Objective: To analyze the relationship between new surrogate marks of insulin resistance (IR) and bone mineral content (BMC) in adolescents, and predictive value of the new surrogate marks on low bone mass, so as to provide scientific basis for early identification and prevention of skeletal related diseases in adolescents. Methods: A total of 1 594 adolescents aged 12-18 years in Yinchuan City were selected by convenience sampling and stratified cluster random sampling from September 2017 to September 2020, and triglyceride and glucose index (TyG), triglyceride glucose-body mass index (TyG-BMI) and triglyceride/high density lipoprotein cholesterol (TG/HDL-C) were calculated as new simplified IR index. The correlation between different simplified IR indexes and BMC level was analyzed by partial correlation. Binary Logistic regression was used to analyze the relationship between IR index and low bone mass, and receiver operating characteristic (ROC) curve was constructed to analyze its evaluation effect on low bone mass. Results: After adjusting for confounding factors such as gender, age, smoking, drinking, family history of hypertension, systolic blood pressure (SBP) and diastolic blood pressure (DBP), the new surrogate marks of IR were positively correlated with BMC level (TyG: r =0.11, TyG-BMI: r =0.58, TG/HDL-C: r =0.21, P <0.01). After further adjustment of body mass index (BMI), fat mass (FM) and lean mass (LM), the relationship between IR indexes and BMC turned into negative correlation (TyG: r =-0.20, TyG-BMI: r =-0.18, TG/HDL-C: r=-0.14, P <0.01). After adjusting for confounding factors such as gender, age, smoking, drinking, family history of hypertension, SBP and DBP, Logistic regression results showed that the increase of TyG, TyG-BMI and TG/HDL-C levels reduced the possibility of low bone mass in adolescents (TyG: OR=0.63, 95%CI = 0.40-0.98, TyG-BMI: OR=0.94, 95%CI =0.93-0.96, TG/HDL-C: OR=0.31, 95%CI=0.17-0.58, P <0.01). After adjusting BMI, FM and LM, the above results were completely reversed. Girls with high TyG and TG/HDL-C levels were 4.95 and 4.38 times more likely to have low bone mass than those with low TyG and TG/HDL-C levels (TyG: OR=4.95, 95%CI =1.29- 18.95 , TG/HDL-C: OR=4.38, 95%CI=1.04-18.50, P <0.05). ROC curve showed that TyG-BMI had the best predictive value on low bone mass (AUC=0.80, 95% CI=0.77-0.83, P <0.01). Conclusion The new surrogate marks of IR in adolescents are negatively correlated with adolescent BMC, of which TyG-BMI is the best for assessing of low bone mass and can serving as a reliable indicator for early identification of low bone mass.

Perinatal depression is a psychological disorder that occurs during pregnancy and within one year of delivery, which can seriously affect the physical and mental health of pregnant and postpartum women, as well as the cognitive and behavioral abilities of offspring, with potential multigenerational effects. Therefore, it is important to identify its potential modifiable risk factors. Phthalic acid esters (PAEs), as common environmental endocrine disruptors, can affect maternal estrogen through multiple mechanisms and are important potential modifiable risk factors for developing maternal perinatal depression. At present, studies on the correlation between PAEs and perinatal depression are still very limited, and the mechanisms by which PAEs affect perinatal depression have not been clarified. Based on existing epidemiological and toxicological studies at home and abroad, the article briefly introduced the characteristics of multiple pathways, high doses, and long-term exposure to maternal PAEs, focused on reviewing the current status of epidemiological studies, pointed out the possible associations between some specific PAEs exposure and elevated risk of perinatal depression. It also summarized the potential roles of hormone-neurotransmitter pathway, inflammation mediation, gene regulation, and other possible mechanisms in the association between exposure to PAEs and perinatal depression. The article concluded with a look at how future research on the association between exposure to PAEs and perinatal depression can be scientifically validated, with a view to providing more high-quality evidence for the scientific prevention of the onset and progression of maternal depressive symptoms.

