Purpose Discover new prostate cancer-related single nucleotide variants.Methods Tissue wax blocks from 21 prostate cancer patients who underwent radical surgery and had relatively complete clinical data were collected for somatic mutation detection to analyze new mutated genes associated with prostate cancer.The levels of cor-responding proteins in the urine of prostate cancer patients were tested according to the results of the selected genes.Results All 21 prostate cancer patients showed obvious somatic mutations,and the mutation types were dominated by C＞T and G＞A.The number of somatic mutations was 521,of which 27 genes had high mutation proportions(≥2 ca-ses),including ZSWIM6(5/21),FOXA1(4/21),SPTA1(2/21),FAM47C(2/21),FLG2(2/21),PRSS3(2/21),TP53(2/21),FLG(2/21),UBR4(2/21),and the mutations occurring in ZSWIM6 were all deletion muta-tions,and the mutations occurring in FOXA1 were missense mutations,deletion mutations,and deletion insertion mu-tations.The urinary levels of UPF1,SPTA1,and IDH1 proteins of the 10 prostate cancer patients were significantly different than those of the healthy controls.Correlation analysis showed that FOXA1 was positively correlated with UBR4(r=0.669,P=0.001),SPTA1 was positively correlated with FLG2(r=1.000,P＜0.001),FAM47C was positively correlated with PRSS3(r=1.000,P＜0.001),and there was a significant positive correlation between TP53 and FLG(r=1.000,P＜0.001).ZSWIM6 and FOXA1 were not correlated with biochemical recurrence.SP-TA1 mutation affected progression-free survival(PFS)[(66.0±0)months vs(30.0±7.8)months,P=0.008].FAM47C was positively correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].ZNF676 was correlated with PFS[(66.0±0)months vs(26.0±5.0)months,P=0.008].FLG2 was correlated with PFS[(66.0±0)months vs(30.0±7.8)months,P=0.008].PRSS3 was correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].Conclusion All 21 prostate cancer patients harbored somatic mutations,including ZSWIM6(5/21)and FOXA1(4/21)mutations.SPTA1,FAM47C,ZNF676,FLG2,and PRSS3 may be associated with prognosis.

Objective:To investigate the value of 24 h urinary aldosterone(24 h-UAC) measurement by liquid chromatography-tandem mass spectrometry(LC-MS/MS) in the subtype classification of primary aldosteronism(PA).Methods:A total of 86 patients with PA, including 51 with unilateral primary aldosteronism(UPA) and 35 with bilateral primary aldosteronism(BPA), were enrolled in the Department of Endocrinology and Metabolism at West China Hospital between January 2018 and December 2022. Plasma aldosterone concentration(PAC), plasma renin concentration(PRC) and 24 h-UAC were measured by LC-MS/MS. 24-hour urinary electrolytes and 24-hour urinary creatinine(24 h-UCR) were also measured. The diagnostic value of 24 h-UAC in PA subtype classification was evaluated using receiver operating characteristic(ROC) curve analysis. Multivariate logistic regression analysis was conducted with PA subtypes as the dependent variable(UPA=1, BPA=0) to establish a diagnostic model for differentiating unilateral from bilateral lesions, and its performance was compared with published Chinese classification models. Results:There were no statistical differences between the UPA and BPA groups in terms of age, gender, BMI, systolic and diastolic blood pressure, 24 h urinary potassium, sodium, chloride, 24 h-UCR and PRC( P<0.05). The lowest plasma potassium level was significantly lower in the UPA group than in the BPA group, while PAC, 24 h-UAC, aldosterone-renin ratio(ARR), and 24 h-UAC/UCR were significantly higher( P<0.05). The detection rate of typical adenomas on imaging also showed a significant difference between the two groups( P<0.05). The area under the ROC curve(AUC) of 24 h-UAC for differentiating UPA from BPA was 0.829(95% CI 0.733-0.902), with an optimal cut-off value of 15.4 μg/24 h, yielding a sensitivity of 68.63% and a specificity of 88.57%( P<0.001). At a cut-off value of 24.5 μg/24 h, specificity reached 100%, with a sensitivity of 27.45%. Multivariate analysis indicated that a combined model incorporating 24 h-UAC, the lowest plasma potassium level, and imaging findings of typical adenomas significantly improved diagnostic accuracy for PA subtyping, achieving a specificity of 91.43%. Compared with the existing Chinese modified Küpers scoring model and CONPASS prediction model, this model demonstrated higher diagnostic efficiency, a lower missed diagnosis rate, and a misdiagnosis rate intermediate between the two. Conclusion:The 24 h-UAC in UPA patients is significantly higher than in BPA patients, making it a valuable marker for PA subtype classification. A predictive model combining 24 h-UAC, the lowest plasma potassium level, and imaging evidence of typical adenomas demonstrated high diagnostic accuracy for PA subtype classification and may provide valuable guidance for clinical decision-making.

