This paper summarizes Professor LIU Fengbin's clinical experience in treating autoimmune liver disease （AILD） using the method of nourishing yin and removing stasis based on stage differentiation. He believes that the pathogenesis of AILD generally involves both deficiency in essence and excess in manifestation， with essence deficiency often presenting as liver and kidney yin deficiency， which may progress to spleen deficiency and yang deficiency over time. The excess manifestation commonly includes qi stagnation， blood stasis， damp-heat， and phlegm toxicity. Clinically， he advocates for the treatment principle of nourishing yin and removing stasis. On the foundation of nourishing liver and kidney yin， different pathological factors causing stasis are eliminated according to their nature. Treatment is also tailored to different stages of AILD. In the early and asymptomatic stages， liver qi stagnation and spleen deficiency are prominent， warranting a therapeutic approach of soothing the liver， regulating qi and strengthening the spleen. The modified Chaishao Qizhi Decoction （柴芍气滞汤） is used. During the symptomatic stage， pathogenic factors become more pronounced， often accompanied by a significant deficiency of vital qi， with damp-heat， water retention， and phlegm toxicity as key pathological features. The treatment should focus on strengthening the spleen and dispelling dampness， using modified Sijunzi Decoction （四君子汤） combined with Yinchen Wuling Powder （茵陈五苓散）. In the liver function decompensation stage， vital qi is severely deficient while pathogenic factors persist， with damp-heat， phlegm toxicity， and blood stasis obstructing the liver collaterals. Treatment should focus on nourishing blood， softening the liver， strengthening the spleen， and resolving stasis， using the modified Ruangan Yangxue Decoction （软肝养血汤）. Throughout the treatment process， emphasis is placed on tonifying the liver and kidneys while protecting yin fluids.

Multiple plant lineages have independently evolved sex chromosomes and variable kary-otypes to maintain their sessile lifestyles through constant biological innovation.Morus notabilis,a dioecious mulberry species,has the fewest chromosomes among Morus spp.,but the genetic basis of sex determination and karyotype evolution in this species has not been identified.In this study,three high-quality genome assemblies were generated for Morus spp.[including dioecious M.notabilis(male and female)and Morus yunnanensis(female)]with genome sizes of 301-329 Mb and were grouped into six pseudochromosomes.Using a combination of genomic approaches,we found that the putative ancestral karyotype of Morus species was close to 14 protochromosomes,and that sev-eral chromosome fusion events resulted in descending dysploidy(2n=2x=12).We also charac-terized a～6.2-Mb sex-determining region on chromosome 3.Four potential male-specific genes,a partially duplicated DNA helicase gene(named MSDH)and three Ty3_Gypsy long terminal repeat retrotransposons(named MSTG1/2/3),were identified in the Y-linked area and considered to be strong candidate genes for sex determination or differentiation.Population genomic analysis showed that Guangdong accessions in China were genetically similar to Japanese accessions of mul-berry.In addition,genomic areas containing selective sweeps that distinguish domesticated mul-berry from wild populations in terms of flowering and disease resistance were identified.Our study provides an important genetic resource for sex identification research and molecular breeding in mulberry.

【Objective】 To make bioinformatics analysis of inflammatory cardiomyopathy so as to screen out hub genes related to etiology and therapeutic targets. 【Methods】 Differential expression analysis of inflammatory cardiomyopathy gene chip data from Gene Expression Omnibus （GEO） Database was carried out via GEO2R tool. Protein-protein interaction（PPI）network and hub genes identification were realized by String database and CytoHubba. GO and KEGG enrichment analysis for functional annotation and pathway analysis of hub genes were conducted by R language. Web-based enrichment analysis platform Enrichr and Drug Signatures database were applied to screen out candidate drugs targeting hub genes for inflammatory cardiomyopathy. 【Results】 The 149 DEGs were statistically significant， among which 44 were upregulated and 105 were downregulated. To identify hub genes， PPI network consisting of 37 nodes and 116 edges was constructed， and 16 hub genes were NDUFB7， POLR2L， NDUFS7， UQCR11， NDUFA13， NDUFA2， PHPT1， NDUFB10， UBA52， ATP5D， NDUFA3， COX6B1， POLR2J， COX4I2， AURKAIP1 and MRPL41. Hub genes were enriched to 113 different GO terms， and the most significant terms were mitochondrial ATP synthesis coupled electron transport， respiratory electron transport chain， oxidative phosphorylation， respiratory chain， mitochondrial inner membrane， NADH dehydrogenase activity and oxidoreductase activity. DEGs were enriched to 13 different signal pathways， including oxidative phosphorylation， non-alcoholic fatty liver disease， diabetic cardiomyopathy， and cardiac muscle contraction. We screened out candidate drugs targeting hub genes， namely， metformin hydrochloride， clindamycin， and hydralazine. 【Conclusion】 Hub genes screened out by decoding the expression profiles are convolved in the etiology and mechanism of inflammatory cardiomyopathy， which might serve as latent therapeutic targets and benefit patients with inflammatory cardiomyopathy.

