OBJECTIVES: To reprogram human placental fibroblasts (HPFs) into chemically induced epithelioid-like cells (ciEP-Ls) using a combination of small-molecule compounds. METHODS: HPFs cultured under normoxic conditions were identified using immunofluorescence assay, PCR and chromosomal karyotyping. Under hypoxic conditions (37 ℃, 5% O₂), HPFs were cultured in a medium containing small-molecule compounds C6TSEDRVAJZ (CHIR99021, 616452, TTNPB, SAG, EPZ5676, DZNep, Ruxolitinib, VTP50469, Afuresertib, JNK-IN-8, and EZM0414), and the cell morphology was observed daily. The expression levels of epithelial cell markers in the induced cells were detected by immunofluorescence, Western blotting and PCR. Chromosomal karyotyping of the induced cells was performed and the induction efficiency was calculated. RESULTS: Before induction, HPFs showed positive expressions of fibroblast surface markers CD34 and vimentin and were negative for epithelial surface markers. PCR results showed high expressions of fibroblast-specific genes S100A4 and COL1A1 in HPFs with a normal human diploid karyotype. After one day of induction, the HPFs underwent morphological changes from a multinodular spindle shape to a round or polygonal shape, which was morphologically characteristic of ciEP-Ls. On day 4 of induction, the cells exhibited high expressions of the epithelial cell markers E-cadherin and Lin28A. RT-qPCR results also showed that the cells expressed the epithelial markers Smad3, GLi3, PAX8, WT1, KRT19, and KRT18 with significantly down-regulated expressions of all the fibroblast surface markers and a normal human diploid karyotype. The reprogramming efficiency of HPFs into ciEP-Ls ranged from (64.53±2.8)% to (68.10±3.6)%. CONCLUSIONS The small-molecule compound combination C6TSEDRVAJZ is capable of inducing HPFs into ciEP-Ls under hypoxic conditions with a high induction efficiency.
Humans ; Fibroblasts/drug effects* ; Pregnancy ; Female ; Cell Differentiation/drug effects* ; Pyrimidines/pharmacology* ; Placenta/cytology* ; Cells, Cultured ; Pyridines/pharmacology* ; Pyrazoles/pharmacology* ; Epithelial Cells/cytology*

Radiochemotherapy-induced oral mucositis (OM) is a common oral complication in patients with tumors following head and neck radiotherapy or chemotherapy. Erosion and ulcers are the main features of OM that seriously affect the quality of life of patients and even the progress of tumor treatment. To date, differences in clinical prevention and treatment plans for OM have been noted among doctors of various specialties, which has increased the uncertainty of treatment effects. On the basis of current research evidence, this expert consensus outlines risk factors, clinical manifestations, clinical grading, ancillary examinations, diagnostic basis, prevention and treatment strategies and efficacy indicators for OM. In addition to strategies such as basic oral care, anti-inflammatory and analgesic agents, anti-infective agents, pro-healing agents, and photobiotherapy recommended in previous guidelines, we also emphasize the role of traditional Chinese medicine in OM prevention and treatment. This expert consensus aims to provide references and guidance for dental physicians and oncologists in formulating strategies for OM prevention, diagnosis, and treatment, standardizing clinical practice, reducing OM occurrence, promoting healing, and improving the quality of life of patients.
Humans ; Chemoradiotherapy/adverse effects* ; Consensus ; Risk Factors ; Stomatitis/etiology*

Predatory bacteriophages have evolved a vast array of depolymerases for bacteria capture and deprotection. These depolymerases are enzymes responsible for degrading diverse bacterial surface carbohydrates. They are exploited as antibiofilm agents and antimicrobial adjuvants while rarely inducing bacterial resistance, making them an invaluable asset in the era of antibiotic resistance. Numerous depolymerases have been investigated preclinically, with evidence indicating that depolymerases with appropriate dose regimens can safely and effectively combat different multidrug-resistant pathogens in animal infection models. Additionally, some formulation approaches have been developed for improved stability and activity of depolymerases. However, depolymerase formulation is limited to liquid dosage form and remains in its infancy, posing a significant hurdle to their clinical translation, compounded by challenges in their applicability and manufacturing. Future development must address these obstacles for clinical utility. Here, after unravelling the history, diversity, and therapeutic use of depolymerases, we summarized the preclinical efficacy and existing formulation findings of recombinant depolymerases. Finally, the challenges and perspectives of depolymerases as therapeutics for humans were assessed to provide insights for their further development.

Objective To compare the clinical effects of arthroscopically-assisted reduction and internal fixation(ARIF)combined with enhanced recovery after surgery(ERAS)and open reduction and internal fixation surgery(ORIF)in the treatment of posterior lateral tibial plateau fractures.Methods Seventy patients with posterior lateral tibial plateau fractures in the Department of Orthopaedics,Xuzhou Central Hospital,from January 2020 to November 2022 were retrospectively selected and divided into ARIF group(with ERAS,n=32)and ORIF group(without ERAS,n=38)according to the treatment methods.All patients were evaluated for fracture type by imaging examination after admission.The operation time,length of hospital stay,early postoperative pain score(evaluated by visual analogue scale[VAS]),knee joint function(evaluated by hospital for special surgery[HSS]scale)at 3 months and thigh circumference difference at 6 months postoperatively were compared between the two groups.Results The operation time in the ARIF group was significantly shorter than that in the ORIF group([67.84±9.89]min vs[85.16±9.18]min,P＜0.001),and the length of hospital stay was significantly shorter in the ARIF group([7.13±1.41]d vs[8.74±1.84]d,P＜0.001).On the third day after operation,the VAS score in the ARIF group was significantly lower than that in the ORIF group([4.00±1.44]vs[5.39±1.24],P＜0.001).ARIF group had better joint function than ORIF group 3 months after operation,and the difference of 10 cm thigh circumference on patella in ARIF group was smaller than that in ORIF group 6 months after operation.Conclusions Compared to ORIF,patients with posterior lateral tibial plateau fractures treated with ARIF combined with ERAS showed faster postoperative recovery,shorter hospital stay,and more precise clinical efficacy.

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

Postzygotic mutations are acquired in normal tissues throughout an individual's lifetime and hold clues for identifying mutagenic factors.Here,we investigated postzygotic mutation spectra of healthy individuals using optimized ultra-deep exome sequencing of the time-series samples from the same volunteer as well as the samples from different individuals.In blood,sperm,and muscle cells,we resolved three common types of mutational signatures.Signatures A and B represent clock-like mutational processes,and the polymorphisms of epigenetic regulation genes influence the pro-portion of signature B in mutation profiles.Notably,signature C,characterized by C＞T transitions at GpCpN sites,tends to be a feature of diverse normal tissues.Mutations of this type are likely to occur early during embryonic development,supported by their relatively high allelic frequencies,presence in multiple tissues,and decrease in occurrence with age.Almost none of the public datasets for tumors feature this signature,except for 19.6％of samples of clear cell renal cell carcinoma with increased activation of the hypoxia-inducible factor 1(HIF-1)signaling pathway.Moreover,the accumulation of signature C in the mutation profile was accelerated in a human embryonic stem cell line with drug-induced activation of HIF-1α.Thus,embryonic hypoxia may explain this novel signature across multiple normal tissues.Our study suggests that hypoxic condition in an early stage of embryonic development is a crucial factor inducing C＞T transitions at GpCpN sites;and indi-viduals'genetic background may also influence their postzygotic mutation profiles.

Objective: To investigate the prevalence and associated factors of eating out among children and adolescents aged 6-17 in Hebei Province, and to explore the association between eating out and overweight/obesity. Methods: Data came from Children and Nurse Nutrition Health Monitoring of China during 2016-2017. Questionnaire surveys and anthropometric measures was conducted among 3 330 children aged 6-17 in 12 survey sites. Multivariate Logistics stepwise regression model was used to analyze the influencing factors of eating out and the relationship between eating out and overweight/obesity. Results: The proportion of eating out was 16.19%, and the rate of overweight and obesity was 29.43%. Multivariate analysis showed that the older children (junior high school students:OR=1.36; high school students:OR=3.57, both P<0.05) and adolescents from highincome families (10 000~<20 000 CNY:OR=1.48; ≥20 000 CNY:OR=2.93, both P<0.05) were more likely to eat out. Children and adolescents living in rural areas (OR=0.20, P<0.01), nononlychild (OR=0.76, P=0.02), day school students (OR=0.21, P<0.01), and the primary caregivers of the elderly (OR=0.69, P=0.03) were less likely to eat out. In addition, eating out was statistically associated with an increased risk of overweight and obesity (OR=1.31, P<0.01). Conclusion Eating out is common among children and adolescents aged 6-17 in Hebei Province. Residency, age, household income, onechild family, boarding and and eating out behaviors of primary caregivers are associated with eating out among children and adolescents. Eating out may increase the risk of overweight/obesity in children.

To unravel the genetic mechanisms of disease and physiological traits, it requires comprehensive sequencing analysis of large sample size in Chinese populations. Here, we report the primary results of the Chinese Academy of Sciences Precision Medicine Initiative (CASPMI) project launched by the Chinese Academy of Sciences, including the de novo assembly of a northern Han reference genome (NH1.0) and whole genome analyses of 597 healthy people coming from most areas in China. Given the two existing reference genomes for Han Chinese (YH and HX1) were both from the south, we constructed NH1.0, a new reference genome from a northern individual, by combining the sequencing strategies of PacBio, 10× Genomics, and Bionano mapping. Using this integrated approach, we obtained an N50 scaffold size of 46.63 Mb for the NH1.0 genome and performed a comparative genome analysis of NH1.0 with YH and HX1. In order to generate a genomic variation map of Chinese populations, we performed the whole-genome sequencing of 597 participants and identified 24.85 million (M) single nucleotide variants (SNVs), 3.85 M small indels, and 106,382 structural variations. In the association analysis with collected phenotypes, we found that the T allele of rs1549293 in KAT8 significantly correlated with the waist circumference in northern Han males. Moreover, significant genetic diversity in MTHFR, TCN2, FADS1, and FADS2, which associate with circulating folate, vitamin B12, or lipid metabolism, was observed between northerners and southerners. Especially, for the homocysteine-increasing allele of rs1801133 (MTHFR 677T), we hypothesize that there exists a "comfort" zone for a high frequency of 677T between latitudes of 35-45 degree North. Taken together, our results provide a high-quality northern Han reference genome and novel population-specific data sets of genetic variants for use in the personalized and precision medicine.

Objective To summarize our experience with surgical management of renal neoplasm involving inferoir veno cava.Methods We review the data of 115 patients,including 74 male patients and 41 female patients,with renal neoplasm involving venous system between March 1993 and December 2015.The mean age was 52 years old,ranging 22 to 77 years old.The tumor was found in right side in 77 cases and left side in 38 cases.There were 15 patients (13.0％) with renal vein thrombus,38 (33.1％) with infrahepatic thrombus,29 (25.2％) with low retrohepatic thrombus,20 (17.4％) with high retrohepatic thrombus,and 13 (11.3％) with supradiaphragmatic thrombus.The mean age was 52 years old,ranging 22 to 77 years old.The tumor was found in right side in 77 cases and left side in 38 cases.All patients accepted the radical nephrectomy.Primary outcomes were overall survival (OS),and cancer special survival (CSS) in patients with renal cell carcinoma (RCC) estimated by Kaplan-Meier method.Secondary outcome included operative and oncological features,past-operative complications and hospital mortality.Cox proportional hazard model was used to univariate and multivariate analysis for risk factor impacting on OS of RCC patients.Results Complete resections of renal neoplasm with tumor thrombus were achieved in 113 patients (98.3％),2 patients died intraoperatively due to the dropping of thrombus.Postoperative complication rate was 16.8％.Hospital mortality was 2.6％.Mean follow-up interval was 48 months.OS rates at 5-,and 10-year in RCC patients were 66.5％,and 61.8％,respectively.Metastasis was an independent risk factor affecting on OS (P =0.000).However,the level of thrombus was not an risk factor affecting the prognosis.Conclusions Radical resection of renal tumor and caval thrombus is an effective treatment for prolonging survival in patients with RCC extending into venous system.Retrohepatic caval tumor thrombus below or above the main hepatic vein should be dichotomized and managed respectively with diverse techniques.Metastatic rather than the level of thrombus was a risk factor impacting on RCC patient survival.

This study investigated the prevalence and risk factors of urinary incontinence (UI) among perimenopausal women in Wuhan. A cross-sectional survey was performed on 1067 women aged 40-65 years sampled in Wuhan urban area from April to October 2014. Information about demographic characteristics, menstruation, parity and UI symptoms was collected using a questionnaire. The data were evaluated by Chi-square test and multiple Logistic regression analysis. The prevalence rate of UI was 37.2%, with stress UI (32.2%) being more prevalent than urgency UI (21.6%) and mixed UI (16.6%). 31.2% women with UI stated that UI had negative impact on their life. Risk factors for UI included menstrual disorder, menopause, overweight, perineal laceration, atrophic vaginitis, constipation and pelvic organ prolapse. Appropriate investigation apropos the factors associated with UI should be performed to diminish its impact on women's life.
Adult ; Aged ; Atrophic Vaginitis ; epidemiology ; physiopathology ; Constipation ; epidemiology ; physiopathology ; Female ; Humans ; Lacerations ; epidemiology ; physiopathology ; Menstrual Cycle ; physiology ; Middle Aged ; Overweight ; epidemiology ; physiopathology ; Pelvic Organ Prolapse ; epidemiology ; physiopathology ; Perimenopause ; physiology ; Pregnancy ; Risk Factors ; Surveys and Questionnaires ; Urinary Incontinence ; epidemiology ; physiopathology