Hepatic ischemia/reperfusion injury (IRI) remains a critical complication contributing to graft dysfunction following liver surgery. As part of an ongoing search for hepatoprotective natural products, five previously unreported homoadamantane-type polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperhomanoons A-E (1-5), and one known analog, hypersampsone O (6), were isolated from Hypericum patulum. Among these, compound 6 demonstrated potent protective effects against CoCl₂-induced hypoxic injury in hepatocytes. Furthermore, in a murine model of hepatic IRI induced by vascular occlusion, pretreatment with 6 markedly alleviated liver damage and reduced hepatocyte apoptosis. This study is the first to identify PPAPs as promising scaffolds for the development of therapeutic agents targeting hepatic IRI, underscoring their potential as lead compounds in drug discovery efforts for ischemic liver diseases.
Reperfusion Injury/prevention & control* ; Animals ; Hypericum/chemistry* ; Phloroglucinol/administration & dosage* ; Mice ; Humans ; Male ; Liver/blood supply* ; Apoptosis/drug effects* ; Molecular Structure ; Protective Agents/pharmacology* ; Hepatocytes/drug effects* ; Mice, Inbred C57BL ; Liver Diseases/drug therapy*

In recent years, surgical research has entered the digital era, and the dissemination of medical knowledge has also begun to confront the challenge posed by we media. When we media first emerged, most doctors in public hospitals, who focused on "medicine, education, and research", held a reserved attitude towards it. However, we media has demonstrated remarkable resilience and has continuously evolved to align with the trend of social development. Faced with the future development direction and the existing sore points, how surgeons comprehend and respond to the surging current of the times is a conundrum before us. In this article, the author has sorted out the rise and development of we media, the status of its application in the medical field, and the predicaments faced by medical we media, and has looked forward to its development to broaden the thinking of surgeons for more comprehensive innovation and development.

In recent years, surgical research has entered the digital era, and the dissemination of medical knowledge has also begun to confront the challenge posed by we media. When we media first emerged, most doctors in public hospitals, who focused on "medicine, education, and research", held a reserved attitude towards it. However, we media has demonstrated remarkable resilience and has continuously evolved to align with the trend of social development. Faced with the future development direction and the existing sore points, how surgeons comprehend and respond to the surging current of the times is a conundrum before us. In this article, the author has sorted out the rise and development of we media, the status of its application in the medical field, and the predicaments faced by medical we media, and has looked forward to its development to broaden the thinking of surgeons for more comprehensive innovation and development.

