AIM:To study the effect of nicotinamide mononucleotide(NMN)on renal fibrosis in mice with Al-port syndrome(AS)through TGFβ/Smad3 pathway.METHODS:SPF grade female X-linked AS(COL4A5 KI)mice were divided into model group(AS group)and model drug administration group(AS+NMN group).while female C57BL/6 mice served as the wild-type(WT)group,with 7 to 8 mice in each group.The mice in the administration group were given oral administration at 8 weeks of age for 8 weeks to 16 weeks of age.The remaining mice were given saline intragastric ad-ministration.The ratio of urinary microalbumin to urinary creatinine(UACR)was measured by biochemical method.After sampling,the renal fibrosis was analyzed by Masson staining.The expression levels of desmin and α-smooth muscle actin(α-SMA)were detected by immunohistochemistry.The expressions of fibrosis-related proteins desmin,α-SMA,trans-forming growth factor β(TGFβ),Smad3,p-Smad3,and fibronectin were detected by Western blot.RESULTS:Com-pared with the model group,UACR(13 weeks,P＜0.01;15 weeks,P＜0.01)and fibrosis-related protein expression(P＜0.05)in AS mice were significantly decreased after NMN treatment.CONCLUSION:Treatment with NMN attenuates renal fibrosis in AS mice through TGFβ/Smad3 signaling pathway.

AIM:To study the effect of nicotinamide mononucleotide(NMN)on renal fibrosis in mice with Al-port syndrome(AS)through TGFβ/Smad3 pathway.METHODS:SPF grade female X-linked AS(COL4A5 KI)mice were divided into model group(AS group)and model drug administration group(AS+NMN group).while female C57BL/6 mice served as the wild-type(WT)group,with 7 to 8 mice in each group.The mice in the administration group were given oral administration at 8 weeks of age for 8 weeks to 16 weeks of age.The remaining mice were given saline intragastric ad-ministration.The ratio of urinary microalbumin to urinary creatinine(UACR)was measured by biochemical method.After sampling,the renal fibrosis was analyzed by Masson staining.The expression levels of desmin and α-smooth muscle actin(α-SMA)were detected by immunohistochemistry.The expressions of fibrosis-related proteins desmin,α-SMA,trans-forming growth factor β(TGFβ),Smad3,p-Smad3,and fibronectin were detected by Western blot.RESULTS:Com-pared with the model group,UACR(13 weeks,P＜0.01;15 weeks,P＜0.01)and fibrosis-related protein expression(P＜0.05)in AS mice were significantly decreased after NMN treatment.CONCLUSION:Treatment with NMN attenuates renal fibrosis in AS mice through TGFβ/Smad3 signaling pathway.

Objective:To analyze the clinical manifestations and fundus multimodal imaging features of patients with acute Vogt-Koyanagi-Harada (VKH) syndrome, and provide a reference for early diagnosis of VKH syndrome.Methods:Retrospective analysis was performed on the clinical data and related examinations including spectral-domain optical coherence tomography (SD-OCT), fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) of patients diagnosed with acute VKH syndrome in the Ophthalmology Department of the Beijing Friendship Hospital from January 2017 to December 2022.Results:A total of 17 patients (34 eyes) with acute VKH syndrome were included. SD-OCT showed exudative retinal detachment in all 34 eyes with punctate hyperreflective signals; 26 eyes had choroidal folds, and 14 patients (28 eyes) had " septum-like" structures under the neuroepithelium. FFA early images showed late retinal fluorescence pooling in a multi-lake pattern in all 34 eyes. ICGA was performed in 15 patients (30 eyes), with early images showing hyperfluorescence of choroidal vessels in all 30 eyes; 26 eyes had scattered hypofluorescent lesions in the fundus. Mid-to-late images showed blurred boundaries of choroidal vessels in 28 eyes.Conclusions:Patients with acute VKH syndrome have characteristic manifestations in SD-OCT, FFA, and ICGA. Fundus multimodal imaging can provide important references for the diagnosis of VKH syndrome.