Objective:To explore the effect of the Internet combined pre-rehabilitation intervention model in patients with chronic hepatitis B liver cirrhosis.Methods:From June 2019 to December 2020, convenience sampling was used to select 140 patients with chronic hepatitis liver cirrhosis in Henan Provincial People's Hospital. The patients were randomly divided into the observation group and the control group according to the order of entry, 70 cases in each group.The observation group carried out the Internet combined pre-rehabilitation model and the control group implemented conventional nursing intervention. We compared the disappearance time of clinical symptoms, mastery of rehabilitation knowledge and the quality of life of the two groups of patients.Results:The disappearance time of abdominal distension, ascites, anorexia, fatigue, and lower extremity edema of the observation group was shorter than that of the control group, and the differences were statistically significant ( P<0.05) .After the intervention, the disease knowledge such as reasonable work and rest, reasonable diet, emotional control, exercise and medical treatment of observation group was better than that of the control group, and the differences were statistically significant ( P<0.05) . After the intervention, the quality of life scores of patients in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:The Internet combined pre-rehabilitation intervention model can shorten the disappearance time of clinical symptoms in patients with chronic hepatitis B liver cirrhosis, improve the patient's knowledge of disease rehabilitation and the quality of life, which is worthy of clinical application.

Objective:To explore the correlation between the level of heart rate deceleration (DC), serum homocysteine(Hcy), the scope and extent of coronary artery lesion in coronary heart disease patients with hypertension.Methods:From January 2019 to October 2019, 103 coronary heart disease patients with hypertension who were diagnosed and hospitalized in cardiovascular department of Binzhou Central Hospital were selected as coronary heart disease(CHD) group, and 52 patients with simple hypertension were selected as control group.The serum Hcy levels of the two groups were measured and analyzed.The DC value and the difference of the two groups were analyzed.The degree of coronary artery lesion was evaluated by the number of coronary artery lesion and Gensini score.The relationship between DC, Hcy and the degree of coronary artery lesion was analyzed.Results:Compared with the control group, the DC value of CHD group was significantly lower [(6.02±1.97)ms vs.(4.97±1.59)ms, t=-3.989, P<0.05], and the serum Hcy level was increased [(11.46±4.38)μmol/L vs.(16.79±6.31)μmol/L, t=4.260, P<0.05]. In the CHD group, the DC values and Gensini scores of the patients with single vessel lesion, double vessel lesions and three vessel lesions were (5.52±1.34)ms, (5.06±1.29)ms, (4.39±1.19)ms, (21.35±17.10)points, (26.93±18.18)points, (49.39±30.14)points, respectively.The DC value of patients with three vessel lesions was lower than that of patients with single vessel lesion( F=7.349, P<0.05), and the Gensini score was higher( F=13.487, P<0.05). There were no statistically significant differences in DC value and Gensini score between patients with three vessel lesions and those with two vessel lesions and those with single vessel lesion( P>0.05). The serum Hcy levels of patients with single, double and three vessel lesions were (14.67±5.97)μmol/L, (15.85±6.29)μmol/L and (16.97±7.13)μmol/L, respectively.The difference among the three groups was statistically significant ( F=12.427, P<0.05). There was a negative correlation between DC and Gensini score( r=-0.310, P<0.05), and a positive correlation between serum Hcy and Gensini score( r=0.369, P<0.05). Conclusion:The DC value and Hcy level in coronary heart disease patients with hypertension are significantly decreased, which are closely related to the degree of coronary artery lesion.

