AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen's method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1× 106/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P＜0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P＜0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P＜0.05);among which the combination therapy group took the lead(P＜0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary injury,and promoting axon and myelin regeneration via PI3K/Akt signaling pathway.

Hypercholesterolemia is pathologically characterized by abnormal accumulation of low-density lipoprotein cholesterol,which is closely associated with metabolic dysfunction-associated fatty liver disease and increased cardiovascular risks.Hepatocytes maintain cholesterol homeostasis through LDL receptor-mediated uptake and esterification storage mechanisms.However,chronic cholesterol overload induces mitochondrial dysfunction,reactive oxygen species accumulation,and endoplasmic reticulum stress,leading to hepatocyte injury.Moreover,systemic hypercholesterolemia disrupts gut microbiota balance and impairs short-chain fatty acid and ketone metabolism,exacerbating metabolic disturbances and aggravating hepatic injury through enhanced metabolic stress.In this article,we review the advance of studies on hypercholesterolemia in recent years and summary its association with hepatic injury,which can provide theoretical support for further research.

Hypercholesterolemia is pathologically characterized by abnormal accumulation of low-density lipoprotein cholesterol,which is closely associated with metabolic dysfunction-associated fatty liver disease and increased cardiovascular risks.Hepatocytes maintain cholesterol homeostasis through LDL receptor-mediated uptake and esterification storage mechanisms.However,chronic cholesterol overload induces mitochondrial dysfunction,reactive oxygen species accumulation,and endoplasmic reticulum stress,leading to hepatocyte injury.Moreover,systemic hypercholesterolemia disrupts gut microbiota balance and impairs short-chain fatty acid and ketone metabolism,exacerbating metabolic disturbances and aggravating hepatic injury through enhanced metabolic stress.In this article,we review the advance of studies on hypercholesterolemia in recent years and summary its association with hepatic injury,which can provide theoretical support for further research.

AIM To investigate the repair effects of tauroursodeoxycholic acid(TUDCA)combined with bone marrow mesenchymal stem cells(BMSCs)transplantation on spinal cord injury(SCI)in rats.METHODS The rats were randomly divided into the sham operation group,the model group,the TUDCA group,the BMSCs transplantation group and the combination therapy of TUDCA and BMSCs transplantation group,with the SCI rat model established by Allen's method.The next day after modeling,the rats of TUDCA and combination therapy groups were given 200 mg/kg TUDCA by gavage.On the 3rd day after modeling,rats in BMSCs transplantation group and combination therapy group were injected with 1 mL tuned bone marrow BMSCs(the 3rd generation,1× 106/mL)via tail vein.Rats in the sham operation group and the model group were given gastric perfusion of normal saline and injection of 1 mL PBS through tail vein.On the 3rd,7th and 14th day after modeling,the rats had their motor function of hind limbs observed and BBB score determined.After the corresponding drug administration,the rats had their movement track of hind limbs recorded by footprint experiment;their the protein expressions of IL-6,IL-10,Arg-1,PI3K and Akt in spinal cord tissue detected by Western blot;their pathological changes of spinal cord tissue observed by HE staining and Nissl staining;and their expressions of MAP2,GAP43 and GFAP detected by immunofluorescence staining.RESULTS Compared with the model group,the groups intervened with TUDCA,or BMSCs transplantation,or combination therapy shared improved hind limb function and spinal cord histomorphology(P＜0.05);increased fluorescence intensity of MAP2 and GAP43,and protein expressions of IL-10,Arg-1,p-PI3K and p-Akt(P＜0.05);decreased fluorescence intensity of GFAP and IL-6 protein expressions(P＜0.05);among which the combination therapy group took the lead(P＜0.05).CONCLUSION The combination therapy of TUDCA and BMSCs transplantation may restore the function of the rat model of SCI by reducing inflammatory reaction,alleviating secondary injury,and promoting axon and myelin regeneration via PI3K/Akt signaling pathway.

