Objective:To investigate the factors related to hypothyroidism induced by programmed death(PD)-1 treatment in elderly patients with cancer.Methods:A total of 193 older patients(≥60 years old)with advanced solid tumors who received PD-1 treatment between January 2018 and January 2021 at the Department of Oncology of Xiangyang Central Hospital were included in this study.The patients were divided into two groups based on whether they were diagnosed with hypothyroidism after PD-1 treatment: the hypothyroidism group(36 cases)and the non-hypothyroidism group(157 cases).The clinical data of both groups, including age, gender, Eastern Cooperative Oncology Group performance status(ECOG PS), PD-1 inhibitors, thyroid function, and thyroid antibody, were compared to analyze the risk factors associated with hypothyroidism.Results:Among the 193 patients, 36(18.7%)were diagnosed with hypothyroidism.The study found no significant differences between the two groups in terms of age, gender, ECOG PS, tumor type, and PD-1 type(all P>0.05).However, significant differences were observed in the baseline levels of thyroid stimulating hormone(TSH)and thyroid antibody subgroups(both P<0.05).The results of multivariate Logistic regression analysis revealed that the presence of baseline anti-thyroid peroxidase antibody(TPOAb)( OR=20.256, 95% CI: 5.709-71.868, P<0.001), the presence of both baseline thyroglobulin antibody(TGAb)and TPOAb( OR=5.853, 95% CI: 1.475-23.227, P=0.012), and an increase in baseline TSH levels( OR=3.065, 95% CI: 1.049-8.959, P=0.041)were identified as risk factors for hypothyroidism induced by PD-1 treatment.On the other hand, there was no significant association between the presence of baseline TGAb and the occurrence of hypothyroidism( OR=1.373, 95% CI: 0.353-5.341, P=0.648). Conclusions:The incidence rate of hypothyroidism induced by PD-1 inhibitors is high among elderly patients with cancer.Additionally, the risk of hypothyroidism is higher in patients with elevated baseline TSH and positive TPOAb.Therefore, it is crucial to remain vigilant for the occurrence of hypothyroidism during PD-1 treatment.Timely diagnosis and treatment of hypothyroidism are necessary to minimize the incidence of adverse events.

Tripartite motif-containing protein 28 is a kind of macromolecular protein with E3 ubiquitin ligase, which belongs to an important member of the TRIM protein family. As a new molecular biomarker, it has attracted wide attention. TRIM28 is highly expressed in many kinds of malignant tumors, which is closely related to clinicopathological features, and is also involved in biological behaviors such as proliferation, apoptosis, migration and invasion of tumor cells. TRIM28 may be a potential marker and therapeutic target for clinical diagnosis and prognosis of tumors. This study reviews the structure and biological function of TRIM28, its relationship with malignant tumors and the molecular mechanism of signal transduction pathway.

Objective:To investigate the risk factors for organoid culture failure in colorectal cancer.Methods:This was a retrospective observational study. Tumor specimens were obtained from 1130 patients with colorectal cancer who had undergone surgery or biopsy and had no other concurrent malignancies at Nanfang Hospital of Southern Medical University from December 2021 to November 2022. Organoid culture was performed on 1231 tumor tissue samples. Univariate analysis and multivariate logistic regression were used to analyze the factors that might have influenced the rate of successful organoid culture of colorectal cancer tissue samples.Results:The median (range) duration of organoid culture was 7 (3–12) days. The overall rate of successful culture was 76.3% (939/1231). The rate of successful organoid cultures varied according to the sampling site, malignant ascites having the highest success rate (96.4%, 27/28), followed by liver metastases (83.1%, 54/65), lung metastases (8/10), primary tumors (76.0%, 816/1074), omental metastases (10/14), peritoneal metastases (61.5%, 16/26), ovarian metastases (3/5), and lymph node metastases (5/9). The difference in rates of successful organoid culture between primary tumors and malignant ascites was statistically significant ( P=0.012), whereas none of the other rates of successful organoid culture success differed significantly (all P>0.05). The rate of successful organoid culture was 96.4% (27/28) for malignant ascites obtained by abdominal puncture, 76.5% (864/1130) for surgical specimens, and 65.8% (48/73) for endoscopic biopsies; these differences are statistically significant (χ 2=10.773, P=0.005). The rate of successful organoid culture was 62.5% (40/64) in the neoadjuvant chemoradiotherapy group, which is significantly lower than in the non-adjuvant (76.9%, 787/1023) and chemotherapy groups (77.8%, 112/144) (χ 2=7.134, P=0.028). Multivariate logistic regression analysis revealed that endoscopic biopsy (OR=0.557, 95%CI: 0.335–0.924, P=0.024) and neoadjuvant chemoradiotherapy (OR=0.483, 95%CI: 0.285–0.820, P=0.007) were independent risk factors for failure of organoid culture of colorectal cancer samples. Malignant ascites (OR=8.537, 95%CI:1.154–63.131, P=0.036) and abdominal puncture (OR=8.294, 95% CI: 1.112–61.882, P=0.039) were identified as independent protective factors. Conclusions:The rate of successful organoid culture was influenced by the sampling site, sampling method, and chemoradiotherapy. The rate of successful organoid culture was lower for endoscopic biopsies and in patients receiving preoperative neoadjuvant chemoradiotherapy, and higher for malignant ascites. We consider that culture of malignant ascites is preferable when peritoneal metastases are suspected.

