Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective To explore the genes related to the pathogenesis of polycystic ovary syndrome(PCOS)through bioinformatics methods and verify them in ovarian granulosa cells,providing a reference for screening potential molecular markers of PCOS.Methods The GSE34526 and GSE137684 datasets were re-spectively used as the training set and validation set.The inflammation-related genes potentially associated with the onset of PCOS were explored through differential expression analysis and weighted gene co-expres-sion network analysis.Subsequently,their predictive value was verified through the receiver operating charac-teristic(ROC)curve.Thirty patients with PCOS(the PCOS group)and 27 patients without PCOS(the con-trol group)who were treated in Affiliated Hospital of Youjiang Medical University for Nationalities were se-lected as the research objects.RT-qPCR was applied to verify the expression level of core genes in granular cells.Spearman correlation and multiple linear regression were used to analyze the correlation between the ex-pression level of core genes and various clinical parameters,and the ROC curve was used to analyze the diag-nostic efficacy of the expression level of core genes for PCOS.Finally,the protein expression level of core genes was verified on animal models.Results A total of 1 888 differentially expressed genes,89 module-relat-ed genes and 366 inflammatory response-related genes were identified.The core gene phosphatidylinositol-4,5-diphosphate 3-kinase catalytic subunit γ(PIK3CG)was ultimately obtained by taking co-expressed genes and verifying with the ROC curve.RT-qPCR results showed that the expression level of PIK3CG in granulosa cells of the PCOS group was higher than that of the control group(P<0.05).Spearman correlation analysis showed that the expression level of PIK3CG was positively correlated with BMI,testosterone(T),fasting in-sulin(FINS),and insulin resistance index(HOMA-IR,P<0.05).Multivariate linear regression analysis showed that FINS,HOMA-IR and BMI were increased with the increasing of PIK3CG expression level(P<0.05).ROC curve analysis showed that the area under the curve for diagnosing PCOS patients with PIK3CG mRNA expression levels in granulosa cells was 0.659 3.The immunohistochemical results showed that the ex-pression of PIK3CG protein in the ovarian tissues of mice in the PCOS group was significantly increased.Con-clusion PIK3CG may be potentially associated with the pathogenesis of PCOS.

Objective To investigate the efficacy of acupuncture therapy combined with acupoint patching in alleviating chronic pelvic pain,a sequela of pelvic inflammatory disease(SPID-CPP).Methods A total of 120 SPID-CPP patients attending our hospital between January 2022 and November 2024 were enrolled and randomly assigned to either an experimental group or a control group,with 60 patients in each group.Both groups received conventional lifestyle guidance and anti-infection therapy.The control group received only acupuncture therapy,while the observation group received acupuncture combined with acupoint patching therapy.The duration of treatment was identical for both groups.The treatment effect,levels of high-sensitivity C-reactive protein(hs-CRP),white blood cell count(WBC),neutrophil percentage(NEUT),fibrinogen(FIB)level,quality-of-life scores,and visual analog scale(VAS)pain scores were compared between the experimental and control groups.Results The treatment efficacy rate of the experimental group was 93.00%,while that of the control group was only 73.33%,and the difference between the two groups was statistically significant(P<0.05).Following therapy,the hs-CRP,WBC,NEUT,and VAS ratings of both the control and experimental groups decreased.Furthermore,findings of the experimental group were significantly lower than those of the control group(P<0.05).The quality-of-life score of the experimental group was higher than that of the control group(P<0.05).Conclusion Acupuncture combined with acupoint patching demonstrates significant efficacy in treating SPID-CPP.This combined therapy effectively reduces pain in SPID-CPP patients,decreases serum levels of inflammatory factors,and significantly improves patients'quality of life.

