Objective: To establish a risk prediction model for diabetic peripheral neuropathy (DPN) among patients with type 2 diabetes mellitus (T2DM), so as to provide a basis for DPN prevention and control. Methods: T2DM inpatients aged 18-65 years admitted to the department of endocrinology and metabolism at Affiliated Hospital Shandong Second Medical University from April to December 2024 were selected as study subjects. Age, T2DM duration, hypertension history, 25-hydroxyvitamin D, serum C-peptide, and high density lipoprotein cholesterol (HDL-C) were collected through electronic medical records. Risk predictors of DPN among T2DM patients were screened using multivariable logistic regression model, and a nomogram was established. The receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis were employed to evaluate the discrimination, calibration and clinical utility of the nomogram, respectively. Results: A total of 598 T2DM patients were enrolled, including 359 (60.03%) males and 239 (39.97%) females. The median age was 54.50 (interquartile range, 15.00) years, the median T2DM duration was 6.00 (interquartile range, 9.00) years. There were 262 cases of T2DM patients with DPN, accounting for 43.81%. Multivariable logistic regression identified hypertension history (OR=3.260, 95%CI: 2.220-4.790), alcohol use history (OR=2.150, 95%CI: 1.390-3.310), diabetes complications (OR=0.430, 95%CI: 0.270-0.680), T2DM duration (OR=1.040, 95%CI: 1.010-1.070), body mass index (OR=1.130, 95%CI: 1.070-1.200), 25-hydroxyvitamin D (OR=0.930, 95%CI: 0.910-0.960), and HDL-C (OR=0.400, 95%CI: 0.230-0.720) as risk predictors for DPN among T2DM patients. The area under the ROC curve of the established risk prediction model was 0.774 (95%CI: 0.737-0.812), with a sensitivity of 0.710 and a specificity of 0.723. The calibration curve after repeated sampling calibration approached the standard curve. Decision curve analysis showed that when the risk threshold probability was 0.2 to 0.4, the model demonstrates favorable clinical applicability. Conclusion The risk prediction model established in this study has favorable discrimination, calibration, and clinical utility, can effectively predict the risk of DPN among T2DM patients aged 18-65 years.

Objective:To summarize the clinical value of fetoscopy in the prenatal diagnosis and treatment of amniotic band syndrome (ABS).Methods:A retrospective analysis was conducted on the clinical data of seven ABS fetuses who underwent prenatal fetoscopic intervention at the Third Affiliated Hospital of Zhengzhou University from December 2020 to August 2023. Literatures related to fetoscopic treatment of ABS were searched in databases including China National Knowledge Infrastructure, Wanfang Data, and PubMed. Clinical data were extracted and the characteristics and intervention effects of fetoscopic surgery in the treatment of ABS were summarized.Results:(1) Preoperative evaluation: the gestational age at diagnosis for the seven ABS fetuses was (19.8±4.4) weeks, and the gestational age at fetoscopic intervention was (22.2±2.8) weeks. The indications for fetoscopic intervention included umbilical cord involvement (3 cases), limb amniotic band with circular constriction (2 cases), and unclear visualization of digits (3 cases). (2) Pregnancy outcomes: among the seven ABS fetuses, four cases underwent selective termination of pregnancy due to severe intrauterine limb amputation, and three cases underwent fetoscopic lysis of amniotic bands. Among the latter three cases, one case experienced intrauterine fetal death (IUFD) two weeks after the procedure, and two cases had good postoperative outcomes. (3) Literature review: a total of 40 cases, including 37 cases from 17 articles and three cases from our institution, were included in the analysis. The indications for fetoscopic surgery included limb amniotic band with circular constriction and involvement of the umbilical cord. The success rate of the surgery was 82% (33/40), and 78% (29/37) of the affected limbs retained good functionality. Premature rupture of membranes was the most common complication, with an incidence rate of 48% (16/33). The average interval from the surgery to membrane rupture was (6.1±5.1) weeks, and the average interval from the surgery to delivery was (10.5±4.1) weeks, with an average gestational age at delivery of (33.7±3.6) weeks. The pregnant women were divided into single Trocar group (27 cases) and double Trocar group (13 cases) based on the surgical approach. The success rates in single Trocar group and double Trocar group were 78% (21/27) and 12/13, respectively, and the difference was not statistically significant ( χ2=0.474, P=0.491). The gestational age of delivery in the single Trocar group and double Trocar group was (32.7±3.4) and (35.4±3.2) weeks, respectively, and the difference was statistically significant ( t=-2.185, P<0.05). There were no statistically significant differences in the success rate of the surgery, incidence of premature rupture of membranes, interval between surgery and membrane rupture, interval between surgery and delivery, and preterm delivery rate between the two groups (all P>0.05). Conclusions:Fetoscopy could be used for prenatal assessment and intrauterine treatment of ABS. Fetoscopic lysis of amniotic bands may be an effective method for treating ABS, which helps preserve limb function and prevent intrauterine limb amputation and IUFD.

