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*

AIM:To explore the roles and associations of hepatocyte nuclear factor 4 alpha(HNF4A)and mu-protocadherin(MUCDHL)in the kidney of diabetic mice.METHODS:(1)A cohort of six 12-week-old db/m mice and six db/db mice were selected and maintained on a standard diet until 16 weeks.The protein levels of fibronectin(FN),collagen type III(Col-III),E-cadherin,α-smooth muscle actin(α-SMA),HNF4A,Snail and MUCDHL in renal tissues were scrutinized using Western blot.Immunohistochemical staining was conducted to observe the distribution and expres-sion of FN,HNF4A and MUCDHL.(2)Mouse renal tubular epithelial cells(mRTEC)were cultured in vitro and catego-rized into groups:normal glucose(NG)group,high glucose(HG)group,overexpression control groups(NG+vector and HG+vector),overexpression groups(NG+OE-MUCDHL,HG+OE-MUCDHL,NG+OE-HNF4A and HG+OE-HNF4A),knockdown control groups(NG+control and HG+control),and knockdown groups(NG+si-MUCDHL,HG+si-MUCDHL,NG+si-HNF4A and HG+si-HNF4A).The relevant protein levels were also detected by Western blot.RESULTS:(1)In db/db group,elevated body weight,blood glucose and urine albumin-to-creatinine ratio(UACR)indicated significant re-nal injury.Compared with db/m group,the mice in db/db group exhibited increased expression of FN,Col-III,α-SMA and Snail,and decreased expression of E-cadherin,HNF4A and MUCDHL.MUCDHL was predominantly expressed in the apical membrane of renal tubular epithelial cells,FN in the tubular mesenchyme,and HNF4A in the plasma and nu-cleus of renal tubular cells.(2)In HG group,there was an up-regulation in the expression of fibrosis-related proteins and a down-regulation in the expression of E-cadherin,HNF4A and MUCDHL compared with NG group.Overexpression of MUCDHL led to a decrease in the expression of FN,Col-III,α-SMA and Snail proteins,an increase in the expression of E-cadherin and MUCDHL proteins,and unaltered expression of HNF4A.Knockdown of MUCDHL resulted in a reversal of the aforementioned effects,with HNF4A expression remaining unaltered.Overexpression of HNF4A led to an increased ex-pression of MUCDHL,and the expression changes of the remaining indicators were consistent with the overexpression of MUCDHL.Knockdown of HNF4A reversed the aforementioned effects.MUCDHL may represent a downstream target gene of HNF4A.CONCLUSION:The diminished expression of HNF4A and MUCDHL in the renal tubules of diabetic mice implies their involvement in the progression of renal fibrosis in diabetic kidney disease(DKD).HNF4A may potentially impede the progression of renal fibrosis in DKD by up-regulating the expression of MUCDHL.

Objective To investigate the application value of 3.0T MR apparent diffusion coefficient(ADC)in prognosis and pathological types of endometrial carcinoma(EC).Methods A total of 114 EC patients were retrospectively selected,and the ADC values of different pathological types were compared.The correlation between ADC and EC prognosis was analyzed by dividing the ADC quintile(Q1-Q5).Results The ADC parameters of EC patients with different pathological types were significantly different(P＜0.05).With the increase of ADC value,the correlation effect size between ADC and EC prognosis also increased(Ptrend＜0.001).ADC had a better predictive effect on EC prognosis.International Federation of Gynecology and Obstetrics(FIGO)stage,myographic invasion and ADC value had interaction with EC prognosis(P interaction＜0.05).Conclusion ADC can be used to distinguish the patho-logical types of EC.Also,ADC is significantly associated with EC prognosis while its correlation effect size increases with the increase of ADC value.ADC value interacted with FIGO stage,as well as with the degree of myographic invasion in predicting EC prognosis.

Objective To observe the value of FOLFOX-hepatic arterial infusion chemotherapy(HAIC)combined with programmed cell death receptor-1(PD-1)inhibitor+targeted drug for treating China liver cancer staging(CNLC)stageⅢa hepatocellular carcinoma(HCC).Methods Sixty-one patients with CNLC stage Ⅲa HCC who underwent PD-1 inhibitor+targeted drug treatment were retrospectively enrolled and divided into observation group(n=30)and control group(n=31)based on whether received FOLFOX-HAIC treatment or not.The general information,treatment strategy,adverse reactions and therapeutic effects were compared between groups,and the value of treatment strategy in observation group was analyzed.Results No significant difference of general information nor PD-1 inhibitor+targeted drug strategy was found between groups(both P＞0.05).Among 1-2 grade adverse reactions,the incidence of nausea,vomiting and abdominal pain in observation group were higher than those in control group(both P＜0.05),while no significant difference of the other 1-2 grade nor 3 grade adverse reactions was observed(all P＞0.05).The objective response rate(ORR),progression free survival(PFS)and overall survival(OS)of observation group were all higher than those of control group(all P＜0.05).Conclusion FOLFOX-HAIC combined with PD-1 inhibitor+targeted drug was more effective for treating CNLC stage Ⅲa HCC with acceptable safety.

