BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Objective:To investigate whether dual-energy computed tomography(DECT) measurement of monosodium urate(MSU) crystal loading can predict the risk of gout flares.Methods:A single-center, prospective, observational study included 229 gout patients initially diagnosed at the Gout Clinic of Qingdao University from August 2021 to February 2022. The patients underwent MSU assessment of the bilateral feet using DECT. Following enrolment, all patients commenced uric acid-lowering therapy(ULT) and were followed up at 3 and 6 months. Patients who experienced at least one flare within 6 months were compared with those who did not, and the odds ratio( OR) for the risk of gout flares was calculated. Results:Patients who experienced gout flare had a significantly longer disease duration[(6.69±5.42) vs(4.14±4.86) years, P<0.01], a higher number of flares in the past year(4.80±1.73 vs 2.02±1. 23, P<0.01), a higher proportion of fatty livers(11.0% vs 1.4%, P<0.05), and a greater volume of MSU crystals in the feet[(3.52±9.74) vs(0.29±0.98)cm 3,P<0.05] compared to patients without gout flare. The results of the multifactorial logistic regression analysis indicated that the number of flares in the past year( OR=1.295, 95% CI 1.032-1.613, P<0.05) and feet MSU crystal volume( OR=3.245, 95% CI 1.164-9.064, P<0.05) were independent risk factors for gout flares. The receiver operating characteristic(ROC) curve indicated the integration of the MSU prediction model into the clinical prediction model resulted in a comprehensive prediction model with an area under curve(AUC) value of 0.780(95% CI 0.710-0.840), sensitivity of 0.83, and specificity of 0.62. Internal validation of the comprehensive prediction model using the Bootstrap method yielded a C-index of 0.770(95% CI 0.701-0.833) for predicting flares. The calibration curve of the model demonstrated a good fit between the predicted probability of flares and the actual probability, indicating high calibration accuracy. Conclusion:The volume of MSU crystals in the feet is an independent risk factor for flares following ULT. A larger volume of MSU crystals in the foot increases the likelihood of a flare. This study provides a basis for early prediction of flare and a reference for early preventive treatment.

BACKGROUND: The clinical importance of hypokalemia is likely underrecognized in Chinese dialysis patients, and whether its clinical effect was mediated by serum albumin is not fully elucidated. This study aimed to explore the association between serum potassium and mortality in dialysis patients of a Chinese nationwide multicenter cohort, taking albumin as a consideration. METHODS: This was a prospective nation-wide multicenter cohort study. Restricted cubic splines were used to test the linearity of serum potassium and relationships with all-cause (AC) and cardiovascular (CV) mortality and a subsequent two-line piecewise linear model was fitted to approach the nadir. A mediation analysis was performed to examine relations of albumin to potassium and mortalities. RESULTS: A total of 10,027 patients were included, of whom 6605 were peritoneal dialysis and 3422 were hemodialysis patients. In the overall population, the mean age was 51.7 ± 14.8 years, 55.3%(5546/10,027) were male, and the median dialysis vintage was 13.60 (4.70, 39.70) months. Baseline serum potassium was 4.30 ± 0.88 mmol/L. After a median follow-up period of 26.87 (14.77, 41.50) months, a U-shape was found between potassium and mortality, and a marked increase in risk at lower potassium but a moderate elevation in risk at higher potassium were observed. The nadir for AC mortality risk was estimated from piecewise linear models to be a potassium concentration of 4.0 mmol/L. Interestingly, the significance of the association between potassium and mortality was attenuated when albumin was introduced into the extended adjusted model. A subsequent significant mediation by albumin for potassium and AC and CV mortalities were found ( P < 0.001 for both), indicating that hypokalemia led to higher mortality mediated by low serum albumin, which was a surrogate of poor nutritional status and inflammation. CONCLUSIONS Associations between potassium and mortalities were U-shaped in the overall population. The nadir for AC mortality risk was at a potassium of 4.0 mmol/L. Serum albumin mediated the association between potassium and AC and CV mortalities.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; East Asian People ; Hypokalemia/etiology* ; Kidney Failure, Chronic/mortality* ; Potassium/blood* ; Prospective Studies ; Renal Dialysis ; Serum Albumin/analysis*