Objective:To analyze the clinical manifestations and fundus multimodal imaging features of patients with acute Vogt-Koyanagi-Harada (VKH) syndrome, and provide a reference for early diagnosis of VKH syndrome.Methods:Retrospective analysis was performed on the clinical data and related examinations including spectral-domain optical coherence tomography (SD-OCT), fundus fluorescein angiography (FFA), and indocyanine green angiography (ICGA) of patients diagnosed with acute VKH syndrome in the Ophthalmology Department of the Beijing Friendship Hospital from January 2017 to December 2022.Results:A total of 17 patients (34 eyes) with acute VKH syndrome were included. SD-OCT showed exudative retinal detachment in all 34 eyes with punctate hyperreflective signals; 26 eyes had choroidal folds, and 14 patients (28 eyes) had " septum-like" structures under the neuroepithelium. FFA early images showed late retinal fluorescence pooling in a multi-lake pattern in all 34 eyes. ICGA was performed in 15 patients (30 eyes), with early images showing hyperfluorescence of choroidal vessels in all 30 eyes; 26 eyes had scattered hypofluorescent lesions in the fundus. Mid-to-late images showed blurred boundaries of choroidal vessels in 28 eyes.Conclusions:Patients with acute VKH syndrome have characteristic manifestations in SD-OCT, FFA, and ICGA. Fundus multimodal imaging can provide important references for the diagnosis of VKH syndrome.

AIM:To investigate the therapeutic effects of chrysin on nonalcoholic steatohepatitis(NASH).METHODS:Eight-week-old male C57BL/6 mice were randomly divided into control group,model group,and chrysin group.The mice in control group were fed with normal diet,and those in model and chrysin groups were fed with methio-nine-and choline-deficient(MCD)diet.After 5 weeks of adaptation,the mice in chrysin group received chrysin treatment(20 mg/kg)by continuous lavage for 6 weeks,while those in control and model groups were given equal volume of saline.During the experiment,the health condition of the mice was monitored.Liver morphology was examined after the mice were sacrificed.Serum triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-den-sity lipoprotein cholesterol(HDL-C),alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were measured using a biochemical analyzer.Liver tissue TG and TC levels were measured using assay kits.Liver cell damage and inflammation were assessed by hematoxylin-eosin(HE)staining and F4/80 immunohistochemistry staining.The ex-tent of liver lipid deposition was explored by oil red O staining.Masson staining and Sirius red staining were performed to assess liver fibrosis.Immunohistochemistry was performed to analyze the expression of fibrosis-related molecules.RE-SULTS:Compared with control group,the mice in model group showed significant decrease in body weight,liver wet weight,and liver volume.Serum TG,LDL-C,ALT and AST levels,as well as liver TG and TC levels were significantly elevated,and HDL-C levels were decreased in model group.Pathological staining showed significant inflammatory cell in-filtration,lipid deposition,and liver fibrosis.After the treatment with chrysin,increased body weight and liver weight,a reddish appearance of the liver,relatively smooth surface,and sharp liver edges were observed.Serum TG,LDL-C,AST and ALT levels,and liver TG levels were significantly reduced by chrysin.Inflammatory cell infiltration,lipid deposition,and liver tissue fibrosis were also significantly attenuated by chrysin.CONCLUSION:Chrysin shows a potential as a can-didate drug for the treatment of NASH by inhibiting hepatic steatosis,inflammation,and liver fibrosis.

Objective To investigate the role and related mechanism of the soluble guanylate cyclase(sGC)-cGMP-protein kinase G(PKG)signaling pathway in the amelioration of isoproterenol(ISO)-induced cardiac hypertrophy in mice by aqueous extract of Curcuma kwangsiensis root tubers(GYJS).Methods 72 KM male mice were divided randomly into 6 groups:normal,model,propranolol control(40 mg/kg),and GYJS low-(1 g/kg),medium-(2 g/kg),and high-dose(4 g/kg)groups.Mice in the experimental groups were injected subcutaneously with ISO 10 mg/kg on days 1～3 and ISO 5 mg/kg on days 4～14 to establish a mouse cardiac hypertrophy model.4h after each subcutaneous injection of ISO,the mice in each group were administered the corresponding drugs orally for a dosing cycle of 14 days.The hearts were then removed and whole heart and left ventricle weight were measured.Myocardial tissue pathology was observed using hematoxylin and eosin and Masson staining,and sGC subunit beta-1(GUCY1B3)and transforming growth factor(TGF-β1)were detected by immunohistochemistry.Serum lactate dehydrogenase(LDH),creatine kinase(CK),and Nitric Oxide(NO),and myocardial superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were measured using respective kits.Serum cGMP was detected by enzyme-linked immunosorbent assay and quantitative reverse transcription PCR(RT-qPCR),and atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),GUCY1B3,PKG Ⅰ,and phosphodiesterase(PDE)5A mRNA expression levels were also determined by RT-qPCR.Results Compared with the model group,whole heart and left ventricle weights were significantly reduced in mice treated with propranolol or GYJS(P＜0.001 or P＜0.0001)and myocardial hypertrophy and myocardial fibrosis were significantly reversed.All the treatments significantly elevated myocardial expression of GUCY1B3(P＜0.05 or P＜0.01)and significantly reduced expression of TGF-β1(P＜0.05 or P＜0.01).The myocardial damage markers LDH and CK were significantly reduced(P＜0.05 or P＜0.01)while NO and cGMP were significantly elevated(P＜0.05 or P＜0.01),the myocardial oxidative stress indicator MDA was significantly reduced(P＜0.05 or P＜0.01)and SOD activity was significantly increased(P＜0.05 or P＜0.01).mRNA levels of the myocardial hypertrophy markers ANP,BNP,and PDE5A were significantly reduced(P＜0.05,P＜0.01,or P＜0.001)and the mRNA levels of GUCY1B3 and PKG Ⅰ were significantly increased(P＜0.01 or P＜0.001).Conclusions GYJS may improve cardiac hypertrophy by modulating the sGC-cGMP-PKG signaling pathway.

Objective To investigate the factors involved in the development of thyroid nodules and the correlation between homocysteine(Hcy)and albumin-globulin ratio(AGR)and thyroid autoantibodies in adults.Methods As a retrospective study,a total of 1 427 people who received physical examination at the Second Hospital Affilia-ted to Hebei North College from October 2019 to August 2020 and the clinical data of the subjects who fulfilled the criteria of NAR were selected for analysis by simple random sampling.All of subjects underwent thyroid color ultrasound scanning and were divided into a control group(without thyroid nodules,n=52)and an observation group(with thyroid nodules,n=48).The general clinical data of the two study groups were compared,and the correlation between Hey and AGR and thyroid autoantibodies was analyzed.Confunding factors affecting the inci-dence of thyroid nodules were screened using multifactorial unconditional logistic regression analysis.Results The observation group showed statistically significant differences in gender,age,diastolic blood pressure,systolic blood pressure,Hey,AGR,TGAb,and TPOAb as compared to the control group(P＜0.05);Using adult Hcy as the dependent variable and Spearman's correlation analysis of AGR,TGAb and TPOAb,adult Hcy was nega-tively correlated with AGR(r=-0.384,P＜0.05)and TGAb and TPOAb were positively correlated(r=0.218,0.224,P＜0.05);Using age,sex,diastolic blood pressure,systolic blood pressure,Hcy,AGR TGAb and TPOAb as independent variables and thyroid nodules as dependent variables,a multifactor logistic regression analysis was performed in 100 subjects who experienced physical check.The analysis showed that age ≥40 years and female were relevant factors for the development of thyroid nodules factors(P＜0.05),Hcy,AGR,TGAb and TPOAb were correlated with thyroid nodules(P＜0.05).Conclusions Thyroid nodules are more common in middle-aged women,and there is a correlation between Hcy,AGR,TGAb,and TPOAb levels and thyroid nod-ules.Regular thyroid screening examination should be carried out based on the above indicators.

