Objective To determine the serum levels of tumor necrosis factor (TNF)-α,interleukin (IL)-17,IL-22 and IL-17F in patients with palmoplantar pustulosis (PP),and to estimate their relationship with disease activity in PP.Methods Venous blood samples were collected from 30 patients with PP at both active stage and stationary stage and from 20 healthy human controls.Enzyme-linked immunosorbent assay (ELISA) was conducted to determine the serum levels of TNF-α,IL-17,IL-22 and IL-17F.The paired Wilcoxon signed rank test was carried out to compare the serum levels of cytokines between patients at active stage and at stationary stage,and the Mann-Whitney U test to compare those among different groups.Results The median serum levels of TNF-α,IL-17 and IL-22 in patients with PP at active stage were 186.35 (range,113.48-412.69) ng/L,420.45 (range,278.55-748.73) ng/L and 106.48 (range,69.13-251.86) ng/L respectively,significantly higher than those at stationary stage (42.52(18.83-95.37) ng/L,48.11 (36.43-80.04) ng/L,20.32 (10.55-48.75) ng/L,respectively,all P ＜ 0.05) and those in the controls (24.30 (12.0-61.56) ng/L,10.49 (6.24-24.44) ng/L,2.58 (1.41-5.78) ng/L,respectively,all P ＜ 0.05).Moreover,the patients at stationary stage showed a significant elevation in serum levels of TNF-α,IL-17 and IL-22 compared with the controls (u =2.71,3.53,2.18,respectively,all P ＜ 0.05).No statistical difference was noted in the serum level of IL-17F among the patients at different stages and controls (P ＞ 0.05).Conclusion The circulating levels of TNF-α,IL-17 and IL-22 were associated with disease activity in PP,hinting that they may be involved in the development of PP.

OBJECTIVE: To observe the effect of herbal cake-partitioned moxibustion (Moxi) on tumor necrosis factor (TNF)-α/ TNF receptor 1 (TNFR1)-associated death domain (TRADD) / Fas-associated death domain (FADD) pathway-mediated apoptosis of intestinal epithelial cells in Crohn's disease (CD) rats, so as to explore its underlying mechanisms in the treatment of CD. METHODS: Forty-eight SD male rats were randomly divided into normal, model, Moxi and medication groups (n＝12 rats in each). The CD model was established by intra-annual perfusion of 2，4，6-trinitrobenzene sulfonic acid (TNBS) solution (TNBS∶50% alcohol＝2∶1, 3 mL/kg), once every 7 days, 4 times altogether. For rats of the Moxi group, moxibustion was given to "Tianshu" (ST25) and "Qihai" (CV6), two moxa-cones every time, once daily for 10 days. For rats of the medication group, intragastric perfusion of mesalazine solution was given twice daily for 10 days. After the treatment, the colonic epithelium tissue was sampled. The epithelial cells were purified and cultured to establish an in vitro intestinal epithelial barrier, and added with TNF-α (a pro-inflammatory factor, 100 ng/mL) in the culture medium for 24 h for making an increased epithelial permeability model. The permeability of intestinal epithelial cell barrier was evaluated by detecting the fluorescence yellow transmittance of the TNF-α-incubated cell medium. Western blot was used to detect the expression levels of TNFR1, TRADD, receptor-interacting protein 1 (RIP1), FADD and zinc finger protein A20 (A20, a ubiquitination enzyme for inhibiting activation of TRADD and RIP1) of the cultured intestinal epithelium cells. The apoptosis of the TNF-α-incubated intestinal epithelial cells was detected by flow cytometry. RESULTS: After modeling and compared with the normal group, the fluorescence yellow transmittance of intestinal epithelia cells, apoptosis rate, and expression levels of TNFR1, TRADD, and RIP1 proteins were significantly increased (P<0.001, P<0.01), and the expression of A20 was significantly decreased (P<0.01) in the model group. In comparison with the model group, the fluorescence yellow transmittance of intestinal epithelial cells, the apoptosis rate and expression levels of TRADD, RIP1 and FADD were remarkably down-regulated (P<0.001, P<0.01), and the expression of A20 was significantly up-regulated (P<0.01) in both the Moxi and medication groups. CONCLUSION: Herbal cake-partitioned moxibustion may down-regulate the permeability of intestinal epithelial barrier and the apoptosis of intestinal epithelial cells by way of suppressing TNF-α-mediated cellular apoptosis pathway of intestinal epithelium in CD rats.

OBJECTIVETo investigate the therapeutic mechanism of Jiawei Mojie Tablet (JMT) in treating primary dysmenorrhea (PD) by observing its effect on plasma oxytocin (OT) level in patients in menstrual period.

