Objective: To investigate the molecular regulatory mechanism of hypoxia-inducible factor-1α (HIF-1α) in mechanical stress-induced inflammatory cytokine expression in human periodontal ligament cells (hPDLCs), providing a theoretical basis and potential therapeutic target for inflammatory control during orthodontic treatment. Methods: This study was approved by the Institutional Ethics Committee. Primary human periodontal ligament cells (hPDLCs) were isolated and cultured in vitro. Self-renewal capacity was confirmed via colony-forming assays, while osteogenic and adipogenic differentiation potential was evaluated via Alizarin Red S staining, alkaline phosphatase (ALP) activity assays, and Oil Red O staining. An in vitro compressive force stimulation model (1.5 g/cm2, 12 h) was established to compare inflammatory cytokine expression of hPDLCs—interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and HIF-1α—between the Control group (no mechanical stimulation) and the Force group (1.5 g/cm2, 12 h) using quantitative real-time PCR (qRT-PCR), Western blot, and immunofluorescence (IF) staining. Mechanically induced HIF-1α-regulated gene expression changes were analyzed through transcriptomic sequencing. To explore pharmacological inhibition, the small-molecule HIF-1α inhibitor LW-6 was applied at varying concentrations (10 μmol/L, 30 μmol/L, 50 μmol/L) to optimize the treatment dose. Subsequently, qRT-PCR, Western blot, and IF staining were conducted to evaluate inflammatory cytokine of hPDLCs and HIF-1α expression in three groups: Control (no force), Force (1.5 g/cm2, 12 h), and Force+LW6 (1.5 g/cm2, 12 h + 30 μmol/L LW-6). Results: Primary hPDLCs demonstrated self-renewal capacity along with osteogenic and adipogenic differentiation potential. Compared to the Control group, the Force group exhibited significantly increased mRNA and protein expression levels of inflammatory cytokines IL-1β, IL-6, and TNF-α, along with enhanced fluorescence intensity of IL-1β and TNF-α. Transcriptomic analysis revealed that mechanical compressive force activated the HIF-1 signaling pathway, which subsequently mediated inflammatory responses and bone remodeling processes in hPDLCs. Furthermore, the mRNA and protein levels of HIF-1α were considerably elevated in the Force group compared to the Control group. Treatment with LW-6 (10, 30, or 50 μmol/L) effectively suppressed HIF-1α expression, with 30 μmol/L LW-6 identified as the optimal concentration for intervention. In subsequent experiments, the Force group showed significant upregulation in mRNA/protein expression of IL-1β, IL-6, and TNF-α compared to the Control group, as well as intensified HIF-1α, IL-1β, and TNF-α fluorescence signals. Conversely, the Force+LW6 group (mechanical force + 30 μmol/L LW-6) exhibited a notable reduction in inflammatory cytokine expression levels and a weakening of HIF-1α, IL-1β, and TNF-α fluorescence signals compared to the Force group. Conclusion HIF-1α potentiates mechanical stress-induced inflammatory responses in hPDLCs and may serve as a promising therapeutic target for mitigating orthodontic-associated periodontal inflammation.

Objective To explore the effects of spermary on sexual behavior,gonadal development and sperm count production.Methods Fifty-six male zebrafishes of 10-month-old AB strain after fertilization were randomly divided into 7 tanks and set up as the normal group,model group,positive control group(clomiphene citrate group,Wuzi Yanzong Pills group),and Spermary low,medium and high concentration groups,8 fishes in each group.Except for the normal group,cyclophosphamide was given in water solution to establish the zebrafish oligospermia model,respectively.On 9 d of modeling,the positive control group was ad-ministered at a concentration of 0.1 μg/mL in the clomiphene citrate group and 6 μg/mL in the Wuzi Yanzong Pill group;the spermary low,medium and high concentration groups were administered at 200,300,900 μg/mL,respectively.On 16 d of modeling,the normal female zebrafishes were placed in the culture tank of each group in a 1∶1 ratio,and the frequency of tail-chasing was observed and recorded in male and female fishes.The body length,weight,testis weight and sperm count were measured and the statistical analysis was performed by comparing the differences among the groups before and after drug administration(one-way ANOVA).Results Com-pared with the normal group,the frequency of tail-chasing of zebrafishes,body length,body weight,testis weight and sperm count in the model group were significantly decreased(P＜0.05).Compared with the model group,the frequency of tail-chasing of zebrafishes,body length,body weight,testis weight and sperm count in the spermary low,medium and high concentration groups all were significantly increased(P＜0.05),in which the vitality change of sexual behavior in the spermary medium concentration group was most obvious,and the increase of sperms count was most obvious.Conclusion A certain dose of spermary could effectively promote the sexual behavior,gonadal development and sperm count production in male zebrafish with oligospermia.The efficacy of spermary in enhancing the male sexual function and treating oligozoospermia and infertility de-serves to be studied.