Objective: To understand social anxiety of Tibetan adolescents aged 10-15 years old in high altitude areas and its correlation with sleep duration, so as to provide a reference and support for social anxiety prevention and mental health interventions for Tibetan adolescents in high altitude areas. Methods: A total of 2 426 Tibetan adolescents from the Lhasa, Chamdo, and Nagchu regions of Tibet were surveyed. From April to June 2022, basic demographics, social anxiety, and sleep status were obtained and analyzed using class based, stratified whole group sampling, and the correlations detected between the two were analyzed by logistic regression analysis. Results: The average social anxiety score of Tibetan adolescents aged 10-15 years in high altitude areas was (6.51±4.32), and the detection rate of social anxiety was 5.23%. The mean sleep duration was (7.42±1.18) hours/day. The differences were statistically significant when compared across gender, overweight/obesity status, level of physically activity, and sleep duration ( χ 2=19.44, 14.39, 7.83, 7.21, P <0.05). After adjusting for relevant variables, the Logistic regression analysis showed that sleep deprivation among boys ( OR =2.91, 95% CI =1.82-4.61), sleep deprivation among girls ( OR = 3.51 , 95% CI =2.01-6.04), and overall sleep deprivation among Tibetan adolescents ( OR =3.12, 95% CI =1.91-4.58) were positively associated with social anxiety( P <0.01). Conclusions A positive association was found between social anxiety and sleep deprivation, indicating that social anxiety is an issue among Tibetan adolescents living in high altitude regions. Sufficient sleep duration plays a positive protective role in reducing social anxiety among Tibetan adolescents in high altitude areas, and the findings provide a reference for future mental health interventions.

Melatonin is mainly an endogenous indoleamine hormone with many physiological functions. Melatonin not only plays an important role in the treatment of sleep disorders, but also plays an important role in the treatment of nervous system diseases, cancer, cardiovascular diseases, and bone diseases. In this paper, the human Melatonin is mainly an endogenous indoleamine hormone with many physiological functions. Melatonin not only plays an important role in the treatment of sleep disorders, but also plays an important role in the treatment of nervous system diseases, cancer, cardiovascular diseases, and bone diseases. In this paper, the human body networks mechanisms and the clinical applications of melatonin were summarized to provide reference for exploring the focus and direction of further clinical application research.

Objective:To investigate the obstetric outcomes of intracytoplasmic sperm injection and frozen-thawed embryo transfer (ICSI-FET) between donor and autologous oocytes.Methods:A retrospective cohort study was conducted to analyze the clinical data of pregnant patients who underwent ICSI-FET in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from June 2016 to January 2020. Totally 73 patients with donor oocytes, and 550 patients who used autologous oocytes in the same period, and the patients were matched at 1∶3 with propensity score matching (PSM), then there were 47 patients in donor group and 131 patients in autologous group. The general conditions and obstetric outcomes were compared among donor group and autologous group. Multivariate logistic regression and linear regression were applied to analyze the factors affecting perinatal complications.Results:The bilateral antral follicle count (3.08±4.78) and basal estradiol level [(71.55±45.29) pmol/L] in donor group were significantly lower than those in autologous group [14.95±6.42, (132.84±74.89) pmol/L, all P<0.001]. The birth weight of singleton in donor group [(2 916.48±537.55) g] was lower than that in autologous group [(3 326.67±503.43) g], and there was significant difference ( P<0.001). There were no significant differences in premature birth rate [21.28% (10/47) vs. 16.03% (21/131), P=0.416] and incidence of hypertensive disorder complicating pregnancy [12.77% (6/47) vs. 7.63% (10/131), P=0.448] between donor group and autologous group, but both of them had an increasing trend in donor group. Oocyte-donated ICSI-FET reduced the birth weight of singleton (MD=-388.225, 95% CI=-625.914--150.537, P=0.002). Conclusion:The perinatal outcome of oocyte-donated ICSI-FET is relatively safe, but the birth weight of singleton is lower than that of self-oocyte ICSI-FET.

