ObjectiveThis paper aims to investigate the mechanism of Jinyang Dingtong plaster in improving the peripheral pain sensitization and synovial fibrosis in rats with knee osteoarthritis （KOA） by blocking the ion channels of transient receptor potentials （TRPs）. MethodsThe active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by using ultra-high performance liquid chromatography-electrospray ionization-quadrupole ion trap tandem mass spectrometry （UPLC-MS/MS） technology. A KOA rat model was established through intra-articular injection of monoiodoacetic acid. The rats were randomly divided into blank control group， KOA group， compound Nanxing Zhitong plaster Group， and Jinyang Dingtong plaster group， with eight rats per group. Among them， the rats in the compound Nanxing Zhitong plaster group and the Jinyang Dingtong plaster group were intervened with external application treatment. After the intervention period， the cold and mechanical stimulus pain thresholds of rats in each group were detected， and the transverse diameter of the knee joint was measured. The levels of inflammatory factors in the serum such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） were determined by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of transient receptor potential ankyrin 1 （TRPA1）， transient receptor potential melastatin 8 （TRPM8）， transient receptor potential vanilloid 1 （TRPV1）， transient receptor potential vanilloid 4 （TRPV4）， transforming growth factor-β （TGF-β）， and vascular endothelial growth factor （VEGF） in synovial tissue were detected by Western blot. Histopathological changes in synovial tissue were observed by using hematoxylin and eosin （HE）， Masson， and Sirius red staining， while the expression of type Ⅰ collagen and alpha-smooth muscle actin （α-SMA） was detected by multiplex immunofluorescence. ResultsA total of 35 active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by UPLC-MS/MS， including phenolic acids， flavonoids， quinones， alkaloids， terpenes， lignans， and coumarins. Among them， the constituents such as berberine， paeoniflorin， ferulic acid， and caffeic acid exhibit clear anti-inflammatory， analgesic， and anti-fibrotic pharmacological effects. Compared to the blank control group， rats in the KOA group showed a significant decrease in cold and mechanical stimuli pain thresholds （P<0.01）. After 14 and 28 days of Jinyang Dingtong plaster intervention， the pain threshold in this group was significantly increased compared to that in KOA group （P<0.01）， showing no significant difference from that in compound Nanxing Analgesic plaster group. Additionally， Jinyang Dingtong plaster reduced the levels of IL-1β， TNF-α， NGF， and CGRP in the serum of KOA rats （P<0.01）， lowered the expression of TRPA1， TRPM8， TRPV1， TRPV4， TGF-β， and VEGF proteins in synovial tissue （P<0.01）， improved synovial pathological damage in KOA rats， and significantly decreased fluorescence intensity of type Ⅰ collagen and α-SMA （P<0.01）. ConclusionJinyang Dingtong plaster can improve the peripheral pain sensitization and synovial fibrosis in KOA rats by downregulating the expression of ion channels of TRPs and related inflammatory and fibrotic factors.