METHODSSixty-three patients with PD enrolled in the study were randomly divided into the JMT group (n = 33) and the control Group (n = 30, treated with Yueyueshu Granule) to observe the change of OT level in the menstrual period before and after treatment.

RESULTSOT level in patients with PD was obviously higher than that in healthy subjects (P < 0.01), and was positively correlated with the degree of pain (r = 0.738, P < 0.01). OT level reduced significantly after treatment (P < 0.01), the reduction was more significant in the JMT group than that in the control group (P < 0.01).

CONCLUSIONJMT could reduce the OT level in menstrual period.

Adolescent ; Adult ; Drugs, Chinese Herbal ; therapeutic use ; Dysmenorrhea ; blood ; drug therapy ; Female ; Humans ; Oxytocin ; blood ; Tablets

The clinical experience of professorfor polycystic ovary syndrome (PCOS) was summarized. According to the main pathogenesis of PCOS, the tonifying kidney should be taken as essence with synchronous treatment on liver, spleen and heart, presenting staging, classification and sorting method for PCOS. In the staging method, the regulation on follicle development should be taken as treatment core to comply with the rules ofand. A four-stage method was proposed, where "regulating method" was suitable in menstrual period, "tonifying method" in follicular phase;"dredging method" in ovulatory period and "adjustment and tonifying " in luteal phase. In the classification and sorting method, attention was paid on individualized treatment, and treatment was based on fat type, thin type and non-fat type as well as childbearing. Besides, psychological counseling and life adjustment for patient was essential, and the unity of body and mind could enhance curative effect.

OBJECTIVE: To observe the difference in the therapeutic effects on rheumatoid arthritis (RA) between the combined -deep needling and bloodletting technique and the regular needling technique. METHODS: A total of 70 patients were randomized into an observation group (35 cases) and a control group (35 cases, 4 cases dropped-out). Dazhui (GV 14), Shenzhu (GV 12), Zhiyang (GV 9), Jinsuo (GV 8), Ganshu (BL 18), Shenshu (BL 23), Zhibian (BL 54), Weizhong (BL 40), Taixi (KI 3) and Tianzong (SI 11), etc. were selected in the two groups. Additionally, in the observation group the -deep needling technique was adopted at Tianzong (SI 11) and Zhibian (BL 54), the bloodletting technique at the local swollen area and the even-needling technique at the rest acupoints. In the control group, the even-needling technique was applied to all of the acupoints. Acupuncture treatment was given once every two days, 3 times a week and for 12 weeks totally. The numbers of tender points at the knee joint, the numbers of swollen sites at the knee joint, the visual analogue scale (VAS) score and the American health assessment questionnaire (HAQ) score were observed in the two groups before and after treatment, as well as the changes in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). The American College of Rheumatology (ACR) criteria was adopted to evaluate the therapeutic effects of the two groups. RESULTS: After treatment, the numbers of tender points, the numbers of swollen sites, VAS score and HAQ score were all improved as compared with those before treatment in the two groups (all <0.01), and the results in the observation group were better than those in the control group (all <0.05). After treatment, ESR and CRP levels were all reduced as compared with those before treatment in the two groups (all <0.01), but there was no significant differences between the two groups (both >0.05). The standard-reaching rates of ACR 20 and ACR 50 in the observation group were 94.3% (33/35) and 31.4% (11/35) respectively, which were better than 67.7% (21/31) and 6.5% (2/31) in the control group (<0.01, <0.05). CONCLUSION The acupuncture with the -deep and bloodletting techniques and the acupuncture with regular needling technique are all effective on RA. The therapeutic effects of the acupuncture treatment with the -deep and bloodletting techniques are better than that with regular needling technique.
Acupuncture Points ; Acupuncture Therapy ; Arthritis, Rheumatoid ; therapy ; Bloodletting ; Humans ; Treatment Outcome