Purpose Discover new prostate cancer-related single nucleotide variants.Methods Tissue wax blocks from 21 prostate cancer patients who underwent radical surgery and had relatively complete clinical data were collected for somatic mutation detection to analyze new mutated genes associated with prostate cancer.The levels of cor-responding proteins in the urine of prostate cancer patients were tested according to the results of the selected genes.Results All 21 prostate cancer patients showed obvious somatic mutations,and the mutation types were dominated by C＞T and G＞A.The number of somatic mutations was 521,of which 27 genes had high mutation proportions(≥2 ca-ses),including ZSWIM6(5/21),FOXA1(4/21),SPTA1(2/21),FAM47C(2/21),FLG2(2/21),PRSS3(2/21),TP53(2/21),FLG(2/21),UBR4(2/21),and the mutations occurring in ZSWIM6 were all deletion muta-tions,and the mutations occurring in FOXA1 were missense mutations,deletion mutations,and deletion insertion mu-tations.The urinary levels of UPF1,SPTA1,and IDH1 proteins of the 10 prostate cancer patients were significantly different than those of the healthy controls.Correlation analysis showed that FOXA1 was positively correlated with UBR4(r=0.669,P=0.001),SPTA1 was positively correlated with FLG2(r=1.000,P＜0.001),FAM47C was positively correlated with PRSS3(r=1.000,P＜0.001),and there was a significant positive correlation between TP53 and FLG(r=1.000,P＜0.001).ZSWIM6 and FOXA1 were not correlated with biochemical recurrence.SP-TA1 mutation affected progression-free survival(PFS)[(66.0±0)months vs(30.0±7.8)months,P=0.008].FAM47C was positively correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].ZNF676 was correlated with PFS[(66.0±0)months vs(26.0±5.0)months,P=0.008].FLG2 was correlated with PFS[(66.0±0)months vs(30.0±7.8)months,P=0.008].PRSS3 was correlated with PFS[(66.0±0)months vs(19.0±0)months,P＜0.001].Conclusion All 21 prostate cancer patients harbored somatic mutations,including ZSWIM6(5/21)and FOXA1(4/21)mutations.SPTA1,FAM47C,ZNF676,FLG2,and PRSS3 may be associated with prognosis.

Objective:To investigate the value of 24 h urinary aldosterone(24 h-UAC) measurement by liquid chromatography-tandem mass spectrometry(LC-MS/MS) in the subtype classification of primary aldosteronism(PA).Methods:A total of 86 patients with PA, including 51 with unilateral primary aldosteronism(UPA) and 35 with bilateral primary aldosteronism(BPA), were enrolled in the Department of Endocrinology and Metabolism at West China Hospital between January 2018 and December 2022. Plasma aldosterone concentration(PAC), plasma renin concentration(PRC) and 24 h-UAC were measured by LC-MS/MS. 24-hour urinary electrolytes and 24-hour urinary creatinine(24 h-UCR) were also measured. The diagnostic value of 24 h-UAC in PA subtype classification was evaluated using receiver operating characteristic(ROC) curve analysis. Multivariate logistic regression analysis was conducted with PA subtypes as the dependent variable(UPA=1, BPA=0) to establish a diagnostic model for differentiating unilateral from bilateral lesions, and its performance was compared with published Chinese classification models. Results:There were no statistical differences between the UPA and BPA groups in terms of age, gender, BMI, systolic and diastolic blood pressure, 24 h urinary potassium, sodium, chloride, 24 h-UCR and PRC( P<0.05). The lowest plasma potassium level was significantly lower in the UPA group than in the BPA group, while PAC, 24 h-UAC, aldosterone-renin ratio(ARR), and 24 h-UAC/UCR were significantly higher( P<0.05). The detection rate of typical adenomas on imaging also showed a significant difference between the two groups( P<0.05). The area under the ROC curve(AUC) of 24 h-UAC for differentiating UPA from BPA was 0.829(95% CI 0.733-0.902), with an optimal cut-off value of 15.4 μg/24 h, yielding a sensitivity of 68.63% and a specificity of 88.57%( P<0.001). At a cut-off value of 24.5 μg/24 h, specificity reached 100%, with a sensitivity of 27.45%. Multivariate analysis indicated that a combined model incorporating 24 h-UAC, the lowest plasma potassium level, and imaging findings of typical adenomas significantly improved diagnostic accuracy for PA subtyping, achieving a specificity of 91.43%. Compared with the existing Chinese modified Küpers scoring model and CONPASS prediction model, this model demonstrated higher diagnostic efficiency, a lower missed diagnosis rate, and a misdiagnosis rate intermediate between the two. Conclusion:The 24 h-UAC in UPA patients is significantly higher than in BPA patients, making it a valuable marker for PA subtype classification. A predictive model combining 24 h-UAC, the lowest plasma potassium level, and imaging evidence of typical adenomas demonstrated high diagnostic accuracy for PA subtype classification and may provide valuable guidance for clinical decision-making.

Objective:To analyze the clinical characteristics, etiological composition, imaging features, and prognosis of adrenal metastases.Methods:This study is a retrospective case series that included 96 patients with pathologically confirmed adrenal metastases who were treated at West China Hospital, Sichuan University, from 2007 to 2017. Clinical features such as sex, age, tumor size, biochemical tests, imaging characteristics, postoperative pathology, treatment methods, and prognosis were collected and analyzed. The prognosis of patients and its influencing factors were analyzed by Kaplan-Meier survival curve and single-factor Cox risk proportional model.Results:Among the 96 included patients, 64 were male and 32 were female, with a median age of 60 years. There were 89 cases of unilateral adrenal metastases, five cases of bilateral metastases, and two cases with unspecified laterality. The median diameter of the metastases was 3.5 cm×2.9 cm, with an average CT value of 31 HU. Thirty-four cases of adrenal hormones were evaluated, and no abnormality was found.The primary tumor sites were as follows: lung ( n=36), kidney ( n=19), liver ( n=12), pancreas ( n=7), rectum ( n=3), stomach ( n=2), and one case each of tumor in the esophagus, skin, thyroid, left maxillary muscle, breast, bladder, cervix, chest wall, and gastrointestinal tract. There were three cases with unknown primary tumors. The most common pathological type was lung adenocarcinoma (20.8%, 20/96), followed by hepatocellular carcinoma (9.4%, 9/96) and high-grade invasive urothelial carcinoma of the kidney (8.3%, 8/96). Thirty-nine cases were diagnosed concurrently with the primary tumor, while 37 cases were diagnosed after the primary tumor, with a median interval of 15 months (range: 2-144 months). There was no significant correlation between the death risk of adrenal metastatic tumor patients and gender, age, and the size of the metastatic tumor (all P>0.05). There were 4 patients with radiotherapy and chemotherapy alone, 19 patients with surgery alone, and 6 patients with combined radiotherapy and chemotherapy. The median overall survival was 1, 3, and 7 years, respectively. Conclusions:Adrenal metastases were mostly diagnosed at the same time as the primary tumor or within 15 months after the diagnosis of the primary tumor. Unilateral metastasis is common. The lungs are the most common primary lesion, followed by the kidney and liver. CT is the preferred method for the diagnosis of adrenal metastases, and the plain CT value is more than 30 HU. The overall prognosis of adrenal metastases is poor. The prognosis was better for patients who underwent surgery combined with radiotherapy and chemotherapy than those who received only surgery or radiotherapy and chemotherapy alone.

