ObjectiveTo investigate the possible mechanism by which Zhiqiao Gancao Decoction （枳壳甘草汤， ZGD） delays intervertebral disc degeneration （IDD） based on the Hippo-yes-associated protein （YAP）/transcriptional co-activator with PDZ-binding motif （TAZ） signaling pathway. MethodsA total of 50 SD rats were randomly divided into sham surgery group， model group， low-dose ZGD group， high-dose ZGD group， and high-dose ZGD + inhibitor group， with 10 rats in each group. In the sham surgery group， the rats were pierced in the skin and muscle at the Co6/7/8 segments of the tail with a 21G needle （depth approximately 2 mm） without damaging the intervertebral disc. In the other groups， rats were injected with a 21G needle at the Co6/7/8 segments of the tail to establish an IDD model by piercing the tail intervertebral disc 5 mm. One week after modeling， rats in the low-dose and high-dose ZGD groups were given 6.24 and 12.24 g/（kg·d） of the decoction via gastric gavage， respectively. The high-dose ZGD + inhibitor group was given 12.24 g/（kg·d） of the decoction and an intraperitoneal injection of YAP/TAZ inhibitor Verteporfin 10 mg/kg. The sham surgery and model groups were given 5 ml/（kg·d） of normal saline via gavage. The gavage was given once a day， and the intraperitoneal injection was given every other day. After 4 weeks of continuous intervention， the pathological changes of the tail intervertebral discs were observed using HE staining， Oil Red O-Green staining， and Toluidine Blue staining. Immunohistochemistry was used to detect the expression of aggrecan and MMP3 in the nucleus pulposus. TUNEL fluorescence staining was performed to detect apoptosis in the nucleus pulposus， and the apoptosis rate was calculated. Western blot was used to detect the Hippo-YAP/TAZ signaling pathway， including YAP， phosphorylated YAP （p-YAP）， phosphorylated MST1/2 （p-MST1/2）， phosphorylated TAZ （p-TAZ） and apoptosis-related proteins， such as Cleaved Caspase 3， P53， Bcl-2 and Bax. ResultsCompared with sham surgery group， the rats in the model group showed significant degenerative changes in the intervertebral disc. The levels of aggrecan， Bcl-2， and YAP proteins in the nucleus pulposus decreased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate increased （P < 0.01）. Compared with the model group， the drug intervention groups showed partial recovery in intervertebral disc degeneration. The levels of aggrecan， Bcl-2， and YAP proteins increased， while the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and the apoptosis rate decreased （P＜0.05 or P＜0.01）. The high-dose ZGD group showed more significant recovery in intervertebral disc degeneration compared to the low-dose ZGD group， with a decrease in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and an increase in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. Compared with the high-dose ZGD group， the high-dose ZGD + inhibitor group showed a reduced recovery in intervertebral disc degeneration， with an increase in the levels of p-MST1/2， p-YAP， p-TAZ， P53， Bax， Cleaved Caspase 3， MMP3 proteins， and apoptosis rate， and a decrease in the levels of aggrecan， Bcl-2， and YAP proteins （P＜0.05 or P＜0.01）. ConclusionZGD may delay intervertebral disc degeneration by inhibiting the phosphorylation of YAP in the nucleus pulposus， maintaining the function of the Hippo-YAP/TAZ signaling pathway， and reducing apoptosis of nucleus pulposus cells.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

BACKGROUND:The occurrence and development of various ophthalmic diseases are closely related to excessive oxidative stress,and the inhibition of oxidative stress response may produce preventive and therapeutic effects. OBJECTIVE:To explore the role of Pax6 gene expression on hydrogen peroxide-induced aging of mouse bone marrow mesenchymal stem cells(BM-MSCs). METHODS:Resuscitated BM-MSCs,Pax6/BM-MSCs,and shPax6/BM-MSCs were treated with hydrogen peroxide for 24 hours,and then β-galactosidase staining was performed.The proliferation index Ki67 expression and apoptosis were detected by flow cytometry.The expression of senescence-associated molecules(Wnt7a,p21,and p53)was detected by RT-PCR. RESULTS AND CONCLUSION:(1)After hydrogen peroxide treatment,the cells of the three groups showed senescence phenotype and β-galactosidase staining was positive.Compared with BM-MSCs group,the expression of positive cells in Pax6/BM-MSCs group was less and that in the shPax6/BM-MSCs group was more,and the difference was statistically significant(P<0.05).(2)The results of flow cytometry showed that compared with BM-MSCs group,the positive expression of Ki67 in the Pax6/BM-MSCs group increased and the level of apoptosis decreased,while the positive expression of Ki67 decreased and the level of apoptosis increased in the shPax6/BM-MSCs group;the difference was significantly different(P<0.05).(3)RT-PCR showed that compared with the BM-MSCs group,the expression of Wnt7a,p53,and p21 decreased in the Pax6/BM-MSCs group,while the expression of Wnt7a,p53,and p21 increased in the shPax6/BM-MSCs group;the difference was significantly different(P<0.05).(4)These findings indicate that overexpression of Pax6 can antagonize the aging progression of BM-MSCs induced by hydrogen peroxide,which may be related to Wnt signaling pathway.

AIM:To observe the effect of curcumin on a C57BL/6J mouse liver cancer model induced by N-ni-trosodiethylamine(DEN)combined with carbon tetrachloride(CCl4),and to explore its mechanism.METHODS:Forty young male C57BL/6J mice were intraperitoneally injected with DEN(25 mg/kg)14 d after birth and randomly divided in-to the following 4 groups at the 4th week(10 in each group):model control group and curcumin(100,200 and 400 mg/kg)groups.Ten male mice of the same age were used as normal control group.The mice in model group and curcumin groups were gavaged with 10%CCl4(5 mL/kg)twice a week from the 8th week on.At the same time,the mice in curcumin groups were gavaged with curcumin,and the mice in normal control group were gavaged with the same volume of distilled water once a day for 14 weeks.After administration,the mice were sacrificed,the liver surface was observed,and the number of tumor nodules was compared.The activity of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum was detected by an automatic biochemical instrument.The pathological changes of liver tissues were ob-served by HE staining.The mRNA expression levels of heme oxygenase-1(HO-1)and NAD(P)H-quinone oxidoreductase 1(NQO1)were detected by RT-qPCR,and the protein expression levels of HO-1,NQO1 and Ki67 were detected by Western blot and immunohistochemistry.RESULTS:Compared with normal control group,the body weight of the mice in model group was decreased significantly(P＜0.01),the liver index was increased significantly(P＜0.01),and the se-rum levels of ALT and AST were increased obviously(P＜0.01).There was no significant difference in the mRNA expres-sion levels of HO-1 and NQO1(P＞0.05),the protein levels of HO-1 and NQO1 were increased distinctly(P＜0.05),and the positive expression rate of Ki67 was increased significantly(P＜0.05).After curcumin treatment,the body weight of the mice was significantly increased(P＜0.01),the liver index was not changed(P＞0.05),and the number of tumor nodules in the liver was decreased significantly(P＜0.05 or P＜0.01).The serum level of AST was decreased significantly(P＜0.01),the mRNA and protein expression levels of HO-1 and NQO1 were decreased significantly(P＜0.05),and the posi-tive expression rate of Ki67 was decreased significantly(P＜0.05).CONCLUSION:Curcumin significantly protects against liver cancer in a C57BL/6J mouse model induced by DEN combined with CCl4,and its mechanism may be related to the inhibition of HO-1 and NQO1 expression.

Objective To explore the molecular mechanism of lipopolysaccharide(LPS)on the contraction of pregnant uterine smooth muscle at tissue and cellular levels.Methods C57BL/6J mice at 16 days of gestation were randomly divided into control group and LPS group.The mice in LPS group were intraperitoneally injected with 20 μg in LPS solution to establish the model of preterm birth,and the mice in control group were intraperitone-ally injected with the same amount of normal saline.Isolated uterine muscle strips were used to detect changes in the contractile function of the tissue,as well as changes in the expression and function of the contraction key signa-ling molecule TWIK-related K+channel 1(TREK-1).Primary cultured pregnant mouse uterine smooth muscle cells were used to detect the expression of TREK-1 under the regulation of LPS.Results The contractility of mouse u-terine tissues was significantly enhanced by LPS,and the protein expression of TREK-1,a key signal for contrac-tion,was significantly reduced,and activation of TREK-1 resulted in a significant down-regulation of the enhanced contractility of mouse uterine tissues in the LPS group.However,there was no significant difference in the expres-sion of TREK-1 protein,which was highly expressed in the smooth muscle of pregnant mice,when LPS acted on the primary uterine smooth muscle cells of pregnant mice.Conclusion Uterine contractility is enhanced in pregnant mice uterine tissues by inhibiting TREK-1 expression and function in response to LPS,and it may be one of the mechanisms by which LPS induces preterm labor.However,the effect of LPS on TREK-1 on mouse pregnant uter-ine smooth muscle cells may be realized through intercellular signaling and not directly on uterine smooth muscle cells.This further suggests that the animal and histological experiments cannot be completely replaced by isolated cell experiments in the study of inflammatory preterm labor.

Objective To describe the distribution characteristics of knee and ankle joint range of motion and muscle atrophy related indexes in patients with Kashin-Beck disease(KBD)in Shaanxi Province so as to explore the correlation of knee and ankle joint range of motion(ROM)with muscle atrophy indexes and provide reference for clinical characteristics analysis of KBD patients.Methods To investigate the registered KBD patients from KBD areas in Shaanxi Province,we measured the general demographic data of the patients were collected and the ROM of the knee joint(flexion and extension),the ankle joint(dorsiflexion and plantar flexion),and the muscle atrophy related indexes such as the upper arm circumference,thigh circumference,calf circumference and grip strength.According to the population characteristics,i.e.,gender,age,body mass index(BMI)and KBD grade,the median and quartile of joint ROM and muscle atrophy of KBD patients were reported,and then the differences in each index among different groups were analyzed.Partial correlation analysis was used to explore the correlation between indicators after controlling for variables such as gender,age and BMI.Results A total of 480 patients with KBD were investigated in this study,who consisted of 249(51.9％)males and 231(48.1％)females,with an average age of(63.10±7.32)years and an average BMI of(23.49±8.90)kg/m2.The knee flexion ROM,knee extension ROM,ankle dorsiflexion ROM and ankle plantar flexion ROM were[105.0(95.0,120.0)]°,[0.0(-15.0,0.0)]°,[5.0(0.0,15.0)]° and[20.0(15.0,30.0)]°,respectively,in KBD patients in Shaanxi Province.The left thigh circumference,right thigh circumference,left calf circumference,right calf circumference,and upper arm circumference were[43.0(40.0,47.0)]cm,[43.0(39.0,47.0)]cm,[29.0(27.0,32.0)]cm,[29.5(27.0,32.0)]cm,[27.0(25.0,30.0)]cm,respectively.The left hand grip strength and right hand grip strength were[13.4(9.5,18.4)]kg and[13.9(9.8,18.2)]kg,respectively.With the increase of age,the extension range of the left and right knee joints of KBD patients showed a decreasing trend(H=31.499,31.847;all P＜0.001).The range of motion of bilateral knee flexion was higher in the normal BMI group than in the overweight or obese group,with statistically significant differences(H=7.753,12.333;P=0.021,0.002).The knee flexion,thigh circumference,and calf circumference of the left and right sides showed a decreasing trend under different KBD grades(H=14.345,17.256,8.000,8.462,8.558,9.633;all P＜0.05).Correlation analysis showed that knee flexion ROM was positively correlated with thigh circumference,calf circumference,and grip strength in patients with KBD(all P＜0.05).There was a positive correlation between knee extension ROM and thigh circumference in patients with KBD(P＜0.01).Conclusion The impaired joint ROM and muscle atrophy are serious in KBD patients in Shaanxi Province,and there is a correlation between joint motion and muscle atrophy.

Objective:To describe the prevalence of food allergy among children aged 0-5 years in China and to explore related influencing factors.Methods:Multistage stratified random sampling method was used to collect data from 275 surveillance sites of the China National Nutrition and Health Survey of Chinese children and lactating mothers programs in 31 provinces (autonomous regions and municipalities) of China in 2016-2017. A total of 70 107 participants aged 0-5 years were included in this study. The study collected information of participants' demographic characteristics and food allergies by face-to-face questionnaire. The prevalence of food allergy was analyzed, using the complex data weighting method. The logistic regression models were used to analyze the influencing factors related to food allergy.Results:The overall prevalence of self-reported food allergy among children aged 0-5 years was 4.81%. Prevalence rates in infants aged 0-5 months, and 6-23 months and preschool children aged 2-5 years were 0.81%, 4.68% and 5.26%, respectively. The results of logistic analysis showed that there was a significantly positive correlation between factors including children from 6 months to 5 years old, urban area, southwest area, first-born, mothers with college education or above, and the prevalence of food allergy in children. Shrimp, poultry eggs, crab shellfish, fruit, milk and fish appeared the common allergic foods in children aged 0-5 years, with prevalence rates of self-reported food allergy as 1.55%, 1.25%, 0.99%, 0.97%, 0.87% and 0.86%, respectively. The proportion of single food allergy in children with allergies was 69.85%.Conclusions:Among children aged 0-5 years, the prevalence of self-reported food allergy increases with age, in China. Foods that is prone to allergies include fish, shrimp, crab, shellfish, poultry eggs, milk and fruits, etc. Most allergies were only caused by single food in children, under observation.

Mitochondria are the main site of energy metabolism in cardiomyocytes， and at the same time mediate apoptosis and immune response， so mitochondrial dysfunction is closely related to the development of heart failure. Combined with the pathogenesis of mitochondrial dysfunction and heart failure， it is proposed that the mitochondrial function is similar to "sweat pore - collaterals - zang and fu organs"， according to which the treatment of heart failure is based on the theory of "sweat pore - collaterals - zang and fu organs". It is believed that the core mechanism of heart failure is qi deficiency， and qi deficiency leads to the weakness of the sweat pore opening and closing， or even the sweat pore closure， then resulting in qi deficiency and blood stasis， collaterals stagnation fail to flourish， and qi， blood， and body fluids can not infiltrate and nourish zang-fu organs， so that the heart fail to be nourished， and the disease will develop. The treatment should be based on the method of boosting qi and opening sweat pore， using acridity to unblock the collaterals， and invigorating blood and draining water， with medicinal of boosting qi， invigorating blood， and draining water as treatment.

Objective To comprehensively analyze the effectiveness of exercise training-based respiratory rehabilitation therapy on patients with occupational pneumoconiosis (hereinafter referred to as "pneumoconiosis"). MethodsLiterature on randomized controlled trials of exercise training-based respiratory rehabilitation therapy for pneumoconiosis patients published from the establishment of the database to July 2023 was retrieved from academic systems such as the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP Database, and China Biology Medicine using bibliometrics method. The RevMan 5.4 software was used for meta-analysis of the selected literatures. Subgroup analysis was conducted to explore the source of study heterogeneity. The funnel plot method was used to test publication bias. Results A total of 55 articles were included, involving 2 436 pneumoconiosis patients in the experimental group and 2 405 pneumoconiosis patients in the control group. The result of random or fixed effect model showed that the six minutes walking distance, the total score of Short from Health Survey-36, forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), FEV₁/FVC, arterial partial pressure of oxygen of pneumoconiosis patients increased after respiratory rehabilitation therapy (all P<0.05), while the total score of the St. George's Respiratory Questionnaire and arterial partial pressure of carbon dioxide decreased compared with the conventional treatment (all P<0.05). The result of subgroup analysis showed that the total score of the St. George's Respiratory Questionnaire, FEV₁, and the index of arterial partial pressure of oxygen of pneumoconiosis patients was better in the rehabilitation treatment for ≥six months compared with those

Objective:To explore the genetic etiology of a pedigree with intellectual disability and explore its pathogenesis.Methods:A Chinese pedigree which had presented at the Henan Provincial People′s Hospital in March 2023 was selected as the study subject. Clinical data of the pedigree were collected, along with peripheral venous blood samples from its members. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. Amniotic fluid was collected for prenatal diagnosis. This study was approved by the Medical Ethics Committee of the Henan Provincial People′s Hospital (No. 2019-134).Results:Both the proband (a 6-year-old male) and his mother (30 years old) had various degrees of intellectual and motor impairment. WES revealed that the proband has harbored a de novo heterozygous c. 2563_2567dup (p.Lys856fs) variant of the UBE3A gene, while his mother, maternal grandmother and fetus had all harbored a novel heterozygous c. 409+ 1G>A variant of the RNF13 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+ PS1+ PM2_Supporting; PVS1+ PM2_Supporting+ PP3). Conclusion:Based on the clinical manifestations and the result of genetic testing, the heterozygous c.2563_2567dup (p.Lys856fs) variant of the UBE3A gene probably underlay the intellectual disability and developmental delay in the proband, whilst the heterozygous c. 409+ 1G>A variant of the RNF13 gene may underlie the intellectual disability in the proband′s mother and grandmother. Above results have enabled genetic counseling and prenatal diagnosis for this pedigree.