Objective:To investigate the comorbidity status of hypertension, diabetes, and dyslipidemia (the"three diseases") among residents aged≥40 in Liaoning Province, and to explore the correlation between the comorbidity and cardiovascular disease mortality.Methods:This investigation was a prospective cohort study. From February 2017 to March 2019, a multi-stage stratified cluster random sampling method was used to carry out a baseline survey of 18 758 permanent residents aged≥40 years in Liaoning Province. Demographic information and history of hypertension, diabetes, and dyslipidemia were collected and followed up every year. Death was mainly identified by linkage to the Population Death Information Registration Management System. Cox proportional hazard regression model was used to analyze the association between the comorbidity of the "three diseases" and cardiovascular disease mortality risk.Results:A total of 18 758 residents aged≥40 in Liaoning Province were included, with an age of (60.3±9.9) years and 7 325 males (39.1%). The comorbidity rate of hypertension, diabetes, and dyslipidemia was 6.7% (1 256/18 758), and the standardized prevalence rate was 5.4%. The comorbidity rate increased with age (P<0.001), which was higher in women than in men, and more significant in urban areas than in rural areas (all P<0.001). The comorbidity of "three diseases" accounted for 39.3% (1 256/3 198), 18.7% (1 256/6 710), and 11.8% (1 256/10 653) in patients with diabetes, dyslipidemia, and hypertension, respectively. With a follow-up of (4.3±0.6) years, 463 people died of cardiovascular disease. The mortality rate of cardiovascular disease in the comorbidity of hypertension, diabetes, and dyslipidemia was 8.74/1 000 person-years. After adjusting potential confounders, Cox proportional hazard regression model analysis showed that compared with normal individuals, the hazard ratio of cardiovascular disease mortality in patients with the "three diseases" was 2.55 (95% CI: 1.63-3.99). Conclusion:The prevalence of comorbidity of hypertension, diabetes, and dyslipidemia among residents aged≥40 in Liaoning Province was relatively high, and the risk of cardiovascular disease mortality in patients with the "three diseases" was increased.

ObjectiveTo investigate the influence of triglyceride （TG）/high-density lipoprotein cholesterol （HDL-C） ratio on the onset of primary liver cancer. MethodsA prospective cohort study was conducted. Physical examination data were collected from 99 750 cases of on-the-job and retired employees of Kailuan Group who participated health examination from July 2006 to December 2007， and they were followed up till December 31， 2021 to observe the onset of primary liver cancer. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups； the chi-square test was used for comparison of categorical data between groups. According to the tertiles of TG/HDL-C ratio， the subjects were divided into Q1， Q2， and Q3 groups， and the incidence density of primary liver cancer was calculated for each group. The Kaplan-Meier method was used to calculate the cumulative incidence rate of primary liver cancer in each group， and the log-rank test was used to compare the difference in cumulative incidence rate between groups. The Cox proportional hazards model was used to analyze the influence of TG/HDL-C ratio on the onset of primary liver cancer. ResultsThere were significant differences between the three groups in age， proportion of male subjects， waist circumference， body mass index， fasting blood glucose， systolic pressure， diastolic pressure， triglyceride， total cholesterol， HDL-C， low-density lipoprotein cholesterol， alanine aminotransferase， high-sensitivity C-reactive protein， chronic liver diseases， hypertension， diabetes， the family history of malignant tumor， drinking， smoking， physical exercise， and educational level （P<0.05）. During the mean follow-up time of 14.06±2.71 years， there were 484 cases of new-onset liver cancer， among whom there were 446 male subjects and 38 female subjects. The incidence density of primary liver cancer was 0.39/1 000 person-years in the Q1 group， 0.35/1 000 person-years in the Q2 group， and 0.30/1 000 person-years in the Q3 group， and the cumulative incidence rates of primary liver cancer in the three groups were 6.03‰， 5.28‰， and 4.49‰， respectively， with a significant difference between the three groups based on the long-rank test （χ²=6.06， P=0.048）. After adjustment for the confounding factors considered， the Cox proportional hazards model showed that compared with the Q3 group， the Q1 group had a hazard ratio of 2.04 （95% confidence interval ［CI］： 1.61‍ ‍—‍ ‍2.58， P_{for trend}<0.05）， and the Q2 group had a hazard ratio of 1.53 （95%CI： 1.21‍ ‍—‍ ‍1.92， P_{for trend}<0.05）. ConclusionThe reduction in TG/HDL-C ratio is associated with an increase in the rask of primary liver cancer， especially in people with chronic liver diseases.

