Objective To investigate the related mechanism which metformin inhibited the proliferation of HCT116 colorectal cancer cells via down-regulating the expression of up-frameshift protein 1(UPF1).Methods TCGA and UALCAN databases were utilized to analyze the expression level of UPF1,while Western blotting and Real-time PCR were performed to validate the differences of UPF1 expressions in colon cancer tissues and adjacent normal tissues.Clone formation assay,CCK-8 assay,wound healing assay and Transwell invasion assay were used to examine the effects of knockdown UPF1 on the proliferation,migration and invasion of HCT116 cells respectively.The HCT116 cell dataset with UPF1 knockdown was screened from GEO database for Kyoto Encydopedia of Genes and Genomes(KEGG)pathway analysis,the expression level of differential genes that enriched in Hippo pathway were verified by Real-time PCR.The HCT116 cells were treated with metformin,Western blotting and Real-time PCR were employed to detect the UPF1 expression.Mendelian randomization analysis was performed to explore the causal association between metformin treatment and colorectal cancer.Results Analysis of TCGA and UALCAN databases showed that both UPF1 mRNA and protein were highly expressed in colon cancer tissues and the expression level of UPF1 was closely correlated with clinicopathologic stage and lymph node metastasis.Compared with adjacent normal tissues,the UPF1 protein and mRNA were highly expressed in colon cancer tissues.Knockdown UPF1 expression could inhibit the proliferation,migration and invasive ability of HCT116 cells.There were 8 differential genes affect the Hippo pathway by KEGG enrichment analysis,Real-time PCR experiments confirmed that CTNNB1,BMP4,TEAD2,PARD6G and FZD1 mRNA decreased in HCT116 cells with UPF1 knockdown.Both UPF1 protein and mRNA expressions decreased after metformin treatment in HCT116 cells.Mendelian randomization analysis showed a negative causal association between metformin treatment and colorectal cancer.Conclusion Knockdown of UPF1 expression inhibits the proliferation of HCT116 cells through regulating Hippo pathway.Metformin can reduce the UPF1 expression for further inhibiting the proliferation of colorectal cancer cells.

AIM To study the chemical constituents from the sticks and leaves of Croton cascarilloides Raeusch.and their biological activities.METHODS The 95％ethanol extract from the sticks and leaves of C.cascarilloides was isolated and purified by MCI,silica gel,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.LPS-induced NO RAW264.7 cell model induced by LPS was used to evaluate its anti-inflammatory activity in vitro.GES-1 injury model induced by taurocholic acid was used to screen the gastric mucosal protection activity.RESULTS Fourteen compounds were isolated and identified as bullatantriol(1),(-)-boscialin(2),(+)-dehydrovomifoliol(3),3-(hydroxylacetyl)-indole(4),pinoresinol(5),3,7-dimethyl-octa-1,7-diene-3,6-ol(6),(+)-syringaresinol(7),curcasinlignan B(8),cleomiscosin C(9),cleomiscosinD(10),2,6-dimethyl-octa-1,7-dien-3,6-diol(11),vanillin(12),vanillic acid(13),methyl vanillate(14).Compound 4 had certain anti-inflammatory activity,with IC50 values of 73.62 μmol/L.The protective rates of 25 μmol/L compounds 1-4,6,9-12 and 14 on gastric mucosal epithelial cells were 30.07％,34.18％,23.91％,30.92％,17.51％,19.69％,31.76％,22.46％,30.56％and 14.49％,respectively.CONCLUSION Compounds 1-14 are isolated from this plant for the first time.Compound 4 shows anti-inflammatory activity,1-4,6,9-12 and 14 show different degrees of gastric mucosal epithelial cell protective activity.

OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

Objective:To analyze the characteristics of obstructive sleep apnea（OSA）in children with Prader-Willi syndrome (PWS),and to improve the understanding of OSA during rapid eye movement sleep.Methods:The clinical data of 13 children with PWS aged 2-14 years admitted to Shenzhen Children's Hospital from June 2017 to June 2024 were retrospectively collected as the PWS group,and 12 children with snoring caused by adenoids,tonsil hypertrophy and/or obesity were selected as the control group.The gender,age,body mass index (BMI),obstructive apnea index (OAI),oxygen desaturation index (ODI),obstructive sleep apnea hypopnea index (OAHI),rapid eye movement period OAHI(OAHIrem),non-rapid eye movement period OAHI(OAHInrem) and OAHIrem/total sleep period OAHI ratio were compared between the two groups.Multivariate linear regression was used to assess the association between PWS and OAHIrem.Results:Among the 13 children in PWS group,there were 7 males and 6 females,with an average age of (7.63±4.05) years and an average BMI of (23.06±6.12) kg/m2.Among the 12 children in control group,there were 10 males and 2 females,with an average age of (7.28±3.92) years and an average BMI of (22.41±5.68) kg/m2.There were no statistically significant differences in age,gender,and BMI between the two groups ( P>0.05).All 13 children (100%) with PWS had OSA,with 8 cases (61.53%) of mild OSA and 5 cases (38.46%) of moderate to severe OSA.OAI and ODI in PWS group were significantly higher than those in control group ( P<0.05).OAHI and OAHInrem in PWS group were higher than those in control group,but the difference was not statistically significant ( P>0.05).OAHIrem and OAHIrem/ total sleep OAHI ratio were significantly higher than those in the control group,with statistical significance ( P<0.05).Multivariate linear regression analysis showed that PWS was significantly correlated with OAHIrem/ total sleep OAH ratio (square root) ( P=0.008). Conclusion:Children with PWS have a high incidence of OSA,with a high proportion of moderate to severe OSA.They are prone to OSA with hypoxemia during rapid eye movement sleep.It is recommended that respiratory monitoring of children with PWS during rapid eye movement sleep should be strengthened,and individualized treatment plan should be formulated according to the type and severity of OSA.