Objective:To investigate the risk factors for organoid culture failure in colorectal cancer.Methods:This was a retrospective observational study. Tumor specimens were obtained from 1130 patients with colorectal cancer who had undergone surgery or biopsy and had no other concurrent malignancies at Nanfang Hospital of Southern Medical University from December 2021 to November 2022. Organoid culture was performed on 1231 tumor tissue samples. Univariate analysis and multivariate logistic regression were used to analyze the factors that might have influenced the rate of successful organoid culture of colorectal cancer tissue samples.Results:The median (range) duration of organoid culture was 7 (3–12) days. The overall rate of successful culture was 76.3% (939/1231). The rate of successful organoid cultures varied according to the sampling site, malignant ascites having the highest success rate (96.4%, 27/28), followed by liver metastases (83.1%, 54/65), lung metastases (8/10), primary tumors (76.0%, 816/1074), omental metastases (10/14), peritoneal metastases (61.5%, 16/26), ovarian metastases (3/5), and lymph node metastases (5/9). The difference in rates of successful organoid culture between primary tumors and malignant ascites was statistically significant ( P=0.012), whereas none of the other rates of successful organoid culture success differed significantly (all P>0.05). The rate of successful organoid culture was 96.4% (27/28) for malignant ascites obtained by abdominal puncture, 76.5% (864/1130) for surgical specimens, and 65.8% (48/73) for endoscopic biopsies; these differences are statistically significant (χ 2=10.773, P=0.005). The rate of successful organoid culture was 62.5% (40/64) in the neoadjuvant chemoradiotherapy group, which is significantly lower than in the non-adjuvant (76.9%, 787/1023) and chemotherapy groups (77.8%, 112/144) (χ 2=7.134, P=0.028). Multivariate logistic regression analysis revealed that endoscopic biopsy (OR=0.557, 95%CI: 0.335–0.924, P=0.024) and neoadjuvant chemoradiotherapy (OR=0.483, 95%CI: 0.285–0.820, P=0.007) were independent risk factors for failure of organoid culture of colorectal cancer samples. Malignant ascites (OR=8.537, 95%CI:1.154–63.131, P=0.036) and abdominal puncture (OR=8.294, 95% CI: 1.112–61.882, P=0.039) were identified as independent protective factors. Conclusions:The rate of successful organoid culture was influenced by the sampling site, sampling method, and chemoradiotherapy. The rate of successful organoid culture was lower for endoscopic biopsies and in patients receiving preoperative neoadjuvant chemoradiotherapy, and higher for malignant ascites. We consider that culture of malignant ascites is preferable when peritoneal metastases are suspected.

Objective To study mechanical properties of the novel micro-movement elastic implant of distal tibiofibular syndesmosis in dorsiflexion position.Methods A combination of simulation and experiment was used. The normal ankle dorsiflexion model, the bone nail repaired model and the micro-movement elastic implant repaired model were established by using Mimics and CT data. Besides, ANSYS Workbench was used for finite element analysis. Mechanical experiments on lower limb specimens were conducted on Instron E10000 mechanical test instrument, and five sets of experimental data were measured and analyzed.Results Mechanical properties of the micro-movement elastic implant repaired model were closer to those of the normal ankle dorsiflexion model, but stress of the micro-movement elastic implant repaired mode was greater than that of the bone nail repaired model. The results of two-sample heteroscedasticity t test indicated that there was no significant difference in resistance torque between the micro-movement elastic implant repaired model and the normal ankle dorsiflexion model.Conclusions For dorsiflexion position, repairing mechanical properties of the novel micro-movement elastic implant are much better than those of the bone nail, and there is still room for optimizing the micro-movement elastic implant.

