Objective:To explore the mechanism of G protein-coupled receptor 120(GPR120)regulating nod-like receptor family pyrin domain containing 3(NLRP3)inflammasome-mediated inflammatory response in polycystic ovary syndrome(PCOS).Methods:Forty-five wild-type female C57BL/6J mice were randomly divided into three groups:control group,model group,and TUG-891 group,with 15 mice in each group.The model and TUG-891 groups were subcutaneously implanted with 35-day testosterone(T)continuous-release pellets to induce the PCOS model,while control mice received placebo pills.Mice in the TUG-891 group were treated with daily in-traperitoneal injections of TUG-891 starting from day 21 after T implantation.The model group and the control group were injected with the same amount of normal saline intraperitoneally.At the end of the experiment(day 35),the mice were euthanized,and blood and ovarian tissue samples were collected.Immunofluorescence stai-ning was used to detect the expression of GPR120 and NLRP3 proteins in ovarian tissues.Sirius Red staining was performed to detect ovarian fibrosis.Western blot analysis was used to measure the expression of fibrosis factors:α-smooth muscle actin(α-SMA),matrix metalloproteinase 2(MMP2),transforming growth factor-β1(TGF-β1),and inflammatory factors NLRP3,Toll-like receptor 4(TLR4),and tumor necrosis factor-α(TNF-α)in tissues.O-varian granulosa cells(GCs)were isolated from female mice and cultured in DMEM-F12 medium containing 10%fetal bovine serum and 1%penicillin-streptomycin.The cells were divided into the control group,TUG-891 group,T group,and T+TUG-891 group.The vitality and apoptosis of GCs were analyzed using the MTT assay and flow cytometry,respectively.Results:Compared with the model group,the TUG-891 group showed significant increa-ses in body growth,ovarian weight,ovarian index,and the number of pre-ovulatory follicles(P<0.05),as well as significant reductions in sex hormones T,estradiol(E2),luteinizing hormone(LH),and follicle-stimulating hormone(FSH)levels and atretic follicle numbers(P<0.05).Compared with the model group,the Sirius red staining and the relative expressions of α-SMA,MMP2,and TGF-β1 in the ovarian tissue of the TUG-891 group were signifi-cantly lower(P<0.05).Compared with the model group,the expression of GRP120 in the ovarian tissue of the TUG-891 group was significantly increased(P<0.05),and the expression of NLRP3 was significantly decreased(P<0.05).In the in vitro experiments,compared with the T group,the T+TUG-891 group significantly increased the proliferation of GCs(P<0.05),and the apoptosis of GCs and the protein expressions of NLRP3,TLR4 and TNF-α in GCs were significantly decreased(P<0.05).Conclusions:The GPR120 agonist TUG-891 may reduce the chronic low-grade inflammation induced by hyperandrogenism in PCOS mice by inhibiting the production of NLRP3 inflammasome,thereby protecting the growth and development of ovaries and follicles in mice.

Objective:To explore the mechanism of G protein-coupled receptor 120(GPR120)regulating nod-like receptor family pyrin domain containing 3(NLRP3)inflammasome-mediated inflammatory response in polycystic ovary syndrome(PCOS).Methods:Forty-five wild-type female C57BL/6J mice were randomly divided into three groups:control group,model group,and TUG-891 group,with 15 mice in each group.The model and TUG-891 groups were subcutaneously implanted with 35-day testosterone(T)continuous-release pellets to induce the PCOS model,while control mice received placebo pills.Mice in the TUG-891 group were treated with daily in-traperitoneal injections of TUG-891 starting from day 21 after T implantation.The model group and the control group were injected with the same amount of normal saline intraperitoneally.At the end of the experiment(day 35),the mice were euthanized,and blood and ovarian tissue samples were collected.Immunofluorescence stai-ning was used to detect the expression of GPR120 and NLRP3 proteins in ovarian tissues.Sirius Red staining was performed to detect ovarian fibrosis.Western blot analysis was used to measure the expression of fibrosis factors:α-smooth muscle actin(α-SMA),matrix metalloproteinase 2(MMP2),transforming growth factor-β1(TGF-β1),and inflammatory factors NLRP3,Toll-like receptor 4(TLR4),and tumor necrosis factor-α(TNF-α)in tissues.O-varian granulosa cells(GCs)were isolated from female mice and cultured in DMEM-F12 medium containing 10%fetal bovine serum and 1%penicillin-streptomycin.The cells were divided into the control