Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4⁺ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Lateral epicondylitis is a common clinical disease with characteristics of lateral elbow pain, insidious onset and easy recurrence, which can cause forearm pain and decreased wrist strength, seriously affecting patients′ daily life and work. Although there are various treatment methods for lateral epicondylitis with different effects, standard treatments are still lacking nowadays. Platelet-rich plasma (PRP) has good effects on bone and tendon repair, and is now widely used in the treatment of lateral epicondylitis. However, there is a lack of a unified understanding of the technology and specifications of PRP in the treatment of lateral epicondylitis. Therefore, the Sports Medicine Branch of the Chinese Medical Association and Physical Medicine and Rehabilitation Branch of the Chinese Medical Association organized experts in the fields of sports medicine and rehabilitation medicine in China to formulate the "clinical expert consensus on platelet-rich plasma treatment for lateral epicondylitis (2022 version)", and proposed suggestions based on evidence-based medicine mainly from the concept, epidemiology and pathophysiology of lateral epicondylitis, symptoms, signs and imaging manifestations of lateral epicondylitis, PRP concept and application component requirements, quality control of PRP preparation technology, indications and contraindications of PRP in the treatment of lateral epicondylitis, PRP injection in the treatment of lateral epicondylitis, application of PRP in the operation of lateral epicondylitis, related problems after PRP treatment of lateral epicondylitis, evaluation of the results after PRP treatment of lateral epicondylitis, and health and economic evaluation of PRP treatment of lateral epicondylitis, so as to provide guidance for clinical diagnosis and treatment.

Objective:To investigate characteristics and changes of skin microbiota in atopic dermatitis-like mouse models induced by different concentrations of 2,4-dinitrochlorobenzene (DNCB) .Methods:Totally, 30 male specific-pathogen-free BALB/c mice were randomly divided into 3 groups by using a random number table: negative control group topically treated with 200 μl of mixture of acetone and olive oil at a volume ratio of 3∶1 on the back twice a week for 6 consecutive weeks; high-and low-concentration DNCB groups both topically treated with 200 μl of 1% DNCB on the first and third day at the first week, followed by topical application of 200 μl of 0.5% and 0.1% DNCB, respectively, twice a week for 5 weeks from the second week. Twenty-four hours after the last treatment, the severity of skin lesions was evaluated, and the transepidermal water loss and stratum corneum hydration were measured. After the experiment, the mice were sacrificed, and skin tissues were resected from the back of the mice for histopathological examination. Full-thickness skin tissue samples were obtained from the back of 3 mice in each group. Illumina Miseq PE300 high-throughput sequencing was performed to sequence the V3-V4 variable region of 16S rRNA gene of skin microbiota on the back of the mice, and the composition and structure of the skin microbiota and changes in the relative abundance of different genera were analyzed. One-way analysis of variance was used to analyze differences in indices among the 3 groups, and the Games-Howell method was used for multiple comparisons.Results:The severity scores of skin lesions were significantly higher in the high-and low-concentration DNCB groups (9.83 ± 2.45 points, 2.71 ± 0.56 points, respectively) than in the negative control group (0.51 ± 0.12 points, t=-7.19,-2.85, respectively, both P < 0.05) . Compared with the negative control group, the high-and low-concentration DNCB groups showed significantly increased transepidermal water loss ( t=-7.72,-2.68, respectively, both P < 0.05) , but significantly decreased stratum corneum hydration ( t=6.77, 5.99, respectively, both P < 0.05) ; the transepidermal water loss was significantly higher in the high-concentration DNCB group than in the low-concentration DNCB group ( t=2.76, P < 0.05) , while no significant difference in the stratum corneum hydration was observed between the high-and low-concentration DNCB groups ( P > 0.05) . There was a significant difference in the relative abundance of Corynebacterium among the 3 groups ( F=249.85, P < 0.001) , which was highest in the high-concentration DNCB group. No significant differences in the observed species and Chao1 index of the skin samples were observed among the 3 groups (both P > 0.05) , and the Shannon index was significantly lower in the high-concentration DNCB group than in the low-concentration DNCB group and negative control group ( t=6.96,-6.37, respectively, both P < 0.05) . Conclusion:DNCB could induce atopic dermatitis-like dermatitis in mice, and the severity of skin lesions and degree of barrier function impairment were related to the concentration of DNCB; the species diversity of skin microbiota markedly decreased in the high-concentration DNCB group, indicating that high-concentration DNCB modeling has more advantages in studying microbiological changes associated with atopic dermatitis.

