Rheumatoid arthritis （RA） is an autoimmune disease involving symmetrical small joints， with clinical manifestations such as small joint swelling， morning stiffness， progressive pain， and even joint deformity and loss of function. Due to the complex immune mechanism， the pathogenesis of RA remains unclear. However， studies have shown that the pathogenesis of RA is related to abnormal immune mechanism， increased synovial inflammatory response， abnormal biological behavior of RA fibroblast-like synoviocytes （RA-FLSs）， and abnormal degradation of extracellular matrix. Mitogen-activated protein kinase （MAPK） plays a key role in the regulation of cell growth， proliferation， differentiation， and apoptosis. It is involved in the abnormal release and activation of inflammatory mediators in RA， the abnormal proliferation， migration， and invasion of RA-FLSs， synovial angiogenesis， bone erosion， and cartilage destruction. The thousands of years of practical experience show that Chinese medicine can effectively mitigate the clinical symptoms such as joint swelling， morning stiffness， and pain and delay the occurrence of joint deformity in RA patients. Moreover， the Chinese medicine treatment has the advantages of overall regulation， personalized treatment， multiple pathways and targets， high safety， few adverse reactions， and stable quality. Modern studies have confirmed that Chinese medicine can play a role in the prevention and treatment of RA by interfering in the MAPK signaling pathway， reducing pro-inflammatory cytokines， inhibiting the abnormal proliferation， migration， and invasion of RA-FLSs， regulating the apoptosis of RA-FLSs， and protecting extracellular matrix. This article elaborates on the key role of MAPK signaling pathway in the development of RA and reviews the latest research results of Chinese medicine intervention in MAPK signaling pathway for the prevention and treatment RA， aiming to provide a basis for the development of new drugs and the clinical application of Chinese medicine in the prevention and treatment of RA.

Objective:To explore the application of an automatic slide-dropping instrument in bone marrow chromosomal karyotyping.Methods:The effects of manual and automatic dropping methods under different environmental humidity were retrospectively analyzed, and the repeatability of the automatic dropping method was analyzed.Results:No statistical difference was found between the results of automatic and manual dropping methods under the optimum ambient humidity and high humidity ( P>0.05). At low humidity, there was a statistical difference between the two methods ( P<0.05). With regard to the repeatability, the coefficient of variations of the automatic dropping method for the number of split phases, the rate of good dispersion and the rate of overlap were all lower than those of the manual dropping method. A statistical difference was also found in the number of split phases ( P<0.05) but not in the discrete excellent rate and overlapping rate between the two methods ( P>0.05). Conclusion:Better effect can be obtained by the automatic dropping instrument. It is suggested to gradually replace manual work with machine.

Objective To investigate the effects of Yishen Jiangu Pills on the expressions of AMPK/Cyclin Y/CDK16 pathway and autophagy and apoptosis-related proteins in cartilage tissue of rats with knee osteoarthritis(KOA);To discuss its mechanism for the treatment of KOA.Methods Totally 60 2-month-old SD rats were selected and randomly divided into sham-operation group,model group,agonist group,and TCM low-,medium-and high-dosage groups,with 10 rats in each group.Except for the sham-operation group,each group underwent medial meniscectomy and cruciate ligamentotomy to establish the KOA rat model,and the corresponding interventions were given for 14 d.Lequesne MG score was used to evaluate rat behavior,morphology of cartilage tissue was observed by HE and Safranin O-fixed green staining,and Mankin score was performed,Western blot was performed to detect expression of AMPK/Cyclin Y/CDK16 pathway proteins and autophagy proteins such as ULK-1,Beclin-1,LC3B,p62 and apoptotic proteins such as Bcl-2,Bax,Caspase-3,Caspase-9 in cartilage tissue,and autophagosome were observed using transmission electron microscopy.Results Compared with the sham-operation group,Lequesne MG score significantly increased in the model group(P<0.01),there was a significant defect in the surface layer of cartilage,thinning of the cartilage layer,disordered arrangement and irregular morphology of chondrocytes,and a significant increase in Mankin score(P<0.01),the expressions of AMPK,Cyclin Y,CDK16,ULK1,Beclin-1,LC3BⅡ/Ⅰ and Bcl-2 protein in cartilage tissue decreased,while the expressions of p62,Bax,Caspase-3 and Caspase-9 protein increased(P<0.01).Compared with the model group,the Lequesne MG scores of rats in the agonist group and TCM high-dosage group were significantly decreased(P<0.01),the TCM high-dosage group showed smoother cartilage surface,more regular arrangement of chondrocytes,basic integrity of cartilage layer structure,weakened cartilage tissue proliferation,and significantly decreased Mankin score(P<0.01),the expressions of AMPK,Cyclin Y,CDK16,ULK1,Beclin-1,LC3BⅡ/Ⅰ and Bcl-2 protein in cartilage tissue of rats in the agonist group and TCM medium-and high-dosage groups significantly increased(P<0.05,P<0.01),while the expressions of p62,Bax,Caspase-3 and Caspase-9 protein significantly decreased(P<0.05,P<0.01).Conclusion Yishen Jiangu Pills may promote chondrocyte autophagy and inhibit cell apoptosis by activating the AMPK/Cyclin Y/CDK16 pathway in cartilage tissue of KOA model rats,thus reduce cartilage damage.