ObjectiveTo observe the clinical efficacy and safety of Chaihu Shugansan combined with Xuanfu Daizhetang （CHSG-XFDZ） in the management of Barrett's esophagus （BE） with liver-stomach disharmony. MethodA randomized， parallel， controlled， double-blind clinical trial was conducted. BE patients who met the inclusion criteria were randomized into an observation group and a control group， with 34 patients in each group. The observation group was treated with CHSG-XFDZ combined with omeprazole capsules， and the control group was treated with CHSG-XFDZ mimetic combined with omeprazole capsules. Both groups were treated for 12 weeks. The traditional Chinese medicine （TCM） symptom scores， response rate， BE lesion area， BE pathological changes， and bile acid profile were taken as the indicators to jointly evaluate the clinical efficacy and safety of the two groups. ResultA total of 62 patients who completed the trial were included for statistical analysis， including 32 in the observation group and 30 in the control group. There were no statistically significant differences in baseline demographics or disease characteristics between two groups， which suggested that the two groups were comparable. The total response rate in the observation group was 93.7% （30/32）， which was higher than that （60.0%， 18/30） in the control group （χ²=24.766， P<0.05）. After treatment， the response rate regarding the pathological changes in the observation group was 62.5% （20/32）， which was higher than that （23.3%， 7/30） in the control group （χ²=10.270， P<0.05）. The response rate regarding the BE lesion area change in the observation group was 21.9% （7/32）， which had no statistically significant difference from that （6.7%， 2/30） in the control group， which indicated that the advantages of the two regimens were not obvious in terms of reducing the area of BE lesions. Compared with the control group after treatment， the observation group regulated the bile acid profile， which pointed out the direction for further exploring the mechanism of CHSG-XFDZ in treating BE. Neither group showcased adverse reactions with clinical significance during the treatment period. ConclusionCHSG-XFDZ outperformed the control group in terms of alleviating TCM symptoms， ameliorating pathological changes， and improving the bile acid profile in the BE patients with liver-stomach disharmony. It demonstrates certain potential in reducing the lesion area. This formula is safe and effective in treating BE patients with liver-stomach disharmony and deserves further clinical research and widespread application.

Sepsis is a multi-organ dysfunction syndrome caused by infection and immune dysfunction, with a high mortality rate. It affects multiple important organs such as the heart, lungs, kidneys, liver, and brain. Establishing corresponding animal models of organ dysfunction syndrome is an essential step in clarifying its pathogenesis, researching potential effective drugs, and evaluating the effectiveness and safety of treatment plans. This article first summarizes classic modeling methods for sepsis related organ injury, including the destruction of intestinal barrier tissue integrity and the implantation of pathogens or toxic drugs. The former mainly includes cecal ligation and puncture, ascending colon stent implantation, and cecal ligation incision. The latter is divided into intraperitoneal injection, intravenous injection, and intratracheal administration based on the clinical infection route being simulated. Cecal ligation and puncture and lipopolysaccharide intraperitoneal injection are the most commonly used methods. Secondly, this article summarizes the common modeling methods and evaluation methods for animal models of sepsis-induced cardiomyopathy, acute lung injury, acute kidney injury, acute liver injury, and brain dysfunction. It points out that almost all organ injuries use classic modeling methods, and different organ injury models have additional modifications according to their different pathogenesis. For example, in addition to the classic modeling methods, lipopolysaccharide instillation in the trachea is more effective in modeling acute lung injury as it better simulates lung barrier dysfunction. Cecal ligation and puncture followed by Pseudomonas instillation in the trachea in a secondary challenge model better represents sepsis-induced acute kidney injury. Intraperitoneal injection of galactosamine is a mature modeling method of sepsis-induced acute liver injury. Intracerebral injection of lipopolysaccharide is a feasible model of sepsis-associated encephalopathy. In addition to the different modeling methods, there are differences in the administration time, dosage and experimental time points according to the different experimental purposes. This article reviews the research progress of animal experimental models for sepsis-induced cardiomyopathy, acute lung injury, acute kidney injury, acute liver injury, and brain dysfunction, aiming to provide a reference for the selection of animal experimental models and optimization of experimental design.

