Liver fibrosis is a common outcome of various chronic hepatic insults, characterized by excessive extracellular matrix (ECM) deposition. The precise mechanisms, however, remain largely undefined. This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3 (Pafah1b3) in liver tissues from both carbon tetrachloride (CCl₄)-treated mice and patients with cirrhosis. Deletion of Pafah1b3 significantly attenuated CCl₄-induced fibrosis, hepatic stellate cell (HSC) activation, and activation of transforming growth factor-β (TGF-β) signaling. Mechanistically, PAFAH1B3 binds to mothers against decapentaplegic homolog 7 (SMAD7), disrupting SMAD7's interaction with TGF-β receptor 1 (TβR1), which subsequently decreases TβR1 ubiquitination and degradation. Pharmacological inhibition using 3-IN-P11, a specific Pafah1b3 inhibitor, conferred protective effects against CCl₄-induced fibrosis in mice. Furthermore, Pafah1b3 deficiency reduced hepatic inflammation. Overall, these results establish a pivotal role for Pafah1b3 in modulating TGF-β signaling and driving HSC activation.

Liver fibrosis is a common outcome of various chronic hepatic insults,characterized by excessive extracellular matrix(ECM)deposition.The precise mechanisms,however,remain largely undefined.This study identified an elevated expression of platelet-activating factor acetylhydrolase 1B3(Pafah1b3)in liver tissues from both carbon tetrachloride(CCl4)-treated mice and patients with cirrhosis.Deletion of Pafah 1b3 significantly attenuated CCl4-induced fibrosis,hepatic stellate cell(HSC)activation,and acti-vation of transforming growth factor-β(TGF-β)signaling.Mechanistically,PAFAH1B3 binds to mothers against decapentaplegic homolog 7(SMAD7),disrupting SMAD7's interaction with TGF-β receptor 1(TβR1),which subsequently decreases TβR1 ubiquitination and degradation.Pharmacological inhibition using 3-IN-P11,a specific Pafah1b3 inhibitor,conferred protective effects against CCl4-induced fibrosis in mice.Furthermore,Pafah 1b3 deficiency reduced hepatic inflammation.Overall,these results establish a pivotal role for Pafahl b3 in modulating TGF-β signaling and driving HSC activation.

Objective:To explore the effect of prognosis appearance of the combination of microneedle array radiofrequency and CO2 array laser on psychological stress response of patients with facial acne scar.Methods:A total of 100 patients with facial acne scar,who admitted to Chengdu Second People's Hospital from August 2020 to August 2020,were selected,and they were divided into study group and control group,with 50 cases in each group.Study group adopted combined treatment with microneedle array radiofrequency and CO2 array laser,and control group adopted microneedle array radiofrequency to conduct treatment.The curative effect after treatment was compared between two groups.The Vancouver scar scale(VSS)was adopted to score the scar condition of patients,and Hamilton anxiety(HAMA)rating scale,Hamilton depression(HAMD)of rating scale and self-esteem scale(SES)were adopted to evaluate the psychological stress response of patients,and the score of the comprehensive evaluation questionnaire of quality of life(GQOLI-74 score)was adopted to evaluate the difference of quality of life of patients between before and after treatment.Results:After treatment,the overall curative effect of study group was 92.00%,which was better than 72.00%of control group,and the difference was significant(x2=6.775,P<0.05).The VSS scores of study group after received treatment of 2,4 times were significantly lower than those before treatment,and were lower than those of control group,and the differences of those between two groups were significant(t=5.850,9.040,P<0.05),respectively.After treatment,the SES scores of two groups all rose,and the HAMD and HAMA scores of two groups all reduced,and the three scores of study group were all better than those of control group,and the differences of them between two groups were significant(t=3.456,3.909,6.063,P<0.05).Pearson correlation showed that the VSS score was negatively correlated with the SES score(r=-0.249,P<0.05),and was positively correlated with the HAMD score and the HAMA score(r=0.653,0.695,P<0.05),respectively.After treatment,the GQOLI-74 scores of each indicator(material and life,physical function,psychological function,and social function)of two groups rose all,and the GQOLI-74 scores of study group were all better than those of control group,and the differences of them between two groups were significant(t=4.324,7.497,3.870,4.534,P<0.05),respectively.Conclusion:The combination of microneedle array radiofrequency and CO2 array laser has better curative effect in treating facial acne scar,which can effectively promote prognosis appearance,and relieve psychological stress response,and improve the quality of life.