Objective:This paper mainly discusses the health policy of early life of pregnant women and infants in Beijing as an example,and to provide the basis for policy formulation and optimization.Methods:By using the content analysis method,149 policy texts are divided into two dimensions:policy objectives and policy instruments.The results are described by manual coding,cross analysis and trend analysis.Results:In regard to Policy Objectives,improvement of maternal and child health service levels accounts for the biggest proportion(61.7%),whereas improvement of research level accounts for the least(8.1%).In the four dimensions of policy instruments,mandatory,spontaneous,capacity-building,and incentive tools account for 90%,55%,48%and 42%respectively.According to the trend analysis,integrity of policy system has been continuously improved and the proportion of infant and child care has also increased.Both cross-analysis and trend analysis have showed the strong use of coercive and incentive tools by relevant policies;The use of spontaneous and capacity-building tools is low and decreases over time.Conclusion:Improving the level of maternal and child health services is the core concern of Beijing's early life health policy.However,relatively little attention is paid to the family,infant and child care,and scientific research construction.As for Policy Instruments,mandatory tools are widely used;Incentive Tools and Spontaneous Tools are mainly applied in well-being and soft guidance;insufficient use of Capacity-building Tools.Suggestions:In the future,the policy system should be further improved,which should be targeted and deficiency-mending.It is suggested that more resources should be increased for the family system,more attention should be paid to vulnerable groups early in life,and more financial support should be applied to scientific research on maternal and child health.

A survey was conduct to analyze the usage situation of post-exposure prophylaxis(PEP) and related factors among men who have sex with men(MSM) in 6 cities of Shandong Province. Total of 2 620 subjects, the use ratio was 2.98% (78/2 620). Compared with age≤24 years,monthly income<5 000 yuan,non-commercial sex, non-DU,non-STD,role for being insert in the anal intercourse,MSM was more likely to use PEP with age≥45 years(OR=3.87, 95%CI:1.12-13.36),monthly income≥5 000 yuan(OR=1.87, 95%CI:1.07-3.28),commercial sex (OR=3.13, 95%CI:1.56-6.28), drug users (DUs) (OR=4.63, 95%CI:2.51-8.52),STD patient (OR=2.35,95%CI:1.05-5.27),the mixed sex role group(OR=2.25,95%CI:1.10-4.62).
Male ; Humans ; Young Adult ; Adult ; Middle Aged ; Homosexuality, Male ; HIV Infections/prevention & control* ; Post-Exposure Prophylaxis ; Sexual and Gender Minorities ; Sexual Behavior

Objective: To understand the characteristics and depressive status of men who have sex with men (MSM) who self-reported HIV infection through heterosexual transmission and to provide evidence for personalized management of HIV infected people. Methods: A cross-sectional survey was carried out in Shandong province from September to December in 2019. Male HIV patients aged ≥15 years who self-reported HIV infection through heterosexual transmission were selected to verify the route of infection by one-to-one interview in Ji'nan, Qingdao, Weifang and Linyi cities of Shangdong province. According to the 1∶1 ratio, local HIV patients with age difference ≤3 years who self-reported MSM were selected as controls. A questionnaire survey was conducted, including data on demographic characteristics, behavior status, CES-D and PSSS. The related factors of the depressive symptoms and characteristics were analyzed. Results: A total of 373 male HIV patients were interviewed, and 39.7%(148/373) were confirmed as MSM after reexamination. The interviewers were: aged (40.3±12.0) years old, 41.9% (62/148) married/cohabiting. 27.0% (40/148) had been tested before HIV diagnosis, 71.6% (106/148) had homosexual partners ≥2 and 55.4% (82/148) had depressive symptom. Multivariate analysis showed that the MSM without HIV testings before diagnosis, had homosexual partners ≥2 before diagnosis, had first homosexual behavior at the age >30 years old and with depressive symptoms were more likely to conceal the true infection route. The incidence of depression among MSM who self-reported HIV infection through heterosexual transmission was related to physical health status social support and occupational stability. Conclusions: Some male HIV persons self-reported as being heterosexually transmitted were really transmitted through homosexual behavior. There were high-risk behaviors such as multiple partners and intersex among this group, and with high incidence of depression. It is necessary to encourage the reexamination program during follow-up and target on psychological and behavioral interventions, continuously.
Male ; Humans ; Adult ; Middle Aged ; Heterosexuality ; Depression/epidemiology* ; HIV Infections/epidemiology* ; Self Report ; Homosexuality, Male ; Cross-Sectional Studies ; Sexual and Gender Minorities

