Objective:To investigate the mechanisms of baicalin in treating septic acute liver injury through a combination of network pharmacology and animal experiments.Methods:Thirty male C57BL/6 mice (6 weeks old) were divided into five groups ( n=6): control group (normal saline), model group [lipopolysaccharide (LPS) 10 mg/kg, intraperitoneal injection], low-dose baicalin group (10 mg/kg), high-dose baicalin group (20 mg/kg), and baicalin-only group (20 mg/kg, without LPS). Baicalin was administered orally for 14 consecutive days prior to modeling. Mice were sacrificed 24 h after LPS injection. Alanine transaminase, aspartate transaminase liver tissue histopathology were measured; neutrophil infiltration was visualized using immunofluorescence; mRNA expression levels of interleukin (IL)-1β, IL-17, IL-6, and tumor necrosis factor (TNF)-α were detected by RT-qPCR; and the expression of Toll-like receptor 4 (TLR4) and phosphorylated nuclear factor (NF)-κB proteins were analyzed by Western blotting. Results:In the LPS model group, the ALT, AST, and histopathological injury score were (148.60±22.02) U/L, (81.58±11.59) U/L, and 8.50(7.75, 9.25), respectively. These indicators were significantly reduced in the high-dose baicalin group with (77.90±16.79) U/L, (49.92±14.89) U/L, and 1.00(1.00, 2.25) (all P<0.05). Compared with the LPS group, neutrophil infiltration in the liver of high-dose baicalin group was also significantly reduced [1.18%(0.98%, 1.22%) vs. 6.13%(5.41%, 8.69%), P<0.05]. RT-qPCR results showed that the relative mRNA expression levels of inflammatory cytokines IL-1β [(1.03±0.06) vs. (2.60±0.34)], IL-17 [(1.21±0.12) vs. (2.94 ± 0.39)], IL-6 [(1.37±0.26) vs. (2.73±0.18)], and TNF-α [(1.18±0.10) vs. (3.30±0.92)] were significantly decreased in the high-dose baicalin group compared with the LPS group (all P<0.05). Western blot analysis revealed that the relative protein expression levels of TLR4 [(1.25±0.13) vs. (1.73±0.06)] and phosphorylated NF-κB [(1.25±0.25) vs. (1.79±0.12)] were also significantly lower in the high-dose baicalin group (both P<0.05). Conclusion:Baicalin reduces liver injury in septic mice by downregula-ting the expression of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and IL-17, potentially through the inhibition of the TLR4/NF-κB signaling pathway.

Objective:To investigate the mechanisms of baicalin in treating septic acute liver injury through a combination of network pharmacology and animal experiments.Methods:Thirty male C57BL/6 mice (6 weeks old) were divided into five groups ( n=6): control group (normal saline), model group [lipopolysaccharide (LPS) 10 mg/kg, intraperitoneal injection], low-dose baicalin group (10 mg/kg), high-dose baicalin group (20 mg/kg), and baicalin-only group (20 mg/kg, without LPS). Baicalin was administered orally for 14 consecutive days prior to modeling. Mice were sacrificed 24 h after LPS injection. Alanine transaminase, aspartate transaminase liver tissue histopathology were measured; neutrophil infiltration was visualized using immunofluorescence; mRNA expression levels of interleukin (IL)-1β, IL-17, IL-6, and tumor necrosis factor (TNF)-α were detected by RT-qPCR; and the expression of Toll-like receptor 4 (TLR4) and phosphorylated nuclear factor (NF)-κB proteins were analyzed by Western blotting. Results:In the LPS model group, the ALT, AST, and histopathological injury score were (148.60±22.02) U/L, (81.58±11.59) U/L, and 8.50(7.75, 9.25), respectively. These indicators were significantly reduced in the high-dose baicalin group with (77.90±16.79) U/L, (49.92±14.89) U/L, and 1.00(1.00, 2.25) (all P<0.05). Compared with the LPS group, neutrophil infiltration in the liver of high-dose baicalin group was also significantly reduced [1.18%(0.98%, 1.22%) vs. 6.13%(5.41%, 8.69%), P<0.05]. RT-qPCR results showed that the relative mRNA expression levels of inflammatory cytokines IL-1β [(1.03±0.06) vs. (2.60±0.34)], IL-17 [(1.21±0.12) vs. (2.94 ± 0.39)], IL-6 [(1.37±0.26) vs. (2.73±0.18)], and TNF-α [(1.18±0.10) vs. (3.30±0.92)] were significantly decreased in the high-dose baicalin group compared with the LPS group (all P<0.05). Western blot analysis revealed that the relative protein expression levels of TLR4 [(1.25±0.13) vs. (1.73±0.06)] and phosphorylated NF-κB [(1.25±0.25) vs. (1.79±0.12)] were also significantly lower in the high-dose baicalin group (both P<0.05). Conclusion:Baicalin reduces liver injury in septic mice by downregula-ting the expression of pro-inflammatory cytokines IL-1β, IL-6, TNF-α, and IL-17, potentially through the inhibition of the TLR4/NF-κB signaling pathway.