Objective:To evaluate the efficacy of radiofrequency thermocoagulation with CT-guided transforaminal puncture of intervertebral foramen through the superior margin of costotransverse joint for refractory post-herpetic neuralgia (PHN) in the upper thoracic segment.Methods:Thirty patients with PHN in the upper thoracic segment underwent radiofrequency thermocoagulation with CT-guided intervertebral foramen puncture. The visual analogue scale and self-rating depression scale were used to evaluate the degree of postoperative pain and mental state before and after treatment, and patients were followed by telephone or outpatient visit.Results:No infection occurred after radiofrequency thermocoagulation in all 31 PHN patients. After operation, all patients had hypoesthesia in skin of the original pain area, the pain was significantly relieved, and the mental state improved significantly. The VAS scores were 5.94±0.93, 2.74±0.69, 2.68±0.70 and 2.45±0.51 before and 3 hours, 1 week, 1 month after treatment( t=18.80, t=18.80, t=16.44, all P<0.01). The SDS scores were 58.6±12.2, 47.7±4.4, 48.1±4.8 before and 1 week, 1 month after treatment( t=6.75, t=5.86, all P<0.01). There were 13 patients with moderate or severe depression before treatment, while no patients with moderate or severe depression after treatment; only 5 patients had mild depression one month after surgery. There was no hypoxemia under nasal catheter during the operation. Intraoperative hypertension was found in 19 cases; after treatment with Urapidil (12.5 - 50.0 mg), the blood pressure was not higher by 20% of the basal blood pressure and<180/100 mmHg (1 mmHg=0.133 kPa). No pneumothorax, perioperative cardiovascular and cerebrovascular accidents occurred. Conclusion:Radiofrequency thermocoagulation with CT-guided intervertebral foramen puncture through the superior margin of costotransverse joint can effectively relieve refractory PHN of the upper thoracic segment with safety.

Objective: In this study, we used HepG2 human hepatocellular carcinoma cells to study the effects of Compound Xishu Granule (CXG) on cell proliferation, apoptosis, and the cell cycle in vitro. We also used a xenograft tumor model to study the anti-tumor effects of CXG and related mechanisms in vivo.Methods: The effect of CXG on cell viability was measured using Cell Counting Kit-8 and a colony for-mation assay. The effect of CXG on apoptosis and the cell cycle was analyzed using flow cytometry. The in vivo anti-tumor effect of CXG was assessed by measuring the volume change in xenograft tumors after drug administration. The CXG anti-tumor mechanism was studied using western blotting assay to detect cell cycle and apoptotic associated proteins. Results: CXG suppressed HepG2 cell proliferation in a time-and dose-dependent manner in vitro. Colony formation experiments showed that CXG administration for 24 h significantly reduced HepG2 cell for-mations (P<.01). Flow cytometric analysis showed that CXG treatment for 48 h promoted apoptosis and blocked HepG2 cells in the G2/M phase. Western blotting results showed that Bax was significantly up-regulated and Bcl-2 was down-regulated in graft tumor tissues and HepG2 cells after CXG administra-tion, which increased the Bax/Bcl-2 ratio. PLK1, CDC25C, CDK1, and Cyclin B1 expression were up-regulated. CXG had a good inhibitory effect on graft tumor growth in vivo. Conclusion: CXG has good anti-tumor effects in vitro and in vivo. In vitro, CXG promoted HepG2 cell apoptosis and induced G2/M phase arrest. In vivo, CXG significantly inhibited graft tumor growth. The CXG mechanism in treating hepatocellular carcinoma may be that CXG can induce abnormal apoptotic and cell cycle associated protein expression, leading to mitotic catastrophe and apoptosis.

