-nosis,to study the function of C-X-C motif chemokine ligand 11(CXCL11)and its receptor in CD8+T cells infiltration into tumors and to explore the potential mechanism,and to provide the necessary clinico-pathological basis for exploring the immunotherapy of MB.Methods:In the study,48 clinical MB sam-ples(12 cases in each of 4 subtypes)were selected from the multiple medical center from 2012 to 2019.The transcriptomics analysis for the tumor of 48 clinical samples was conducted on the NanoString Pan-Cancer 10360?Panel(NanoString Technologies).Immunohistochemistry(IHC)staining of formalin-fixed,paraffin-embedded sections from MB was carried out using CD8 primary antibody to analyze diffe-rential quantities of CD8+T cells in the MB four subtypes.Through bioinformatics analysis,the relation-ship between CD8+T cells infiltration and prognosis of the patients and the expression differences of various chemokines in the different subtypes of MB were investigated.The expression of CXCR3 receptor on the surface of CD8+T cells in MB was verified by double immunofluorescence staining,and the under-lying molecular mechanism of CD8+T cells infiltration into the tumor was explored.Results:The charac-teristic index of CD8+T cells in the WNT subtype of MB was relatively high,suggesting that the number of CD8+T cells in the WNT subtype was significantly higher than that in the other three subtypes,which was confirmed by CD8 immunohistochemical staining and Gene Expression Omnibus(GEO)database analysis by using R2 online data analysis platform.And the increase of CD8+T cells infiltration was posi-tively correlated with the patient survival.The expression level of CXCL11 in the WNT subtype MB was significantly higher than that of the other three subtypes.Immunofluorescence staining showed the presence of CXCL11 receptor,CXCR3,on the surface of CD8+T cells,suggesting that the CD8+T cells might be attracted to the MB microenvironment by CXCL11 through CXCR3.Conclusion:The CD8+T cells infiltrate more in the WNT subtype MB than other subtypes.The mechanism may be related to the activation of CXCL11-CXCR3 chemokine system,and the patients with more infiltration of CD8+T cells in tumor have better prognosis.This finding may provide the necessary clinicopathological basis for the regulatory mechanism of CD8+T cells infiltration in MB,and give a new potential therapeutic target for the future immunotherapy of MB.

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