This study aims to investigate the regulatory effect of Sishen Pills(SSP) and its split prescriptions Ershen Pills(EP) and Wuweizi Powder(WP) on T follicular helper(Tfh) cell subset in the dextran sodium sulfate(DSS)-induced colitis mice and the mechanism. A total of 60 male SPF BALB/c mice were used, 10 of which were randomly selected as the normal group. The rest 50 were induced with 3% DSS solution for colitis modeling. After modeling, they were randomized into 5 groups: model group, SSP group, EP group, WP group, and mesalazine group. Body mass, colon mass, colon mass index, colon length, and unit colon mass index in each group were observed. After hematoxylin-eosin(HE) staining, the pathological injury of colon tissue was scored. The expression levels of molecules related to the STAT/SOCS signaling pathway in colon tissues were analyzed by Western blot. Differentiation levels of Tfh cells such as CD4~+CXCR5~+IL-9~+(Tfh9), CD4~+CXCR5~+IL-17~+(Tfh17), and CD4~+CXCR5~+Foxp3~+(Tfr) in peripheral blood of mice were detected by flow cytometry. The results showed each treatment group demonstrated significant increase in body mass and colon length, decrease in colon mass, colon mass index, unit colon mass index, and histopathological score(P<0.05, P<0.01), reduction of the expression of p-STAT3, STAT3, p-STAT6, and STAT6(P<0.05, P<0.01), rise of the expression of SOCS1 and SOCS3(P<0.05, P<0.01), decrease of Tfh9 and Tfh17 cells, and increase of Tfr cells(P<0.05, P<0.01) compared with the model group. These results indicated that SSP and the split EP and WP may alleviate ulcerative colitis by inhibiting the activation of STAT/SOCS signaling pathway and regulating the balance of Tfr/Tfh9/Tfh17 cells.
Animals ; Colitis/genetics* ; Colitis, Ulcerative/metabolism* ; Male ; Mice ; Mice, Inbred BALB C ; Prescriptions ; T-Lymphocytes, Regulatory

This study evaluated the regulatory effect of curcumin on memory follicular T cells (mTf) in obese mice with ulcerative colitis on the basis of determining its effective treatment of ulcerative colitis in obese mice. Forty male leptin mutant (ob/ob) mice were randomly divided into control group, control + curcumin group, dextran sodium sulfate (DSS) group and DSS + curcumin group, with 10 mice in each group. Mice in the DSS group and the DSS + curcumin group were induced by DSS to establish chronic ulcerative colitis model, and mice in the control + curcumin group and the DSS + curcumin group were given curcumin (200 mg·kg^-1·d^-1) by intragastric administration. Mice were sacrificed under anesthesia, and colon mass index, colon length and other conditions were observed in each group. Pathological injury of colonic was performed after HE staining. The levels of memory follicular helper T cells (mTfh) and memory follicular regulatory T cells (mTfr) in spleen of mice were detected by flow cytometry. The expression levels of interleukin-10 (IL-10) and interleukin-17A (IL-17A) in colon tissue were detected by ELISA. The results showed that curcumin significantly increased the body weight and colon length of obese mice with colitis, and decreased the colon weight, colon mass index and pathological score (P < 0.05). Curcumin significantly reduced the levels of central memory follicular T cells (cmTf), mTfh1, mTfh17 cells and the content of pro-inflammatory cytokine IL-17A (P < 0.01). The levels of effector memory follicular T cells (emTf) and mTfr and the content of anti-inflammatory cytokine IL-10 were increased (P < 0.05, P < 0.01). Therefore, curcumin may treat colitis in obese mice by regulating the balance of mTf cell subsets.

Objective:To explore the underlying mechanism of volatile oil from Sishenwan in treating chronic ulcerative colitis through the Toll-like receptor （TLR）/myeloid differentiation factor 88 （MyD88） signaling pathway. Method:The BALB/c mice were randomly divided into a normal group （normal）， a model group ［dextran sodium sulfate （DSS）］， a Sishenwan volatile oil group， an Ershen pill volatile oil group， a Wuweizi powder volatile oil group， and a mesalazine control group. The chronic ulcerative colitis model was induced by DSS in mice. Seven days after intragastric administration， the efficacy was evaluated based on the body weight， colon weight， colon weight index， colon length， and pathological damage score under colonoscopy. The levels of interleukin （IL）-4， IL-10， IL-17A， IL-21， and interferon-γ （IFN-γ） in the supernatant of colon tissues were detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression levels of proteins related to the TLR/MyD88 signaling pathway in the colon mucosa of mice， including TLR2， MyD88， Ras-related C3 botulinum toxin substrate 1 （Rac1）， IL-1 receptor-associated kinase 4 （IRAK4）， IRAK1， tumor necrosis factor receptor （TNFR）-associated factor 6 （TRAF6）， transforming growth factor-β-activated kinase 1 binding protein 1 （TAB1）， TAB2， mitogen-activated protein kinase kinase 6 （MKK6）， p38 mitogen-activated protein kinase （p38 MAPK）， and cyclic adenosine monophosphate response element-binding protein （CREB）. Result:Compared with the normal group， the model group showed decreased colon length， increased colon weight， colon weight index， and pathological damage score under colonoscopy， decreased IL-10 level in the colon tissues， increased IL-4， IL-17A， IL-21， and IFN-γ levels （P<0.05， P<0.01）， and up-regulated protein expression of TLR2， MyD88， Rac1， IRAK4， IRAK1， TRAF6， TAB1， TAB2， MKK6， p38MAPK， and CREB （P<0.01）. Compared with the model group， the Sishenwan volatile oil group showed increased colon length， reduced colon weight， colon weight index， and pathological damage score under colonoscopy， elevated IL-10 level in the colon tissues， decreased IL-4， IL-17A， IL-21， and IFN-γ levels （P<0.05， P<0.01），and down-regulated protein expression of TLR2， MyD88， Rac1， IRAK4， IRAK1， TRAF6， TAB1， TAB2， MKK6， p38MAPK， and CREB （P<0.05， P<0.01）. Conclusion:The volatile oil from Sishenwan can effectively improve the inflammatory response of chronic ulcerative colitis， which may be achieved by regulating the TLR/MyD88 signaling pathway.