Aminopeptidase N (APN) belonging to zinc-dependent metalloproteinase, not only catalyzes protein proteolytic process, but also is involved in the pathogenic process as the receptor of pathogenic toxin. In Bombyx mori, APN gene family consists of 16 members, of which BmAPN4 binds trypsin-activated parasporal crystal (PC) toxin isolated from Bacillus bombysepticus (Bb). In order to verify whether or not other APNs interact with PC toxin during the pathogenesis of Bb, we cloned BmAPN5, a member of aminopeptidase family, from the silkworm midgut. The full length of BmAPN5 is 3313 bp, encoding 953 amino acids, containing a zinc peptidase_M1 and ERAP1_C domains. A recombinant GST-BmAPN5 was purified by a prokaryotic expression system. Far-Western blotting, co-immunoprecipitation and ELISA. Binding saturation assays demonstrated that PC after activated by trypsin could be bound by BmAPN5. Additionally, cytotoxic activity of trypsin-activated PC in Sf9 cells transfected with BmAPN5 showed that cells exhibited dramatic cytological changes, including swelling and lysis, revealing BmAPN5 serves as a functional receptor that participates in Bb and PC pathogenicity. These provide some clues for further exploring the pathogenesis relationships of Bb and host.

Objective To develop the preliminary version of a new scale on the severity of myasthenia gravis ( MG) suitable for Chinese patients .Methods The item pool was established based on the four widely used MG severity scales .Then the Delphi method was applied to collect the opinions from MG experts in China.Based on the consistency of expert opinions and previous evaluation of the items in source scales , the preliminary version of a new scale was developed .Results The item pool consists of 19 items from the above four scales .The enthusiasm coefficients of experts in two rounds of survey are 91.4%(32/35) and 96.9%(31/32).The authority coefficients are 0.79 and 0.80.The Kendall′s coefficients of concordance of expert opinions are 0.22 (χ2 =127.01, P<0.01) and 0.42 (χ2 =231.56, P<0.01), respectively.The preliminary version consists of 10 items, which cover six commonly involved muscle groups in MG, including the ocular, bulbar, facial, limb, axial and the respiratory muscles.Conclusion The preliminary version of the MG severity scale was established by combining Delphi method with the previous evaluation of items from source scales .

Objective: To investigate the impact of symptom onset to first medical contact (SO-to-FMC)time on the prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI). Methods: The clinical data of 341 consecutive STEMI patients, who were hospitalized to our hospital and received primary percutaneous coronary intervention(PCI) from August 2011 to April 2016, were retrospectively analyzed. The patients were divided into ≤90 min group (201 cases) and >90 min group (140 cases) according to the SO-to-FMC time. The treatment time, mortality and incidence of major adverse cardiac and cerebro-vascular events(MACCE) were analyzed. The risk factor of 1-year mortality after PCI and 1-year incidence of MACCE during the post-discharge follow-up period were analyzed by binary logistic regression analysis. The predictor of 4.5-year mortality after PCI was analyzed by multivariate Cox regression analysis. Methods The door to balloon time (104(88, 125) min vs. 111(92, 144)min, P=0.023), first medical contact to balloon time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset-to-balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001)were all significantly shorter in the ≤90 min group than in>90 min group. The 30-day mortality (2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality (2.89 (5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the post-discharge follow-up period(1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5-year cumulative mortality(3.00% vs. 11.20%, P=0.007) after PCI were significantly lower in the ≤90 min group than in the >90 min group. Moreover, the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the post-discharge follow-up period was significantly higher in the ≤90 min group than in the >90 min group. In-hospital mortality was similar between the two groups (2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results: The door to balloon time (104(88, 125) min vs. 111(92, 144)min, P=0.023) , first medical contact to balloon time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset-to-balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001) were all significantly shorter in the ≤90 min group than in >90 min group. The 30-day mortality(2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality (2.89(5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the post-discharge follow-up period (1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5-year cumulative mortality (3.00% vs. 11.20%, P=0.007) after PCI were significantly lower in the ≤90 min group than in the >90 min group. Moreover, the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the post-discharge follow-up period was significantly higher in the ≤90 min group than in the >90 min group. In-hospital mortality was similar between the two groups (2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results of binary logistic regression analysis showed that the SO-to-FMC time >90 min was the risk factor of 1-year mortality(OR=2.90, 95%CI 1.22-6.92, P=0.016) and 1-year incidence of MACCE (OR=5.19, 95%CI 1.21-22.20, P=0.026) during the post-discharge follow-up period. Multivariate Cox regression analysis demonstrated that the SO-to-FMC time >90 min was the risk factor of 4.5-year mortality after PCI in patients with STEMI (HR=2.88, 95%CI 1.10-7.53, P=0.031). Conclusion Shorting the SO-to-FMC time can significantly reduce the treatment time of STEMI patients, short and long-term mortalities and the incidence of MACCE, and improve the prognosis of patients with STEMI.