group,TUG-891 group,T group,and T+TUG-891 group.The vitality and apoptosis of GCs were analyzed using the MTT assay and flow cytometry,respectively.Results:Compared with the model group,the TUG-891 group showed significant increa-ses in body growth,ovarian weight,ovarian index,and the number of pre-ovulatory follicles(P<0.05),as well as significant reductions in sex hormones T,estradiol(E2),luteinizing hormone(LH),and follicle-stimulating hormone(FSH)levels and atretic follicle numbers(P<0.05).Compared with the model group,the Sirius red staining and the relative expressions of α-SMA,MMP2,and TGF-β1 in the ovarian tissue of the TUG-891 group were signifi-cantly lower(P<0.05).Compared with the model group,the expression of GRP120 in the ovarian tissue of the TUG-891 group was significantly increased(P<0.05),and the expression of NLRP3 was significantly decreased(P<0.05).In the in vitro experiments,compared with the T group,the T+TUG-891 group significantly increased the proliferation of GCs(P<0.05),and the apoptosis of GCs and the protein expressions of NLRP3,TLR4 and TNF-α in GCs were significantly decreased(P<0.05).Conclusions:The GPR120 agonist TUG-891 may reduce the chronic low-grade inflammation induced by hyperandrogenism in PCOS mice by inhibiting the production of NLRP3 inflammasome,thereby protecting the growth and development of ovaries and follicles in mice.

Objective To explore clinical effect of distal tibial tubercle-high tibial osteotomy(DTT-HTO)in treating knee osteoarthritis(KO A)with medial meniscus posterior root tear(MMPRT).Methods A retrospective analysis was performed on 21 patients with varus KOA with MMPRT from May 2020 to December 2021,including 3 males and 18 females,aged from 49 to 75 years old with an average of(63.81±6.56)years old,the courses of disease ranged from 0.5 to 18.0 years with an average of(5.9±4.2)years,and 4 patients with grade Ⅱ,14 patients with grade Ⅲ,and 3 patients with grade Ⅳ according to Kellgren-Lawrence;14 patients with type 1 and 7 patients with type 2 according to MMPRT damage classification.The distance of medi-al meniscusextrusion(MME)and weight-bearing line ratio(WBLR)of lower extremity were compared before and 12 months after operation.Visual analogue scale(V AS),Western Ontarioand and McMaster Universities(WOMAC)osteoarthritis index,and Lysholm knee score were used to evaluate knee pain and functional improvement before operation,1,6 and 12 months after operation,respectively.Results Twenty-one patients were followed up for 12 to 18 months with an average of(13.52±1.72)months.MME distance was improved from(4.99±1.05)mm before operation to(1.87±0.76)mm at 12 months after operation(P＜0.05).WBLR was increased from(15.49±7.04)％before operation to(62.71±2.27)％at 12 months after operation(P＜0.05).VAS was decreased from(7.00±1.14)before operation to(2.04±0.80),(0.90±0.62)and(0.61±0.50)at 1,6 and 12 months after operation.WOMAC were decreased from preoperative(147.90±9.88)to postoperative(103.43±8.52),(74.00±9.54)and(47.62±9.53)at 1,6 and 12 months,and the difference were statistically significant(P＜0.05).Lysholm scores were increased from(46.04±7.34)before oepration to(63.19±8.93),(81.10±6.41)and(89.29±3.04)at 1,6 and 12 months after operation(P＜0.05).Conclusion For the treatment of varus KOA with MMPRT,DTT-HTO could reduce medial meniscus pro-trusion distance,improve the ratio of lower limb force line,and effectively reduce knee pain and improve knee joint function.

Objective To isolate the secondary metabolites of endophytic fungus Aspergillus sp. J218 from Anectochilus roxburhii. Methods Different chromatographic methods, including Sephadex LH-20 and silica gel chromatography as well as HPLC, were used to isolate compounds from the EtOAc fraction of the solid fermentation of J218, and their structures were identified by spectral methods. Results Ten compounds were isolated from the fermentation of J218 and their structures were individually identified as kotanin（1）, flavasperone（2）, aurasperone B（3）, fonsecinone B（4）, fonsecinone D（5）, ensidol A（6）, fonsecinone A（7）, fonsecinone C（8）, aurasperone A（9）, and fonsecinone F（10）. Conclusion Most compounds isolated from endophytic fungus Aspergillus sp. J218 in Anectochilus roxburhii were identified as dimeric naphthopyrones. These results suggest that this strain contains rich dimerization synthase, which could provide clues for the further exploration of the rational biosynthesis pathway of dimeric naphthopyrones in this strain.