BACKGROUND: Recently, T-helper 17 (Th17) cells have been proved to play an important role in promoting cervical cancer. But, till now, few study has been carried out to understand the involvement of these cells in efficacy of anti-tumor treatments. This study aimed to investigate the alterations in the percentage of circulating Th17 cells and related cytokines in locally advanced cervical cancer (LACC) patients before and after concurrent chemoradiotherapy (cCRT) and to analyze the correlations between the alterations in Th17 cells and treatment efficacy. METHODS: A prospective study with 49 LACC (International federation of gynecology and obstetrics [FIGO] stage IIB-IIIB) patients and 23 controls was conducted. Patients received the same cCRT schedule and were followed up for 3 years. Circulating Th17 cells (CD3+CD8- interleukin [IL]-17+ T cells) and related cytokines IL-17, transforming growth factor-β (TGF-β), IL-10, IL-23, IL-6, and IL-22 were detected before and after cCRT. Correlations between alterations of circulating Th17 cells and treatment efficacy were analyzed. Kaplan-Meier analysis was used for overall survival (OS) and progression-free survival (PFS). RESULTS: We found that 40 patients finished the entire cCRT schedule and met the endpoint of this study. The percentage of circulating Th17 cells in the LACC patients was higher than that in the controls, and it significantly decreased after cCRT (P < 0.05). After cCRT, patients were divided into two groups based on the average of the Th17 cells declined. The subgroup of patients with a prominent decrease in circulating Th17 cells after cCRT had a higher treatment efficacy and longer PFS and OS times. Compared with the control patients, LACC patients had higher IL-6, IL-10, IL-22, TGF-β levels and a lower IL-23 level (P < 0.05). After cCRT, IL-6, IL-10, IL-17, IL-23 level significantly increased and TGF-β level significantly decreased compared with the levels before cCRT (P < 0.05). CONCLUSION Circulating Th17 cells in the LACC patients (FIGO stage IIB-IIIB) were higher than those in the controls, but they generally decreased after cCRT. A more pronounced decrease in circulating Th17 cells after cCRT was correlated with better therapeutic effect and longer PFS and OS times.
Chemoradiotherapy ; Disease-Free Survival ; Female ; Humans ; Neoplasm Staging ; Prospective Studies ; Retrospective Studies ; Th17 Cells ; Treatment Outcome ; Uterine Cervical Neoplasms/therapy*

Pathological cardiac hypertrophy is a maladaptive response in a variety of organic heart disease(OHD),which is characterized by mitochondrial dysfunction that results from disturbed energy metabolism. SIRT3, a mitochondria-localized sirtuin, regulates global mitochondrial lysine acetylation and preserves mitochondrial function. However, the mechanisms by which SIRT3 regulates cardiac hypertrophy remains to be further elucidated. In this study, we firstly demonstrated that expression of SIRT3 was decreased in AngiotensionⅡ(AngⅡ)-treated cardiomyocytes and in hearts of AngⅡ-induced cardiac hypertrophic mice. In addition, SIRT3 overexpression protected myocytes from hypertrophy, whereas SIRT3 silencing exacerbated Ang II-induced cardiomyocyte hypertrophy.In particular,SIRT3-KO mice exhibited significant cardiac hypertrophy. Mechanistically, we identified NMNAT3 (nicotinamide mononucleotide adenylyltransferase 3), the rate-limiting enzyme for mitochondrial NAD biosynthesis, as a new target and binding partner of SIRT3.Specifically,SIRT3 physically interacts with and deacety-lates NMNAT3,thereby enhancing the enzyme activity of NMNAT3 and contributing to SIRT3-mediated anti-hypertrophic effects.Moreover,NMNAT3 regulates the activity of SIRT3 via synthesis of mitochon-dria NAD.Taken together,these findings provide mechanistic insights into the negative regulatory role of SIRT3 in cardiac hypertrophy.Sirtuin 3(SIRT3),a mitochondrial deacetylase that may play an impor-tant role in regulating cardiac function and a potential target for CHF