Objective To observe the effects of mesenchymal stem cells (BMSCs) on the expression of Bcl2 and Bax in atrophied muscles.Methods Immature rats (80～ 100 g) were anesthetized to collect marrow from their femurs and tibias.BMSCs were isolated from the marrow,cultured and purified using the whole bone marrow adherence method.Their right hindlimbs were immobilized fiom the thigh to the paw with the knee in extension and the ankle in plantar flexion.After the modeling,24 of the male rats were divided into a sham-operation group,a BMSC group and a phosphate buffer solution (PBS) group,each of 8.The BMSC and PBS groups were injected with either approximately 106 BMSCs or an equal volume of PBS into the belly of the soleus muscle after they had been immobilized for 48 hours,while the control group did not undergo any treatment except for the injection of PBS.All of the rats were sacrificed for analysis after 14 days.Results The BMSCs were mainly spindle cells,showing radial colony arrangement.They grew vigorously and could passage in a continuous and stable manner over 10 passages.At the 4th passage the BMSCs were positive for CD44 (95.84％) and CD90 (96.00％),but negative for CD34 and CD45.Western blotting assay demonstrated that the expression of Bax protein as measured in grey-scale value (0.41±0.08)in the BMSC group was significantly lower than in the PBS group (0.63±0.10),but significantly higher than in the control group (0.14±0.11) on average.The expression of Bcl-2 (0.47±0.14) was also significantly higher in the BMSC group than in the PBS group (0.22-± 0.13),but significantly lower than in the control group (0.81 ± 0.06).Conclusion Bone marrow mesenchymal stem cells can upregulate the expression of anti-apoptotic Bcl-2 protein and downregulate that of the apoptotic Bax protein when injected early into the belly of a muscle in an immobilized limb.

Objective To verify the anti-inflammatory effects of intra-articular injection of botulinum toxin type A (BoNT/A) on adjuvant-induced arthritis using a rat model.Methods A murine model of chronic ankle arthritis was established in 90 Wistar rats by injection of 0.1 ml of complete Freund adjuvant (CFA) into the pads of their left paws.They were then randomly divided into a BoNT group (n =30) which received an intra-articular injection of 0.1 ml (20 IU) of BoNT/A,an NS group (n=30) which received intra-articular injection of0.1 ml of normal saline solution and a sham group (n =30) which were punctured without any injection.In addition,30 normal rats formed a control group.Infrared thermal imaging was performed and an index of arthritis was evaluated every three days.The infrared thermal imaging revealed the expression of interleukin-1β (IL-1β) through hematoxy-eosin (HE) staining.Results The arthritis index began to increase 3 days after the injection of CFA and it had increased significantly after 10 days,reaching a peak value of 18,24 days after the injection.The infrared thermal imaging showed that the temperature in the right paw increased greatly after the injection.Following the development of arthritis,the temperature declined gradually,arriving at a steady temperature of between 37.5 and 38.0 ℃ in both ankles 20 days after the injection.The average temperature in both paws of the BoNT group had decreased significantly more by 7 and 14 days after the injection than in the NS and sham groups.The expression of IL-1β in the synovium of the ankle joint also had decreased significantly more in the BoNT group after 7 and 14 days.HE scoring showed an obvious histopathologic change in the hypertrophic synovium,inflamnatory cell infiltration,cartilage destruction and exposure of subchondral bone after 7 and 14 days compared with right after the injection in all groups except the control group.Moreover,the average HE scores of the BoNT group rats after 7 and 14 days were significantly lower than those seen in the NS and sham groups at the same time points.Conclusion Intra-articular injection of botulinum toxin type A has an anti-inflammatory effect on arthritis induced by complete Freund adjuvant,at least in rats.