Objective To analyze the characteristics,causes,influencing factors of compensation,and appraisal features of second-instance medical malpractice cases involving cardiovascular diseases in Henan Province from 2017 to 2022,and to provide reference for forensic appraisal and judicial trial.Methods Cases were retrieved from China Judgments Online between 2017 and 2022.A total of 1,957 documents were reviewed,including 1,397 medical malpractice cases and 130 cardiovascular disease cases.Results The total compensation awarded in these second-instance cases was 27.04 million yuan,with a median of 158,600 yuan.Cases involving patient death accounted for 80.00％(104/130).Among 107 cases with first-instance appraisals,55.14％(59/107)raised objections,while 74.62％(97/130)of the second-instance trials upheld the original judgment.The most common degree of responsibility borne by medical institutions was secondary responsibility(41.54％,54/130).The top three medical faults were:inadequate observation and management of patient conditions(46.15％),omission of auxiliary examinations(37.50％),and insufficient notification(36.54％).In terms of violations-including medical record documentation,inappropriate treatment,misdiagnosis or missed diagnosis,out-of-scope practice,and improper medication use-the actual proportions in judgments(24/113,34/113,12/113,7/113,14/113)were all significantly lower than the patients' claims(all P＜0.05).Conclusion Cardiovascular medical malpractice cases in second-instance trials involve substantial compensation and a high proportion of death outcomes.Both medical institutions and patients should pay greater attention to first-instance trials.Appraisal organizations should proactively provide explanation and education regarding issues likely to raise patient doubts,thereby reducing unnecessary appeals.They should also avoid hasty revisions of appraisal opinions when faced with objections and instead focus on improving the quality and credibility of appraisals.In determining medical faults,emphasis should be placed on evaluating whether there was inadequate patient monitoring and management,omission of auxiliary examinations,and insufficient notification.

OBJECTIVE: To investigate the relationship between serum levels of fibroblast growth factor-23 (FGF-23), heparanase (HPSE) and early renal impairment (RI) in patients with multiple myeloma (MM). METHODS: A retrospective analysis was conducted on the clinical data of 125 MM patients who were initially diagnosed in the Department of Hematology of the First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology from June 2020 to June 2023. The patients were divided into RI group (>176.80 μmol/L) and non-RI group (≤176.80 μmol/L) based on their serum creatinine levels when diagnosed. The baseline data and laboratory indexes of the two groups were compared. The relationship between serum FGF-23, HPSE and early RI in MM patients was analyzed. RESULTS: Among 125 newly diagnosed MM patients, 33 cases developed early RI, accounting for 26.40%. The proportion of light chain type, blood urea nitrogen (BUN), blood uric acid, lactate dehydrogenase, FGF-23, and HPSE levels in RI group were higher than those in non-RI group (all P <0.05). There was no statistical significant difference in other data between the two groups (P >0.05). Multivariate logistic regression analysis showed that BUN, FGF-23 and HPSE were associated with early RI in MM patients (all P <0.05). The serum FGF-23 level was divided into Q1-Q4 groups by quartile, and the serum HPSE level was divided into q1-q4 groups. The correlation analysis showed that with the increase of serum FGF-23 and HPSE levels, the incidence of early RI increased (r =0.668, 0.592). Furthermore, logistic regression analysis showed that after controlling for confounding factors, elevated levels of serum FGF-23 and HPSE were still influencing factors for early RI in MM patients (OR>1, P <0.05). According to Pearson's linear correlation test, there was a positive correlation between serum FGF-23 level and HPSE level (r =0.373). CONCLUSION There is a certain correlation between serum levels of FGF-23, HPSE and early RI in MM patients, and the incidence of early RI is higher in patients with abnormally high levels of both.
Humans ; Multiple Myeloma/complications* ; Fibroblast Growth Factor-23 ; Retrospective Studies ; Fibroblast Growth Factors/blood* ; Glucuronidase/blood* ; Male ; Female ; Middle Aged ; Renal Insufficiency/blood* ; Aged