As a chronic metabolic disease,type 2 diabetes poses a significant threat to human health with increasing incidence.An increasing number of studies confirm that the pathogenesis of diabetes is closely related with alterations in multiple cellular signaling pathways.Although numerous studies have reported that traditional Chinese medicine compounds prevent diabetes by modulating cell signaling pathways,asystematic review of the mechanism of action of traditional Chinese medicine compounds in modulating cell signaling pathways is still lacking.Therefore,this paper summarizes the research of type 2 diabetes prevention and treatment,which was found mainly related to the signaling pathways such as PI3K/AKT,AMPK,MAPK,NF-κB,PPAR,TGF-β.This family of signaling pathways can treat type 2 diabetes by inhibiting pancreatic islet cell apoptosis,protecting pancreatic β-cell function,ameliorating insulin resistance,inhibiting hepatic gluconeogenesis,promoting glycogen synthesis,attenuating inflammation,and resisting oxidative stress.At the same time,we analyze the problems in current research and the future development trend,in order to provide a scientific theoretical basis for the drug development and clinical application of traditional Chinese medicine compound in the prevention and treatment of diabetes.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective:To evaluate the efficacy and safety of 532-nm picosecond laser in the treatment of early-stage facial seborrheic keratosis.Methods:A total of 95 patients with early-stage facial seborrheic keratosis were prospectively enrolled from the Department of Dermatology, General Hospital of Ningxia Medical University between December 2020 and September 2022. All the patients received a session of 532-nm picosecond laser treatment, and were followed up for 6 months. A 4-point scale was used to evaluate the overall improvement of skin lesions for assessing the clinical efficacy. A VISIA skin detector was used to quantitatively determine the characteristic counts, absolute scores, and percentiles of brown spots before and after treatment, and the paired sample t-test was used to compare the quantitative indicators of brown spots before and after treatment. The patients′ pain grades were evaluated, and adverse reactions were recorded. Results:All the 95 patients with early-stage facial seborrheic keratosis received a session of 532-nm picosecond laser treatment, and completed a 6-month follow-up. All the patients achieved over 25% regression of skin lesions in the treatment area, of whom 10 received mild improvement, 17 received favorable improvement, and 68 received marked improvement, with the response rate being 89.47% (85/95). The examination with the VISIA skin detector showed that the characteristic counts (195.19 ± 51.06) and absolute scores (28.80 ± 6.20 points) of brown spots significantly decreased, while the percentiles of brown spots (38.48% ± 10.80%) significantly increased at 6 months after treatment compared with the corresponding baseline indicators (211.48 ± 50.94, 35.16 ± 6.84 points, 30.61% ± 10.27%, t = 12.73, 16.90, -15.73, respectively, all P < 0.001). All the patients experienced varying degrees of pain during the treatment, with the pain scores being 2 - 6 (3.64 ± 1.67) points, but all of them could tolerate the pain and completed the treatment. Temporary postinflammatory hyperpigmentation and hypopigmentation occurred in 9 (9.47%) and 4 (4.21%) patients respectively, and the skin color restored to normal during the 6-month follow-up. Conclusion:The 532-nm picosecond laser was safe and effective for the treatment of early-stage facial seborrheic keratosis.

OBJECTIVE To analyze the influential factors for potentially inappropriate medication （PIM） in elderly cancer patients. METHODS The data of elderly cancer patients hospitalized in a hospital from January to December 2021 were collected. According to the Beers standard of the American Geriatrics Society in 2019 （hereinafter referred to as the “2019 version of Beers standard”） and Criteria for Potentially Inappropriate Drug Use in Chinese Elderly （2017 version） （hereinafter referred to as the “Chinese PIM standard”）， the PIM status of elderly cancer patients was retrospectively analyzed. Multivariate Logistic regression analysis was used to identify influential factors for PIM. RESULTS A total of 293 patients were included in the study. According to the 2019 version of Beers standard， 211 patients （72.01%） had PIM， of which 204 （69.62%） had PIM related to drugs， 6 （2.05%） had PIM related to diseases or symptoms， 46 （15.70%） had PIM that should be used with caution， 32 （10.92%） had PIM with drug-drug interaction that should be avoided， and 11 （3.75%） had PIM based on renal function； the top 5 drugs in the list of incidence were proton pump inhibitors， metoclopramide， the first-generation antihistamines as promethazine， analgesics as ibuprofen and megestrol. According to the Chinese PIM standard， there were 132 patients （45.05%） with PIM， of which 119 （40.61%） had PIM related to drugs， involving 25 drugs （included 7 high-risk drugs and 18 low-risk drugs）， and 24 （8.19%） with PIM in disease status； top 4 drugs in the list of incidence were promethazine， megestrol， ibuprofen and cimetidine. Multivariate Logistic regression analysis showed that compared with patients with hospital stay≤10 days， patients with hospital 20054） stay between 11 and 30 days had a higher risk of PIM [odds ratio （OR）＝8.836 8， 95% confidence interval （CI） （3.217 8， 31.940 9）， P＝0.000 1]； compared with the patients with the 65895198。E-mail：fjman@cmpt.ac.cn number of clinical disease diagnosed≤5， patients with the number of clinical disease diagnosed≥11 had a higher risk of PIM [OR＝10.930 1， 95%CI （3.000 9， 70.922 9）， P＝0.001 8]； compared with surgical treatment， patients receiving antineoplastic drugs had a higher risk of PIM [OR＝2.209 5， 95%CI （1.180 2， 4.176 9）， P＝0.013 6]. CONCLUSIONS Elderly cancer patients have multiple diseases， complicated medication， and a high incidence of PIM. The length of hospital stay （11-30 d）， the number of clinical disease diagnosed （≥11） and anti-tumor drugs are main influential factors for PIM in patients.