Humans ; Asthma/drug therapy* ; Biological Therapy

Indolylarylsulfones (IASs) are classical HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with a unique scaffold and possess potent antiviral activity. To address the high cytotoxicity and improve safety profiles of IASs, we introduced various sulfonamide groups linked by alkyl diamine chain to explore the entrance channel of non-nucleoside inhibitors binding pocket. 48 compounds were designed and synthesized to evaluate their anti-HIV-1 activities and reverse transcriptase inhibition activities. Especially, compound R₁₀L₄ was endowed with significant inhibitory activity towards wild-type HIV-1 (EC_50(WT) = 0.007 μmol/L, SI = 30,930) as well as a panel of single-mutant strains exemplified by L100I (EC₅₀ = 0.017 μmol/L, SI = 13,055), E138K (EC₅₀ = 0.017 μmol/L, SI = 13,123) and Y181C (EC₅₀ = 0.045 μmol/L, SI = 4753) which were superior to Nevirapine and Etravirine. Notably, R₁₀L₄ was characterized with significantly reduced cytotoxicity (CC₅₀ = 216.51 μmol/L) and showed no remarkable in vivo toxic effects (acute and subacute toxicity). Moreover, the computer-based docking study was also employed to characterize the binding mode between R₁₀L₄ and HIV-1 RT. Additionally, R₁₀L₄ presented an acceptable pharmacokinetic profile. Collectively, these results deliver precious insights for next optimization and indicate that the sulfonamide IAS derivatives are promising NNRTIs for further development.

Objective:To find out the variety, producing area, fluorine content of brick tea in Qinghai Province, and the drinking situation of brick tea among people, so as to provide basis for preventing and curing endemic fluorosis of drinking tea type.Methods:From April to November 2019, according to historical data, in 3 066 administrative villages in 39 counties (cities, districts, hereinafter referred to as counties) in Qinghai Province that had the habit of drinking brick tea, 10 families were randomly selected from each village to investigate the demographic data of each family and the drinking situation of brick tea, to collect brick tea samples to determine the fluorine content, and to calculate the daily average brick tea fluorine intake of the population > 16 years old.Results:A total of 31 067 brick tea samples were collected. The main brick tea consumed by the residents in the whole province was Fu brick tea, accounting for 89.97% (27 952/31 067), followed by Kang brick tea [5.12% (1 592/31 067)], Green brick tea [2.29% (710/31 067)], Black brick tea [1.85% (574/31 067)], and golden tip, mosaic, black wool and other brick tea [0.77% (239/31 067)]. There were 523 brands of brick tea in circulation in the province, among which there were 410 brands produced in Hunan Province, 26 brands in Sichuan Province, 11 brands in Hubei Province, and 76 brands in Henan Province and other provinces. The average content of fluorine in brick tea was 646.1 mg/kg, which ranged from 40.0 to 2 295.0 mg/kg. Brick tea with fluorine content ≤300 mg/kg accounted for 7.80% (2 422/31 067) of all samples. The annual average consumption of brick tea by population > 16 years old was 1.09 (0.35 - 7.40) kg, and the daily average brick tea fluorine intake was 1.93 (0.39 - 18.64) mg. There were 15 counties and 486 administrative villages in which the daily average brick tea fluorine intake exceeded the national standard (3.5 mg).Conclusion:The main brick tea in circulation in Qinghai Province is Fu brick tea, which has high fluorine content and is harmful to people, and prevention and control measures should be taken as soon as possible.

Objective To investigate the current situation of labor analgesia in Shanghai, provide data supportion and decision-making basis for further popularization of labor analgesia.Methods Using the self-made questionnaire, Shanghai Medical Doctor Association of Anesthesiologist issued a notice on the purpose of the study and the way how to fill it up.The questionnaire was distributed and recycled through the website wjx.com.Results The 58 hospitals included in this survey accounted for 90.44％ of the total delivery in Shanghai in 2017, and the overall labor analgesia rate was37.22％.The number of deliveries in 13 maternal and child specialist hospitals accounted for 58.44％of 58 hospitals, and the labor analgesia rate was 56.75％.It accounted for 93.50％of the 58 hospitals analgesic deliveries.There are 44 (75.86％) hospitals carrying labor analgesia by intraspinal nerve block as the main method of labor analgesia.42 (95.45％) of these hospitals began to analgesia during the incubation period, 30 (68.18％) of these hospitals closed the analgesic pump during childbirth, and 40 (90.9％) hospitals had a maternal satisfaction of 85 or more, 36 (81.82％) of these hospitals charged labor analgesia in accordance with the anesthesia clause.However, among the 14 hospitals that did not practive labor analgesia, 13 (92.86％) were due to inadequate anesthesiologists and other relevant factors.Conclusion The overall labor analgesia rate in Shanghai was 37.22％.The service has been mainly provided in maternal and child specialist hospitals.The main factors restricting the labor analgesia are the shortage of anesthesiologists and the lack of specific charges.In order to promote the labor analgesia, policy support is an important aspect, and the labor analgesia process and innovative management mode should also be optimized.