Objective:Based on bioinformatics,new immune-related LncRNAs related to the prognosis of gastric cancer were screened,and a prognostic risk model of immune-related LncRNA was further constructed,in order to be used as a new indicator for early diagnosis and prognostic status of gastric cancer.Methods:The gastric cancer transcriptome data and corresponding clinical prog-nosis data were downloaded from multiple data platforms,and the immune-related LncRNAs of gastric cancer were screened by bioin-formatics methods.Cox regression analysis was used to screen LncRNAs related to immune prognosis in gastric cancer,and LncRNAs related to immune prognosis with independent prognostic significance were identified to construct a prognostic risk model,and the risk score of each patient was calculated.Patients were divided into low-risk and high-risk groups according to the cutpoint.Kaplan-Meier analysis was performed for survival analysis and survival curves were drawn,nomograms were drawn and internal validation was per-formed,and univariate and multivariate Cox regression analysis was performed to analyze the relationship between risk scores and clin-icopathological characteristics and survival prognosis of gastric cancer patients.Results:Three immune prognosis-related LncRNAs(UCA1,MIR4435-1HG,RP11-617F23.1)were identified by Cox regression analysis,and a predictive scoring model was constructed to divide the patients into high-risk group and low-risk group according to the prognosis score.There was a statistically significant dif-ference in the prognosis of patients between the two groups(P<0.05).The multivariate Cox regression analysis risk score was an inde-pendent risk factor for the prognosis of gastric cancer,and the internal verification of the nomogram showed good reliability.Conclu-sion:Three immune-related LncRNAs in gastric cancer are significantly correlated with the prognosis of gastric cancer patients,and the predictive scoring model constructed based on them can effectively predict the prognosis and can be used as their independent prog-nostic biomarkers.

Objective:To evaluate the value of endogenous digitalis-like factor (EDLF) dynamic changes in predicting myocardial injury and prognosis in patients with sepsis.Methods:A total of 160 sepsis patients admitted to the emergency department of Beijing Friendship Hospital Affiliated to Capital Medical University from July 2017 to January 2019 were selected and divided into the myocardial injury(MI) group ( n=75) and the non-myocardial injury (NMI) group ( n=85) according to whether there was myocardial injury. The plasma EDLF concentration was tested on the 1 st, 3 rd and 7 th day after admission. The predictive factors of MI and 90-days outcome were evaluated by logistics regression analysis. Cox proportional hazards regression model was used to estimate the prognostic value of EDLF concentration on the 90 days after admission for sepsis. Results:Septic patients with MI had increased levels of myocardial enzymes, decreased left ventricular fractional shortening index (FS) and interventricular septum (IVS) amplitude and abnormal wall motion, when compared to NMI patients (all P<0.05). EDLF concentration on the 7 th day in the MI group was significantly lower than in the NMI group ( P=0.019). Logistic regression showed that EDLF 7 th was an independent protective factor for MI and 90-day mortality in sepsis respectively ( OR=0.964, 95% CI: 0.934-0.994, P=0.021; OR=0.931, 95% CI: 0.871-0.995, P=0.036). Cox proportional hazards regression analysis suggested that EDLF 7 th concentration <26.7 pmol/L was an independent predictor of 90-day mortality in patients with sepsis ( HR=4.601, 95% CI: 1.030-20.563, P=0.046). Conclusions:EDLF 7 th may serve as a protective factor for sepsis-induced MI and adverse outcome. The exogenous supplement of cardiotonic drugs at one week after MI may be a potential treatment to improve the survival rate of septic patients.

Cashmere, also known as soft gold, is produced from the secondary hair follicles (SHFs) of cashmere goats. The number of SHFs determines the yield and quality of cashmere; therefore, it is of interest to investigate the transcriptional profiles present during cashmere goat hair follicle development. However, mechanisms underlying this development process remain largely unexplored, and studies regarding hair follicle development mostly use a murine research model. In this study, to provide a comprehensive understanding of cellular heterogeneity and cell fate decisions, single-cell RNA sequencing was performed on 19,705 single cells of the dorsal skin from cashmere goat fetuses at induction (embryonic day 60; E60), organogenesis (E90), and cytodifferentiation (E120) stages. For the first time, unsupervised clustering analysis identified 16 cell clusters, and their corresponding cell types were also characterized. Based on lineage inference, a detailed molecular landscape was revealed along the dermal and epidermal cell lineage developmental pathways. Notably, our current data also confirmed the heterogeneity of dermal papillae from different hair follicle types, which was further validated by immunofluorescence analysis. The current study identifies different biomarkers during cashmere goat hair follicle development and has implications for cashmere goat breeding in the future.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

OBJECTIVE：To optimize the formul ation of Polygala japonica cream，and to evaluate the quality of prepared cream. METHODS ：With centrifugal stability ，heat resistance stability and viscosity as evaluation indexes ，the weight coefficient was determined by analytic hierarchy process （AHP），criteria importance through intercriteria correlation （CRITIC）method and mixed weighted AHP-CRITIC ，and the comprehensive score was calculated. The amount of octadecyl alcohol ，hexadecanol and mixed emulsifier （polysorbate 60 mixed with glycerin monostearate at the mass ratio of 2.82）in the formulation of P. japonica cream were screened by central composite design-response surface methodology. The optimized formulation was validated. P. japonica cream prepared by the optimal preparation was evaluated in terms of apperance ，particle，pH，stability and rheological characteristics. RESULTS ：The weight coefficients of centrifugal stability ，heat resistance stability and viscosity were 0.428 5， 0.415 6 and 0.155 9 respectively，according to the mixed weighted AHP-CRITIC. The optimal formulations were 1.96 g of hexadecyl alcohol ，5.17 g of octadecyl alcohol ，2.48 g of mixed emulsifier ，1.83 g of polysorbate 60，0.65 g of glyceride monostearate，1 g of benzyl alcohol ，5 g of propylene glycol ，6 g of isopropyl myristate and 5 g of P. japonica extract，and then added water to 100 g. Prepared cream was a light yellow fluid paste with particle size of 0.5-2.5 μm and pH value of 6.5；the results of centrifugal test ，heat resistance test and cold resistance stability test showed that the cream had no oil-water separation or thickened paste. The prepared cream was shear-thinning non-Newtonian fluid. CONCLUSIONS ：P. japonica cream is prepared successfully，which shows good apperance ，particle，acidity and stability.