ObjectiveTo investigate the analgesic effect of Tuina at the "Weizhong （BL 40）" on neuropathic pain in a rat model of chronic constriction injury （CCI） of the sciatic nerve and its potential central spinal mechanisms. MethodsThirty-two Sprague-Dawley rats were randomly divided into four groups （8 rats in each group）， sham-operated group， model group， Tuina group， and blockade group. The CCI model was established in the model group， Tuina group， and the blockade group by ligating the sciatic nerve with catgut， while the sham-operated group underwent only sciatic nerve exposure without ligation. From postoperative day 4 to day 14， rats in the Tuina group and the blockade group received Tuina manipulation at the "Weizhong （BL 40）" using a dynamic pressure distribution measurement system （5 N pressure， 2 Hz frequency， 10 min per session， once daily）. The blockade group also received intraperitoneal injections of the microglial inhibitor minocycline （10 mg/kg） once daily. The sham-operated and the model group underwent the same handling and fixation as the Tuina group without actual Tuina. Mechanical withdrawal threshold （MWT） and paw withdrawal latency （PWL） were measured before surgery and on day 3， 7， 10， and 14 post-surgery. Transmission electron microscopy was used to evaluate sciatic nerve injury and repair， measuring axon diameter and total myelinated fiber diameter to calculate the g-ratio. Western Blotting was performed to detect the protein levels of ionized calcium-binding adapter molecule 1 （Iba-1）， CD206， CD68， interleukin-10 （IL-10）， and β-endorphin （β-EP） precursor pro-opiomelanocortin （POMC） in the ipsilateral spinal dorsal horn. ResultsCompared with the sham-operated group， the model group showed significantly reduced MWT and PWL on day 3， 7， 10， and 14 （P＜0.01）. Compared with the model group， the Tuina group and the blockade group showed increased MWT and PWL on day 10 and 14 （P＜0.05）. Compared with the Tuina group， the blockade group exhibited higher MWT on day 7， 10， and 14， and higher PWL on day 10 （P＜0.05）. Sciatic nerve pathological morphology revealed intact and well-structured myelin in the sham-operated group， while the model group exhibited myelin collapse， distortion， and myelin ovoid formation. The Tuina group displayed partially irregular myelin with occasional myelin collapse， whereas the blockade group exhibited partial myelin irregularities and phospholipid shedding. Compared with the sham-operated group， the model group showed a decreased g-ratio and increased levels of Iba-1 and CD68 in the spinal dorsal horn （P＜0.05 or P＜0.01）. Compared with the model group， the Tuina group and the blockade group exhibited an increased g-ratio and reduced Iba-1 and CD68 levels. Additionally， the Tuina group showed elevated levels of CD206， IL-10， and POMC， whereas the blockade group had decreased CD206 levels （P＜0.05）. ConclusionTuina at "Weizhong （BL 40）" alleviates neuropathic pain in CCI rats， potentially by regulating microglial activation in the spinal cord， inhibiting M1 polarization while promoting M2 polarization， and activating the IL-10/β-EP pathway to exert analgesic effects.

Dehydration is one of the key steps in the biosynthesis of mycolic acids and is vital to the growth of Mycobacterium tuberculosis (Mtb). Consequently, stalling dehydration cures tuberculosis (TB). Clinically used anti-TB drugs like thiacetazone (TAC) and isoxyl (ISO) as well as flavonoids inhibit the enzyme activity of the β-hydroxyacyl-ACP dehydratase HadAB complex. How this inhibition is exerted, has remained an enigma for years. Here, we describe the first crystal structures of the MtbHadAB complex bound with flavonoid inhibitor butein, 2',4,4'-trihydroxychalcone or fisetin. Despite sharing no sequence identity from Blast, HadA and HadB adopt a very similar hotdog fold. HadA forms a tight dimer with HadB in which the proteins are sitting side-by-side, but are oriented anti-parallel. While HadB contributes the catalytically critical His-Asp dyad, HadA binds the fatty acid substrate in a long channel. The atypical double hotdog fold with a single active site formed by MtbHadAB gives rise to a long, narrow cavity that vertically traverses the fatty acid binding channel. At the base of this cavity lies Cys61, which upon mutation to Ser confers drug-resistance in TB patients. We show that inhibitors bind in this cavity and protrude into the substrate binding channel. Thus, inhibitors of MtbHadAB exert their effect by occluding substrate from the active site. The unveiling of this mechanism of inhibition paves the way for accelerating development of next generation of anti-TB drugs.
Amino Acid Sequence ; Bacterial Proteins ; chemistry ; metabolism ; Catalytic Domain ; Enzyme Inhibitors ; chemistry ; pharmacology ; Flavonoids ; chemistry ; pharmacology ; Hydro-Lyases ; antagonists & inhibitors ; chemistry ; Molecular Sequence Data ; Mycobacterium tuberculosis ; drug effects ; enzymology ; Protein Binding ; drug effects ; Protein Multimerization ; drug effects ; Protein Structure, Secondary ; Sequence Alignment

Objective To investigate the dyadic coping experience of patients undergoing cancer surgery and their spouses.Methods Sixteen cancer patients who were initially diagnosed with cancer and underwent cancer surgery in a general hospital in Henan province as well as and their spouses were selected as the study subjects by objective sampling method.All the patients and their spouses were included in the postoperative follow-up for dyadic coping experiences though a 3 months interview.The acquired data were summarised and analysed by Colaizzi's phenomenological method to identify relevant themes.Results A total of eight themes were identified,including three themes over the phase of confirmed diagnosis,strong stress response,coping with stress alone and consistent attitude towards seeking medical treatment;two themes over the perioperative phase,lack of coping ability and change in relationship;and three themes over the phase of home recovery,lack of disease information,poor communication skills and post-trauma growth of both patient and spouse.Conclusions The dyadic coping experience of patients who undergo cancer surgery and their spouses varies with the stages across the treatment.Therefore,medical staff should offer targeted nursing care according to the dyadic coping experience at different stages,hence to improve the physical and mental health of the cancer patients and their spouses.