Objective:To study the long-term clinical effect of transvaginal mesh (TVM) and pelvic floor reconstruction with native tissue repair (NTR) in the treatment of advanced pelvic organ prolapse (POP).Methods:Totally 207 patients with advanced POP who were treated in Hunan Provincial Maternal and Child Health Care Hospital from Jan. 2016 to Sep. 2019 were enrolled. The patient′s pelvic organ prolapse quantification were all at degree Ⅲ or above, and they all complained for different degree of symptoms. They were divided into two groups according to the different surgical methods, TVM group and NTR group. In TVM group, the mesh was implanted through the vagina for pelvic floor reconstruction, while in NTR group, the traditional transvaginal hysterectomy combined with uterosacral ligament suspension and anterior and posterior wall repair, as well as perineal body repair were performed. The median follow-up time was 60 months, during the follow up time, 164 cases (79.2%, 164/207) had completed follow-up, including 76 cases in TVM group and 88 cases in NTR group. The perioperative data and complication rates of the two groups were compared, and the subjective and objective outcomes of the two groups at 1, 3 and 5 years were observed, respectively. The objective efficacy was evaluated by three composite criteria, namely: (1) the distance from the farthest end of the prolapse of the anterior and posterior wall of the vagina to the hymen is ≤0 cm, and the descending distance of the top is ≤1/2 of the total length of the vagina; (2) determine the disappearance of relevant POP symptoms according to “Do you often see or feel vaginal mass prolapse？”; (3) no further operation or pessary treatment was performed due to prolapse. If the above three criteria were met at the same time, the operation is successful; otherwise, it was recurrence. The subjective efficacy was evaluated by the pelvic floor distress inventory-short form 20 (PFDI-20) and pelvic floor impact questionnaire-short form 7 (PFIQ-7).Results:The median follow-up time of the two groups was 60 months (range: 41-82 months). Five years after the operation, the subjective and objective cure rates of TVM group were 89.5% (68/76) and 94.7% (72/76), respectively. The subjective and objective cure rates in NTR group were 80.7% (71/88) and 85.2% (75/88), respectively. There were significant differences in the subjective and objective cure rates between the two groups ( χ2=9.869, P=0.002; χ2=3.969, P=0.046). The recurrence rate of TVM group was 5.3% (4/76), and that of NTR group was 14.8% (13/88). There was a significant difference between the two groups ( P=0.046). The postoperative PFDI-20 and PFIQ-7 scores of the two groups were significantly lower than those before surgery, and there were significant differences of the two groups before and after surgery (all P<0.05). Postoperative mesh exposure in TVM group was 1.3% (1/76). Conclusions:The long-term outcomes between the two groups show that the subjective and objective outcomes of pelvic floor reconstruction in TVM group are significantly higher than those in NTR group, and the recurrence rate is significantly lower than that in NTR group. TVM has certain advantages in the treatment of advanced POP.

OBJECTIVE: To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients. METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro. RESULTS: The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4⁺ and CD8⁺ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4⁺ and CD8⁺ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01). CONCLUSION The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.
Humans ; Anemia, Aplastic ; CD8-Positive T-Lymphocytes ; Melatonin ; Blood Cell Count

Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtained from PB and bone marrow(BM).Methods:The lymphocyte subsets in hypo-MDS(n=25)and AA(n=33)patients were investigated by flow cytometry.Meanwhile,the differences in PB cell counts,biochemical indicators,BM cell counts and abnormal chromosomes between the two groups were analyzed.Results:The percentage of CD8+T cells in A A group was significantly higher than that in hypo-MDS group(P=0.001),while the percentage of CD4+T cells and the CD4+/CD8+ratio in AA group were obviously lower than those in hypo-MDS group(P=0.015 and0.001,respectively).Furthermore,the proportion of CD4+andCD8+activated T(TA)cells,and memory Tregs in AA group was distinctly lower than those in hypo-MDS group(P=0.043,0.015 and 0.024,respectively).Nevertheless,the percentage of CD8+naive T(TN)cells in AA patients was remarkably higher(P=0.044).And hypo-MDS patients had declined lymphocyte counts(P=0.025),increased levels of total bilirubin(TBil),lactate dehydrogenase(LDH),vitamin B12 and proportion of BM blasts than AA patients(P=0.019,0.023,0.027 and 0.045,respectively).Conclusion:In this study it was confirmed that the percentages of CD4+and CD8+TA cells,memory Tregs and CD8+TN cells were significantly different between AA and hypo-MDS patients,which provide an essential basis for the identification of these two diseases.