Objective:To analyze the health screening results for adult men from high altitude areas in a Chengdu health screening center at high altitudes.Methods:The medical and physical examination results of 1 333 plateau people in Sichuan province people′s hospital health physical examination data management center who participated from 2014—2019 and aged 18-80 years old were analyzed. The general data of different age groups were compared using ANOVA analysis. The two groups were compared by independent sample t-test and Mann-Whitney U test, and χ 2 test was used to compare physical examination abnormalities among different age groups. Results:This population was generally overweight and obese, compared to the control group, with systolic blood pressure [(125.29±14.97) vs (123.52±14.87) mmHg(1 mmHg=0.133 kPa), height (168.64±6.26) vs (169.31±6.26) cm, weight (79.47±13.69) vs (71.02±10.62) kg, body mass index (27.91±4.45) vs (24.75±3.24) kg/m2, haemoglobin (169.03±15.18) vs (157.50±11.52) g/L, uric acid (393.12±75.48) vs (410.42±82.14) μmol/L, triacylglycerols 1.18(0.90, 1.69) vs 1.64(1.12, 2.37) mmol/L, total cholesterol 4.58(4.02, 5.15) vs 4.82(4.33, 5.36) mmol/L, HDL cholesterol 1.28(1.14, 1.46) vs 1.26(1.08, 1.46) mmol/L, LDL cholesterol 2.91(2.41, 3.42) vs 3.03(2.49, 3.60) mmol/L] levels were statistically significant (all P<0.05). The physical examination abnormalities detected were fatty liver, hyperlipidemia, abnormal liver function, hyperuricemia, elevated blood glucose, elevated blood pressure, gallbladder disease, abnormal kidney function, prostate hyperplasia, and erythrocytosis. The differences in the detection rates of the above abnormalities were statistically significant when compared between different age groups. Conclusion:The health status of the adult population from high altitude areas screened in our center is critical; therefore, appropriate health interventions need to be made.

Objective:To investigate the clinical application value of plasma SEPT9 gene methylation combined with serum carcinoembryonic antigen (CEA) and carbohydrate antigen 724 (CA724) in the diagnosis of colorectal cancer.Methods:A total of 219 patients with colorectal diseases in Baoji Central Hospital and Yunnan Province New Kun Hua Hospital from May 2018 to October 2021 were selected, including 149 cases of colorectal cancer and 70 cases of colorectal polyp diagnosed by pathology. A total of 100 healthy people in the same period were selected as the healthy control group. The methylation of SEPT9 gene in plasma was measured by using real-time fluorescent polymerase chain reaction (PCR), and the levels of serum CEA and CA724 were measured by using electrochemiluminescence. The expressions of three indicators in each group were compared, and the effect of every single indicator and the combination of the three indicators on the diagnosis of colorectal cancer was analyzed by using receiver operating characteristic (ROC) curve.Results:The positive rate of SEPT9 gene methylation in colorectal cancer group (74.50%, 111/149) was higher than that in colorectal polyp group (22.86%, 16/70) and healthy control group (1.00%, 1/100), and the difference was statistically significant ( P < 0.001). The positive rate of CEA in colorectal cancer group (46.98%, 70/149) was higher than that in colorectal polyp group (40.00%, 28/70) and the healthy control group (3.00%, 3/100) and the difference was statistically significant ( P < 0.001). The positive rate of CA724 in colorectal cancer group (38.93%, 58/149) was higher than that in colorectal polyp group (32.86%, 23/70) and the healthy control group (2.00%, 2/100), and the difference was statistically significant ( P < 0.001). The area under the curve (AUC) of ROC of SEPT9 gene methylation, CEA and CA724 in the single diagnosis of colorectal cancer was 0.823 (95% CI 0.753-0.891), 0.788 (95% CI 0.725-0.852) and 0.689 (95% CI 0.624-0.754), respectively. The optimal cut-off Ct value of SEPT9 gene methylation in the diagnosis of colorectal cancer was 36.5, the sensitivity was 90.30%, and the positive predictive value was 84.68%, which were higher than those of CEA and CA724. The optimal cut-off value of CEA in the diagnosis of colorectal cancer was 8.80 ng/ml, and the specificity (77.50%) and negative predictive value (78.48%) were higher than those of SEPT9 gene methylation and CA724. The sensitivity (97.66%), positive predictive value (93.98%), negative predictive value (81.25%) and AUC (0.846, 95% CI 0.749-0.944) of the combined detection of the three indexes taking the optimal cut-off value of every single indicator were higher than those of the single indicator. Conclusions:The combined detection of plasma SEPT9 gene methylation, CEA and CA724 in the diagnosis of colorectal cancer has high sensitivity and accuracy. The three combined detection can complement each other and improve the diagnostic efficiency, which is of high clinical value for the diagnosis of colorectal cancer.