OBJECTIVE: To summarize the pathological characteristics of medication-related osteonecrosis of the jaw (MRONJ) specimens after jaw curettage or jaw osteotomy treatment and to comprehensively analyze the relationship between the different pathological features, treatment methods, and treatment effects to provide new ideas for effective treatment of MRONJ in clinical work. METHODS: The clinical and pathological data were collected from 23 patients with MRONJ who were treated with curettage (18 patients) and jaw osteotomy (5 patients) at the Department of Oral and Maxillofacial Surgery of Peking University Hospital of Stomatology between June 2014 and December 2015. The pathological characteristics of MRONJ were summarized and analyzed with treatment effects based on various surgical treatment methods. The diagnostic criteria and disease staging of MRONJ were determined according to the 2014 American Association of Oral and Maxillofacial Surgeon's Position Paper. RESULTS: In this study, 5 patients have treated with jaw segmental osteotomy, and all of them were in stage Ⅲ; the other 18 patients were treated with jaw curettage, including 5 patients in stage Ⅱ and 13 patients in stage Ⅲ. The pathological features of MRONJ in five cases of jaw segmental osteotomy were divided into three adjacent regions from shallow to deep: inflammation region (IR), sclerosis region (SR), and bone remodeling layer (BRL). Moreover, three types of pathological features of specimens from traditional curettage were defined as type 1 (IR), type 2 (IR + SR), and type 3 (IR + SR + BRL). The pathological features of the patients treated with jaw curettage were: type Ⅰ, 38.9% (7/18); type Ⅱ, 44.4% (8/18); type Ⅲ, 16.7% (3/18). Complete healing was achieved in 5 patients treated with jaw segmental osteo-tomy. Moreover, 2 cases with type Ⅰ, 1 case with type Ⅱ, and 1 with type Ⅲ completely healed after jaw curettage, while 5 cases with type Ⅰ, 7 cases with type Ⅱ, and 2 cases with type Ⅲ experienced recurrence after surgery. CONCLUSION Pathological features of continuous regions of inflammation, sclerosis, and bone remodeling layer were identified from shallow to deep, based on the microscopic observation of jaw segmental osteotomy samples. Insufficient removal of the sclerotic region during jaw curettage that blocks the required blood, nutritional factors, and mesenchymal stem cells seems to be a common cause for failed treatment of MRONJ after curettage surgery.
Humans ; Bisphosphonate-Associated Osteonecrosis of the Jaw/etiology* ; Sclerosis/complications* ; Wound Healing ; Treatment Outcome ; Inflammation/complications* ; Bone Density Conservation Agents/adverse effects* ; Diphosphonates/adverse effects*

Objective: To investigate the effect and mechanism of cinnamaldehyde on the angiogenesis of diabetic retinopathy, and the effect of cinnamaldehyde on vascular endothelial growth factor (VEGF) induced proliferation, migration, tube formation and Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway of EA.hy 926 cells were observed. Method:EA.hy 926 cells were divided into normal control group, model group (7 μg·L^-1 VEGF), and VEGF+cinnamaldehyde group (60, 90, 120, 150 μmol·L^-1). The methyl thiazolyl tetrazolium (MTT) assay and scratch test were used to observe the effect of cinnamaldehyde on the proliferation and migration of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L^-1 VEGF), and VEGF+cinnamaldehyde group (90, 150 μmol·L^-1). The tube formation experiment was used to observe the effect of cinnamaldehyde on the tube formation of EA. hy 926 cells induced by VEGF. EA. hy 926 cells were divided into normal control group, model group (7 μg·L^-1 VEGF), VEGF+AG490 group (50 μmol·L^-1), VEGF+cinnamaldehyde group (90 μmol·L^-1), VEGF+cinnamaldehyde group (150 μmol·L^-1), and VEGF+cinnamaldehyde group (150 μmol·L^-1)+AG490 group (50 μmol·L^-1). Western Blot method was used to explore the effect of cinnamaldehyde on the JAK2/STAT3 signaling pathway in EA.hy 926 cells induced by VEGF. Result:Compared with the control group, model group obviously promoted the proliferation and migration of EA.hy 926 cells(P<0.01). Compared with the model group, cinnamaldehyde (60, 90, 120, 150 μmol·L^-1) significantly suppressed VEGF-induced proliferation and migration of EA.hy 926 cells (P<0.01). Compared with the control group, VEGF group could promote the tube formation of EA.hy 926 cells. The number of nodes, junctions, meshes and vascular branches were increased, but with no statistical difference. Compared with the model group, cinnamaldehyde (90, 150 μmol·L^-1) showed an obvious inhibitory effect on the number of nodes, junctions and meshes of tubules (P<0.05, P<0.01).Compared with the control group, the expressions of p-JAK2, p-STAT3, and STAT3 in the model group were significantly increased (P<0.05, P<0.01). Compared with the model group, Cinnamaldehyde (150 μmol·L^-1) significantly reduced the expressions of P-JAK2, P-STAT3, STAT3 proteins (P<0.01). Cinnamaldehyde (90 μmol·L^-1) obviously reduced the expressions of p-STAT3 and STAT3 proteins (P<0.05, P<0.01). Conclusion:Cinnamaldehyde showed a significantly inhibitory effect on the proliferation, migration and tube formation of VEGF-induced EA.hy 926 cells, which was related to the inhibition of the activation of JAK2/STAT3 pathway.