Ankle Fractures/surgery* ; Ankle Injuries ; Ankle Joint ; Bone Cysts/surgery* ; Fracture Fixation, Internal ; Fractures, Bone ; Humans ; Talus/surgery*

Objective To observe the clinical effect of sling exercise therapy(S-E-T)combined with drug treatment for cervical vertigo in elderly patients.Methods Forty-nine elderly patients with cervical vertigo admitted to our hospital between January 2011 and July 2014 were randomly divided into an observation group(n=27)and a control group(n=22).The observation group was given 80 mg Ginaton(Extract of Ginkgo Biloba Leaves Tablets)produced by German Dr.Willmar Schwabe GmbH & Co.KG three times a day,combined with S-E-T,including cervical stability and stretching training for 40min,focusing on the neck global muscle and local stabilize muscle rehabilitation,once every other day.The control group was provided with the same drug treatment.During the 6-month intervention,both groups were given health education by the same therapist.Both groups were assessed using the neck disability index(NDI),visual analogue scale(VAS)and evaluation scale for cervical vertigo(ESCV) before and after the intervention,as well as at the last follow-up visit.Before the treatment and at the last follow-up visit,the cervical X-ray examination and trigger point check were also conducted for both groups.Results All the forty-nine patients were followed up for 4.83 to 6.70 months,with an average of(6.01 ± 0.49)months.Significant improvement was observed in the average ESCV score for both groups after the treatment.Compared with before the treatment,there was significant improvement in the average NDI and VAS right after the treatment and at the last follow-up visit in the observation group,but only at the last follow-up visit in the control group.From the cervical X-ray,no significant differences were found in the vertebral osteophyte formation,facet joints and uncovertebral joint degeneration between the 2 groups(P＞0.05),while significant differences were observed in the number of the neck trigger points(P＜0.05).Conclusion The sling exercise therapy combined with drug treatment can significantly improve cervical function,relieve pain and vertigo symptoms in elderly patients with cervical vertigo.The effect is better than drug treatment alone.

Brucella is a facultative intracellular pathogen that causes infection in domestic animal and humans,mainly parasitizing in cells and macrophages of hosts.Brucella can lead to abortion and sterility in animals.Meanwhile,it also causes arthralgia,weakness,undulat fever,hepatosplenomegaly and other symptoms in humans.Brucella relies on immune escape mechanism in the confrontation with the host.It can help Brucella "camouflage" to evade the identification of the immune system of the hosts and replicate within cells to persist to establish a long-term infection in the host.As a result of the existence of this mechanism,the treatment of Brucella infection is quite difficult.Type Ⅳ secretion system (T4SS) is a key virulence factor and it is essential for Brucella to survive in host cells.The effector proteins secreted by T4SS can help regulate the immune response against Brucella.In this article,we reviewed the studies on related proteins of the type Ⅳ secretion system of Brucella and its immune response,especially the relationship between the secretions of effector proteins mediated by VirB operon and immunity of the host.

Aim To investigate the effects of anti-in-flammation and antioxidation of an amphiphilic curcu-min derivative (Curc-OEG)on CCl4-induced hepatic fibrosis in rats.Methods Rats were randomly divided into four groups:control group,model group,curcumin and Curc-OEG treatment group.All rats except those in control group were given subcuta-neous injection of CCl4 and olive oil mixture,twice a week for 8 weeks.After 4 weeks,rats of control and model group were trea-ted with normal saline intravenously,curcumin group were ad-ministered with curcumin 400 mg.kg -1 .d -1 by gavage and Curc-OEG group were treated with Curc-OEG 1 00 mg.kg -1 .d -1 intra-venously respectively.After 4 weeks treatment,the serum levels of ALT and AST were tested.HE and Sirus staining were used to evaluate the extent of liver inflammation and fibrosis.The mRNA expression levels of proinflammatory cytokines of NF-kB,IL-1 β, IL-6,TNF-α,COX-2 were observed with Real Time PCR.The level of MOD,SOD and GSH in liver of rats were quantified. Results The levels of ALT in control,model,curcumin and Curc-OEG group was (31 .7 ±8.7)U·L -1 ,(383.0 ±75.6) U·L -1 ,(406.3 ±204.7)U·L -1 ,(1 07.0 ±73.7)U·L -1 respectively;that of AST was (1 37.7 ±32.7)U·L -1 ,(585.3 ±36.7)U·L -1 ,(485.0 ±246.5)U·L -1 ,(202.7 ±56.0) U·L -1 respectively,Curc-OEG possessed more hepatoprotective effects than that of curcumin.Liver pathology showed Curc-OEG treatment could significantly alleviate steatosis,reduce inflamma-tion and apparently suppress hepatic fibrogenesis by reducing the thickness of bridging fibrotic septa.Compared with curcumin, Curc-OEG down-regulated mRNA and protein expression levels of NF-kB,IL-1 β,IL-6,TNF-α,COX-2 (P <0.05 ).Moreo-ver,Curc-OEG reduced the level of MOD and increased the lev-els of SOD and GSH.Conclusion Curc-OEG could more sig-nificantly protect the rat liver from CCl4-caused fibrogenesis by anti-inflammatory and antioxidant effect than curcumin.

Amniotic Fluid ; metabolism ; Biomarkers ; metabolism ; Diagnosis, Differential ; Embolism, Amniotic Fluid ; metabolism ; pathology ; Female ; Humans ; Infant, Newborn ; Keratin-13 ; metabolism ; Pregnancy ; Respiratory Aspiration ; metabolism ; pathology