Purpose This study aimed to investigate the expression and clinical significance of TLDC2 in colorec-tal adenocarcinoma.Methods Data from the human protein atlas(HPA)and the cancer genome atlas(TCGA)indi-cated that TLDC2 was highly expressed in colorectal adenocarcinoma.We further analyzed the expression of TLDC2 in 400 colorectal adenocarcinomas and 447 other solid tumors using tissue microarrays and immunohistochemical(IHC)staining.Result The positive expression rate of TLDC2 was significantly higher than that of SATB2 in colorectal ade-nocarcinomas(96.5％vs 87.0％,P＜0.000 1).TLDC2 positivity exceeded that of SATB2 in both low-or high-grade colorectal adenocarcinoma(99.4％vs 88.7％,P＜0.000 1;83.3％vs 79.2％,P=0.669 9).In addition,the expression of TLDC2 and SATB2 was evaluated in 447 cases of other types of solid tumors.TLDC2 was expressed in neuroendocrine tumors as well as in gastric and appendiceal adenocarcinomas,whereas SATB2 was detected in a small number of melanomas,ovarian cancers,breast cancers and gallbladder cancers.The positive and specificity of TLDC2 for colorectal adenocarcinoma were 97％(95％CI=0.94-0.98)and 85％(95％CI=0.81-0.88),respectively.Combined detection of TLDC2 and SATB2 yielded a sensitivity of 96％(95％CI=0.93-0.97)and a specificity of 93％(95％CI=0.90-0.95).Conclusion Analysis of large-scale datasets and IHC staining demonstrated that TLDC2 is a highly sensitive and specific biomarker for colorectal adenocarcinoma.

Objective:To explore the mechanism of the influence of nitrate on the determination of calcium content in pitavastatin calcium by flame atomic absorption spectrometry.Methods:By comparing the absorbance of calci-um standard test solutions using hydrochloric acid and nitric acid as solution media,and measuring the changes in calcium absorbance in calcium ion solutions prepared by adding different concentrations of nitric acid using flame atomic absorption spectrophotometry,the relationship between calcium atomization efficiency and calcium ion con-centration,nitrate concentration,and their concentration ratios was explored.Results:Nitrate had a significant effect on reducing the absorbance value of the calcium standard test solution;The degree of interference varied with the concentration of the element calcium in the sample,and was related to the ratio of the concentration of the ele-ment calcium to the concentration of the interfering substance nitrate.Moreover,the interference of nitrate on calci-um affected the slope of the working curve.Conclusion:The interference mechanism of nitrate in the determination of calcium by flame atomic absorption spectrophotometry is due to the decomposition of calcium nitrate formed by ni-trate and calcium into difficult to melt,evaporate,and effectively dissociate calcium oxide at high temperatures,which reduces the atomization efficiency of calcium atoms and results in low absorbance values in the measurement.It is not advisable to select calcium standard stock solutions containing nitric acid when determining calcium containing samples such as pitavastatin calcium,and it is also necessary to be vigilant against the interference of nitrate ions.

Objective: To analyze the relationship between vitamin D and ferritin nutritional status with physical indicators in primary and secondary school students in the key nutrition monitoring counties of Xinjiang, so as to provide reference for early prevention and intervention of students nutrition issues. Methods: From November to December 2023, 1 071 students aged 6-18 from key nutrition monitoring counties in the Xinjiang Nutrition Improvement Plan area were selected via stratified random sampling for physical and biochemical tests. The U test and Kruskal-Wallis H-test were used to compare the differences in physical indicators and the distribution of vitamin D and ferritin levels. Chi-square test was used to compare the prevalence of vitamin D and ferritin deficiencies among different groups of primary and secondary school students. Pearson correlation was used to analyze the relationship between the nutritional levels of vitamin D and ferritin and physical indicators. Results: The median vitamin D level was 14.7 (10.7, 19.0)ng/mL, with deficiency and insufficiency rates of 30.8% and 37.4% among primary and secondary school students in the key nutrition monitoring counties of Xinjiang Nutrition Improvement Plan area. Ferritin levels were 57.4 (37.7, 83.9)μg/L, with a deficiency rate of 5.7%. Males, primary school students, and rural residents had higher vitamin D and ferritin levels than females, secondary school students, and urban residents ( U =-11.35, -6.88, -4.52; -3.94, -9.17, -5.23, P <0.05). Vitamin D deficiency was more prevalent in females, secondary school students, and urban students ( χ 2=97.52, 49.01, 21.89, P <0.05), while ferritin deficiency was higher in primary school students and urban areas ( χ 2=34.11, 5.63, P <0.05). Significant differences in body mass index (BMI) and waist circumstance (WC) were observed across vitamin D/ferritin statuses ( U/H =35.47, 22.82; -4.19 , -5.36, P <0.05). Vitamin D and ferritin levels negatively correlated with age, BMI, and WC but positively with waist-to-height ratio (WHtR) ( r = -0.31, -0.19, -0.19, 0.20; -0.32, -0.13, -0.21, 0.08, P <0.05). Conclusions Vitamin D and ferritin levels in primary and secondary school students in key nutritional monitoring counties in Xinjiang are correlated with age, BMI, WC and WHtR, and there are nutrient deficiencies. Targeted measures are recommended to improve nutritional status and physical health.