OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules （WYJYG） via the NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/apoptosis-associated speck-like protein containing a CARD （ASC）/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group， model group， MCC950 （NLRP3 inflammasome inhibitor） group （10 mg/kg）， fluoxetine group （positive control，2.08 mg/kg），low-dose WYJYG（3.78 g/kg） and high-dose WYJYG group （7.56 g/kg），with 10 rats in each group. From the 22nd day of the experiment， rats in the fluoxetine group， low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration， the contents of ASC， ionized calcium binding adaptor molecule 1 （Iba1）， interleukin-1β （IL-1β）， and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3， cluster of differentiation 68 （CD68）， Caspase-1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein were determined， and neuronal apoptosis was observed. RESULTS After the last administration， compared with the model group， the open-field activity time was significantly prolonged （ P ＜0.05）， and the latency to feed in a novel environment was significantly shortened （ P ＜0.05） in rats of the high-dose WYJYG group. In hippocampal tissue， the contents of ASC， Iba1， IL-1β， and IL-18， as well as the protein expression levels of NLRP3， Caspase-1， and CD68， and the positive rate of neuronal apoptosis were all significantly decreased/downregulated （ P ＜0.05）. Bcl-2 protein expression was significantly upregulated （ P ＜0.05）， and the density of neuronal apoptosis-positive cells was significantly reduced （ P ＜0.05）. CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway， reducing microglia-mediated neuroinflammation， and inhibiting hippocampal neurons apoptosis.

Objective:To observe the effects of palmitic acid(PA)and static pressure on the expression of receptor activator of NF-κB ligand(RANKL)and osteoprotegerin(OPG)in human periodontal ligament cells(HPDLCs)cultured from the subjects of differ-ent ages.Methods:The effects of PA with the dose(μmol/L)of 10,100,200,250,300,400 and 500 respectively on the prolif-erative activity of HPDLCs cultured in vitro from the subjects aged 12-45 years were determined by CCK-8 method.200 μmol/L PA was selected to treat HPDLCs,and the static pressure of 200 Pa was applied in the in vitro culture.Under different conditions(PA group,static pressure group,PA+static pressure group and blank control group),The expression of RANKL and OPG in HPDLCs was determined by ELISA before and after the treatment at 3,6,12,24,36,48 and 72 h respectively,and the OPG/RANKL ratio was calculated.Results:PA inhibited the proliferation of HPDLCs of all ages(P＜0.05),and the proliferation activity of HPDLCs decreased gradually with the increase of PA concentration,patient age and treatment time.Under static pressure,PA up-regulated the expression of RANKL protein,down-regulated the expression of OPG protein and the ratio of OPG/RANKL(P＜0.05),but RANKL protein expression decreased and OPG protein expression and the ratio of OPG/RANKL increased with age.Conclusion:Combined treatment of PA and static pressure can synergistically promote remodeling of periodontal bone.The expressions of RANKL and OPG is closely related to age of the subjects.

Objective To elucidate the expression characteristics of the NUAK family SNF1-like kinase 2(NUAK2)in ovarian serous carcinoma and determine its regulatory roles in cell proliferation and apoptosis.Methods Fifty-seven patients with ovarian serous car-cinoma(observation group)and 57 patients with ovarian serous cystadenoma(control group)were selected from June 2019 to December 2022.The GEPIA database was used to assess the expression patterns of NUAK2 in ovarian serous carcinoma.Immunohistochemistry was used to detect the expression of NUAK2,proliferating cell nuclear antigen(PCNA),and B-cell lymphoma-associated X antigen(BAX).Western blotting was performed to evaluate the expression of NUAK2 in the human ovarian serous carcinoma cell lines(SKOV3)and the human ovarian surface epithelial cell lines(HOSEpiC).SKOV3 cells were transfected with the siRNA-NUAK2 plasmid to establish the si-NUAK2 group,or with the empty transfection vector(EV)or a blank solution(NC)to establish control groups.Western blotting was sub-sequently used to detect the expression of NUAK2,PCNA,and BAX.The CCK-8 method was used to assess cell proliferation activity,and flow cytometry was used to quantify apoptosis.Results The GEPIA database analysis showed a significant increasing trend in the expres-sion of NUAK2 in ovarian cancer(P<0.05).Immunohistochemical analysis revealed a significantly higher NUAK2 positive rate in ovarian serous carcinoma tissue than that in the control group.Moreover,significant differences in the expression of NUAK2 were observed across different lesion grades and maximum tumor diameters(P<0.05).A significant positive correlation was found between NUAK2 and PCNA(P<0.05),whereas a significant negative correlation was observed between NUAK2 and BAX(P<0.05)in ovarian serous carcinoma.In vitro cell culture experiments showed that the expression level of NUAK2 was significantly higher in SKOV3 cells than that in HOSEpiC cells(P<0.05).The si-NUAK2 group exhibited significantly lower cell proliferation activity and PCNA expression and significantly higher apoptosis rate and BAX expression than those in the EV and NC groups(P<0.05).Conclusion NUAK2 is overexpressed in ovarian serous carcinoma and promotes tumor progression by enhancing cell proliferation and suppressing apoptosis.