Background: and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). Methods: We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. Results: Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. Conclusion The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*

OBJECTIVE: To observe the effects of abdominal acupuncture and the periodic therapy of Chinese herbal medicine on follicular development and endometrial receptivity in the patients with infertility induced by ovulation failure and differentiated as kidney deficiency in TCM. METHODS: A total of 84 patients with infertility induced by ovulation failure and differentiated as kidney deficiency were randomized into a combined therapy group (27 cases), an abdominal acupuncture group (27 cases) and a western medication group (30 cases). In the combined therapy group, abdominal acupuncture and the periodic treatment of Chinese herbal medicine was provided. In the abdominal acupuncture group, the simple abdominal acupuncture therapy was used. In the western medication group, clomiphene citrate (CC) and human chorionic gonadotrophin (HCG) prescribed. The treatment for one menstrual cycle was taken as one session and 3 sessions of treatment were required except the pregnancy. The folicle development, endometrial thickness and morphology, menstrual condition and TCM symptom score were observed before and after treatment in the three groups, and the clinical efficacy was evaluated. RESULTS: After treatment, the ovulation was recovered to different degrees in the three groups. The ovulation rate was 59.3% (16/27) in the combined therapy group, 55.6% (15/27) in the abdominal acupuncture group and 53.3% (16/30) in the western medication group. The difference was not significant in comparison among the three groups (>0.05). After treatment, the endometrial thickness in the periovulatory period was increased as compared with the thickness before treatment in the combined therapy group and the abdominal acupuncture group (both <0.05). After treatment, the endometrial thickness in the combined therapy group was higher than the western medication group (<0.05). In comparison before and after treatment, the difference in the endometrial morphology was significant in the combined therapy group and the abdominal acupuncture group (both <0.05). In comparison between the combined therapy group and the western medication group, the difference in the endometrial morphology was significant after treatment (<0.05). After treatment, the menstrual condition and TCM symptom score in the combined therapy group and the abdominal acupuncture group were all improved as compared with those before treatment (all <0.05). The score of menstrual condition in the combined therapy group was higher than the western medication group (<0.05) and TCM symptom score in the combined therapy group and abdominal acupuncture group was higher than the western medication group after treatment (all <0.05). The total effective rate was 88.9% (24/27) in the combined therapy group and was 92.6% (25/29) in the abdominal acupuncture group, which was higher than 56.7% (17/30) in the western medication group (<0.01). There was no adverse reaction in the combined therapy group and the abdominal acupuncture group. CONCLUSION Abdominal acupuncture combined with the periodic therapy of Chinese herbal medicine improve the menstrual condition and relieve the clinical symptoms of infertility induced by ovulation failure of kidney deficiency in the patients and the therapeutic effects are better than the medication with CC + HCG. This combined therapy improves the ovulation rate and the endometrial receptivity at periovulatory stage to increase the pregnancy rate. There is no adverse reaction discovered in clinical practice.
Acupuncture Therapy ; Clomiphene ; Drugs, Chinese Herbal ; Female ; Humans ; Infertility, Female ; Ovulation ; Pregnancy

Meridians in human body were classified as white meridian and black meridian according to Tibetan medicine.Season and environment,improper diet,toxic heat and trauma were recognized as main reasons damaging the white meridian in Tibetan Medicine,leading to the emerge of white meridian disease induced by Long (one of the three factors) and blood disorder.White meridian disease in Tibetan medicine involved a series diseases,such as many clinical diseases,due to the damage of white meridian system caused by pathogenic factors.Stroke also belonged to white meridian disease.Drugs and treatments were selected based on the nature of disease such as cold and heat,onset,thelocation of disease and the three factors (Chi Ba,Long and Pei Gen).It was the fundamental principle of the treatment rules of white meridian disease in Tibetan medicine,namely,prescribing medication with the rule of diagnosis and treatment,comprehensive analysis of the causes of diseases and mastering the change law of diseases and syndromes in clinic.

Objective To explore the relationship between blood glucose level and blood pressure variability in hypertensive patients. Methods A total of 125 hypertensive patients hospitalized in the department of cardiology in our hospital during May 2015 to October 2016 were retrospectively analyzed. Patients were divided into hypertension with diabetes mellitus group (n=59) and hypertension without diabetes mellitus groups (n=66). Data of blood pressure, blood pressure variability and blood glucose levels were analyzed in the two groups. Results (1) Hyperlipidemia, low density lipoprotein and cholesterol levels were significantly lower in the hypertension with diabetes mellitus group than those of hypertension without diabetes mellitus group. Level of glycosylated hemoglobin (HbA1c), 24 h diastolic pressure variability coefficient (24 hDBPCV), daytime systolic blood pressure variability coefficient (dSBPCV), and daytime diastolic pressure variability coefficient (dDBPCV) were significantly higher in the hypertension with diabetes mellitus group than those of hypertension without diabetes mellitus group (P<0.05). (2) Spearman correlation analysis showed that hypertension with diabetes mellitus was positively correlated with 24 hDBPCV, dSBPCV and dDBPCV. (3) ROC curves of HbA1c for diagnosis of non-dipper blood pressure in hypertensive patients showed that the cut-off value of HbA1c was 5.85%and the area under curve was 0.692 (P<0.05). The sensitivity was 71.1% and the specificity was 63.7%. Conclusion The present results demonstrate that blood pressure variability is increased in hypertension patients with higher blood glucose. HbA 1c level has potential clinical value for diagnosis of non-dipper blood pressure in hypertensive patients.