Objective To explore the expression of cullin 4A (CUL4A) in cholangiocarcinoma tissues and its clinical significance.Methods Primary fresh cholangiocarcinoma tissues (n =35) and normal bile duct tissues (n =15) from patients who underwent curative surgery in Binzhou People's Hospital of Shandong Province from February 2011 to December 2013 were collected.The expressions of CUL4A mRNA were detected by quantitative real-time PCR (qRT-PCR).Then,cholangiocarcinoma tissues (n =72) and normal bile duct tissues (n =36) from patients who underwent curative surgery in Binzhou People's Hospital of Shandong Province from January 2008 to January 2014 were collected.The expressions of CUL4A protein were tested by immunohistochemistry.The relationships between the expression of CUL4A and the patients' clinicopathologic features and prognosis were analyzed.Results The expression of CUL4A mRNA in cholangiocarcinoma tissues was obviously higher than that in normal bile duct tissues (3.876 ±0.975 vs.1.216 ±0.265),and the difference was statistically significant (t =12.23,P ＜ 0.001).The positive rates of CUL4A protein in cholangiocarcinoma and normal bile duct tissues were 70.8％ (51/72) and 2.8％ (1/36) respectively,and the difference was statistically significant (x2 =44.524,P ＜ 0.001).The expression of CUL4A protein in cholangiocarcinoma was related to the differentiated degree (x2 =4.341,P =0.037),neural invasion (x2 =8.326,P =0.004),TNM stage (x2 =7.745,P =0.005),lymph node metastasis (x2 =3.869,P =0.049) and vascular invasion (x2 =5.555,P =0.018).Survival analysis results showed that the median survival time of CUL4A positive patients was significantly shorter than that of CUL4A negative patients (32.40 months vs.51.30 months),and the difference was statistically significant (x2 =6.561,P =0.011).Conclusion The expression of CUL4A in cholangiocarcinoma tissues is higher than that in normal bile tissues.CUL4A plays an important role in the process of tumor invasion and metastasis and indicates poor prognosis,which may become a potential target for the diagnosis and therapy of the cholangiocarcinoma.

Objective To investigate the expressions of TRIM59,Twist and E-cadherin in hepatocellular carcinoma and their clinical significance. Methods The expressions of TRIM59,Twist and E-cadherin protein were tested by immunohistochemistry in 80 cases of hepatocellular carcinomas and the adjacent paracancerous tissues. Results The positive rate of TRIM59 in hepatocellular carcinoma was significantly higher than that in the adjacent paracancerous tissue(76.3%vs. 8.0%,P<0.05). Significant difference was also observed in the expres-sion rate of Twist between the hepatocellular carcinomas and the paracancerous tissue(66.3%vs. 6.0%,P<0.05). The positive rate of E-cadherin in hepatocellular carcinoma was significantly lower than that in the adjacent para-cancerous tissue(27.5%vs. 90.0%,P<0.05). The differences of the expression of TRIM59 in hepatocellular carci-noma of pathological grading,tumor differentiation,vascular invasion and clinical TNM stage were significant(P<0.05). The differences of the expression of Twist in hepatocellular carcinoma of pathological grading ,differentia-tion,vascular invasion and clinical TNM stage was also significant(P<0.05,respectively). The differences of the expression of E-cadherin in hepatocellular carcinoma of pathological grading,differentiation,vascular invasion and clinical TNM stage were also significant(P<0.05,respectively). Significantly positive correlation was also found between TRIM59 and Twist by using spearman correlation analysis(P<0.05). Negative correlations were observed between TRIM59 and E-cadherin(P < 0.05),and between Twist and E-cadherin(P < 0.05). Survival analysis showed that TRIM59 expression was an independent prognostic factor in hepatocellular carcinoma. Conclusion TRIM59,Twist and E-cadherin protein expression might be associated with the development,invasion,and metas-tasis of hepatocellular carcinoma. TRIM59 may become a new target gene for the treatment of human hepatocellular carcinoma.

Objective To study the human papilloma virus(HPV) infection in lesion tissues of patients with common anus and rectal disease .Methods Gene amplification combined with gene chip technology were employed to conduct genotyping test in lesion tissue of 566 patients with common anus and rectal disease .Results In lesion tissues of 566 patients with common anus and rectal disease ,the overall HPV infection rate was 32 .86% (186/566) .In male patients ,the overall HPV infection rate ,monopole infection rate and multiple infection rate were 32 .14% (117/364) ,23 .35% (85/364) and 8 .79% (32/364) ,respectively ,which showed no sta-tistically significant difference with female [34 .16% (69/202) ,24 .75% (50/202) and 9 .41% (19/202) ,respectively ] (P>0 .05) . HPV 18 ,16 ,33 ,31 types were the main types of common anus and rectal disease .Conclusion HPV genotyping test of anus and rectum tissues is important for molecular epidemiological studies of HPV infection in anus and rectum .