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.

Objective:To observe any effect of exosomes derived from umbilical cord mesenchymal stem cells on pain, cartilage repair and the expression of transcriptional activator 3 (ATF-3) and growth related protein 43 (GAP-43) in the dorsal root ganglia (DRG), as well as to explore the mechanism of their relieving pain.Methods:Fifty-four male Sprague-Dawley rats were randomly divided into a sham-operation group, a monoiodoacetate group and an exosome group, each of 18. The knee cavities of the left hind limbs of all of the rats except those in the sham-operation group were injected with 50μl of monoiodoacetate to establish an arthritis pain model. The sham-operation group received only 50μl of saline solution as controls. Two weeks after the modelling, the knee joint cavities of the exosome group were injected with 50μl of exosomes, while the other two groups were injected with 50μl of normal saline. The rats′ mechanical and thermal pain thresholds were measured 1 day before the modeling, 7 and 14 days after the monoiodoacetate injection, as well as 7, 14 and 28 days after the exosome injection. Western blotting was used to detect the expression of ATF-3 and GAP-43 in the rats′ DRG, while hematoxylin and eosin staining was used to detect any cartilage repair.Results:Compared with the monoiodoacetate group, the latency of the mechanical and thermal pain thresholds had increased significantly in the exosome group 7 days after the exosome injection. The difference remained significant until the 28th day after the injection. The expression of ATF-3 protein decreased significantly and that of the GAP-43 protein increased significantly. Significant differences were observed in the average Osteoarthritis Research Society International (OARSI) knee cartilage score.Conclusions:Exosomes can alleviate the pain induced by monoiodoacetate adjuvant. The analgesic mechanism may be related to reducing nerve injury and promoting nerve and cartilage repair, with the nerve repair earlier than cartilage repair.

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 explore the possible correlation between serum detection of IL-7, IL-21, HBV-specific cytotoxic T lymphocytes (CTLs), HBV DNA, and the expression of CD127 on the T lymphocytes, and discuss the effect of IL-7 to cellular immune response in patients with chronic hepatitis B (CHB).Methods:Five hundred and sixty serum samples were collected from patients with CHB in Beijing Friendship Hospital from September 2017 to March 2020. The serum IL-7 and IL-21 were detected by enzyme-linked immunosorbent assay (ELISA), and HBV-specific CTLs and the expression of CD127 on the T lymphocytes were determined by flow cytometry. While HBV DNA were tested using quantitative real-time PCR (qRT-PCR). Subjects were divided into groups A, B, and C, according to the IL-7 levels (low: IL-7<20 pg/ml, medium: 20 pg/ml≤IL-7<30 pg/ml, and high: IL-7≥30 pg/ml).Results:The average concentration of serum IL-7 in patients with CHB was significantly lower than that of healthy controls ( P<0.01), and the difference among three groups was statistically significant ( P<0.01). Meanwhile, levels of IL-21, percentages of HBV-specific CTL, and the expression of CD127 on the CD8 + T lymphocytes showed an upward trend among groups, and there were significant differences among three groups ( P<0.01) with a positive correlation between each two variables ( P<0.01). However, HBV DNA showed a downward trend in group A, B and C, and the difference of the three groups were statistically significant ( P<0.01), which were negatively correlated with other variables ( P<0.01). Multiple linear regression analysis showed that HBV-specific CTL was an independent influencing factor for HBV DNA ( P<0.01), and IL-7, the expression of CD127 on the CD8 + T lymphocytes and IL-21 had an independent effect on HBV-specific CTL ( P<0.05). Conclusions:IL-7 could regulate HBV-specific immune response, and might be used as an effective cellular immune indicator to evaluate the cellular immune status of patients with chronic hepatitis B.

Objective:To observe the effect of botulinum toxin A (BTX-A) on pain, the activation of microglia and the expression of tumor necrosis factor-α (TNF-α) in the spinal cord in arthritis, and to explore how BTX-A treatment relieves pain.Methods:Sixty clean, male Sprague-Dawley rats were randomly divided into a sham operated group, a Freund′s adjuvant group and a BTX-A group. The ankle cavities of the left hind limbs of all of the rats except those in the sham group were injected with 50μl of Freund′s adjuvant to establish an arthritis pain model. The sham operated group received 50μl of saline solution as controls. Afterward the sham operation group and the Freund′s adjuvant group were given another 20μl of normal saline, while the BTX-A group was injected with 20μl of botulinum toxin A, again into the ankle joint cavity of the left hind limb. The mechanical and thermal pain thresholds of the rats in each group were measured 1 day before the modeling and 1, 3, 7, 14 and 21 days afterward. Western blotting and immunofluorescence staining were used to detect the expression of IBA-1 and IBA-1-IR. In addition, the expression of TNF-α protein and TNF-α mRNA in the spinal cord was detected using ELISA and RT-PCR.Results:Compared with the Freund′s adjuvant group, the latency of the mechanical and thermal pain thresholds had increased significantly in the BTX-A group after 3 days. The differences remained significant until the 14th day after the injection. The expression of IBA-1 protein and the number of immunopositive cells in the spinal cord decreased significantly, as did the expression of TNF-α protein and mRNA.Conclusions:Botulinum toxin A can alleviate the pain induced by Freund′s adjuvant. The analgesic mechanism may be related to inhibiting the activation of spinal microglia and the release of TNF-α.