Kidney stones are a common urinary system condition that can progress to kidney disease. Previous studies on the association between tea consumption and kidney stones are inconsistent. A cross-sectional study to investigate the association between tea consumption and kidney stones was conducted from 2013 to 2014 and recruited 9,078 northern Chinese adults. A total of 8,807 participants were included in the final analysis. Participants' prevalence of kidney stones was 1.07%, 1.73%, and 2.25% based on their tea consumption frequency of never, occasionally, and often groups, respectively. Compared with the 'never' group, the odds ratios (95% confidence intervals) for the occurrence of kidney stones were 1.57 (1.00-2.46) and 1.65 (1.06-2.57) in the 'occasionally' and 'often' groups, respectively. After adjusting for sex, age, and other potential confounding factors, tea consumption still significantly increased the risk of kidney stones. Tea consumption is independently associated with an increased risk of kidney stones in the investigated population, suggesting that a decrease in the consumption of tea may be a preventive strategy for kidney stones.

Objective·To investigate the effectiveness of nerve transfer in repairing defecation function after spinal cord injury by the pseudorabies virus (PRV) retrograde tracing. Methods·The spinal cords were transected between L6 and S1 nerve root in 20 rats. The nerve transferring surgery was then conducted in 10 rats (Group B) and the remaining rats were control (Group A). After six months, all rats were injected with 6 μL PRV, sacrificed after 3 d and perfused with paraformaldehyde. Spinal cords were then harvested and frozen sections were prepared for observation. Results·There was no detectable infection of PRV proximal to the injury level in Group A, while infected neurons proximal to the injury level were widely observed in Group B.Conclusion·Nerve transfer has potent effect on defecation reconstruction after spinal cord injury in rats. PRV retrograde tracing can prove the existence of new neuron pathway.

Central neurocytomas (CNs), initially asymptomatic, sometimes become huge before detection. We described and analyzed the clinical, radiological, operational and outcome data of 13 cases of huge intraventricular CNs, and discussed the treatment strategies in this study. All huge CNs (n=13) in our study were located in bilateral lateral ventricle with diameter ≥5.0 cm and had a broad-based attachment to at least one side of the ventricle wall. All patients received craniotomy to remove the tumor through transcallosal or transcortical approach and CNs were of typical histologic and immunohistochemical features. Adjuvant therapies including conventional radiation therapy (RT) or gamma knife radiosurgery (GKRS) were also performed postoperatively. Transcallosal and transcortical approaches were used in 8 and 5 patients, respectively. Two patients died within one month after operation and 3 patients with gross total resection (GTR) were additionally given a decompressive craniectomy (DC) and/or ventriculoperitoneal shunt (VPS) as the salvage therapy. Six patients received GTR(+RT) and 7 patients received subtotal resection (STR)(+GKRS). Eight patients suffered serious complications such as hydrocephalus, paralysis and seizure after operation, and patients who underwent GTR showed worse functional outcome [less Karnofsky performance scale (KPS) scores] than those having STR(+GKRS) during the follow-up period. The clinical outcome of huge CNs seemed not to be favorable as that described in previous reports. Surgical resection for huge CNs should be meticulously considered to guarantee the maximum safety. Better results were achieved in STR(+GKRS) compared with GTR(+RT) for huge CNs, suggesting that STR(+GKRS) may be a better treatment choice. The recurrent or residual tumor can be treated with GKRS effectively.
Antineoplastic Agents ; therapeutic use ; Combined Modality Therapy ; Humans ; Neurocytoma ; therapy ; Radiotherapy ; Surgical Procedures, Operative

Objective To investigate the value of dexmedetomidine in intraoperative wake -up test during language functional surgery with nar-cotrend monitor.Methods Forty patients needing language functional surgery were randomly divided into treatment group and control group , which were pumped with dexmedetomidine (0.5 μg? kg -1? min-1 ) and propofol(4 μg? mL-1 ) combined with remifentanyl (4.5 ng? mL -1 ), respectively.Narcotrend scale, heart rate ( HR) and mean arterial pre-ssure(MAP) were recorded at the beginning of anesthesia (T0), before cut skin ( T1 ) , when the craniotomy ( T2 ) , waking up ( T3 ) , at every 5 min before 10 min of the beginning of waking up ( T4 and T5 ) , 10 min before the end of waking up ( T6 ) , abd the end of wakeing up ( T7 ) . Arousing time and recovery quality including the degree of cooperateing , bucking and agitation were also recorded .Results There was no statisti-cally significant difference of MAP and HR between the two groups at T 0 , T1, T2, T3 and T4(P>0.05).MAP, HR of treatment group at T5,T6 and T7 were lower than those of control group (P<0.05).There was no difference of Narcotrend index(NI) between the two groups(P>0.05).Arousing time and the degree of cooperateing of treatment group were significantly higher than that of control group ( P<0.05 ) .Bucking and agitation of treatment group were significantly lower than those of control group ( P<0.05 ) . Conclusion Dexmedetomidine used in language function surgery does not reduce the NI value , but can reduce the MAP and HR, maintain hemodynamic stability and reduce adverse reactions .

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications