Protein arginine methyltransferase 5 (PRMT5) acts as an oncogene in liver cancer, yet its roles and in-depth molecular mechanisms within the liver cancer immune microenvironment remain mostly undefined. Here, we demonstrated that disruption of tumor-intrinsic PRMT5 enhances CD8⁺ T-cell-mediated antitumor immunity both in vivo and in vitro. Further experiments verified that this effect is achieved through downregulation of the inhibitory immune checkpoint molecule, fibrinogen-like protein 1 (FGL1). Mechanistically, PRMT5 catalyzed symmetric dimethylation of transcription factor 12 (TCF12) at arginine 554 (R554), prompting the binding of TCF12 to FGL1 promoter region, which transcriptionally activated FGL1 in tumor cells. Methylation deficiency at TCF12-R554 residue downregulated FGL1 expression, which promoted CD8⁺ T-cell-mediated antitumor immunity. Notably, combining the PRMT5 methyltransferase inhibitor GSK591 with PD-L1 blockade efficiently inhibited liver cancer growth and improved overall survival in mice. Collectively, our findings reveal the immunosuppressive role and mechanism of PRMT5 in liver cancer and highlight that targeting PRMT5 could boost checkpoint immunotherapy efficacy.

Metabolic reprogramming plays a central role in tumors. However, the key drivers modulating reprogramming of gluconeogenesis/lipogenesis are poorly understood. Here, we try to identify the mechanism by which histone acetyltransferase 1 (HAT1) confers reprogramming of gluconeogenesis/lipogenesis in liver cancer. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl₄)-induced hepatocarcinogenesis was hardly observed in HAT1-knockout mice. Multi-omics identified that HAT1 modulated gluconeogenesis and lipogenesis in liver. Protein phosphatase 2 scaffold subunit alpha (PPP2R1A) promoted gluconeogenesis and inhibited lipogenesis by phosphoenolpyruvate carboxykinase 1 (PCK1) serine 90 dephosphorylation to suppress the tumor growth. HAT1 succinylated PPP2R1A at lysine 541 (K541) to block the assembly of protein phosphatase 2A (PP2A) holoenzyme and interaction with PCK1, resulting in the depression of dephosphorylation of PCK1. HAT1-succinylated PPP2R1A contributed to the remodeling of gluconeogenesis/lipogenesis by PCK1 serine 90 phosphorylation, leading to the inhibition of gluconeogenic enzyme activity and activating sterol regulatory element-binding protein 1 (SREBP1) nuclear accumulation-induced lipogenesis gene expression, which enhanced the tumor growth. In conclusion, succinylation of PPP2R1A lysine 541 by HAT1 converses the role in modulation of gluconeogenesis/lipogenesis remodeling through PCK1 S90 phosphorylation to support liver cancer. Our finding provides new insights into the mechanism by which post-translational modifications (PTMs) confer the conversion of tumor suppressor function to oncogene.

BACKGROUND: The STAR (Scientific, Transparent, and Applicable Rankings) working group conducts regular evaluations of Chinese guidelines and consensus statements. This study gathered insights from STAR working group members using qualitative interviews. METHODS: From March to August 2023, members of the STAR specialist committees were interviewed using semi-structured interview outline. The interviewees were selected through purpose-based sampling. Subject analysis was employed to summarize the findings. RESULTS: We conducted interviews with 37 members from 36 committees and summarized the contents into four main themes and 16 specific topics. The value of STAR in enhancing the development and selection of high-quality guidelines in China was commonly mentioned. Challenges identified included the lack of resources and suboptimal organizational structures, collaboration, and evaluation efficiency. Suggestions for the STAR tool included developing extensions for different guideline types, adjusting certain items, and better covering guideline applicability. The promotion of STAR and the consideration of an international committee for global outreach were also highlighted. CONCLUSION STAR has exerted a substantial influence on the evaluation of Chinese guidelines, and the insights gained from interviews offer valuable directions for its further enhancement.
Humans ; China ; Qualitative Research ; Practice Guidelines as Topic ; Interviews as Topic

Purpose To investigate the clinicopathological features,diagnosis,differential diagnosis,immuno-phenotype,and prognosis of ovarian mature cystic teratoma(MCT)with an associated mucinous tumor(MT).Meth-ods Clinicopathological and follow-up data from 14 cases of MCT with MT were retrospectively analyzed and supple-mented with a literature review.Results 14 patients' ages ranged from 21-70 years,with a median age of 33 years.Tumors were located in the left ovary(4 cases),right ovary(9 cases),or bilaterally(1 case).The tumors,cystic or cyst-solid,measured 6.0-24.0 cm in maximum diameter(mean:11.7±5.7 cm).Histologically,the MT compo-nents were classified as mucinous cystadenoma(MCA)in 9 cases,borderline mucinous cystadenoma(MBT)in 4 ca-ses,and mucinous adenocarcinoma(MAC)in 1 case.Microscopically,MCT elements from multiple germ layers were identified in 13 cases,with one case showing only mature thyroid tissue.The mucinous epithelium in MCA showed no significant atypia.Mucinous epithelial proliferation accounted＞10％in MBT.MAC demonstrated moderate-to-severe atypia and invasive growth.Immunohistochemically,the MT epithelium was frequently positive for CK7(6/7),CK20(4/5),CDX2(5/6),Villin(4/4),SATB2(3/3),MUC2(2/3),MUC5AC(2/2),MUC6(1/1),and PAX-8(2/7),while negative for ER(6/6),PR(5/5),and WT-1(5/5).The Ki-67 proliferation index was low(＜5％)in 6 cases and high(50％)in one case.During a follow-up of 9-110 months,patients with MCT associated with MCA or MBT were alive without recurrence.The patient with MCT and MAC experienced recurrence 34 months after surgery.Conclusion Ovarian MCT with MT is rare and lacks specific clinical manifestations.Pathological examina-tion combined with immunophenotyping is essential for accurate diagnosis and classification.

Purpose To investigate the clinicopathological features,diagnosis,differential diagnosis,immuno-phenotype,and prognosis of ovarian mature cystic teratoma(MCT)with an associated mucinous tumor(MT).Meth-ods Clinicopathological and follow-up data from 14 cases of MCT with MT were retrospectively analyzed and supple-mented with a literature review.Results 14 patients' ages ranged from 21-70 years,with a median age of 33 years.Tumors were located in the left ovary(4 cases),right ovary(9 cases),or bilaterally(1 case).The tumors,cystic or cyst-solid,measured 6.0-24.0 cm in maximum diameter(mean:11.7±5.7 cm).Histologically,the MT compo-nents were classified as mucinous cystadenoma(MCA)in 9 cases,borderline mucinous cystadenoma(MBT)in 4 ca-ses,and mucinous adenocarcinoma(MAC)in 1 case.Microscopically,MCT elements from multiple germ layers were identified in 13 cases,with one case showing only mature thyroid tissue.The mucinous epithelium in MCA showed no significant atypia.Mucinous epithelial proliferation accounted＞10％in MBT.MAC demonstrated moderate-to-severe atypia and invasive growth.Immunohistochemically,the MT epithelium was frequently positive for CK7(6/7),CK20(4/5),CDX2(5/6),Villin(4/4),SATB2(3/3),MUC2(2/3),MUC5AC(2/2),MUC6(1/1),and PAX-8(2/7),while negative for ER(6/6),PR(5/5),and WT-1(5/5).The Ki-67 proliferation index was low(＜5％)in 6 cases and high(50％)in one case.During a follow-up of 9-110 months,patients with MCT associated with MCA or MBT were alive without recurrence.The patient with MCT and MAC experienced recurrence 34 months after surgery.Conclusion Ovarian MCT with MT is rare and lacks specific clinical manifestations.Pathological examina-tion combined with immunophenotyping is essential for accurate diagnosis and classification.

  Objective  To promote the development of high-quality health standards in China and summarize the characteristics of global health standards management systems and development processes.  Methods  We conducted a systematic search of relevant databases and the websites of standardization institutions. A descriptive method was used to analyze the basic characteristics of the standard management systems and development processes.  Results  The majority of the investigated countries and organizations primarily implement voluntary standards, with the exception of Chinese and the European Committee for Standardization that enforce compulsory standards. All countries and organizations have health standards at the national, group, and enterprise levels. In China and Japan, standards authorities are subordinate to the government, while in other countries or organizations, they operate as independent civil societies. The development process for health standards generally involves five stages: "Project/Proposal → Draft → Enquiry → Review → Publication". However, the specific steps in the development of health standards vary across different countries and organizations. Furthermore, China ranks high in the number of both standards and health standards issued, but the proportion of health standards is only 2.06%.  Conclusions  There are significant differences between China and other countries in terms of the management system and development process of health standards. To promote the management and development of high-quality health standards in China, we recommend promoting the coordination mechanism for standard development, increasing efforts to publicize standards and evaluate the implementation effect, strengthening the construction of personnel for the development of health standards, optimizing the efficiency of standard development and improving the internationalization level of health standards.

Objective:To explore the incidence and risk factors of parastomal hernia after colostomy.Methods:The retrospective cohort study was conducted. The clinicopathological data of 145 patients undergoing colostomy in Xinxiang Central Hospital from January 2015 to January 2019 were collected. There were 86 males and 59 females, aged(59±11) years. Patients received pelvic and abdominal computed tomography once every 6 months after colostomy to detect the occurrence of parastomal hernia. Measurement data with normal distribution were represented as Mean± SD, and the independent sample t test was used for comparison between groups. Measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers, and chi-square test or Fisher exact probability was used for comparison between groups. Kaplan-Meier method was used to analyze the cumulative annual incidence of parastomal hernia. Logarithmic rank test was used to analyze the cumulative incidence based on clinical variables. COX proportional hazard regression model was used for univariate and multivariate analyses. Results:(1) Incidence of parastomal hernia after colostomy. All the 145 patients were followed up for 86(range, 60?108)months after colostomy, of which 46 cases had parastomal hernia and 99 cases had no parastomal hernia. There were significant differences in gender, age, body mass index (BMI) and chronic liver disease between patients with and without parastomal hernia after colostomy ( χ2=23.28, t=13.27, χ2=6.17, 5.82, P<0.05). (2) Annual cumulative incidence of parastomal hernia after colostomy. The 1-, 3-, and 5-year cumulative incidence of parastromal hernia after colostomy was 8.5%, 26.4% and 42.7%, respectively. When the follow-up time is more than 5 years, the incidence of parastromal hernia tended to be stable. The 5-year incidence of parastomal hernia after colostomy in female patients was higher than that in male patients (70.7% vs 20.3%, χ2=12.37, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients≥60 years old was higher than that in patients under 60 years old (49.8% vs 20.0%, χ2=10.52, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients with BMI >28 kg/m 2 was higher than that in patients with BMI ≤28 kg/m 2 (55.3% vs 33.2%, χ2=11.76, P<0.05). The 5-year incidence of parastomal hernia after colostomy in patients with chronic liver disease was higher than that in patients with non-chronic liver disease (45.2% vs 32.4%, χ2=15.32, P<0.05). (3) Analysis of risk factors for parastomal hernia after colostomy. Results of multivariate analysis showed that female, age >60 years old, BMI ≥28 kg/m 2 and chronic liver disease were independent risk factors for parastomal hernia after colostomy ( hazard ratio=2.70, 2.51, 1.85, 5.88, 95% confidence intervals as 1.39?6.74, 1.01?4.59, 1.02?4.87, 1.05?8.24, P<0.05). Conclusions:The incidence of parastomal hernia after colostomy is increasing year by year, and tends to be stable after 5 years. Female, age >60 years old, BMI≥28 kg/m 2, and chronic liver disease are independent risk factors for parastomal hernia after colostomy.

Objective To study the the expression of cytokeratin 5/6(CK5/6)and cell proliferation an-tigen(Ki-67)in apocrine triple-negative breast carcinoma(ATNBC)and their relationship with clinicopatho-logical features and prognosis.Methods Twenty-one patients with pathologically diagnosed invasive apocrine breast cancer and negative estrogen receptor(ER),progesterone receptor(PR)and human epidermal growth factor-2(Her-2)in this hospital were selected as the ATNBC group,Twenty-two cases in non-ATNBC(NATNBC)were randomly selected as negative control(NATNBC group).The clinical pathological data and follow-up data of all patients were collected,and the expressions of CK5/6 and Ki-67,as well as their relation-ship with clinicopathological characteristics was analyzed.The prognosis in the patients with ATNBC was ana-lyzed.Results There were statistically significant differences in age(P＜0.001),age distribution(P=0.001),histological grading(P＜0.001),and distant metastasis(P=0.020)between the ATNBC group and the NATNBC group(P=0.020).There were 7 cases(33.33％)of CK5/6 positive expression in the ATNBC group and 17 cases(80.95％)in NATNBC group.There was statistically significant difference in the positive expression rate of CK5/6 between the ATNBC group and NATNBC group(P＜0.05).There were 3 cases(14.29％)of Ki-67 high proliferation in the ATNBC group and 17 cases(77.27％)in the NATNBC group.The high proliferation rates of Ki-67 had statistically significant difference between the ATNBC group and NATNBC group(P＜0.05).The positive expression rate of CK5/6 was correlated with the tumor sites and lymph node metastasis in ATNBC patients(P＜0.05).The high proliferation rate of Ki-67 was correlated with nerve invasion in ATNBC patients(P＜0.05).The survival analysis showed that there was statistically significant difference in the 5 years disease-free survival(DFS)rate between the ATNBC group and NATNBC group(P＜0.05).Conclusion ATNBC has its unique clinicopathological features,CK5/6 is less expressed in ATN-BC,the high proliferation of Ki-67 is also less,and the prognosis of ATNBC is better than that of NATNBC.

Objective : To investigate the occupational exposure to blood-borne pathogens among medical workers in a tertiary general hospital in Hangzhou City from 2010 to 2022, so as to provide the evidence for improving occupational protective measures among medical workers. Methods: The registration and follow-up data of occupational exposure to blood-borne pathogens among medical workers from 2010 to 2022 were collected from the blood-borne occupational exposure monitoring system in a tertiary general hospital in Hangzhou City. The population distribution, occurrence, protection and disposal of occupational exposure to blood-borne pathogens were analyzed using a descriptive epidemiological method. Results: A total of 1 230 cases were reported with occupational exposure to blood-borne pathogens among medical workers in the study hospital from 2010 to 2022, with the highest incidence in 2021 (4.67%) and the lowest incidence in 2010 (0.99%). The incidence of occupational exposure to blood-borne pathogens appeared a tendency forwards a rise from 2010 to 2022 (P<0.05). Of all cases with occupational exposure to blood-borne pathogens, there were 934 women (75.93%), 656 nurses (53.33%), and 514 cases with working experiences of one year and shorter (41.79%). Hand was the predominant site of occupational exposure to blood-borne pathogens (92.03%) and ward was the predominant place of exposure (35.37%), while scalp needle was the predominant mode of exposure (32.68%), and removal of needle was the predominant procedure of exposure (32.36%). A total of 1 106 cases were tested for the blood-borne pathogens in the exposure sources, and 448 cases were tested positive for blood-borne pathogens, with a detection rate of 40.51%. Hepatitis B virus, treponema pallidum and human immunodeficiency virus were the three most common blood-borne pathogens, and there were 739 cases (60.08%) with personal protective equipment during exposure. Following the follow-up surveillance for more than 6 months post-exposure, no infections occurred. Conclusions Junior nurses and hand exposure were predominant among medical workers with occupational exposure to blood-borne pathogens in the study hospital from 2010 to 2022, and hepatitis B virus was the predominant blood-borne pathogen. No post-exposure infections occurred.

OBJECTIVE: To explore the clinical features and genetic basis for a Chinese pedigree diagnosed with congenital glycosylation disease (CGD). METHODS: Clinical manifestations of two brothers were analyzed. Whole exome sequencing was carried out for the sib pair. Suspected variants were verified by Sanger sequencing. RESULTS: Both the proband and her younger brother were found to carry compound heterozygous variants of the PMM2 gene, which included a known pathogenic mutation of c.395T>C (p.I132T) and a previously unreported c.448-1(delAG) in the 5' end of exon 6 of the gene. CONCLUSION The compound heterozygous variants of the PMM2 gene probably underlay the CGD in the sib pair.
Asians/genetics* ; China ; Female ; Glycosylation ; Humans ; Male ; Mutation ; Pedigree ; Whole Exome Sequencing