Role of SIRT5 in the analgesic effectiveness of moxibustion at ST36 in mice with inflammatory pain.

Sirtuine5 (SIRT5) is an important molecule involved in the pathology of inflammatory diseases. To investigate the impact of SIRT5 on the analgesic effectiveness of moxibustion, we established a complete Freund's adjuvant- (CFA-) induced inflammatory pain in mice model. Moxibustion was applied at the Zusanli (ST36) acupoint in mice with inflammatory pain. The analgesic effectiveness was evaluated by thermal hyperalgesia and mechanical allodynia tests in the right paws after CFA injection. The expression of inflammatory cytokines, including the pro-inflammatory factors IL-1ß and TNF-α, and the anti-inflammatory factors IL-4 and TGF-ß expressions, was evaluated using by ELISA. Furthermore, SIRT5 was evaluated by immunofluorescence and western blotting. The results showed that, compared with the CFA group, both thermal and mechanical pain thresholds increased with moxibustion and the SIRT5 inhibitor MC3482 intervention at ST36. Additionally, compared to the CFA-induced group, the inflammatory mediators, including IL-1ß and TNF-α, decreased, while the anti-inflammatory cytokines IL-4 and TGF-ß increased with moxibustion and MC3482 ST36 acupoint injection. Western blot results showed a decreased expression of SIRT5 at the ST36 site with moxibustion and MC3482 injection, compared to the CFA-induced group. SIRT5 expression in the right paw of mice injected with moxibustion and MC3482 was higher than that in the CFA-induced group. This study revealed that SIRT5 expression is involved in moxibustion analgesia and may be a potential mediator in the regulation of analgesia.

Effects of Chinese Medicine on Symptoms, Syndrome Evolution, and Lung Inflammation Absorption in COVID-19 Convalescent Patients during 84-Day Follow-up after Hospital Discharge: A Prospective Cohort and Nested Case-Control Study.

OBJECTIVE: To observe the changes of symptoms, Chinese medicine (CM) syndrome, and lung inflammation absorption during convalescence in patients with coronavirus disease 2019 (COVID-19) who had not totally recovered after hospital discharge and whether CM could promote the improvement process. METHODS: This study was designed as a prospective cohort and nested case-control study. A total of 96 eligible patients with COVID-19 in convalescence were enrolled from Beijing Youan Hospital and Beijing Huimin Hospital and followed up from the hospital discharged day. Patients were divided into the CM (64 cases) and the control groups (32 cases) based on the treatment with or without CM and followed up at 14, 28, 56, and 84 days after discharge. In the CM group, patients received the 28-day CM treatment according to two types of CM syndrome. Improvements in clinical symptoms, CM syndrome, and absorption of lung inflammation were observed. RESULTS: All the 96 patients completed the 84-day follow-up from January 21 to March 28, 2020. By the 84th day of follow-up, respiratory symptoms were less than 5%. There was no significant difference in the improvement rates of symptoms, including fatigue, sputum, cough, dry throat, thirst, and upset, between the two groups (P>0.05). Totally 82 patients (85.42%) showed complete lung inflammation absorption at the 84-day follow-up. On day 14, the CM group had a significantly higher absorption rate than the control group (P<0.05) and the relative risk of absorption for CM vs. control group was 3.029 (95% confidence interval: 1.026-8.940). The proportions of CM syndrome types changed with time prolonging: the proportion of the pathogen residue syndrome gradually decreased, and the proportion of both qi and yin deficiency syndrome gradually increased. CONCLUSIONS: Patients with COVID-19 in convalescence had symptoms and lung inflammation after hospital discharge and recovered with time prolonging. CM could improve lung inflammation for early recovery. The types of CM syndrome can be transformed with time prolonging. (Registration No. ChiCTR2000029430).

[Light and heat of moxibustion for knee osteoarthritis：a multi-center randomized controlled trial].

OBJECTIVE: To explore the clinical therapeutic effect of light and heat of moxibustion for knee osteoarthritis (KOA). METHODS: A total of 216 patients with KOA were randomized into a traditional moxibustion group (72 cases, 8 cases dropped off), a moxibustion light group (72 cases, 9 cases dropped off) and a moxibustion heat group (72 cases, 10 cases dropped off).The special light-heat separation moxibustion cup was applied, the patients in the traditional moxibustion group received the treatment of moxibustion, the patients in the moxibustion light group received the treatment of moxibustion light and the patients in the moxibustion heat group received the treatment of moxibustion heat. The acupoint selection of the three groups was Neixiyan (EX-LE 4), Dubi (ST 35) and Zusanli (ST 36), the treatment was given 20 min each time, 3 times a week, 4 weeks were required totally, and the follow-up surveys were made 4 and 8 weeks after treatment. The scores of Western Ontario and McMaster University osteoarthritis index (WOMAC) and visual analogue scale (VAS) were observed before treatment, after 2 and 4 weeks of treatment, 4 and 8 weeks after treatment. The therapeutic effects were evaluated according to the criterion of patient global assessment (PGA) after 4 weeks of treatment and 8 weeks after treatment. RESULTS: Compared with before treatment, the pain scores, stiffness scores, physical function scores and total scores of WOMAC were reduced after 2, 4 weeks of treatment and 4 weeks after treatment in the three groups (P<0.05). The pain scores, stiffness scores, physical function scores and total scores of WOMAC were reduced 8 weeks after treatment in the traditional moxibustion group and the moxibustion heat group (P<0.05). The stiffness score, physical function score and total score of WOMAC were reduced 8 weeks after treatment in the moxibustion light group (P<0.05). The pain score, physical function score and total score of WOMAC in the traditional moxibustion group after 4 weeks of treatment were lower than the moxibustion light group (P<0.05). Compared with before treatment, the VAS scores were reduced after 2, 4 weeks of treatment and 4 , 8 weeks after treatment in the three groups (P<0.05). The improvement rates in the traditional moxibustion group and the moxibustion heat group after 4 weeks of treatment and 8 weeks after treatment were superior to the moxibustion light group (P<0.05). CONCLUSION: The light and heat of moxibustion have therapeutic effect for KOA, and the therapeutic effect of moxibustion heat is superior to moxibustion light.

[Expert consensus statement on Hugan Tablets in clinical practice].

Hugan Tablets is a Chinese patent medicine,it has the function of anti-inflammation and reducing transaminase. Based on questionnaire investigation of doctors and a systematic review of research literature on Hugan Tablets,using international clinical practice guidelines' developing methods,with the best available evidence and fully combining expert experience,and following the principle of " evidence-based,consensus-based and experience-based",Expert consensus statement on Hugan Tablets in clinical practice was developed by more than 30 multidisciplinary experts from the nationwide,aimed at guiding and standardizing the rational use of Hugan Tablets by clinicians and to improve clinical efficacy and safety. The expert consensus adopts internationally recognized recommendation criteria for classification of evidence: GRADE. The formation of expert consensus adopts the nominal group technique. Six main considerations are quality of evidence,curative effect,safety,economical efficiency,patient acceptability and other factors. If there is sufficient evidence,a " recommendation" is formed,using GRADE grid voting rule. If there isn' t sufficient evidence,a " consensus opinion" is formed,using majority counting rule. Focus on the indication,usage and dosage,drug use in special population and safety of Hugan Tablets,two recommendations and eight consensus opinions were put forward. Through expert meetings and correspondence,a nationwide consultation and peer review was conducted. This consensus applies to clinicians in hospitals and grass-roots health services,to provide guidance and reference for the rational use of Hugan Tablets.

Cancer of the Liver Italian Program score helps identify potential candidates for transarterial chemoembolization in patients with Barcelona Clinic Liver Cancer stage C.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system for hepatocellular carcinoma (HCC) recommends transarterial chemoembolization (TACE) as the first line therapy for stage B patients and sorafenib treatment for stage C patients. However, stage C patients exhibit variations in terms of tumor burden, liver function, and extrahepatic metastasis, which could potentially affect disease outcome. Here, we assessed whether the Cancer of the Liver Italian Program (CLIP) scores can help identify stage C patients likely to benefit from TACE. METHODS: Out of 295 BCLC stage C HCC patients enrolled between January 2009 and December 2011, those with platelet counts >30 X 10(9) cells/L, total bilirubin <51 µmoL/L, and an unobstructed main portal vein were scheduled for TACE (n=195). The remaining patients received best supportive care (BSC, n=100). All the patients were followed up for symptoms, performance status, and Child-Pugh classification scores every 4 weeks until death or December 2013. The prognosis of each group was evaluated by using the log-rank test and Cox-Mantel test. RESULTS: The median overall survival (OS) was 6 months [95% confidence interval (CI): 4.64-7.36]. The OS was 9 months for the TACE group and 4 months for the BSC group. The TACE group had a longer OS than the BSC subgroup for CLIP scores 0-2 [13 months (95% CI: 8.55-17.45) vs 4 months (95% CI: 0.00-10.96), P=0.001]. No significant differences were found between the TACE and BSC groups for CLIP scores 3-5. The CLIP score and treatment methods were found to be independent prognostic factors. CONCLUSIONS: BCLC stage C HCC patients exhibit definite disease heterogeneity and can be reclassified by using the CLIP scoring system. Moreover, patients with CLIP scores 0-2 are likely to benefit from TACE. However, additional studies with long-term follow-up will be required to validate these findings.

[Changes and significance of peripheral blood fibrinogen level in patients with severe acute respiratory syndrome].

OBJECTIVE: To investigate variations and significance of plasma fibrinogen in patients with severe acute respiratory syndrome (SARS). METHODS: Totally 148 patients with SARS were divided into the following groups: initial stage group (44 cases) and after the initial stage group (104 cases), common type group (87 cases) and severe type group (61 cases), unilobar lung involvement group (49 cases), bilobar lung involvement group (53 cases) and diffuse lung involvement group (46 cases). The values of plasma fibrinogen of the 148 SARS patients were analyzed and compared among the different groups. RESULTS: The mean value of plasma fibrinogen (x +/- SD, 522.29 +/- 154.87 mg/dl) of the 148 cases was higher than the normal value (p less than 0.01). There were significant differences between the initial stage and after initial stage groups, between the common and severe type groups, and among the unilobar, bilobar and diffuse lung involvement groups (p less than 0.05). CONCLUSION: theses results suggested that elevation of peripheral blood fibrinogen in SARS patients may play an important role in development and progress of the disease and its treatment.

Association of HLA-DQB1 gene polymorphisms with outcomes of HBV infection in Chinese Han population.

BACKGROUND: Host genetic factors and environmental factors including hepatitis B virus (HBV) genotype are widely studied for the different outcomes of HBV infection. Human leukocyte antigen (HLA) plays an important role in the immunological reaction to HBV infection. AIMS: To explore whether the HLA-DQB1 allele polymorphisms are associated with the outcome of HBV infection in a Chinese Han population. PATIENTS: One hundred and thirty three HBV subjects with spontaneous recovery and 151 chronic hepatitis B patients were recruited into this case-control study in the Beijing area of China. METHODS: Sequence specific primer-polymerase chain reaction (SSP-PCR) was used to detect 13 alleles of HLA-DQB1 gene and 13 alleles of HLA-DRB1 gene. Multivariate logistic regression model was performed to detect the association of candidate factors with outcome of HBV infection by SAS 9.1.2 software package. RESULTS: The frequency of HLA-DQB1*0502 allele in the chronic hepatitis B group was significantly higher than that in the group with spontaneous recovery independent of HLA-DRB1 (odds ratio 95%CI 1.8-190). In this study there was no evidence to indicate that cigarette smoking or alcohol consumption was associated with the outcome of HBV infection. CONCLUSION: HLA-DQB1*0502 is independently associated with the outcome of HBV infection and is one host genetic factor affecting HBV infection outcome. At the same time, we can not rule out the possibility that excluded genes and alleles may also affect outcome.

[Association of Taq I T/C and Fok I C/T polymorphisms of vitamin D receptor gene with outcome of hepatitis B virus infection].

OBJECTIVE: To determine whether Taq I T/C and Fok I C/T polymorphisms of vitamin D Receptor (VDR) gene was associated with the outcomes of hepatitis B virus (HBV) infection. METHODS: A total of 212 HBV self-limited infection individuals, 244 asymptomatic HBsAg carriers and 391 chronic hepatitis B (HB) patients were recruited to conduct a case-control study. VDR-Taq I T/C and VDR-Fok I C/T polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of VDR-Fok I allele C in the chronic HB patients was 45.8%, significantly higher than 38.2% of the self-limited infection individuals (chi(2) = 6.43, P = 0.01). The frequencies of VDR-Fok I genotypes TT, TC, and CC in HB patients were 30.7%, 47.1%, and 22.2% respectively, and 41.0% (TT), 41.5% (TC), and 17.5% (CC) in the self-limited infection individuals. There was a statistically significant difference between HB patients and self-limited infection individuals (chi(2) = 6.76, P = 0.03). The results of univariate analysis showed that the subjects carrying VDR-Fok I CC/TC genotype had 1.57-fold elevated risk for developing chronic HB when they were infected HBV (OR = 1.57, P = 0.01). A multiple logistic regression analysis revealed that VDR-Fok I CC/CT was independently associated with chronic HB after adjusting both potential confounding effects of gender (OR = 1.70, P = 0.021). The statistically significant association between TaqI T/C polymorphism and outcome of HBV infection was not demonstrated in the study. The frequency of haplotype TC of VDR-TaqI and Fok I in HB patients was 2.3080%, significantly higher than 0.5391% of the self-limited infection individuals (chi(2) = 6.08, P = 0.01). However, the frequency of haplotype TT in the HB patients was 1.5283%, significantly lower than 3.7061% of the self-limited infection individuals (chi(2) = 5.65, P = 0.02) and 3.4820% of the HBV carriers (chi(2) = 5.12, P = 0.02). CONCLUSION: VDR gene polymorphism is probably an influence factor on the genetic susceptibility of HBV infection.

[Study on association between vitamin D receptor gene polymorphisms and the outcomes of HBV infection].

OBJECTIVE: To explore whether the vitamin D receptor gene (VDR) polymorphisms are associated with the outcomes of hepatitis B virus (HBV) infection in Chinese Han population. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the polymorphisms of Fok I locus in exon 2 and Taq I locus in exon 9 of VDR gene. One hundred and eighty-four chronic hepatitis B patients and 205 asymptomatic HBV carriers were recruited to make the comparison of frequencies of genotype and haplotype of the VDR gene between the patients and the carriers. RESULTS: The univariate analysis showed a significant difference in Fok I polymorphism between chronic hepatitis B patients group and asymptomatic HBV carriers group. The FF genotype frequency in chronic hepatitis B patients group was 44.6%,higher than 31.7% in asymptomatic HBV carriers group (P<0.05). After adjusting the confounders by multiple logistic regression analysis, the result still showed a significant difference in Fok I site polymorphism between chronic hepatitis B patients group and asymptomatic HBV carriers group (OR=1.95, P<0.05). The FT haplotype frequency in chronic hepatitis B patients group was higher than that in asymptomatic HBV carriers group (OR=1.45, P<0.05). The fT haplotype frequency in chronic hepatitis B patients group was lower than that in asymptomatic HBV carriers group (OR=0.72, P<0.05). CONCLUSION: VDR gene polymorphism may be an influence factor of genetic susceptibility to HBV infection.

Association of-238G/A and -857C/T polymorphisms of tumor necrosis factor-alpha gene promoter region with outcomes of hepatitis B virus infection.

OBJECTIVES: To determine whether -238G/A and -857C/T polymorphisms of tumor necrosis factor-alpha (TNF-alpha) gene promoter were associated with outcomes of hepatitis B virus infection. METHODS: A total of 246 HBV self-limited infected subjects and 443 chronic hepatitis B (HB) patients were recruited in this case-control study. TNF-alpha-238G/A and -857C/T gene promoter polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The frequency of TNF-alpha-238 GG (90.7%) in chronic HB group was significantly lower than that (95.1%) in self-limited group (P = 0.041). The frequency of TNF-alpha-857 CC (79.7%) in chronic HB patients was significantly higher than that (70.9%) in self-limited infected subjects (P = 0.021). Multiple logistic regression analysis revealed that both TNF-alpha-238GA and -857CC were independently associated with chronic HB. CONCLUSIONS: TNF-alpha promoter variants are likely to play a substantial role in influencing the outcomes of HBV infection.

[Controlled observation on Guan-moxibustion and suspended moxibustion for treatment of herpes simplex virus facial neuritis].

OBJECTIVE: To evaluate clinical therapeutic effect of Guan-moxibustion on herpes simplex virus facial neuritis. METHODS: One hundred and sixty cases were enrolled in 3 centers and 157 cases were completed the study. All he patients were randomly divided into 2 groups, a Guan-moxibustion group and a suspended moxibustion plus acupuncture group. All of them were treated with basic acupuncture, and the Guan-moxibustion group were added with Guan-moxibustion and the suspended moxibustion group with suspended moxibustion. They were treated for 8 weeks, and facial disability index (FDI) and House-Brackmann facial nerve grading system were used to assess therapeutic effects. RESULTS: The effective rate was 91.0% in the Guan-moxibustion group and 72.2% in the suspended moxibustion group with a significant difference between the two groups (P < 0.05), the Guan-moxibustion being better than the suspended moxibustion group. CONCLUSION: The therapeutic effect of Guan-moxibustion plus acupuncture on herpes simplex virus facial neuritis is better than that of suspended moxibustion plus acupuncture.

[Association of TNFA polymorphisms with the outcomes of HBV infection].

OBJECTIVE: To explore whether the TNFA promoter single nucleotide polymorphisms (SNPs) are associated with the outcomes of hepatitis B virus(HBV) infection in Chinese Han population. METHODS: One hundred and forty-eight self-limited HBV infection subjects and 207 chronic hepatitis B patients were recruited. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequence specific primer-PCR(PCR-SSP) were used to detect the SNPs of five sites in TNFA promoter (-238G/A, -308G/A, -857C/T, -863C/A, -1031T/C). The frequency distributions of genotypes and haplotypes in different groups were analyzed by EPI and EH programs. RESULTS: The frequencies of -238GG genotype in chronic hepatitis B patients were significantly higher than that in self-limited infection subjects (P=0.02). The frequencies of -857TT genotype in chronic hepatitis B patients were clearly lower than that in self-limited infection subjects (P=0.02). Haplotypic frequencies of GGCCT (-238/-308/-857/-863/-1031) in chronic hepatitis B patients was significantly lower than that in self-limited infection subjects (P=0.03), and the frequencies of haplotype GGCAT or GGTAT in chronic hepatitis B patients were clearly higher than those in self-limited infection subjects (P=0.0001; P=0.004). CONCLUSION: TNFA promoter polymorphisms are important host genetic factors affecting the outcomes of HBV infection.

Association of polymorphism of tumor necrosis factor-alpha gene promoter region with outcome of hepatitis B virus infection.

AIM: To determine whether -238G/A and -857C/T polymorphisms of tumor necrosis factor-alpha (TNF-alpha), gene promoter and hepatitis B (HB) viral genotypes were associated with outcomes of HBV infection. METHODS: A total of 244 HBV self-limited infected subjects, 208 asymptomatic carriers, and 443 chronic HB patients were recruited to conduct a case-control study. TNF-alpha-238G/A and -857C/T gene promoter polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and HBV genotypes were examined by nested PCR. RESULTS: The positive rate of HBV DNA in asymptomatic carrier group and chronic HB group was 46.6% and 49.9%, respectively. HBV genotype proportion among the asymptomatic carriers was 2.1% for genotype A, 25.8% for genotype B, 68.0% for genotype C, and 4.1% for genotype B+C mixed infection, and 0.9% for genotype A, 21.7% for genotype B, 71.5% for genotype C, 5.9% for genotype B+C mixed infection in chronic HB group. There was no significant difference in genotype distribution between the asymptomatic carrier group and chronic HB group (chi2 = 1.66, P = 0.647). The frequency of -238GG genotype in self-limited group was 95.1%, significantly higher than 90.7% in chronic HB group and 89.0% in asymptomatic carrier group (P = 0.041 and P = 0.016, respectively). The frequency of TNF-alpha-857 CC in chronic HB group was 79.7%, significantly higher than 64.4% in asymptomatic carrier group and 70.9% in self-limited group (P<0.001 and P = 0.023, respectively). A multiple logistic regression analysis revealed that TNF-alpha-238GA and -857CC were independently associated with chronic HB after gender and age were adjusted. CONCLUSION: TNF-alpha promoter variants are likely to play a substantial role in the outcome of HBV infection.