Objective:To investigate the effect of estrogen supplementation therapy on vaginal microbiota and local immunity of postmenopausal high-risk human papillomavirus (HPV) infected women.Methods:A total of 74 postmenopausal women who underwent gynecological examinations or visits at Department of Gynecology, Shanghai Ruijin Rehabilitation Hospital from June 2018 to June 2023 were included in this study. According to HPV test, they were divided into the high-risk HPV-negative women (normal group, n=14) and the high-risk HPV-positive women ( n=60). A randomized controlled clinical trial was designed. Within the high-risk HPV-positive women, they were further randomly assigned by using the random number table method to the experimental group (high-risk HPV-positive women receiving low-dose estrogen therapy orally, n=30) and control group (high-risk HPV-positive women not receiving low-dose estrogen therapy, n=30). Vaginal microbiota composition and expression of inflammatory cytokines in vaginal lavage fluid were measured using fluorescence quantitative PCR and enzyme-linked immunosorbent assay at baseline (week 0), 4th week, and 8th week after enrollment. Results:There were no significant differences in age, menopausal time, body mass index, systolic pressure, diastolic pressure, heart rate, pH value and vaginal cell maturation index (VMI) among the normal group, the experimental group and control group (all P>0.05) which indicated the baseline was comparable. After estrogen treatment, the pH value of the experimental group at 4th and 8th weeks (5.27±0.13, 4.84±0.15) was significantly lower than that at week 0 (6.59±0.17, all P<0.001), while the vaginal cell maturation index (VMI) at 4th and 8th weeks (41.62±2.62, 58.28±2.16) was significantly higher than that at week 0 (25.97±2.60, all P<0.001). The quantitative results showed no significant differences in the abundance of Escherichia coli among the normal group, the experimental group, and control group, and within each group at different time points (all P>0.05). The abundance of Gardnerella and Atopobium in the experimental group was significantly higher at week 0 compared with 4th week and 8th week (all P<0.001). However, after estrogen treatment, the abundance of Gardnerella and Atopobium in the experimental group at 4th week was significantly lower than those in control group (all P<0.001), with no significant difference compared with the normal group (all P>0.05). There were no significant differences in the abundance of Prevotella, L. Gasseri, and L. Iners among the normal group, the experimental group, and control group at week 0, 4th week and 8th week (all P>0.05). The abundance of L. Crispatus and L. Jensenii in the experimental group and control group at week 0 was significantly lower than that in the normal group (all P<0.001). The abundance of L. Crispatus in the experimental group at 4th week and 8th week was significantly higher than that in control group (all P<0.001), with no significant difference compared with the normal group ( P>0.05). There were no significant differences in the concentrations of interleukin (IL)-6, IL-8, and interferon (IFN)-α in vaginal lavage fluid among the normal group, the experimental group, and control group (all P>0.05). The concentration of IL-1β in the experimental group and control group was significantly higher than that in the normal group ( P<0.001), with no significant difference between the experimental group and control group ( P>0.05). The concentration of tumor necrosis factor alpha (TNF-α) in the experimental group at 8th week was significantly lower than that at week 0 ( P<0.001), while there was no significant difference in TNF-α concentration after week 4 compared with week 0 ( P>0.05). Compared with the experimental group at week 0, the concentration of chemokine C-X-C motif ligand 14 (CXCL14) and IFN-β significantly decreased after 8 weeks of estrogen treatment (all P<0.001), with no significant change after 4 weeks of treatment ( P>0.05). Compared with the normal group, the concentration of IFN-γ inducible protein 16 in the experimental group and control group significantly increased (all P<0.001), with no significant difference between the experimental group and control group ( P>0.05). Conclusion:HPV infection can increase the abundance of Gardnerella and Atopobium in the vagina of postmenopausal women and decrease the abundance of L. Crispatus and L. Jensenii, which further disrupts the homeostasis of microorganisms in the vaginal microenvironment. Estrogen replacement therapy has a certain improvement effect on vaginal flora and local immunity in postmenopausal women with high-risk HPV infection.

The World Health Organization (WHO) classification serves as the internationally recognized standard for diagnosing and classifying hematopoietic and lymphoid tissue tumors(WHO-HEAM). Since 2001, it has undergone multiple upgrades and revisions, updating, clarifying, and refining previous tumor diagnostic and classification standards while incorporating numerous new genetic and molecular biological subtypes. In 2022, two classification proposals emerged due to a wealth of clinical and scientific research results: the fifth edition of the WHO hematopoietic and lymphoid tissue classification (WHO-HAEM5), published in Leukemia journal; and the International Consensus Classification (ICC), published in Blood journal. These two schemes differ in their approach to classifying hematopoietic and lymphoid tissue tumors, posing challenges for clinical laboratory diagnosis and treatment.

