OBJECTIVETo explore the effects of Wenyang Huazhuo Tongluo Recipe (WYHZTLR) containing serum on transforming growth factor β1 (TGF-β1)/Smad signaling pathway of skin fibroblasts in systemic sclerosis (SSc).

METHODSTotally 36 SSc patients were randomly assigned to Chinese medicine (CM) group, Western medicine (WM) group, and integrative medicine (IM) group according to random digit table, 12 in each group. Patients in the CM group took WYHZTLR decoction (one dose per day). Patients in the WM group took penicillamine tablet (0. 125 g each time, bid) and Prednisone Acetate Tablet (PAT 20 mg, qd). Patients in the IM group took penicillamine, PAT, and WYHZTLR decoction (in the same dosage of corresponding drugs as aforesaid). All patients were treated for one month to get drug containing serum. Besides, 10 untreated SSc patients' serum was taken as the control group. Healthy subjects' skin fibroblasts were originated from healthy skin tissue of the upper arms of 2 female patients undergoing plastic surgery. Corresponding serum of each group was added in the culture system of SSc patients' and healthy subjects' dermal fibroblasts respectively. Expression levels of TGF-β1 receptor type I (TGF-β1 RI), TGF-β1 receptor II (TGF-β1 RII), p-Smad2/3 and Smad7 protein were examined by Western blot. Expression levels of collagen type I and collagen type III (Col-I, Col-III) mRNA were examined by reverse transcription PCR. Contents of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) in the supernatant of SSc, skin fibroblasts were examined by ELISA.

RESULTSCompared with the control group, expression levels of TGF-β1 R I and p-Smad2/3 protein significantly decreased, but expression levels of Smad7 protein significantly increased in skin fibroblasts of SSc patients and healthy subjects of WM, CM, and IM groups (P <0.05, P <0. 01). Meanwhile, the expression level of TGF-β1 RII decreased in the IM group (P <0. 05, P <0. 01). Compared with the WM group, expression levels of TGF-β1 RI and p-Smad2/ 3 protein significantly decreased, but that of Srnad7 protein significantly increased in IM groups (P <0. 01). mRNA expression levels of Col-I and Col-II in SSc skin fibroblasts significantly decreased more in WM, CM, and IM groups than in the control group (P <0. 05, P <0. 01). Besides, the expression level of Col-III mRNA was significantly lower in the IM group than in the WM group (P <0.01). Compared with the control group, serum levels of MMP-9 and MMP-9/TIMP-1 ratios increased more obviously in WM, CM, and IM groups (P <0.05, P <0.01). But expression levels of TIMP-1 decreased significantly in CM and IM groups (P <0.01). Expression levels of MMP-9 and MMP-9/TIMP-1 ratios increased more in the IM group than in the WM group (P <0. 01). Expression levels of TIMP-1 decreased more in CM and IM groups than in the WM group (P <0.01).

CONCLUSIONWYHZTLR containing serum could reduce expression levels of Col-I and Col-III possibly through regulating key signal molecules, such as TGF-β1 RI, p-Smad2/3, and Smad7 in TGF-β1/Smad signaling pathway of SSc skin fibroblasts, and inhibiting transduction of TGF-β1/Smad signaling pathway.

Collagen Type I ; Collagen Type III ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Fibroblasts ; Humans ; Matrix Metalloproteinase 9 ; Scleroderma, Systemic ; drug therapy ; metabolism ; Signal Transduction ; drug effects ; Smad2 Protein ; Smad7 Protein ; Transforming Growth Factor beta1 ; metabolism

Flammulin, an anti-tumor protein, was purified from the aqueous extract of basidiomes of Flammulina Velutipes. Purified flammulin emulsified with Freund's adjuvant was injected subcutaneously into New Zealand white rabbits. After several immune enhancements, these animals were bled and sera were separated. Antiserum against flammulin in Western blots were applied to determine if flammulin be present in the liquid state culture or fruiting body. The result showed that anti-flammulin serum could recognize the aqueous extract of fruiting body in SDS-PAGE gels under the reducing conditions, no flammulin was detected in mycelia of Flammulina Velutipes.

Objective: To investigate the role of NF-?B in signal transduction of hepatocyte apoptosis in liver injury. Methods: A total of 42 Chang-Bai piglets were divided into 7 groups: control group, 1, 2, 4, 8, 12, and 24 hours wound group. The model of intestinal perforations due to abdominal firearm wound was established in wound groups. Hepatic NF-?B activity was measured with immunohistochemical staining and image analysis in all groups. Hepatocyte apoptosis indexes and serum ALT levels were also determined. Results: Levels of hepatic NF-?B activity in wounded groups were significantly elevated compared with control group, and there were two peaks (1 and 8 hours group P

Objective To develop a practical synthetic process of vonoprazan fumarate with high-yield and lower impurities to meet the quality requirements. Methods By using 5-(2-fluorophenyl)pyrrole-3-carboxaldehyde as the starting material,the qualified vonoprazan fumarate was synthesized via the following steps:①N-sulfonylation and the chloride impurity was removed by recrystalli-zation from MeOH;②the aldehyde was converted to amine by reductive amination,followed by forming the vonoprazan chloride to re-move the dimethylamino impurity;③vonoprazan free base was obtained by neutralization and then converted to fumarate at room tem-perature and finally recrystallized from MeOH/H2O(1:1). Results An impurity controllable synthetic process was developed with a 4％total yield improving. The final product was confirmed by ESI-MS and 1H NMR. Conclusion The synthetic process with single im-purity less than 0.1％and purity above 99.5％was obtained and suitable for scale production of vonoprazan fumarate.