Objective To investigate the expression of autophagy marker in peripheral blood T and B lymphocytes of patients with autoimmune hepatitis (AIH) and its clinical significance. Methods Peripheral blood samples were collected from 62 AIH patients who were treated in Beijing YouAn Hospital affiliated to Capital Medical University from October 2019 to October 2020 who were treated in Beijing YouAn Hospital affiliated to Capital Medical University from October 2019 to October 2020 and 8 healthy controls to detect autophagy of T and B lymphocyte subsets, and then subgroup analyses were performed based on treatment, diagnostic type, and presence or absence of liver cirrhosis and liver failure. The t -test was used for comparison of normally distributed continuous data between two groups; the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups, and the Mann-Whitney U test was used for comparison between two groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between two groups. Results Compared with the healthy control group, the AIH group had a significantly higher mean fluorescence intensity (MFI) of the autophagy marker LC3B in CD4 + T, CD8 + T, CD19 + B, and CD4 + CD25 + T lymphocytes (all P < 0.05), especially in CD19 + B lymphocytes. The non-treatment group and the partial remission group had a significantly higher MFI of autophagy marker in CD19 + B lymphocytes than the complete remission group ( P =0.037 and 0.040); the idiopathic AIH (I-AIH) group and the drug-induced AIH(DI-AIH) group had a significantly higher MFI than the primary biliary cholangitis (PBC)-AIH overlap syndrome group ( P =0.037 and 0.031); the non-cirrhosis group and the decompensated cirrhosis group had a significantly higher MFI than the compensated cirrhosis group ( P =0.009 and 0.003); the liver failure group had a significantly higher MFI than the non-liver failure group ( P =0.042). The PBC-AIH group had a significantly higher MFI of autophagy marker in CD4 + CD25 + T lymphocytes than the I-AIH group and the DI-AIH group ( P =0.042 and 0.044), the compensated cirrhosis group had a significantly lower MFI than the non-cirrhosis group ( P =0.037), and the non-liver failure group had a significantly higher MFI than the liver failure group ( P =0.043). Conclusion AIH patients have a significant increase in the expression of autophagy marker in peripheral blood T and B lymphocyte subsets compared with healthy individuals, and the level of autophagy is associated with treatment, diagnostic type, and disease severity.