OBJECTIVETo investigate the prevalence of serum antibodies against Japanese encephalitis virus (JEV) in bats.

METHODSBlood samples from the heart were obtained from bats captured in Guangdong and Hainan Provinces in 2013. The anti-JEV antibodies in bat sera were tested using indirect ELISA and virus neutralization test.

RESULTSA total of 201 bat serum samples were tested, in which the total positivity rate of anti-JEV antibodies was 46.27% (93/201). The positive rate of anti-JEV antibodies in bats from Hainan and Guangdong Provinces was 88.89% (48/54) and 30.61% (45/147), respectively. All the samples from Rousettus leschenaultia, Miniopterus schreibersii, Pipistrellus abramus, and Rhinolophus macrotis were positive for anti-JEV antibodies, and up to 95.56% (43/45) of the samples from Miniopterus schreibersii (from Hainan Province) yielded positive results. Of the 28 samples with positive results by indirect ELISA, 15 showed positive results in virus neutralization test (53.57%) with neutralization antibody titers ranging from 1:10 to 1:28.22.

CONCLUSIONBats from different regions and of different species can be naturally infected with JEV and have a high prevalence of anti-JEV antibodies in their sera. The role of bats in the natural cycle of JEV awaits further study.

Animals ; Antibodies, Viral ; blood ; China ; Chiroptera ; immunology ; virology ; Encephalitis Virus, Japanese ; Enzyme-Linked Immunosorbent Assay ; Neutralization Tests

Objective Investigate the prognosis of patients undergoing liver transplantation (LT) for end-stage autoirnmune liver disease (ALD).Method The clinical data of 45 patients with endstage ALD undergoing LT from April 2001 to March 2015 in the first affiliated hospital of Zhejiang University were analyzed retrospectively.The postoperative cumulative survival rate of the recipients was calculated,and the causes of death were analyzed.The postoperative rejections,new onset viral hepatitis and ALD recurrence were also analyzed.Result In 45 ALD recipients,33 cases survived and the postoperative 5-year cumulative survival rate was 78.8％.Causes for 12 dead cases were mnultiple organ failure,liver graft failure,respiratory complications,hemorrhage and hepatic artery embolization.In 45 ALD recipients,6 cases suffered rejection after operation with the incidence bing 13.3％.One case suffered new onset hepatitis B infection 8 years after opcration.One recipient suffered primary disease (primary biliary cirrhosis) recurrence 2 years after operation,and 1 recipient with primary disease (primary sclerosing cholangitis) developed into overlap syndrome.They all survived for a long term after active treatments.Conclusion Most LT recipients with endstage ALD can obtain a long term survival.Attentions should be paid to the immunosuppressive regimens in early period after LT,prevention of infection,rejection and postoperative new onset viral hepatitis,and timely diagnosis of primary disease recurrence.

Objective To investigate the prevalence of serum antibodies against Japanese encephalitis virus (JEV) in bats. Methods Blood samples from the heart were obtained from bats captured in Guangdong and Hainan Provinces in 2013. The anti-JEV antibodies in bat sera were tested using indirect ELISA and virus neutralization test. Results A total of 201 bat serum samples were tested, in which the total positivity rate of anti-JEV antibodies was 46.27%(93/201). The positive rate of anti-JEV antibodies in bats from Hainan and Guangdong Provinces was 88.89% (48/54) and 30.61% (45/147), respectively. All the samples from Rousettus leschenaultia, Miniopterus schreibersii, Pipistrellus abramus, and Rhinolophus macrotis were positive for anti-JEV antibodies, and up to 95.56%(43/45) of the samples from Miniopterus schreibersii (from Hainan Province) yielded positive results. Of the 28 samples with positive results by indirect ELISA, 15 showed positive results in virus neutralization test (53.57%) with neutralization antibody titers ranging from 1∶10 to 1∶28.22. Conclusion Bats from different regions and of different species can be naturally infected with JEV and have a high prevalence of anti-JEV antibodies in their sera. The role of bats in the natural cycle of JEV awaits further study.