Objective:To investigate the prevalence of diabetes in the elderly aged ≥60 years in Liaoning Province from 2017 to 2019 and analyze the impact of blood glucose control on all-cause mortality and cardiovascular disease (CVD) mortality.Methods:A survey was conducted in the elderly aged ≥60 years in Liaoning from 2017 to 2019 to collect the information about the prevalence of diabetes and other chronic diseases in the diabetes patients. The mortality of the enrolled subjects was investigated in September 2023. Cox proportional hazards regression models were used to estimate the association between blood glucose control in the elderly with diabetes and the risks of all-cause mortality and CVD mortality.Results:The crude prevalence of diabetes in the elderly aged ≥60 years was 20.2% (2 014/9 958) in Liaoning from 2017 to 2019, and the standardized prevalence rate was 19.9%. The prevalence rates of hypertension, dyslipidemia, and overweight/obesity in the diabetes patients were 77.0%, 51.7%, and 67.5% respectively. The median follow-up time was 5.5 years, and the all-cause mortality and CVD mortality rates in the diabetes patients were 244.3/10 000 person-years and 142.9/10 000 person-years, respectively. The results of the Cox proportional hazards regression model analysis showed that compared with non-diabetic individuals, diabetes patients had an increased risk of all-cause mortality by 1.68 times [hazard ratio ( HR)=1.68, 95% CI: 1.44-1.94] and an increased risk of CVD mortality by 1.56 times ( HR=1.56, 95% CI: 1.29-1.89). The differences in risks of all-cause mortality and CVD mortality between the diabetes patients with normal fasting blood glucose and glycated hemoglobin levels and people without diabetes were not significant (all P>0.05). The failure to meet either the FPG or HbA1c target increased the risk of all-cause mortality (all P<0.05). For individuals who failed to meet the HbA1c target, there was an increased risk of CVD mortality (all P<0.05). Conclusions:The comorbidity rate of chronic diseases was higher in the elderly with diabetes than in the elderly without diabetes in Liaoning. Elderly diabetes patients can benefit from good blood glucose control.

Primary hypertrophic osteoarthropathy(PHO)is a rare disease also known as pachydermo-periostosis.We reported a painless case whose diagnosis was confirmed by genetic test.A 24-year-old male presented a series of symptoms that first began at 14.He suffered from progressive clubbed-fingers accompa-nied by swelling of the wrist and ankle joints.Facial skin concentric thickening and alar nose broadening ap-peared simultaneously and increased progressively.He was also prone to acne and hyperhidrosis.X-rays showed thickening of the metacarpal and phalangeal bones,as well as symmetrical periosteal ossification of both the tibia and fibula.Clinical diagnosis of PHO is difficult because of the variable features.With acromeg-aly excluded,the diagnosis was confirmed by a genetic test.Whole exome sequencing revealed a heterozygous SLCO2A1 c.611C＞T(p.Ser204Lue)and SLCO2A1 c.1602C＞A(p.Asn534Lys)mutation from each par-ent.It suggests that primary hypertrophic osteoarthropathy should be considered for young limb hypertrophic patients especially when periosteal thickening signs were showed in X-ray.A confirmatory diagnosis can be made through the genetic test.

Cognitive frailty is a reversible neurodegeneration, and its early identification and prevention are crucial. This paper summarizes the current situation, risk factors, and risk prediction models of cognitive frailty in elderly patients with chronic diseases, aiming to provide a reference for clinical medical and nursing staff to identify the risk of cognitive frailty in elderly patients with chronic diseases as early as possible and formulate intervention measures.

This article reported a survived case of amniotic band syndrome (ABS) following fetal reduction by radiofrequency ablation. The woman conceived monochorionic diamniotic twin pregnancy spontaneously. Prenatal ultrasound at 24 weeks of gestation indicated twin-twin transfusion syndrome (stage Ⅲ), and radiofrequency ablation for fetal reduction was successfully performed after formal consent. At 28 +6 weeks, ultrasound reexamination revealed significant edema in the left foot of the fetus, with banding around the ankle, as well as the strangulation mark and narrowing rings. Fetal ABS (ⅡB stage) was diagnosed after multidisciplinary consultation. An immediate emergency cesarean section was performed and a live male baby was born. A thin amniotic band could be seen wrapping around the left ankle of the newborn for several rounds, with obvious strangulation marks about 1 cm deep into the skin, and significant edema on the dorsum and sole of the foot, and the submalleolus area. The amniotic band was released at once, and the edema faded gradually after surgery. After a follow-up of 28 days, the lower limbs of the newborn became normal.

PIK3CA-related overgrowth spectrum (PROS) is a rare condition characterized by disproportionate overgrowth of head, neck, trunk, or extremity, caused by PIK3CA gene mutation. This condition has negative impact on the physical appearance, functions, and psychosocial well-being of the patients. The condition causes social and economic burden, too. The gold standard for the diagnosis of PROS is the genetic testing using somatic tissue, but detecting low-level mosaic mutations of PIK3CA gene remains a challenge. There is no specific treatment now. Supportive management including surgery and other interventions have limited effects in improving cosmetic outcome and functions. Multidisciplinary collaboration is the key to the success of managing PROS. Targeted gene therapy is promising in improving the outcome for patients with severe PROS. Patients diagnosed with negative genetics test by the clinical measures are often ineligible for novel gene therapy. This article reviews the clinical manifestations, diagnosis, and treatments of PROS, aiming to improve the current understanding of this rare condition.