Objective:To investigate the correlation of serum hepatitis B virus large protein (HBV-LP), HBV-DNA, and Pre S1 antigen (Pre S1-Ag) with HBV replication.Methods:Serum samples were collected from 650 patients with chronic hepatitis B (CHB) who were treated in Beijing Friendship Hospital from March 2017 to March 2019. Serum HBV-LP and Pre S1-Ag were detected by enzyme-linked immunosorbent assay (ELISA). HBV markers (HBV-M) were measured using chemiluminescent microparticle immunoassay (CMIA). Quantitative real-time PCR (qRT-PCR) was used to detect HBV-DNA. The positive detection rates of HBV-DNA, HBV-LP and Pre S1-Ag were calculated and compared, and the correlation of HBV-LP (S/CO value) and hepatitis B surface antigen (HBsAg, log 10 IU/ml) with HBV-DNA(log 10 IU/ml)was analyzed. Results:In the 650 CHB patients, the positive rates of HBV-DNA, HBV-LP and Pre S1-Ag were 65.4% (425/650), 79.2% (515/650) and 43.1% (280/650), respectively ( P<0.01). The positive rates of HBV-DNA and HBV-LP in 243 HBeAg-positive patients were 93.0% (226/243) and 94.6% (230/243), and no significant difference was found between them ( P=0.45). However, there was significant difference between the positive rates of HBV-DNA and HBV-LP in 407 patients negative for HBeAg [48.9% (199/407) vs 70.0% (285/407), P<0.01]. The positive rates of HBV-DNA and HBV-LP in HBsAg-, HBeAg- and HBcAb-positive groups were 92.8% (206/222) and 94.1% (209/222), which showed no significant difference ( P=0.56). In HBsAg-, HBeAb- and HBcAb-positive groups, the positive rates of HBV-DNA and HBV-LP were 45.4% (124/273) and 69.9% (191/273) ( P<0.01). The detection rate of HBeAg was lower than that of HBV-LP significantly in both HBV-DNA-positive and HBV-DNA-negative groups ( P<0.01). With the increasing of HBV-DNA load, the S/CO value and the positive rate of HBV-LP increased significantly ( P<0.05). Conclusions:HBV-LP had a good correlation with HBV-DNA load as compared with Pre S1-Ag, HBeAg and HBsAg. HBV-LP in combination with HBV-M might be used as predictive markers that could efficiently reflect the status of HBV replication.

OBJECTIVE：To investigate the problem s and improvement measures in the application of automatic drug delivery system in outpatient pharmacy of our hospital ，and to provide reference for the construction of automatic drug delivery system in outpatient pharmacy. METHODS ：Combined with the pharmacy module function of HIS system in our hospital and the actual needs of the pharmacist in drug delivery process ，the automatic delivery system of our hospital （including automatic delivery machine ， prescription dispensing and delivery mode ，intelligent medicine basket ）was established for operation and optimization. RESULTS ： After six months of running period ，the hardware of the automatic dispensing machine had been stabilized ，and the software functions had been optimized ，including the mode of pre-dispensing ，drug storage ，system prompt ，quantity of dispensing ， management of the drug period of validity ，and the mode of dispensing at the peak of drug taking. At the same time ，the emergency plan was formulated for automatic dispensing system. The application of the automatic dispensing machine shared 80％ of pharmacists ’prescription dispensing on an average day ，saved labor cost （reduce the labor cost of about 2 pharmacists）， shortened patients ’waiting time for drug-taking （down from 7.45 min to 6.61 min on average ，P＜0.01），reduced prescription dispensing error rate （down from 0.040 9％ to 0.019 5％ on average ，P＜0.01）. CONCLUSIONS ：The establishment of automatic drug delivery system in our hospital has reduced the workload of pharmacists ，improved the work efficiency ，decreased prescription dispensing error and promoted the quality of pharmaceutical care.

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.

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 .