BACKGROUND: Congenital scoliosis (CS) is a complex spinal malformation of unknown etiology with abnormal bone metabolism. Fibroblast growth factor 23 (FGF23), secreted by osteoblasts and osteocytes, can inhibit bone formation and mineralization. This research aims to investigate the relationship between CS and FGF23. METHODS: We collected peripheral blood from two pairs of identical twins for methylation sequencing of the target region. FGF23 mRNA levels in the peripheral blood of CS patients and age-matched controls were measured. Receiver operator characteristic (ROC) curve analyses were conducted to evaluate the specificity and sensitivity of FGF23. The expression levels of FGF23 and its downstream factors fibroblast growth factor receptor 3 (FGFr3)/tissue non-specific alkaline phosphatase (TNAP)/osteopontin (OPN) in primary osteoblasts from CS patients (CS-Ob) and controls (CT-Ob) were detected. In addition, the osteogenic abilities of FGF23-knockdown or FGF23-overexpressing Ob were examined. RESULTS: DNA methylation of the FGF23 gene in CS patients was decreased compared to that of their identical twins, accompanied by increased mRNA levels. CS patients had increased peripheral blood FGF23 mRNA levels and decreased computed tomography (CT) values compared with controls. The FGF23 mRNA levels were negatively correlated with the CT value of the spine, and ROCs of FGF23 mRNA levels showed high sensitivity and specificity for CS. Additionally, significantly increased levels of FGF23, FGFr3, OPN, impaired osteogenic mineralization and lower TNAP levels were observed in CS-Ob. Moreover, FGF23 overexpression in CT-Ob increased FGFr3 and OPN levels and decreased TNAP levels, while FGF23 knockdown induced downregulation of FGFr3 and OPN but upregulation of TNAP in CS-Ob. Mineralization of CS-Ob was rescued after FGF23 knockdown. CONCLUSIONS Our results suggested increased peripheral blood FGF23 levels, decreased bone mineral density in CS patients, and a good predictive ability of CS by peripheral blood FGF23 levels. FGF23 may contribute to osteopenia in CS patients through FGFr3/TNAP / OPN pathway.
Humans ; Osteopontin/genetics* ; Alkaline Phosphatase/metabolism* ; Receptor, Fibroblast Growth Factor, Type 3/metabolism* ; Scoliosis/genetics* ; Osteoblasts/metabolism* ; Calcinosis ; RNA, Messenger/metabolism* ; Bone Diseases, Metabolic/metabolism* ; Fibroblast Growth Factors/genetics*

Malocclusion is one of the three most common oral diseases reported by World Health Organization(WHO). In China, its incidence rate is rising. Malocclusion seriously affects the dental and maxillofacial function, facial appearance and growth development of nearly 260 million children in China, and what is more, it affects their physical and mental health development. Malocclusion occurrence is related to genetic and environmental factors. Early treatment of malocclusion can create a good dental and maxillofacial development environment, correct abnormal growth and control the adverse effects of abnormal genetic factors. It can effectively reduce the prevalence of children's malocclusion and enhance their physical and mental health. This is an urgent need from the economic perspective of our society, so it has great practical and social significance. Experts from the project group "standard diagnose and treatment protocols for early orthodontic intervention of malocclusions of children" which initiated by China National Health Institute of Hospital Administration wrote the "China Experts' Consensus on Preventive and Interceptive Orthodontic Treatments of Malocclusions of Children", which aims to guide and popularize the clinical practice, improve the clinical theory and practice level, and accelerate the disciplinary development of early treatment of children's malocclusion in China. The consensus elaborates the harmfulness of malocclusion and the necessity of early treatment, and brings up the principles and fundamental contents. Based on the law of dental and maxillofacial development, this paper puts forward the guiding suggestions of preventive and interceptive treatments in different stages of dental development ranging from fetus to early permanent dentition. It is a systematic project to promote and standardize the early treatment of malocclusion. Through scientific and comprehensive stratified clinical practice and professional training, the clinical system of early treatment of malocclusion in China will eventually be perfected, so as to comprehensively care for children's dental and maxillofacial health, and improve their oral and physical health in China.