Objective:To investigate the obstetric outcomes of intracytoplasmic sperm injection and frozen-thawed embryo transfer (ICSI-FET) between donor and autologous oocytes.Methods:A retrospective cohort study was conducted to analyze the clinical data of pregnant patients who underwent ICSI-FET in the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University from June 2016 to January 2020. Totally 73 patients with donor oocytes, and 550 patients who used autologous oocytes in the same period, and the patients were matched at 1∶3 with propensity score matching (PSM), then there were 47 patients in donor group and 131 patients in autologous group. The general conditions and obstetric outcomes were compared among donor group and autologous group. Multivariate logistic regression and linear regression were applied to analyze the factors affecting perinatal complications.Results:The bilateral antral follicle count (3.08±4.78) and basal estradiol level [(71.55±45.29) pmol/L] in donor group were significantly lower than those in autologous group [14.95±6.42, (132.84±74.89) pmol/L, all P<0.001]. The birth weight of singleton in donor group [(2 916.48±537.55) g] was lower than that in autologous group [(3 326.67±503.43) g], and there was significant difference ( P<0.001). There were no significant differences in premature birth rate [21.28% (10/47) vs. 16.03% (21/131), P=0.416] and incidence of hypertensive disorder complicating pregnancy [12.77% (6/47) vs. 7.63% (10/131), P=0.448] between donor group and autologous group, but both of them had an increasing trend in donor group. Oocyte-donated ICSI-FET reduced the birth weight of singleton (MD=-388.225, 95% CI=-625.914--150.537, P=0.002). Conclusion:The perinatal outcome of oocyte-donated ICSI-FET is relatively safe, but the birth weight of singleton is lower than that of self-oocyte ICSI-FET.

Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P < 0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.
Animals ; Cell Death ; Cell Line, Tumor ; Ferroptosis ; Lung Neoplasms/drug therapy* ; Mice ; Orlistat

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Objective:To study the incidence and classification of chromosomal abnormalities in villi of missed abortion patients with assisted reproductive technology (ART) and natural conception (NC).Methods:Totally 637 patients with missed abortion villi from the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University during January 2016 and January 2020 were collected and divided into ART group and NC group according to the mode of pregnancy in this retrospective cohort study. The ART group was further divided into artificial insemination by husband (AIH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Next generation sequencing (NGS) was used to detect the copy number variations (CNVs) and chromosome number abnormalities of chorionic villi of missed abortion. Results:Among 637 missed abortion chorionic villi, 45.2% (288/637) of the samples had normal chromosome and 54.8% (349/637) had abnormal chromosome. CNVs accounted for 3.8% (14/637) of the total samples, and chromosome number abnormalities accounted for 52.5% (335/637) of the total samples. The abnormal rates of villi chromosome in ART group and NC group were 59.2% (226/382) and 51.0% (130/255), respectively, and there was no significant difference between ART group and NC group ( P>0.05). The abnormal rates of villus chromosome in AIH group, IVF group and ICSI group were 52.1% (25/48), 58.9% (146/248) and 64.0% (55/86), respectively. Compared with NC group, the abnormal rate of villus chromosome in IVF group and ICSI group was increased, but there was no significant difference ( P>0.008). Conclusion:In general, ART did not increase the incidence of chromosomal abnormalities in missed abortion villi. However, compared with natural pregnancy and AIH assisted pregnancy, IVF/ICSI had a higher chromosomal abnormality in missed abortion villi.

Objective:To study the incidence and classification of chromosomal abnormalities in villi of missed abortion patients with assisted reproductive technology (ART) and natural conception (NC).Methods:Totally 637 patients with missed abortion villi from the Reproductive Center of the Third Affiliated Hospital of Zhengzhou University during January 2016 and January 2020 were collected and divided into ART group and NC group according to the mode of pregnancy in this retrospective cohort study. The ART group was further divided into artificial insemination by husband (AIH), in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Next generation sequencing (NGS) was used to detect the copy number variations (CNVs) and chromosome number abnormalities of chorionic villi of missed abortion. Results:Among 637 missed abortion chorionic villi, 45.2% (288/637) of the samples had normal chromosome and 54.8% (349/637) had abnormal chromosome. CNVs accounted for 3.8% (14/637) of the total samples, and chromosome number abnormalities accounted for 52.5% (335/637) of the total samples. The abnormal rates of villi chromosome in ART group and NC group were 59.2% (226/382) and 51.0% (130/255), respectively, and there was no significant difference between ART group and NC group ( P>0.05). The abnormal rates of villus chromosome in AIH group, IVF group and ICSI group were 52.1% (25/48), 58.9% (146/248) and 64.0% (55/86), respectively. Compared with NC group, the abnormal rate of villus chromosome in IVF group and ICSI group was increased, but there was no significant difference ( P>0.008). Conclusion:In general, ART did not increase the incidence of chromosomal abnormalities in missed abortion villi. However, compared with natural pregnancy and AIH assisted pregnancy, IVF/ICSI had a higher chromosomal abnormality in missed abortion villi.