Objective To study the relation between alcohol-induced osteonecrosis of femoral head (AIONFH) related with high morbidity TCM constitution type with CYP2C8 gene polymorphisms.Methods Totally 152 Han nationality NONFH cases from Feburary 2014 to September 2015 from outpatient and the inpatient departments in Gansu Province Hospital of TCM were collected. 50 AIONFH cases were set as medical case group; meanwhile, 45 healthy volunteers were enrolled as control group. Database for medical materials of all patients and volunteers was established. TCM distribution for AIONFH patients was determined. Solution DNA extraction kit was used to extract DNA, and detect the concentration and purity of DNA. The target gene was amplified by PCR and the target gene was amplified by gel electrophoresis. The length of the fragment was confirmed to conduct target gene sequencing. With the results of sequencing and gel electrophoresis, the relation of AIONFH with CYP2C8 gene polymorphism in AIONFH patients with phlegm-dampness syndrome and the control group.ResultsThe CYP2C8 gene loci rs17110453 gene polymorphism was not statistically significant between the two groups (χ2=0.253,P>0.05). There was no significant difference in allele between the two groups (χ2=0.077,P>0.05). The risk of disease in CC genotype was 1.37 times higher than the AA genotype (95%CI: 0.339-5.540), without statistical significance (P>0.05). There was no significant difference in genotype and allele distribution between AIONFH patients with phlegm-dampness and non-phlegm-dampness and the control group (P>0.05).Conclusion CYP2C8 gene loci rs17110453 gene polymorphism A/C mutation has no obvious relation with AIONFH risk. There is no clear relationship between CYP2C8 gene loci rs17110453 gene polymorphism with AIONFH.

Objective To construct a scoring system of combination of procalcitonin and C-reactive protein for diagnosis of invasive bacterial diarrhea in children. Methods The clinical data of hospitalized children with acute diarrhea were retrospectively analyzed. All of the children were divided into two groups, invasive bacterial diarrhea group and nonbacterial diarrhea group. The scoring system of combination of two markers for diagnosis of invasive bacterial diarrhea in children was constructed by means of two categories logistic regression analysis using procalcitonin and C- reactive protein as parameters. In addition,receiver operating characteristic curve(ROC)was used to evaluate the diagnostic accuracy.Results One hundred ten cases of invasive bacterial diarrhea and 108 cases of nonbacterial diarrhea were included. The levels of serum procalcitonin and C-reactive protein in invasive bacterial diarrhea group were significantly higher than those in nonbacterial diarrhea group, and there were statistical difference(P all<0.05).The area under the ROC curve(AUC)of invasive bacterial diarrhea was 0.894 when the established scoring system was used, which was higher than the AUCs when either serum procalcitonin or in C- reactive protein was used (P<0.05). The best diagnostic boundary value for combination of serum procalcitonin and C- reactive protein scoring was 0.52 with a sensitivity at 80.9% and specificity at 88.9%. Conclusions The scoring system of combination of procalcitonin and C- reactive protein has good accuracy in diagnosis of invasive bacterial diarrhea in children, and can assist the early diagnosis of the disease.

Objective To investigate the expression of early growth response protein 1 (Egr-1),NGFI-A binding protein 2 (Nab2) and caveolin 1 (Cav-1) in normal skin,flat-cicatrix and hypertrophic scar,and explore its role in the formation of hypertrophic scar.Methods The expression of Egr-1,Nab2 and Cav-1 protein in 9 normal skin tissues,8 flat-cicatrix tissues and 9 hypertrophic scar tissues were examined with immunohistochemistry SP method and were analyzed statistically.Results The expression of Egr-1 in epidermal cells of hypertrophic scar was significantly higher than that in normal skin and flat scar tissue.The expression of Egr-1 increased in the course of scar proliferation.The distribution patterns of Nab2 were different from Egr-1.The expression of Egr-1 was increased,while expression of Nab2 was decreased.The expression of Cav-1 in normal skin and flat-cicatrix was significantly higher than that in hypertrophic scar.Conclusions The expression of Egr-1,Nab2 and Cav-1 is closely related to the formation of hypertrophic scar,and the up-regulated expression of Egr-1 and the deficient expression of Nab2 and Cav-1 may be the indicators of the progress of formation of hypertrophic scar.