Objective To establish a differential model of phlegm and blood stasis pattern and qi deficiency and blood stasis pattern in stable angina pectoris using radiomics.Methods A total of 91 patients with stable angina pectoris who underwent coronary artery CT angiography in Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from January 2021 to January 2022 were collected,including 47 cases of phlegm and blood stasis pattern and 44 cases of qi deficiency and blood stasis pattern.The patients were divided into train set(64 cases)and test set(27 cases)according to the ratio of 7∶3 by stratified random sampling method.3D-slicer software was used to extract the radiomics features of pericoronary adipose tissue(PCAT)images.Principal component analysis was used to visualize the distribution of radiomics features of pattern of phlegm and blood stasis and pattern of qi deficiency and blood stasis.The least absolute shrinkage and selection operator regression analysis and support vector machine decreasing feature elimination were used for feature selection.The multinomial logistics regression was used for model construction.The receiver operating characteristic(ROC)curve was used to verify the model in the train set and the test set to evaluate the effectiveness of the radiomics features in differentiating phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.Finally,Spearman coefficient was used to analyze the correlation between the differential features and clinical physicochemical data.Results A total of 837 radiomics features were extracted from PCAT images by 3D-slicer software.In the principal component analysis,PC1 and PC2 explained 77.9%and 8.1%of the total variance,respectively,and there was a relatively obvious separation trend between the two pattern groups.After feature screening,7 radiomics features were used to construct the differential model of phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.The area under the ROC curve(AUC)of the differential model was 0.844 in the train set and 0.834 in the test set.Spearman correlation analysis showed that the differential features were significantly correlated with cTnI,neutrophil,triglyceride,total cholesterol,and leukocyte.Conclusion The CT radiomics model based on PCAT has a high discrimination efficiency for stable angina pectoris with phlegm and blood stasis pattern and qi deficiency and blood stasis pattern.

Objective:To investigate the effect of estrogen supplementation therapy on vaginal microbiota and local immunity of postmenopausal high-risk human papillomavirus (HPV) infected women.Methods:A total of 74 postmenopausal women who underwent gynecological examinations or visits at Department of Gynecology, Shanghai Ruijin Rehabilitation Hospital from June 2018 to June 2023 were included in this study. According to HPV test, they were divided into the high-risk HPV-negative women (normal group, n=14) and the high-risk HPV-positive women ( n=60). A randomized controlled clinical trial was designed. Within the high-risk HPV-positive women, they were further randomly assigned by using the random number table method to the experimental group (high-risk HPV-positive women receiving low-dose estrogen therapy orally, n=30) and control group (high-risk HPV-positive women not receiving low-dose estrogen therapy, n=30). Vaginal microbiota composition and expression of inflammatory cytokines in vaginal lavage fluid were measured using fluorescence quantitative PCR and enzyme-linked immunosorbent assay at baseline (week 0), 4th week, and 8th week after enrollment. Results:There were no significant differences in age, menopausal time, body mass index, systolic pressure, diastolic pressure, heart rate, pH value and vaginal cell maturation index (VMI) among the normal group, the experimental group and control group (all P>0.05) which indicated the baseline was comparable. After estrogen treatment, the pH value of the experimental group at 4th and 8th weeks (5.27±0.13, 4.84±0.15) was significantly lower than that at week 0 (6.59±0.17, all P<0.001), while the vaginal cell maturation index (VMI) at 4th and 8th weeks (41.62±2.62, 58.28±2.16) was significantly higher than that at week 0 (25.97±2.60, all P<0.001). The quantitative results showed no significant differences in the abundance of Escherichia coli among the normal group, the experimental group, and control group, and within each group at different time points (all P>0.05). The abundance of Gardnerella and Atopobium in the experimental group was significantly higher at week 0 compared with 4th week and 8th week (all P<0.001). However, after estrogen treatment, the abundance of Gardnerella and Atopobium in the experimental group at 4th week was significantly lower than those in control group (all P<0.001), with no significant difference compared with the normal group (all P>0.05). There were no significant differences in the abundance of Prevotella, L. Gasseri, and L. Iners among the normal group, the experimental group, and control group at week 0, 4th week and 8th week (all P>0.05). The abundance of L. Crispatus and L. Jensenii in the experimental group and control group at week 0 was significantly lower than that in the normal group (all P<0.001). The abundance of L. Crispatus in the experimental group at 4th week and 8th week was significantly higher than that in control group (all P<0.001), with no significant difference compared with the normal group ( P>0.05). There were no significant differences in the concentrations of interleukin (IL)-6, IL-8, and interferon (IFN)-α in vaginal lavage fluid among the normal group, the experimental group, and control group (all P>0.05). The concentration of IL-1β in the experimental group and control group was significantly higher than that in the normal group ( P<0.001), with no significant difference between the experimental group and control group ( P>0.05). The concentration of tumor necrosis factor alpha (TNF-α) in the experimental group at 8th week was significantly lower than that at week 0 ( P<0.001), while there was no significant difference in TNF-α concentration after week 4 compared with week 0 ( P>0.05). Compared with the experimental group at week 0, the concentration of chemokine C-X-C motif ligand 14 (CXCL14) and IFN-β significantly decreased after 8 weeks of estrogen treatment (all P<0.001), with no significant change after 4 weeks of treatment ( P>0.05). Compared with the normal group, the concentration of IFN-γ inducible protein 16 in the experimental group and control group significantly increased (all P<0.001), with no significant difference between the experimental group and control group ( P>0.05). Conclusion:HPV infection can increase the abundance of Gardnerella and Atopobium in the vagina of postmenopausal women and decrease the abundance of L. Crispatus and L. Jensenii, which further disrupts the homeostasis of microorganisms in the vaginal microenvironment. Estrogen replacement therapy has a certain improvement effect on vaginal flora and local immunity in postmenopausal women with high-risk HPV infection.

The application of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) can be limited due to a lack of compatible protospacer adjacent motif (PAM) sequences in the DNA regions of interest. Recently, SpRY, a variant of Streptococcus pyogenes Cas9 (SpCas9), was reported, which nearly completely fulfils the PAM requirement. Meanwhile, PAMs for SpRY have not been well addressed. In our previous study, we developed the PAM Definition by Observable Sequence Excision (PAM-DOSE) and green fluorescent protein (GFP)‍-reporter systems to study PAMs in human cells. Herein, we endeavored to identify the PAMs of SpRY with these two methods. The results indicated that 5'-NRN-3', 5'-NTA-3', and 5'-NCK-3' could be considered as canonical PAMs. 5'-NCA-3' and 5'-NTK-3' may serve as non-priority PAMs. At the same time, PAM of 5'-NYC-3' is not recommended for human cells. These findings provide further insights into the application of SpRY for human genome editing.
CRISPR-Associated Protein 9/metabolism* ; CRISPR-Cas Systems ; DNA ; Gene Editing/methods* ; Humans ; Streptococcus pyogenes/metabolism*

Objective:To investigate the survival prognosis of patients with primary liver cancer and its influencing factors.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 3 106 patients with primary liver cancer who had health insurance for special illness in the Chongqing Malignant Tumor Treatment System from January 2000 to August 2018 were collected. There were 2 559 males and 547 females, aged (60±13)years, with a range from 19 to 95 years. Observation indicators: (1) demographic characteristics; (2) clinical treatment and pathological examination; (3) follow-up and survival; (4) analysis of prognostic factors. Follow-up using telephone interview, outpatient or inpatient reexamination was preformed to detect survival of patients. Follow-up was done once every 3 months within the first year and once a year thereafter up to December 2018. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represent as M (range). Count data were expressed as absolute numbers or percentages. Survival analysis was done after excluding missing data of follow-up. The survival rate was calculated and survival curve was drawn by Kaplan-Meier method. The prognostic factors were analyzed after excluding missing data of follow-up, pathological type, and TNM staging. The log-rank test was used for univariate analysis, and COX proportional hazard model was used for multivariate analysis. Results:(1) Demographic characteristics: of the 3 106 patients with primary liver cancer, the number of males and females (gender), cases with age < 30 years, from 30 to 44 years, from 45 to 59 years, from 60 to 74 years, ≥75 years, cases of Han nationality or other ethnic groups, cases being married or other status (marital status), cases with occupation as enterprise unit staff and (or) workers, public institution personnel and (or) civil servants, freelancers and (or) self-employed entrepreneurs, unemployed, company staff, and other professionals were 2 559, 547, 35, 362, 1 131, 1 163, 415, 3 053, 53, 2 896, 210, 880, 342, 130, 101, 124, and 1 529, respectively. (2) Clinical treatment and pathological examination: of the 3 106 patients with primary liver cancer, cases with hospitalization time < 10 days, from 10 to 19 days, from 20 to 29 days, ≥30 days, cases without surgery or with surgery, cases with hepatocellular carcinoma, cholangiocarcinoma, hybrid type and other pathological types, cases of stage Ⅰ, Ⅱ, Ⅲ, Ⅳ of TNM staging were respectively 771, 1 312, 661, 362, 915, 2 191, 836, 63, 24, 29, 28, 90, 624. There were 2 183 out of 3 106 patients without pathological data and 2 335 without TNM staging data. (3) Follow-up and survival: of the 3 106 patients with primary liver cancer, 2 561 were followed up for 3.0-96.0 months, with a median follow-up time of 27.6 months. The 2 561 patients had survived for 1.0-96.0 months, with a median survival time of 24.7 months. The 1-, 3-, 5-year survival rates were 63.2%, 42.3%, 29.5%, respectively. (4) Analysis of prognostic factors: results of univariate analysis showed that age, marital status, occupation, hospitalization time, surgical treatment, pathological types, and TNM staging were related factors for prognosis of patients ( χ2=31.820, 6.752, 39.100, 120.889, 226.700, 10.452, 48.602, P<0.05). Results of multivariate analysis showed that being married, hospitalization time no less than 30 days, surgical treatment were independent protective factors for prognosis ( hazard ratio=1.463, 0.572, 0.575, 95% confidence interval: 1.044-2.049, 0.413-0.793, 0.438-0.755, P<0.05), stage Ⅲ and Ⅳ of TNM staging were independent risk factors for prognosis of patients ( hazard ratio=3.941, 5.036, 95% confidence interval: 1.687-9.211, 2.237-11.335, P<0.05). Conclusions:Patients with primary liver cancer have poor prognosis. Being married, hospitalization time no less than 30 days, and surgical treatment are independent protective factors for prognosis, stage Ⅲ and Ⅳ of TNM staging are independent risk factors for prognosis.