Objective:To explore the effect of prognosis appearance of the combination of microneedle array radiofrequency and CO2 array laser on psychological stress response of patients with facial acne scar.Methods:A total of 100 patients with facial acne scar,who admitted to Chengdu Second People's Hospital from August 2020 to August 2020,were selected,and they were divided into study group and control group,with 50 cases in each group.Study group adopted combined treatment with microneedle array radiofrequency and CO2 array laser,and control group adopted microneedle array radiofrequency to conduct treatment.The curative effect after treatment was compared between two groups.The Vancouver scar scale(VSS)was adopted to score the scar condition of patients,and Hamilton anxiety(HAMA)rating scale,Hamilton depression(HAMD)of rating scale and self-esteem scale(SES)were adopted to evaluate the psychological stress response of patients,and the score of the comprehensive evaluation questionnaire of quality of life(GQOLI-74 score)was adopted to evaluate the difference of quality of life of patients between before and after treatment.Results:After treatment,the overall curative effect of study group was 92.00%,which was better than 72.00%of control group,and the difference was significant(x2=6.775,P<0.05).The VSS scores of study group after received treatment of 2,4 times were significantly lower than those before treatment,and were lower than those of control group,and the differences of those between two groups were significant(t=5.850,9.040,P<0.05),respectively.After treatment,the SES scores of two groups all rose,and the HAMD and HAMA scores of two groups all reduced,and the three scores of study group were all better than those of control group,and the differences of them between two groups were significant(t=3.456,3.909,6.063,P<0.05).Pearson correlation showed that the VSS score was negatively correlated with the SES score(r=-0.249,P<0.05),and was positively correlated with the HAMD score and the HAMA score(r=0.653,0.695,P<0.05),respectively.After treatment,the GQOLI-74 scores of each indicator(material and life,physical function,psychological function,and social function)of two groups rose all,and the GQOLI-74 scores of study group were all better than those of control group,and the differences of them between two groups were significant(t=4.324,7.497,3.870,4.534,P<0.05),respectively.Conclusion:The combination of microneedle array radiofrequency and CO2 array laser has better curative effect in treating facial acne scar,which can effectively promote prognosis appearance,and relieve psychological stress response,and improve the quality of life.

Leber's hereditary optic neuropathy (LHON) is an ocular mitochondrial disease that involves the impairment of mitochondrial complex I, which is an important contributor to blindness among young adults across the globe. However, the disorder has no available cures, since the approved drug idebenone for LHON in Europe relies on bypassing complex I defects rather than fixing them. Herein, PARKIN mRNA-loaded nanoparticle (mNP)-engineered mitochondria (mNP-Mito) were designed to replace dysfunctional mitochondria with the delivery of exogenous mitochondria, normalizing the function of complex I for treating LHON. The mNP-Mito facilitated the supplementation of healthy mitochondria containing functional complex I via mitochondrial transfer, along with the elimination of dysfunctional mitochondria with impaired complex I via an enhanced PARKIN-mediated mitophagy process. In a mouse model induced with a complex I inhibitor (rotenone, Rot), mNP-Mito enhanced the presence of healthy mitochondria and exhibited a sharp increase in complex I activity (76.5%) compared to the group exposed to Rot damage (29.5%), which greatly promoted the restoration of ATP generation and mitigation of ocular mitochondrial disease-related phenotypes. This study highlights the significance of nanoengineered mitochondria as a promising and feasible tool for the replacement of dysfunctional mitochondria and the repair of mitochondrial function in mitochondrial disease therapies.