Ulcerative colitis (UC) is one of types of inflammatory bowel disease with high recurrence. Recent studies have highlighted that microbial dysbiosis as well as abnormal gut immunity are crucial factors that initiate a series of inflammatory responses in the UC. Modulating the gut microbiota-intestinal immunity loop has been suggested as one of key strategies for relieving UC. Many Chinese herbal medicines including some of single herb, herbal formulas and the derived constituents have been reported with protective effect against UC through modulating gut microbiome and intestinal immunity. Some clinical trials have shown promising results. This review thus focused on the current knowledge on using Chinese herbal medicines for treating UC from the mechanism aspects of regulating intestinal homeostasis involving microbiota and gut immunity. The existing clinical trials are also summarized.

OBJECTIVES: Frizzled 7 (FZD7) is abnormally expressed and activated in a variety of cancers. In ovarian cancer, overexpression of FZD7 reduces the sensitivity of platinum-resistant ovarian cancer cells to ferroptosis, thereby allowing cancer cells to survive. However, whether FZD7 inhibits ferroptosis in ovarian cancer cells and its mechanisms are remain unclear. This study aims to explore the effects of FZD7 and its upstream regulator miR-1-3p on ferroptosis in ovarian cancer cells are evaluated to clarify the molecular mechanism for miR-1-3p and FZD7's involvement in ferroptosis in ovarian cancer cells. METHODS: Human ovarian cancer cell lines HO8910 and SKOV3 were used as the research subjects. In the first part of the experiment, human ovarian cancer cells were transfected with blank plasmid and FZD7 overexpression plasmid, respectively; in the second and third parts, human ovarian cancer cells were transfected with miR-1-3p mimics negative control, miR-1-3p mimics, miR-1-3p inhibitors negative control, and miR-1-3p inhibitors, respectively; in the fourth part of the experiment, human ovarian cancer cells were transfected with miR-1-3p mimics and miR-1-3p mimics+FZD7 overexpression plasmid, respectively, and normal cultured cells were set as the control group. The human ovarian cancer cell ferroptosis model was established by incubating human ovarian cancer cells with different treatments with ferroptosis inducer Erastin or RSL3. Real-time RT-PCR was used to detect the mRNA expression levels of FZD7 and miR-1-3p; Western blotting was used to detect the protein expression levels of FZD7; CCK-8 assay was used to detect the cell viability; lipid peroxidation colorimetric assay kit was used to detect the level of intracellular MDA; and iron assay kit was used to detect the level of intracellular Fe2+. Dual-luciferase assay was used to detect the targeting relationship between miR-1-3p and FZD7. RESULTS: Overexpression of FZD7 increased the cell viability of human ovarian cancer cell lines HO8910 or SKOV3 (P<0.05, P<0.01, or P<0.001) and decreased the intracellular MDA levels (P<0.01) in Erastin-treated or RSL3-treated ovarian cancer cells. FZD7 was a direct target of miR-1-3p, which inhibited the expression of FZD7 (P<0.01) by binding to the 3'-untranslated region (3'UTR) site of FZD7. MiR-1-3p mimics decreased the cell viability of human ovarian cancer cell lines HO8910 or SKOV3 (P<0.05, P<0.01, or P<0.001) and increased the intracellular MDA levels (P<0.01) in Erastin-treated or RSL3-treated ovarian cancer cells; while miR-1-3p inhibitors significantly increased the cell viability of human ovarian cancer cell lines HO8910 or SKOV3 (P<0.05, P<0.01, or P<0.001) and decreased the intracellular MDA levels (P<0.01) in Erastin-treated or RSL3-treated ovarian cancer cells. The effect of miR-1-3p mimics on enhancing the sensitivity of human ovarian cancer cells to Erastin-induced or RSL3-induced ferroptosis was abrogated by overexpression of FZD7(P<0.05 or P<0.01). CONCLUSIONS MiR-1-3p enhances the sensitivity of ovarian cancer cells to ferroptosis by targeting FZD7.
Female ; Humans ; Frizzled Receptors/genetics* ; MicroRNAs/genetics* ; Ovarian Neoplasms/genetics* ; Ferroptosis

Objective:To investigate risk factors for the efficacy for appropriate medication use in elderly patients with type 2 diabetes mellitus(T2DM)and to establish a risk prediction model for the efficacy for appropriate medication use by using Logistic regression analysis and the receiver operating characteristic(ROC)curve.Methods:A total of 305 elderly patients with T2DM admitted to pharmacy department of our hospital from Jan.2018 to Aug.2018 were enrolled in this retrospective study.Of the 305 patients, 166(54.4%)were female, with a mean age of (74.9±7.2) years old, a disease course of (15.2±9.6) years and a hospital stay of (10.4±3.2) d, receiving (2.0±0.9) types of antidiabetic drugs.Patients were assessed by the Self-Efficacy for Appropriate Medication Use Scale(SEAMS), the Morisky Medication Adherence Scale-8(MMAS), the Adherence to Refills and Medications Scale(ARMS), the Charlson Comorbidity Index(CCI)and the Mini Mental State Exam(MMSE). Main biochemical indicators were recorded.The influencing factors for appropriate medication use efficacy were analyzed by Logistic regression analysis, and a risk prediction model was consequently established by the ROC curve.Results:According to SEAMS results, 233 patients(76.4%)had sufficient efficacy(≥26 points)and 72 patients(23.6%)had insufficient efficacy(<26 points). There were significant differences in parameters including age, disease course, hospital stay and fasting blood glucose(FBG)between the above two groups( P<0.05). Logistic regression analysis showed that age, FBG level and ARMS score had correlation with self-efficacy for appropriate medication use( P<0.05). ROC curves showed that the predictive efficiency of joint predictor Y [Logit(P)=-15.164+ 0.434X ARMS score-0.067X age-0.082X FBG reaching standard]was better than that of the other three single factors(AUC=0.910, 95% CI: 0.873-0.947, P<0.01)and could be used as an optimal predictor for the evaluation of self-efficacy for appropriate medication use. Conclusions:Compared with MMAS, ARMS is more suitable for medication adherence assessment in elderly T2DM patients.In clinical practice, pharmacists can provide individualized medication services through evaluating the efficacy of rational drug use and the risk prediction model, in order to elevate the ability of self-medication management and quality of life.