OBJECTIVE: To evaluate the effect of rosmarinic acid (RA) on mitophagy and hypertrophy of cardiomyocytes exposed to high glucose (HG). METHODS: Rat cardiomyocytes (H9c2) exposed to HG (25 mmol/L) were treated with 50 μmol/L RA or with both RA treatment and Parkin siRNA transfection, with the cells cultured in normal glucose (5.5 mmol/L) and HG as the controls. The expressions of PINK1, Parkin and LC3II/LC3I in the cells were detected by Western blotting. The formation of mitochondrial autophagosomes was observed by transmission electron microscope. Flow cytometry was employed to detect the level of reactive oxygen species (ROS) and apoptotic rate of the cells. The activities of respiratory chain complex enzymes were measured by spectrophotometry. Fluorescence enzyme labeling and RESULTS: RA treatment significantly increased the expression levels of PINK1, Parkin and LC3-II/I ( CONCLUSIONS RA can protect rat cardiomyocytes against oxidative stress injury and cardiomyocyte hypertrophy induced by HG by activating Parkin-mediated mitophagy.
Animals ; Cinnamates ; Depsides ; Glucose ; Hypertrophy ; Mitophagy ; Myocytes, Cardiac ; Protein Kinases ; Rats ; Reactive Oxygen Species ; Ubiquitin-Protein Ligases/genetics*

Objective To study the effect of menopause status and the time of taking tamoxifen (TAM) on endometrial lesions after breast cancer surgery. Methods A total of 330 patients with postoperative vaginal irregular bleeding after breast cancer surgery or endometrial lesions after B ultrasonic from August 2007 to August 2017 in Northern Jiangsu People 's Hospital were retrospectively analyzed, including 180 cases of taking TAM treatment (medicine-taking group), and 150 cases of not taking TAM treatment (non medicine-taking group). The patients were also divided into the menopause group and the premenopausal group. According to the time of taking TAM, the patients were divided into < 2 years group, 2-5 years group and > 5 years group. Chi-square and Fisher test were used to compare the differences. Results The endometrial lesions incidence in the medicine-taking group was higher than that in the non medicine-taking group [84.44 ％ (152/180) vs. 56.00％(84/150);χ2=51.701, P=0.000]. The endometrial lesions rate in the menopause group was higher than that in the premenopause group [medicine-taking group: 69.70 ％ (46/66) vs. 92.98 ％ (106/114), χ2= 17.254, P= 0.000; non medicine-taking group: 46.15 ％ (35/65) vs. 63.53 ％(54/85), χ2 = 4.513, P= 0.034]. For the patients in the menopause group and the premenopause group, the incidence of endometrial lesions for those who took medicine for>5 years [96.00％(48/50), 85.19％(23/27)] was higher than that in the<2 years group and 2-5 years group [78.26％(18/23), 42.86％(6/14);95.12％(39/41), 72.00％(18/25) respectively], and there were statistical differences (χ2=7.619, P=0.022;χ2= 8.070, P= 0.018). The menopause was not correlated with staging, muscular lawyer infiltration and lymph metastasis postoperative (P> 0.05), but with the type of endometrial cancer (P= 0.013); the length of taking medicine was related with the type of endometrial cancer and the lymph metastasis (P=0.027). With the prolonged time of medicine-taking for postmenopause patients, the incidence of type Ⅱendometrial cancer and positive rate of lymph metastasis were also increased. Conclusions Taking TAM after surgery for breast cancer patients increases the risk of endometrial lesions. The longer the patients take the medicine, the greater risk of the lesions take, and the worse the pathological, histological type and prognosis of endometrial carcinoma are, which is more obvious for postmenopausal women who take TAM for more than 5 years.