Child ; Humans ; Factor VII Deficiency

Objective: To analyze the incidence and related factors of drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019. Methods: From April 2017 to April 2019, face-to-face questionnaires and blood sample testing were conducted in all health care institutions providing maternal and perinatal care and midwifery-assisted services in 7 prevention of mother-to-child transmissi project areas in Xinjiang, Yunnan and Guangxi provinces/autonomous regions. Information was collected during the perinatal period and viral load, CD4⁺T lymphocytes and drug resistance genes were detected at the same time. The multivariate logistic regression model was used to analyze the relationship between different factors and drug resistance in HIV-infected pregnant and postpartum women. Results: A total of 655 HIV-infected pregnant and postpartum women were included in this study. The incidence of drug resistance was 3.4% (22/655), all of whom were cross-drug resistant. The rate of low, moderate and high drug resistance was 2.1% (14/655), 1.2% (8/655) and 0.8% (5/655), respectively. The drug resistance rate in the people who had previously used antiviral drugs was 1.9% (8/418), and the drug resistance rate in the people who had not used drugs was 5.9% (14/237). The NNRTI drug resistance accounted for 2.8% (18/655) and the NRTI drug resistance rate was 2.5% (16/655). The multivariate logistic regression model showed that the risk of HIV resistance was lower in pregnant women who had previously used antiviral drugs (OR=0.32, 95%CI: 0.11-0.76). Conclusion: Strengthening the management of antiviral drug use and focusing on pregnant and postpartum women who have not previously used antiviral drugs can help reduce the occurrence of drug-resistant mutations. Personalized antiviral therapy should be considered to achieve viral inhibition effects in clinical practice.
Female ; Humans ; Pregnancy ; HIV Infections/drug therapy* ; Incidence ; China/epidemiology* ; Infectious Disease Transmission, Vertical/prevention & control* ; Postpartum Period ; Drug Resistance, Viral/genetics* ; Antiviral Agents/therapeutic use*

Objective: To analyze the incidence and related factors of drug resistance in HIV-infected pregnant and postpartum women in some areas of three western provinces of China from 2017 to 2019. Methods: From April 2017 to April 2019, face-to-face questionnaires and blood sample testing were conducted in all health care institutions providing maternal and perinatal care and midwifery-assisted services in 7 prevention of mother-to-child transmissi project areas in Xinjiang, Yunnan and Guangxi provinces/autonomous regions. Information was collected during the perinatal period and viral load, CD4⁺T lymphocytes and drug resistance genes were detected at the same time. The multivariate logistic regression model was used to analyze the relationship between different factors and drug resistance in HIV-infected pregnant and postpartum women. Results: A total of 655 HIV-infected pregnant and postpartum women were included in this study. The incidence of drug resistance was 3.4% (22/655), all of whom were cross-drug resistant. The rate of low, moderate and high drug resistance was 2.1% (14/655), 1.2% (8/655) and 0.8% (5/655), respectively. The drug resistance rate in the people who had previously used antiviral drugs was 1.9% (8/418), and the drug resistance rate in the people who had not used drugs was 5.9% (14/237). The NNRTI drug resistance accounted for 2.8% (18/655) and the NRTI drug resistance rate was 2.5% (16/655). The multivariate logistic regression model showed that the risk of HIV resistance was lower in pregnant women who had previously used antiviral drugs (OR=0.32, 95%CI: 0.11-0.76). Conclusion: Strengthening the management of antiviral drug use and focusing on pregnant and postpartum women who have not previously used antiviral drugs can help reduce the occurrence of drug-resistant mutations. Personalized antiviral therapy should be considered to achieve viral inhibition effects in clinical practice.
Female ; Humans ; Pregnancy ; HIV Infections/drug therapy* ; Incidence ; China/epidemiology* ; Infectious Disease Transmission, Vertical/prevention & control* ; Postpartum Period ; Drug Resistance, Viral/genetics* ; Antiviral Agents/therapeutic use*