Objective To evaluate the intervention effects of cognitive behavior therapy (CBT) on the patients with first episode schizophrenia. Methods A total of 80 patients with first episode schizophrenia were randomly divided into study group (n =40) and control group (n =40). The study group was treated by routine drugs and psychiatric nursing after two weeks combining with CBT while the control group was treated only by routine drugs and psychiatric nursing. Both groups were assessed with Positive and Negative Syndrome Scale (PANSS), Nurses Observation Scale for Inpatient Evaluation (NOSIE) , Scale of Social-skill for Psychiatric Inpatients (SSPI) , and Symptom Check List-90 (SCL-90) before and after CBT intervention. The scores of those scales were compared between two groups. Results There were significant differences after CBT intervention in all factors, total negative factors and total positive factors of NOSIE, total score of SSPI and PANSS (P<0.01) between two groups. Factors score of interpersonal sensitivity, depression, anxiety, panic, paranoid ideation, and psychosis of SCL-90 in the study group decreased significantly after intervention. Conclusions It is suggested that CBT can improve social function and quality of life and facilitate recovery of the first-episode schizophrenia patients.

Objective To evaluate the safety and efficacy of cefaze-done injection ( CZD) compared with cefazolin injection ( CZL) in the treatment of acute bacterial respiratory infections.Methods Eligible subjects were divided randomly to receive 2.0 g cefazedone injection or cefazolin injection twice a day for 7 to 14 days.Efficacy and safety evaluation were done in accordance with the clinical trial protocol.Results Two hundred and sixty patients in 11 hospitals were en-rolled, 126 in CZD group( trial) and 134 in CZL group( control).There were no statistical differences in basic conditions between two groups( P >0.05 ).Cure rates of CZD group and CZL group were 95.5% and 94.9% in PPS ( P>0.05 ).Bacteria clearance rates of CZD group and CZL group were100% and 91.7% in BPPS and the total cure rates of CZD group and CZL group were 94.4% and 91.7% in BPPS, respectively ( P>0.05).Ten out off 126 patients in CZD group and 14 out off 134 in CZL group developed adverse events( AE ).Six and eleven events in CZD group and CZL group
were evaluated to be related with study drugs.One case in CZL group developed severe AE , which was considered not related with study drug.Conclusion Cefazedone injection is safe and effective in the treatment of respiratory infections.

OBJECTIVE: To compare the clinical efficacy between moxibustion and acupuncture for knee osteoarthritis (KOA), and to observe the effect on serum tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), superoxide dismutase (SOD) and malondialdehyde (MDA). METHODS: A total of 60 patients with KOA were randomized into a moxibustion group (30 cases, 2 cases dropped off) and an acupuncture group (30 cases, 2 cases dropped off). In the aucpuncture group, acupuncture was applied at Neixiyan (EX-LE 4), Dubi (ST 35), Heding (EX-LE 2), Xuehai (SP 10), Liangqiu (ST 34), Zusanli (ST 36) and point on the affected side for 30 min.In the moxibustion group, moxibustion was adopted at knee for 60 min. The treatment was given once every two days for 4 weeks, totally 14 times. Before and after treatment, the western ontario and McMaster universities osteoarthritis index (WOMAC) score was compared, and the therapeutic effect was evaluated in the two groups. The contents of serum TNF-αand IL-1β, the activity of serum SOD and the serum level of MDA were detected in the two groups. RESULTS: Compared before treatment, the WOMAC scores and the contents of serum TNF-α, IL-1β and MDA after treatment were reduced (<0.05), the activity of serum SOD was increased (<0.05) in the two groups. In the moxibustion group, the WOMAC score and the contents of serum TNF-α, IL-1β and MDA after treatment were lower than the acupuncture group (<0.05), the activity of serum SOD was higher than the acupuncture group (<0.05). The total effective rate was 89.3% (25/28) in the moxibustion group, which was superior to 42.9% (12/28) in the acupuncture group (<0.05). CONCLUSION Moxibustion and acupuncture can relieve KOA symptoms, and the therapeutic effect of moxibustion is superior to acupuncture. The mechanism may be related to the reduction of serum inflammatory factor and oxidative stress factor.

Gut microbiome sequencing studies have great potential to translate microbial analysis outcomes into human health research. Sequencing strategies of 16S amplicon and whole-metagenome shotgun (WMS) are two main methods in microbiome research with respective advantages. However, how sample heterogeneity, sequencers and library preparation protocols affect the sequencing reproducibility of gut microbiome needs further investigation. This study aims to provide a reference for the selection of sequencing technologies by comparing differences in microbial composition from different sampling sites. The results of three widely adopted sequencers showed that the technical repetition correlation (r= 0. 94) was high in WMS method, while the biological repetition correlation (r = 0. 69) was low. Bray-Curtis distance identified that dissimilarity from biological replicates was larger than that of technical replicates (P<0. 001). In addition, dissimilarity and specific taxonomic profiles were observed between 16S and WMS datasets. Our results imply that homogenization is a necessary step before sample DNA extraction. The sequencers contributed less to taxonomic variation than the library preparation protocols. We developed an empirical Bayes approach that " borrowed information" in calculations and analyzed batch effect parameters using standardized data and prior distributions of (non-) parameters, which may improve population comparability between 16S and WMS and provide a basis for further application to fusion analysis of published 16S and microbial datasets.