Parkinson′s disease (PD) is the second most common neurodegenerative disease in middle-aged and elderly people. In addition to motor symptoms, PD also has many non motor symptoms, such as dysosmia, constipation, cognitive impairment, etc. Among them, dysosmia is a common non motor symptom of early Parkinson′s disease. Research has confirmed that olfactory dysfunction (OD) can appear before the typical clinical symptoms of PD, which is of great significance to the diagnosis and treatment of diseases. However, at present, the pathogenesis of OD is still unclear, and the inspection methods have not been unified, and there is no complete cure. This article reviews the latest research progress of dysosmia in Parkinson′s disease.

Objective:To investigate the clinical features and influencing factors of long-term prognosis of tuberculous meningitis(TBM), and to provide a recommendation for treatment and early intervention of TBM.Methods:Clinical data of TBM patients were retrospectively collected at Peking Union Medical College Hospital from January 2014 to December 2021. Patients who were followed-up more than one year were divided into two groups according to modified Rankin Scale (mRS). Risk factors associated with long-term prognosis were analyze by conditional logistic stepwise regression.Results:A total of 60 subjects were enrolled including 33 (55%) males and 27 (45%) females with age 15-79 (44.5±19.8) years. There were 30 cases (50%) complicated with encephalitis, 21 cases (35%) with miliary tuberculosis. The diagnosis was microbiologically confirmed in 22 patients (36.7%), including 5 cases (22.7%, 5/22) by acid-fast staining, 8 cases (36.4%, 8/22) by Mycobacterium tuberculosis (MTB) culture, and 20 cases (90.9%, 20/22) by molecular biology. The median follow-up period was 52(43, 66 ) months in 55 cases surviving more than one year. Among them, 40 cases (72.7%) were in favorable group (mRS 0-2) and 15 cases (27.3%) were in unfavorable group (mRS 3-6) with poor prognosis. The mortality rate was 20% (11/55). Elderly ( OR=1.06, P=0.048 ) , hyponatremia( OR=0.81, P=0.020), high protein level in cerebrospinal fluid (CSF) ( OR=3.32, P=0.033), cerebral infarction( OR=10.50, P=0.040) and hydrocephalus( OR=8.51, P=0.049) were associated with poor prognosis in TBM patients. Conclusions:The mortality rate is high in patients with TBM. Molecular biology tests improves the sensitivity and shorten the diagnosis time of TBM. Elderly, hyponatremia, high protein level in CSF, cerebral infarction and hydrocephalus are independent risk factors of long-term survival in TBM patients.

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Objective To investigate the effect of baicalin on CT26.WT cells of colon cancer in mice, and to discuss the cell death form. Methods CT26.WT cells were divided into four groups including of control group , routine cultured in fresh medium, the baicalin group, added with concentration of 100 μmol·L-1 baicalin, the z-VAD-fmk group, was added with final concentration of 20 μmol·L-1 z-VAD-fmk, and the combination group, added final concentration of 20 μmol·L-1 z-VADfmk,1 h before adding 100 μmol·L-1 baicalin. Then the inhibitory effect of baicalin on cell proliferation and cell viability were detected by CCK-8 method. The changes of nucleus were detected by DAPI staining, the ultrastructure of cells was observed by TEM, and the effect of baicalin on the expression of RIP3 gene and protein in cells was detected by QPCR method and Western blotting. Results Compared with control group, the differences of baicalin group and combination group had statistically significance (P<0.05) . cell death rate for control group was (10.54±0.19) ％ ,for baicalin group was (34.93±0.16) ％ ,for z- VAD group was (11.23±0.59) ％, and combination group was (23.27±1.20) ％ (P<0.01) . Compared with the normal control group, baicalin group showed nuclear concentration and fragmentation. there was obvious nuclear fragmentation in the combination group against baicalin group. The results of electron microscopy showed that the cells of baicalin were necrotic, cell swelling, mitochondria swelling and contents leaking. Baicalin group significantly up - regulated RIP3 mRNA expression (P < 0. 01) and enhanced RIP3 protein expression (P < 0. 05) . Conclusion Baicalin induces the necrosis of ct26. WT cells, and can significantly increase the gene and protein expression of RIP3.