Fingerprints of lipophilic components in the roots of Salvia miltiorrhiza and S.yunnanensis were analyzed by UPLC-DADand UPLC coupled with mass spectroscopy to evaluate the differences and similarities of the lipophilic components in the two kinds of herbs.The UPLC analysis of 18 batches of S.miltiorrhiza and 16 batches of S.yunnanensis was performed on a 25℃Thermo Accucore C_(18)column(2.1 mm×100 mm,2.6μm)by Shimadzu LC-20AD;mobile phase was 0.026%phosphoric acid(A)-acetonitrile(B)with gradient elution;flow rate was 0.4 m L·min~(-1);detection wavelength was set at 270 nm;injection volume was 2μL.The molecular structures of the lipophilic components were analyzed on a 25℃Thermo Accucore C_(18)column(2.1 mm×100 mm,2.6μm)by Thermo U3000 UPLC Q Exactive Orbitrap LC-MS/MS with a mobile phaseconsisting of 0.1%formic acid water(A)and 0.1%formic acidacetonitrile(B).The mass spectrometry was acquired in positive modes using ESI.There are 10 common peaks in the lipophilic components of S.miltiorrhiza.The similarity between the 16 batches of S.miltiorrhiza and their own reference spectra was greater than 0.942,and the average similarity was 0.973.There are 12 common peaks in the lipophilic components of S.yunnanensis.The similarity between the 18 batches of S.yunnanensis and their own reference spectra was greater than 0.937,and the average similarity was 0.976.The similarity between the reference chromatograms of S.miltiorrhiza and S.yunnanensis was only 0.900.There are three lipophilic components in S.yunnanensis,which are not found in S.miltiorrhiza,and one of which isα-lapachone.There is a lipophilic component in S.miltiorrhiza not found in S.yunnanensis,which may be miltirone.The two herbs contain 8 common lipophilic components including dihydrotanshinoneⅠ,cryptotanshinone,tanshinoneⅠ,tanshinoneⅡ_A,nortanshinone in which the content of tanshinoneⅡ_A,dihydrotanshinoneⅠand cryptotanshinone of S.yunnanensisis significantly lower than that of S.miltiorrhiza(P<0.01),and the contents of tanshinoneⅠand nortanshinone are significantly lower than that of S.miltiorrhiza too(P<0.05).There are significant differences in the types and contents of lipophilic components between the roots of S.miltiorrhiza and S.yunnanensis,and the similarity between the fingerprints of interspecies is much lower than that between the same species.Therefore,the roots of S.miltiorrhiza and S.yunnanensis are two kinds of herbs which are quite different in chemical compounds and compositions.
Chromatography, Liquid ; Diterpenes, Abietane ; Molecular Structure ; Plant Roots ; Salvia miltiorrhiza ; Tandem Mass Spectrometry