Objective To explore the clinical value of serum ferritin (SF),erythrocyte sedimentation rate (ESR) and erythrocyte average indexes [mean corpuscular volume (MCV),mean corpuscular hemoglobin (MCH),mean corpuscular hemoglobin concentration (MCHC)] in the prognosis evaluation of patients with small cell lung cancer (SCLC).Methods A total of 72 SCLC patients were enrolled in the Haian People's Hospital Affiliated to Nantong University from January 2013 to October 2016 (SCLC group),and 80 health controls were selected at the same time (control group).The levels of serum SF,ESR and erythrocyte average indexes in SCLC group and control group were detected,and their relationships with clinical features,prognosis and survival time were analyzed.Results The serum levels of SF,ESR,MCV,MCH and MCHC in SCLC patients were (309 ±59) μg/L,(16 ±4) mm/h,(104 ± 12) fl,(32 ±4) pg and (307 ±21) g/L,respectively.The serum levels of SF,ESR,MCV,MCH and MCHC in control group were (186 ±26) μg/L,(15 ±5)mm/h,(85 ± 7) fl,(30 ± 3) pg and (335 ± 25) g/L,respectively.Compared with the control group,the patients in SCLC group were significantly increased on the levels of SF (t =14.168,P ＜ 0.001) and MCV (t =6.143,P ＜ 0.001),and were significantly decreased on the level of MCHC (t =-4.220,P =0.003).There were no significant difference in the levels of ESR (t =1.931,P =0.102) and MCH (t =1.220,P =0.313) between the two groups.The serum levels of SF and MCV were significantly correlated with the stage of SCLC (t =-4.092,P =0.009;t =-4.985,P ＜ 0.001).Multivariate logistic regression analysis showed that high serum SF (OR =5.31,95％ CI:3.09-9.31,P ＜ 0.001) and MCV (OR =1.78,95％ CI:1.10-3.08,P =0.013) were independent risk factors of SCLC.Survival analysis showed that the survival time of the patients in the high SF group was significantly shorter than that in the low SF group (6 months vs.20 months;x2 =6.556,P =0.001).Conclusion Serum ESR,MCH and MCHC levels are not significantly correlated with SCLC,but serum SF and MCV levels are of important clinical significance in evaluating the prognosis of SCLC patients.

Objective To evaluate the value of acoustic radiation force impulse (ARFI) elastography in assessment of nonalcoholic fatty liver disease (NAFLD) and hepatic fibrosis in rats.Methods Models with various degrees of NAFLD severity were conducted in 110 rats by feeding high fat emulsion.The right liver lobe of rat models were processed and embedded in a fabricated gelatin solution to measure the shear wave velocity (SWV) by ARFI.And the other liver lobes were used for histologic assessment.Based on NAFLD activity score (NAS),the final pathologic NAFLD diagnosis were considered as normal group (NAS=0),simple steatosis (SS) group (1≤NAS≤2),borderline (3≤NAS≤4) group and nonalcoholic steatohepatitis (NASH) group (NAS≥5).The diagnostic accuracy of the SWV parameters in evaluating NAFLD severity and fibrosis stages was studied using ROC curves.Results The difference of SWV values among normal group,SS group,borderline group and NASH group was statistically significant (F=31.53,P＜0.001).Taking SWV≥ 2.54 m/s as the diagnostic standard to differentiate normal rats from rats with SS,and SWV≥2.90 m/s to differentiate SS from NASH in rats,the area under ROC curve (AUC) was 0.922 (95％CI [0.871,0.973],P＜0.001) and 0.882 (95％ CI [0.807,0.956],P＜0.001) respectively.The sensitivity and specificity were 93.5 ％ and 100 ％ for differentiating normal and SS groups,83.3 ％ and 84.2 ％ for differentiating SS and NASH groups.Taking SWV≥3.48 m/s as cutoff to predict fibrosis (≥F2 stage),the AUC was 0.963 (95％CI [0.909,1.000],P＜0.001),the sensitivity was 92.9％ and the specificity was 97.6％.Taking SWV≥3.61 m/s as cutoff to predict severe fibrosis (≥F3 stage),the AUC was 0.997 (95％CI [0.990,1.000],P＜0.001),sensitivity was 100％ and specificity was 98.9％.The same high validity was maintained as in the prediction of cirrhosis (F4 stage) with the cutoff as SWV≥4.50 m/s,and the AUC was 0.993 (95％CI [0.982,1.000],P＜0.001),the sensitivity was 100 ％ and the specificity was 96.8％.Conclusion ARFI elastography is a promising method for differentiating the different severity of NAFLD and staging the degree of hepatic fibrosis with NAFLD in rat models.