Objective To observe the effects of Baishile Capsules on neonatal neuronal activity and synaptic plasticity in hippocampus of depression model rats;To explore its mechanism of antidepressant.Methods Totally 32 SD rats were randomly divided into blank group,model group,fluoxetine group(5.4 mg/kg)and Baishile Capsules group(2.88 g/kg),with 8 rats in each group.The depression rat model was established by chronic unpredictable mild stress and single cage feeding,and drugs were administered at the same time as modeling for 21 consecutive days.Forced swimming test and open field test were used to evaluate the depressive-like behavior of rats,Golgi staining was used to observe the synaptic morphology of hippocampal neurons,and immunofluorescence was used to detect the positive expressions of BrdU/GABA-B,BrdU/c-fos,BrdU/GAP-43,BrdU/MAP-2 and CXCR4 in hippocampal tissue.Results Compared with the blank group,the immobility time of forced swimming experiment in the model group increased,and the horizontal and vertical time of open field experiment decreased significantly(P<0.01);the hippocampal neurons dendrites and dendritic spines atrophied,the density decreased,the branches became shorter,synaptic structure becomes blurred,and the longest and total lengths of synaptic branches significantly decreased(P<0.01);the positive expressions of GABA-B,c-fos,GAP-43 and MAP-2 proteins in hippocampal neonatal neurons decreased(P<0.05,P<0.01),and the expression of CXCR4 in hippocampal tissue decreased significantly(P<0.01).Compared with the model group,the immobility time of the forced swimming experiment in fluoxetine group and Baishile Capsules group significantly reduced,and the horizontal and vertical activity time of the open field experiment significantly increased(P<0.01);the number of dendritic spines in hippocampal neurons increased,synaptic damage improved,and the length of the longest and total branches of synapses significantly increased(P<0.01);the positive expressions of GABA-B,c-fos,GAP-43 and MAP-2 in hippocampal neonatal neurons significantly increased(P<0.05,P<0.01),and the positive expression of CXCR4 in hippocampal tissue significantly increased(P<0.01).Conclusion Baishile Capsules can regulate hippocampal synaptic plasticity and nerve regeneration by improving the activity and function of hippocampal neonatal neurons in depression model rats,exerting antidepressant effects.

Background::Hepatitis B poses a heavy burden for children in China, however, the national studies on the distributional characteristics and health care costs of children with severe hepatitis B is still lacking. This study aimed to analyze the disease characteristics, health economic effects, and medical cost for children with severe hepatitis B in China.Methods::Based on patient information in the Hospital Quality Monitoring System, cases with severe hepatitis B were divided into four groups according to age, and the etiology and symptoms of each group were quantified. The cost of hospitalization was calculated for cases with different disease processes, and severity of disease. The spatial aggregation of cases and the relationship with health economic factors were analyzed by Moran’s I analysis. Results::The total number of children discharged with hepatitis B from January 2016 to April 2022 was 1603, with an average age of 10.5 years. Liver failure cases accounted for 43.48% (697/1603) of total cases and cirrhosis cases accounted for 11.23% (180/1603). According to the grouping of disease progression, there were 1292 cases without associated complications, and the median hospitalization cost was $818.12. According to the spatial analysis, the aggregation of cases was statistically significant at the prefectural and provincial levels in 2019, 2020, and 2021 (all P <0.05). The number of severe cases was negatively correlated with gross domestic product (Moran’s I <0) and percentage of urban population (Moran’s I <0), and positively correlated with the number of pediatric beds per million population (Moran’s I >0). Conclusion::The number of severe hepatitis B cases is low in areas with high gross domestic product levels and high urban population ratios, and health care costs have been declining over the years.

OBJECTIVE: To analyze the time characteristics of the Ethos online adaptive radiotherapy (OART) process in clinical practice and provide guidance for the comprehensive optimization of each stage of adaptive radiotherapy. METHODS: The study involved 61 patients with cervical, rectal, gastric, lung, esophageal, and breast cancers who underwent Ethos OART. The mean ± standard deviation of segmental time, total time, and target volume for these patients were tracked. The time characteristics for different cancer types were evaluated, and the average time for target and organ at risk (OAR) modifications was compared with the average target volume for each cancer type. RESULTS: Cervical cancer born the longest total treatment time, while breast cancer had the shortest. For all cancer types except breast cancer, the modification time for target and OAR was the most time-consuming segment. The average time for target and OAR modifications aligned with the trend of the average target volume. CONCLUSION The total treatment time for various cancers ranges from 15 to 35 minutes, indicating room for improvement.
Humans ; Radiotherapy Planning, Computer-Assisted/methods* ; Neoplasms/radiotherapy* ; Female