Humans ; Renal Dialysis ; Pruritus

Objective: To provide reference and evidence for clinical application of neoadjuvant immunotherapy in patients with colorectal cancer through multicenter large-scale analysis based on real-world data in China. Methods: This was a retrospective multicenter case series study. From January 2017 to October 2021, data of 94 patients with colorectal cancer who received neoadjuvant immunotherapy in Peking University Cancer Hospital (55 cases), Union Hospital of Tongji Medical College of Huazhong University of Science and Technology (19 cases), Sun Yat-sen University Cancer Center (13 cases) and Changhai Hospital of Navy Medical University (7 cases) were retrospectively collected, including 48 males and 46 females. The median age was 58 years. Eighty-one cases were rectal cancer and 13 cases were colon cancer (2 cases of double primary colon cancer). Twelve cases were TNM staging II and 82 cases were stage III. Forty-six cases were well differentiated, 37 cases were moderately differentiated and 11 cases were poorly differentiated. Twenty-six patients (27.7%) with mismatch repair defects (dMMR) and microsatellite instability (MSI-H) were treated with immunotherapy alone, mainly programmed cell death protein-1 (PD-1); sixty-eight cases (72.3%) with mismatch repair proficient (pMMR) and microsatellite stability (MSS) were treated with immune combined with neoadjuvant therapy, mainly CapeOx (capecitabine+oxaliplatin) combined with PD-1 antibody plus long- or short-course radiotherapy, or PD-1 antibody combined with cytotoxic T lymphocyte associated antigen 4 (CTLA-4) antibody. Analysis and evaluation of adverse events during neoadjuvant immunotherapy were performed according to the National Cancer Institute Common Toxicity Standard version 3.0; the surgical complications were evaluated according to the Clavien-Dindo grading standard; the efficacy evaluation of neoadjuvant immunotherapy included the following indicators: major pathological remission (MPR) was defined as tumor regression induced by neoadjuvant therapy in pathology residual tumor ≤10%; pathological complete response (pCR) was defined as tumor regression induced by neoadjuvant therapy without residual tumor in pathology; the tumor response rate was disease control rate (DCR), namely the proportion of complete response (CR), partial response (PR) and stable disease (SD) in the whole group; the objective response rate (ORR) was CR+PR. Results: The median cycle of neoadjuvant immunotherapy was 4 (1-10) in whole group, and the incidence of immune-related adverse reactions was 37.2% (35/94), including 35 cases (37.2%) of skin-related adverse reactions, 21 cases (22.3%) of thyroid dysfunction and 8 cases (8.5%) of immune enteritis, of which grade III or above accounted for 1.1%. The median interval between completion of neoadjuvant therapy and surgery was 30 (21-55) days. There were 81 cases of radical resection of rectal cancer, 11 cases of radical resection of colon cancer, and 2 cases of colon cancer combined with other organ resection. The primary tumor resection of all the patients reached R0. The incidence of surgical-related complications was 22.3% (21/94), mainly anastomotic leakage (4 cases), pelvic infection (4 cases), abdominal effusion (3 cases), anastomotic stenosis (3 cases ) and abdominal and pelvic hemorrhage (2 cases). Grade I-II complications developed in 13 cases (13.8%), grade III and above complications developed in 8 cases (8.5%), no grade IV or above complications were found. During a median follow-up of 32 (1-46 ) months, DCR was 98.9% (93/94), ORR was 88.3 % (83/94), pCR was 41.5% (39/94), MPR was 60.6% (57/94). The pCR rate of 26 patients with dMMR and MSI-H undergoing simple immunotherapy was 57.7% (15/26), and MPR rate was 65.4% (17/26). The pCR rate of 68 pMMR and MSS patients undergoing combined immunotherapy was 35.3%(24/68), and MPR rate was 58.8% (40/68). Conclusions: Neoadjuvant immunotherapy has favorable tumor control rate and pathological remission rate for patients with initial resectable colorectal cancer. The incidences of perioperative adverse reactions and surgical complications are acceptable.
Colorectal Neoplasms/surgery* ; Female ; Humans ; Immunotherapy ; Male ; Middle Aged ; Neoadjuvant Therapy ; Rectal Neoplasms/surgery* ; Retrospective Studies

Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.
Aged ; Anxiety ; Cross-Sectional Studies ; Depression ; Female ; Humans ; Male ; Middle Aged ; Quality of Life ; Rectum ; Surveys and Questionnaires