Child ; China/epidemiology* ; Consensus ; Dental Care ; Humans ; Malocclusion/prevention & control* ; Orthodontics, Interceptive

OBJECTIVE: To establish and evaluate the model of chronic obstructive pulmonary disease (COPD) with osteoporosis induced by elastase in mice. METHODS: Twenty four healthy female 8-week-old C57BL / 6 mice (weighing about 18 g) were randomly divided into three groups. The control group was given intratracheal drip of normal saline, the experimental group 1 and the experimental group 2 were given intratracheal drip of elastase, the control group and the experimental group 1 were kept for 8 weeks and then killed, the experimental group 2 was kept for 12 weeks and then killed. HE staining was used to evaluate the histopathological changes of lung and tibia in the control and experimental groups. The levels of serum inflammatory factors and broncho alveolar lavage factors (BALF) were detected by ELISA. Micro CT was used to detect the bone mass related parameters of mouse femur. The expression of osteoclastic and osteogenic genes was detected by real-time fluorescence quantitative PCR. RESULTS: Lung histopathology showed that the structure of alveoli in the experimental group was disordered, the walls of alveoli became thin or broken, and the alveoli cavity expanded. IL-6 and TNF-α in BALF were significantly higher than those in control group (<0.001), while IL-1β and TNF-α in serum inflammatory factors were significantly higher than those in control group (<0.001). BV / TV(bone volume fraction), TB.Th(average bone trabecular thickness) and TB.N(average bone trabecular number) in the experimental group were significantly lower than those in the control group (<0.05), TB.Sp (average bone trabecular separation) and BS / BV (bone surface area fraction) in the experimental group were significantly higher than those in the control group (<0.01). Compared with the control group, the expression of osteoclast related marker genes increased in the experimental group (<0.05), but decreased in the experimental group(<0.05). The results of experiment 1 and experiment 2 were time-dependent. CONCLUSION In this study, elastase was used to construct a COPD model with osteoporosis successfully, which provides a suitable animal model for the future study of the pathogenesis of COPD with osteoporosis.
Animals ; Bone Density ; Female ; Mice ; Mice, Inbred C57BL ; Osteoporosis ; etiology ; Pancreatic Elastase ; Pulmonary Disease, Chronic Obstructive ; complications

Objective To observe the effects of proximal gastric electrical stimulation (GES) on body weight and gastrointestinal motility in SD rats,and investigate the regulation of gastric nerve stimulation and serum gastrointestinal hormones by neuro-humoral regulation.Methods 12 SD rats were divided into experimental group (n =6) and control group (n =6),with gastric electrical stimulator implanted,and in experimental group dual-channel GES was activated.General status was observed for 4 weeks after GES activation,including body weight,feeding and water intake,urine and stool volumes,the resting gastric volume and gastric emptying were monitored via the establishment of intestinal fistula,and serum gastrointestinal hormones change was detected.Results During 4-week GES process,one rat had gastric retention and died at 1 week after GES activated.Compared with the control group,body weight,food intake,urine and stool volumes levels of the rats in experimental group decreased significantly (t =4.005,2.530,3.350,all P＜0.05).Resting gastric volume was significantly lower than that in the control group [(2.93 ± 0.50) ml vs.(5.10 ± 0.53) ml,Z =2.460,P =0.014],and the intestinal juice drainage was lower than the control group [(0.18 ±0.15)ml vs.(0.44 ±0.05)ml,Z =2.513,P =0.012],while serum GLP-1 levels were similar between the two groups [(0.44 ± 0.05) ml vs.(0.18 ± 0.15) ml,Z =1.026,P =0.305],but Ghrelin was significantly higher than that in the control group [(1.65 ± 0.58) vs.(0.65 ±0.36),Z =2.380,P =0.017].Conclusion The proximal GES may lead to the change of the body weight,food intake,gastrointestinal function and motility,possibly by stimulating nerve reflex inducing gastrointestinal hormones secretion and affect gastrointestinal function.