Objective To investigate the effects of formulated granules of Tianma Gouteng Yin(TGY)on motor deficits in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced subacute Parkinson's disease(PD)and explore the possible molecular mechanisms.Methods Ninety C57BL/6 mice were randomized equally into 6 groups,including a control group,a PD model group,a NEC-1(6.5 mg/kg)treatment group,two TGY treatment groups at 5 and 2.5 g/kg,and a Madopar(76 mg/kg)treatment(positive control)group.Mouse models of PD were established by intraperitoneal injection of MPTP(30 mg/kg)for 5 consecutive days with the corresponding treatments for 15 days.The mice were randomly selected for motor function tests.Western blotting was used to detect the changes in expressions of TH,α-syn,RIPK1,RIPK3 and MLKL in the striatum of the mice.Network pharmacology analysis and molecular docking studies were performed to explore TGY-mediated regulation of the necroptosis pathway for PD treatment.Results Compared with those in the control group,the PD model mice exhibited obvious motor deficits with significantly increased α-syn protein expression and lowered TH protein expression in the striatum.Treatment with NEC-1 obviously improved motor deficits,inhibited the necroptosis pathway,and alleviated the changes in TH and α-syn proteins in PD mice.Network pharmacology and molecular docking analyses suggested that the therapeutic effect of TGY in PD was associated with the modulation of RIPK1,a key protein in the necroptosis pathway.In PD mouse models,TGY treatment at the two doses significantly improved motor deficits of the mice,increased TH expression,and decreased the expressions of α-syn and necroptosis-related proteins in the striatum.Conclusion TGY can effectively inhibit the necroptosis pathway,increase TH expression and decrease α-syn expression in the striatum to improve motor deficits in PD mice.

OBJECTIVES: To investigate the effects of formulated granules of Tianma Gouteng Yin (TGY) on motor deficits in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced subacute Parkinson's disease (PD) and explore the possible molecular mechanisms. METHODS: Ninety C57BL/6 mice were randomized equally into 6 groups, including a control group, a PD model group, a NEC-1 (6.5 mg/kg) treatment group, two TGY treatment groups at 5 and 2.5 g/kg, and a Madopar (76 mg/kg) treatment (positive control) group. Mouse models of PD were established by intraperitoneal injection of MPTP (30 mg/kg) for 5 consecutive days with the corresponding treatments for 15 days. The mice were randomly selected for motor function tests. Western blotting was used to detect the changes in expressions of TH, α-syn, RIPK1, RIPK3 and MLKL in the striatum of the mice. Network pharmacology analysis and molecular docking studies were performed to explore TGY-mediated regulation of the necroptosis pathway for PD treatment. RESULTS: Compared with those in the control group, the PD model mice exhibited obvious motor deficits with significantly increased α-syn protein expression and lowered TH protein expression in the striatum. Treatment with NEC-1 obviously improved motor deficits, inhibited the necroptosis pathway, and alleviated the changes in TH and α‑syn proteins in PD mice. Network pharmacology and molecular docking analyses suggested that the therapeutic effect of TGY in PD was associated with the modulation of RIPK1, a key protein in the necroptosis pathway. In PD mouse models, TGY treatment at the two doses significantly improved motor deficits of the mice, increased TH expression, and decreased the expressions of α-syn and necroptosis-related proteins in the striatum. CONCLUSIONS TGY can effectively inhibit the necroptosis pathway, increase TH expression and decrease α-syn expression in the striatum to improve motor deficits in PD mice.
Animals ; Mice, Inbred C57BL ; Mice ; Necroptosis/drug effects* ; Drugs, Chinese Herbal/therapeutic use* ; Parkinson Disease/drug therapy* ; Disease Models, Animal ; Male

Objective:To observe the effects of palmitic acid(PA)and static pressure on the expression of receptor activator of NF-κB ligand(RANKL)and osteoprotegerin(OPG)in human periodontal ligament cells(HPDLCs)cultured from the subjects of differ-ent ages.Methods:The effects of PA with the dose(μmol/L)of 10,100,200,250,300,400 and 500 respectively on the prolif-erative activity of HPDLCs cultured in vitro from the subjects aged 12-45 years were determined by CCK-8 method.200 μmol/L PA was selected to treat HPDLCs,and the static pressure of 200 Pa was applied in the in vitro culture.Under different conditions(PA group,static pressure group,PA+static pressure group and blank control group),The expression of RANKL and OPG in HPDLCs was determined by ELISA before and after the treatment at 3,6,12,24,36,48 and 72 h respectively,and the OPG/RANKL ratio was calculated.Results:PA inhibited the proliferation of HPDLCs of all ages(P＜0.05),and the proliferation activity of HPDLCs decreased gradually with the increase of PA concentration,patient age and treatment time.Under static pressure,PA up-regulated the expression of RANKL protein,down-regulated the expression of OPG protein and the ratio of OPG/RANKL(P＜0.05),but RANKL protein expression decreased and OPG protein expression and the ratio of OPG/RANKL increased with age.Conclusion:Combined treatment of PA and static pressure can synergistically promote remodeling of periodontal bone.The expressions of RANKL and OPG is closely related to age of the subjects.