Objective To investigate the relationship between circKIF4A expression and clinicopathologic features and prognosis of thyroid cancer patients.Methods A total of 120 patients diagnosed with thyroid cancer in our hospital from April 2016 to April 2017 were selected by random sampling method.Cancer tissues and adjacent tissues were taken during surgery and divided into thyroid cancer group and adjacent cancer group according to surgical pathologic detection.The relative expression level of circKIF4A in thyroid cancer group and paracancer group was detected by qRT-PCR,and the relationship between circKIF4A expression and clini-copathological features of thyroid cancer was analyzed.Kaplan-Meier survival curve was used to analyze the relationship between circKIF4A expression and prognosis of thyroid cancer patients.Cox regression analysis was performed to analyze the factors influencing the poor prognosis of patients with thyroid cancer 5 years af-ter surgery.Results The relative expression level of circKIF4A in thyroid cancer group was higher than that in paracancer group,and the difference was statistically significant(P＜0.05).The expression of circKIF4A was correlated with the degree of capsule invasion,lymph node metastasis and differentiation(P＜0.05).Kap-lan-Meier survival curve analysis showed that the 5-year cumulative survival rate of patients with high cir-cKIF4A expression was lower than those with low circKIF4A expression,and the difference was statistically significant(x2=11.368,P=0.001).Multivariate analysis showed that envelope invasion,degree of differenti-ation,lymph node metastasis and circKIF4A expression level were the influencing factors for poor prognosis of thyroid cancer patients at 5 years after surgery(P＜0.05).Conclusion circKIF4A is highly expressed in thy-roid cancer tissues,which is related to the clinicopathological features and 5-year postoperative survival of thy-roid cancer patients,and may be used as a potential prognostic marker for thyroid cancer.

Objective:To understand intensive care unit(ICU)doctors'opinions and suggestions on implementing palliative care,and provides a reference basis for the implementation of palliative care in Chinese ICU.Methods:A purposive sampling technique was used to conduct one-on-one semi-structured interviews with 11 ICU doctors.Colaizzi's phenomenological analysis method was utilized to code,classify,interpret,and comprehensively analyze the interview data.Results:A total of 4 themes and 18 sub-themes was extracted,including cognitive biases toward palliative care,the belief that implementing palliative care in the ICU has significant humanistic implications(palliative care practice is the most perfect embodiment of medical humanities,palliative care in the ICU can alleviate patient pain and reduce invasive operations,palliative care can achieve comfortable care for ICU patients,palliative care focuses on maintaining the dignity of ICU patients,palliative care can pay attention to the inner voice of ICU patients,and implementing palliative care will help to more effectively allocate resources),difficulties faced by ICU in carrying out palliative care(lack of clarity in relevant policies at the legal level,closed management environment in the ICU,insufficient manpower in the ICU and lack of palliative care professional team,inadequate understanding of ICU patients'families,lack of death education,not included in medical insurance payments,and lack of communication skills of young doctors),strategies to promote the development of palliative care in the ICU(ICU palliative care can be piloted first,the development of ICU palliative care screening tools will help with the development of palliative care,the palliative environment and the handling of death procedures can be further optimized,and the application and implementation of scientific methods to shorten the gap between evidence and practice of palliative care).Conclusions:The integration of palliative care and ICU in China is still blank.The significance of implementing palliative care in ICU should be emphasized,ICU doctors'knowledge and skills of palliative care should be improved from multiple perspectives,patient preference should be emphasized to improve the knowledge and acceptance of palliative care of ICU patients'families,and the promotion of palliative care in ICU clinical practice should be pioneered and piloted.

A 60-year-old male patient with lumbar disc herniation and sciatica received Sanqi Shangyao 3 tablets thrice daily orally by himself. After 6 days of administration, the patient developed upper abdominal stuffy pain, nausea, vomiting, and yellowish skin. Laboratory tests showed total bilirubin (TBil) 155.2 μmol/L, direct bilirubin (DBil) 87.1 μmol/L, alanine aminotransferase (ALT) 817 U/L, aspartate aminotransferase (AST) 367 U/L, and alkaline phosphatase (ALP) 136 U/L. The concentration of γ-glutamyltransferase (GGT) was 455 U/L. The drug was stopped, liver protective treatments were given for 8 days, and the above symptoms in the patient were improved; after 38 days of treatments, laboratory tests showed TBil 27.3 μmol/L, DBil 9.3 μmol/L, ALT 46 U/L, AST 28 U/L, ALP 83 U/L, and GGT 55 U/L. The patient′s liver injury was possibly related to the aconitine contained in the Radix Aconiti Kusnezoffii and Aconitum racemulosum Franch of Sanqi Shangyao tablets.