Objective To evaluate the practicability of using CRISPR/Cas9 genome editing tech-nology for inhibition of hepatitis B virus ( HBV) replication. Methods Two sgRNA targeting sites were de-signed for the S region of HBV genome. The CRISPR/Cas9 expression plasmids specific for HBV were con-structed and then transfected into a cell line expressing HBV genome(HepG2-N10). The cytotoxicity of cells transfected with different expression plasmids were detected by MTT assay. The levels of hepatitis B surface antigen ( HBsAg ) were determined by using chemiluminescent immunoassay ( CLIA ) . The expression of HBV at mRNA level was analyzed by quantitative real-time PCR ( qRT-PCR) . The qPCR was performed for the detection of extracellular and intracellular HBV DNA. The next-generation sequencing ( NGS) Illumina MiSeq Platform was used to analyze HBV genome editing. Results No significant cytotoxic effects were de-tected in HepG2-N10 cells transfected with different expression plasmids. Compared with the cells carrying pCas-Guide-GFP-Scramble, the levels of HBsAg in the supernatants of transfected cell culture harboring pCas-Guide-GFP-G1 and pCas-Guide-GFP-G2 were decreased by 24. 2% (P<0. 05) and 16. 9% (P>0. 05), respectively. The levels of HBsAg in cells transfected with pCas-Guide-GFP-G1 and pCas-Guide-GFP-G2 were respectively decreased by 16. 4% (P>0. 05) and 32. 1% (P>0. 05) as compared with that of pCas-Guide-GFP-Scramble transfected group. The expression of HBV at mRNA level was inhibited as indica-ted by the results of qRT-PCR. Moreover, the levels of extracellular HBV DNA were respectively suppressed by 23% (P>0. 05) and 35% (P<0. 05), and the levels of intracellular HBV DNA were respectively sup-pressed by 7. 2% (P>0. 05) and 18% (P>0. 05). Different types of insertion/deletion mutation were de-tected in HBV genome by high-throughput sequencing. Conclusion HBV-specific CRISPR/Cas9 system could inhibit the expression of HBV gene and the replication of virus. Therefore, the CRISPR/Cas9 genome editing technology might be used as a potential tool for the treatment of persistent HBV infection.

ObjectiveTo investigate the prognostic value of fluid responsiveness in patients with acute respiratory stress syndrome (ARDS).Methods Fifty-nine mechanically ventilated patients with ARDS were enrolled.Their stroke volume variations (SVV) were detected by pulse contour continuous cardiac output (PiCCO) analysis device,and then the patients were subsequently divided into fluid responsive group (SVV≥15％) and fluid non-responsive group (SVV ＜ 15％ ).The differences in 28-day survival,length of ICU stay and duration of mechanical ventilation between the 2 groups were compared.Thereafter,the 28-day survival of patients was analyzed by Kaplain-Meier survival model and the relationship between SVV and mortality within 28 days was analyzed by logistic regression model.Results In comparison with fluid non-responsive group,the 28-day survival of fluid responsive group was significantly increased (85.3％ vs.56.0％,P =0.012),the length of ICU stay was significantly shortened [( 13.1 ±5.2 ) d vs. (21.6±9.0) d,P=0.008],and the duration of mechanical ventilation was significantly shortened as well [( 11.4 ± 5.3 ) d vs.( 18.3 ± 4.9) d,P =0.022] ; Logistic analysis revealed that SVV ＜ 15％ increased the risk of 28-day mortality ( OR =4.82 ; 95％ CI:2.67 ～ 11.71,P =0.009 ).ConclusionsSVV-based fluid responsiveness can be served as a prognostic predictor for ventilated patients with ARDS.

Objective To investigate the quality of life(QOL)of patients with stroke and its related factors.Methods The QOL of eighty-two stroke survivors was assessed in terms of SF-36 scores,motor impairment (Fugl-Meyer),disability[Barthel index(BI)]and depression(HAMD)more than one year after their first episode.Their social demographic characteristics such as age,gender,education and income were recorded,as were the characteristics of their disease and any complications.Multiple regression analysis was used to analyse the related factors.Results The average age of the 82 subjects was 61.89 + 9.81 years(range,33-81).56 of them were male (68.2％).Scores on all items of the SF-36 for these subjects were lower than those of a normal population.Correlation analysis showed income,cost for medical care,regular exercise,movement function,ability in the activities of daily living,depression,hypertension and shoulder pain were significantly correlated with most of the SF-36 domain scores.Motor function,income and cost for medical care explained 34％ of the variance in SF-36 scores.Motor function was the single most important factor.Conclusion The major factors affecting the QOL of stroke patients are motor function,level of income and cost for medical care.Paying more attention to rehabilitation treatment,taking regular exercise and more income could help improve the QOL of stroke survivors.