Background Lattice corneal dystrophy (LCD) is a progressive disease,whose clinical features are varied in different stages.It is rarely be reported that clinical findings of different stages and factors of promoting the occurrence and development on LCD in a family.Objective The aim of this study was to identify the characteristics of the pedigree and clinical features of different stages in a LCD family,and further to discuss its influence factors.Methods A cross-sectional study was performed in this study.A Chinese family with LCD was enrolled in Shenzhen Eye Hospital from 2015 to 2016.Questionnaires for disease-related history,visual acuity measurement,ocular anterior segment examination and color photography were carried out for all the members of the family.In addition,anterior segment OCT (AS-OCT),laser scanning confocal microscope and corneal endothelium microscope were used to observe the morphology of corneal stroma and changes of corneal endothelial cells.The pedigree chart was drawn by Cyrillic2.1 software and analyzed based on Mendel law.Results This family included 5 generations of 73 members.Patients with LCD were found in each generation with similar morbidity in different gender,which followed the law of autosomal dominant inheritance.Eleven patients were found in 49 members related with Ⅲ1 of this family with the prevalence rate of 22.45％ and onset age at 21-50 years old,and the course of disease was 3-34 years.All of the members had no systemic disease except for two patients (Ⅲ 1 and Ⅲ 5) with hypertension.In the early stage of LCD,some bifurcate striolae appeared in the patients' corneal stroma without symptoms for many years.In the progressive stage,there was corneal irritation symptom accompanying with vision's decrease in the eyes with LCD.The bifurcate striolae were increased,widened and interwoven into lattice lines that the boundaries gradually became fuzzy,then corneal macula was formed because of recurrent corneal infiltration,and eventually resulted in corneal leucoma.High reflection corresponding to the pathologic region was showed by laser scanning confocal microscope and AS-OCT.No significant differences were found in corneal endothelial cell density and the percentage of hexagonal cells between LCD patients and normal phenotype families (t =1.887,P=0.075;t=-0.719,P =0.481).Penetrating keratoplasty was performed in a patient with corneal opacity and serious corneal opacity occurred near the surgical incision one year after the surgery.One patient was diagnosed as LCD 2 years after laser assisted in-situ keratomileusis.One patient was a welder.Conclusions LCD is autosomal dominant inheritance in the family.The clinical manifestations of LCD in the early,progressive and late stage can be seen in the pedigree,which offers a reference for ophthahnologists.Corneal surgery and lesion may induce the onset or aggravation of LCD.