Objective To investigate the application value of dynamic single-photon emission computed tomography (SPECT) 99m-technetium galactosyl human serum albumin diethylenetriamine pentaacetic acid injection (99 Tcm-GSA) scintigraphy assessing regional liver function changes before and after portal vein embolization (PVE).Methods The retrospective cross-sectional study was conducted.The clinical data of 11 patients with Bismuth Ⅲ a hilar cholangiocarcinoma who were admitted to the General Hospital of People's Liberation Army (10 patients) and Beijing Tsinghua Changgung Hospital (1 patient) from October 2010 to October 2016 were collected.B ultrasound-guided percutaneous transhepatic ipsilateral exbolization was performed before radical resection of hilar cholangiocarcinoma.Dynamic SPECT 99 Tcm-GSA scintigraphy was performed to calculate and compare the changes of functional liver volume (FLV),morphological liver volume (MLV) and functional liver density (FLD) in embolized lobe and non-embolized lobe before PVE and 2 weeks after PVE.Observation indicators:(1) the changes of serum indexes in 2 weeks before and after PVE;(2) the changes of FLV,MLV and FLD in the whole liver,embolized and non-embolized lobes in 2 weeks before and after PVE;(3) surgical and postoperative situations of hilar cholangiocarcinoma;(4) follow-up and survival situations.Follow-up using outpatient examination and telephone interview was performed to detect postoperative serum toal bilirubin (TBil) level,with or without peritoneal effusion and survival up to June 2017.Measurement data with normal distribution were represented as x-±s.The comparisons of pre-and post-operative data were analyzed by the paired t test.Results (1) The changes of serum indexes in 2 weeks before and after PVE:11 patients underwent successful right PVE.The alanine aminotransferase (ALT),TBil,albumin (Alb),Platelets (PLT) and prothrombin time (PT) were respectively (113±20) U/L,(73± 8) μmol/L,(35.0±2.5) g/L,(209±58) × 109/L,(11.4±0.7) seconds in 2 weeks before PVE and (120± 18) U/L,(36± 7) μmol/L,(34.4± 3.2) g/L,(224± 82) × 109/L,(11.2±0.8)seconds in 2 weeks after PVE,with a statistically significant difference in TBil level (t=-10.592,P＜0.05) and no statistically significant difference in ALT,Alb,PLT and PT (t=0.981,-0.350,-0.591,0.533,P＞0.05).(2) The changes of FLV,M LV and FLD in the whole liver,embolized and nonembolized lobes in 2 weeks before and after PVE:the FLV,MLV and FLD of the whole liver were respectively (894±255) mL,(1 552±504) mL,0.59±0.14 in 2 weeks before PVE and (812±206) mL,(1 521±422) mL,0.55±0.16 in 2 weeks after PVE,with no statistically significant difference (t =1.569,0.666,1.980,P＞ 0.05).The FLV,MLV and FLD of the embolized lobe were respectively (623±275) mL,(1 047± 394) mL,0.62±0.14 in 2 weeks before PVE and (375±240) mL,(865±337) mL,0.44±0.24 in 2 weeks after PVE,with statistically significant differences (t =5.909,3.736,3.359,P ＜ 0.05);the descending percentages were respectively 38.1％,9.8％ and 24.6％.The FLV,MLV and FLD of the non-embolized lobe were respectively (274±152)mL,(530±176)mL,0.52±0.21 in 2 weeks before PVE and (436±149) mL,(656±133)mL,0.68± 0.24 in 2 weeks after PVE,with statistically significant differences (t =-6.019,-6.345,-3.933,P＜0.05);the elevated percentages were respectively 80.1％,19.9％ and 23.8％.(3) Surgical and postoperative situations of hilar cholangiocarcinoma:of 11 patients,10 received successful peri-hilar right hemihepatectomy,the right hepatic atrophy and an obvious demarcation line between left and right liver were found intraoperatively;1 stopped operation due to detect intraoperatively peritoneal metastasis of tumor.The operation time,volume of intraoperative blood loss and time of postoperative abdominal drainage-tube removal were respectively (585± 194)minutes,(472± 274)mL and (8±5)days.Of 10 patients undergoing operations,2 were complicated with massive peritoneal effusion at 2 days postoperatively,volume of peritoneal effusion remained more than 500 mL up to 7 days after drainage,and were improved by 1-month conservative treatment;other 8 patients were not complicated with hepatic dysfunction.Duration of hospital stay of 11 patients was (16± 4) days.(4) Follow-up and survival situations:10 patients were followed up for 4-72 months,with a median time of 39 months.During the follow-up,there was no evaluated TBil level and peritoneal effusion in 10 patients.The median survival time,1-,3-and 5-year overall survival rates were 88.8％,74.6％ and 36.8％,respectively.Conclusions The dynamic SPECT 99Tcm-GSA scintigraphy can effectively evaluate liver function changes of embolized and non-embolized lobes before and after PVE.The increased rate of FLV of non-embolized lobe is higher than that of MLV.