[Abstract] Objective: To investigate the effect and mechanism of miR-449b-5p on the proliferation of ovarian cancer cells. Methods: Cancer tissue and corresponding para-cancerous tissue specimens from 20 patients who underwent surgery in the Department of Obstetrics and Gynecology of Sichuan Provincial People's Hospital from June 2018 to June 2020 were collected for this study; in addition, normal ovarian epithelial cell line (HOSEpiC) and six human cervical cancer cell lines (SKOV3, ES-2, OVCAR-3, HO8910, CaOV-3 and A2780) were also selected. mRNA expressions of miR-449b-5p and CCNE2 in ovarian cancer tissues and cells were detected by qPCR. The plasmids miR-NC, miR-499b-5p mimic, miR-499b-5p inhibitor and pc-CCNE2 were transfected into SKOV3 cells separately or in combination. Cell growth and cell cycle were measured by the CCK-8 method and Flow cytometry, the expression of CCNE2 protein was detected by WB assay, respectively. The targeting relationship between miR-449b-5p and CCNE2 was verified by Dual luciferase reporter assay. miR-499b-5p transfected SKOV3 cells were injected subcutaneously in nude mice to construct xenograft model, and the tumor volume was measured weekly. Nude mice were sacrificed at day 42. The weight of the subcutaneous tumors was weighed by an electronic balance, and the expressions of CCNE2 and Ki67 were detected by immunohistochemistry. Results: Compared with normal ovarian tissues and epithelial cell line HOSEpiC, miR-499b expression was significantly downregulated in human cervical cancer tissues and cell lines SKOV3, ES-2, OVCAR-3, HO8910, CaOV-3 and A2780 (P<0.01). Compared with the Control group, the proliferation of SKOV3 cells in the miR-499b mimic group was significantly reduced (P<0.01) and the cell proportion in G0/G1 phase was significantly increased ( P<0.01); while the proliferation of SKOV3 cells in the miR-499b inhibitor group was significantly increased (P<0.01) and the cell proportion in G0/G1 phase was significantly reduced (P<0.01). Over-expression of miR-499b-5p significantly inhibited the luciferase activity of wild type CCNE2 plasmid (P<0.01) but had no effect on the luciferase activity of the mutant CCNE2 plasmid. Compared with the miR-499b mimic group, the growth of SKOV3 cells in the miR-499b mimic+pc-CCNE2 group was significantly increased (P<0.01) and the cell proportion in G0/G1 phase was significantly reduced (P<0.01). Compared with the miR-NC group, the tumor volume and weight of nude mice in the miR-499b mimic group were significantly reduced (all P<0.01), and the proportion of CCNE2 and Ki67 positive cells was significantly decreased (P<0.01). Conclusion: miR-449b-5p inhibits the growth and cell cycle progression of ovarian cancer cells by targeting Cyclin E2.

Objective:To analyze the anti-drug resistance, molecular epidemiology and virulence gene distribution of non-A-F group serotype isolates of Salmonella enterica enteric subspecis, so as to provide epidemiological basis for clinical diagnosis and treatment.Methods:Serotyping, antimicrobial susceptibility test and whole genome sequencing were performed on 11 isolates of non-A-F group serotype isolates of Salmonella enterica enteric subspecies that were isolated from The Children′s Hospital, Zhejiang University School of Medicine between 2017 and 2020. The serotype, multilocus sequence typing and virulence gene of the whole genome sequencing results were analyzed. Results:In our hospital, the detection rate of non-A-F group serotype isolates of Salmonella enterica enteric subspecies was low (1.13%). Among the 11 strains, there were 3 strains belong to Jangwani serotype, 2 strains of Hvittingfoss serotype, and Wandsworth, Pomona, Kedougou, Urbana, Poona and Kumasi serotypes have 1 strain each. Except for the two multi-drug resistant strains, the other strains were sensitive to most antibiotics, and the MICs were at low levels. A total of 9 ST types were detected in the 11 strains, the 3 Jangwani serotype strains were ST3918, and the other isolates were of different ST types. The phylogenetic tree shown that the three strains of Jangwani serotype were closely related. A total of 103 virulence genes were detected in the 11 strains, including 78 genes related to secretion system, 21 genes related to adherence, 2 genes related to magnesium uptake, 1 gene related to resistance to antimicrobial peptides and 1 gene related to typhoid toxin. Conclusions:The detection rate of the non-A-F group serotype isolates of Salmonella enterica enteric subspecies was low, and the sensitivity of the isolates to common antibiotics was high. The ST types and genetic relationship showed diversity. Clinical laboratory should pay attention to the detection of the non-A-F group serotype isolates of Salmonella enterica enteric subspecies, and the changes in drug resistance and virulence genes of the isolates should be closely monitored.

OBJECTIVE: To explore the clinical and genetic characteristics of a patient with 17-hydroxylase/17,20-lyase deficiency. METHODS: The patient was infertile without contraception. Laboratory examination showed her chromosomal karyotype to be 46, XX. DNA sequencing was performed to detect variants of CYP17A1 gene in the patient and her family members. RESULTS: Sanger sequencing revealed that the patient has carried homozygous variant c.1486C>T in the exon 8 of the CYP17A1 gene, which resulted in substitution of arginine by cysteine (p.Arg496Cys). Her family members were all heterozygotes for the same variant. CONCLUSION Homozygous variant of the CYP17A1 gene c.1486C>T probably underlay the 17-hydroxylase deficiency in this patient. Above finding has enabled accurate genetic counseling and prenatal diagnosis for her family.