ObjectiveThis paper aims to investigate the mechanism of Jinyang Dingtong plaster in improving the peripheral pain sensitization and synovial fibrosis in rats with knee osteoarthritis （KOA） by blocking the ion channels of transient receptor potentials （TRPs）. MethodsThe active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by using ultra-high performance liquid chromatography-electrospray ionization-quadrupole ion trap tandem mass spectrometry （UPLC-MS/MS） technology. A KOA rat model was established through intra-articular injection of monoiodoacetic acid. The rats were randomly divided into blank control group， KOA group， compound Nanxing Zhitong plaster Group， and Jinyang Dingtong plaster group， with eight rats per group. Among them， the rats in the compound Nanxing Zhitong plaster group and the Jinyang Dingtong plaster group were intervened with external application treatment. After the intervention period， the cold and mechanical stimulus pain thresholds of rats in each group were detected， and the transverse diameter of the knee joint was measured. The levels of inflammatory factors in the serum such as interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， nerve growth factor （NGF）， and calcitonin gene-related peptide （CGRP） were determined by enzyme-linked immunosorbent assay （ELISA）. Protein expression levels of transient receptor potential ankyrin 1 （TRPA1）， transient receptor potential melastatin 8 （TRPM8）， transient receptor potential vanilloid 1 （TRPV1）， transient receptor potential vanilloid 4 （TRPV4）， transforming growth factor-β （TGF-β）， and vascular endothelial growth factor （VEGF） in synovial tissue were detected by Western blot. Histopathological changes in synovial tissue were observed by using hematoxylin and eosin （HE）， Masson， and Sirius red staining， while the expression of type Ⅰ collagen and alpha-smooth muscle actin （α-SMA） was detected by multiplex immunofluorescence. ResultsA total of 35 active components in the transdermal absorption solution of Jinyang Dingtong plaster were identified by UPLC-MS/MS， including phenolic acids， flavonoids， quinones， alkaloids， terpenes， lignans， and coumarins. Among them， the constituents such as berberine， paeoniflorin， ferulic acid， and caffeic acid exhibit clear anti-inflammatory， analgesic， and anti-fibrotic pharmacological effects. Compared to the blank control group， rats in the KOA group showed a significant decrease in cold and mechanical stimuli pain thresholds （P<0.01）. After 14 and 28 days of Jinyang Dingtong plaster intervention， the pain threshold in this group was significantly increased compared to that in KOA group （P<0.01）， showing no significant difference from that in compound Nanxing Analgesic plaster group. Additionally， Jinyang Dingtong plaster reduced the levels of IL-1β， TNF-α， NGF， and CGRP in the serum of KOA rats （P<0.01）， lowered the expression of TRPA1， TRPM8， TRPV1， TRPV4， TGF-β， and VEGF proteins in synovial tissue （P<0.01）， improved synovial pathological damage in KOA rats， and significantly decreased fluorescence intensity of type Ⅰ collagen and α-SMA （P<0.01）. ConclusionJinyang Dingtong plaster can improve the peripheral pain sensitization and synovial fibrosis in KOA rats by downregulating the expression of ion channels of TRPs and related inflammatory and fibrotic factors.

Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

AIM: To evaluate the bioequivalence of two candesartan cilexetil tablet formulations in healthy Chinese subjects after administration of a single dose, and an artificial neural network model was established to predict the candesartan plasma concentration, and provide a basis for clinical rational use of drugs. METHODS: Thirty-two healthy Chinese subjects were enrolled for oral administration of a single 8 mg dose of candesartan cilexetil tablet (test or reference product) under fasting or fed conditions to conduct a bioequivalence study. The bioequivalence results were used to build a back-propagation artificial neural network model by MATLAB software, and the model was internally and externally verified to predict the plasma concentration. RESULTS: Under both fasting and fed conditions, the C

Antibodies, Neutralizing ; Antibodies, Viral/isolation & purification* ; B-Lymphocytes/virology* ; COVID-19/virology* ; Humans ; Immunity/genetics* ; RNA, Viral/immunology* ; SARS-CoV-2/pathogenicity* ; Single-Cell Analysis

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
COVID-19 ; Humans ; Medicine, Chinese Traditional ; Research ; SARS-CoV-2 ; Treatment Outcome

AIM: To compare the bioavailability of norfloxacin tablets produced by Zhejiang Pharmaceutical Co., Ltd with the original product BACCIDAL, and to evaluate bioequivalence of two formulations, a randomized, open, two-cycle, self-crossing trial in healthy Chinese population was designed. METHODS: Under fasting and fed conditions, healthy volunteers were given a single dose of norfloxacin test or reference tablets for 100 mg. Liquid chromatography-mass spectrometry (LC-MS/MS) method were used to determine drug concentration in the plasma taken at different time points before and after dosing. Pharmacokinetic parameters and the bioequivalence of the two formulations were calculated by WinNonlin 7.0 software. RESULTS: A total of 28 healthy volunteers were enrolled and completed the fasting test. The pharmacokinetic parameters for test and reference preparations in fasting state were as follows: C

Objective: To carry out the 4^th round of third-party evaluation on the implementation and effect of the 1^st year of the 2^nd Phase National Healthcare Improvement Initiative(abbreviated as Initiative)since 2015. Methods: The 4^th round of the evaluation survey adopted the same methods, organization and execution, and technical roadmap as the former three rounds of evaluations. Results: The 4^th round of evaluation was carried out from 18 March to 9 April, 2019 at 185 public hospitals in 31 provinces(autonomous regions, municipalities directly under the Central Government)and Xinjiang Production and Construction Corps.Facility survey, health professional survey and patient survey were conducted at each of the sample health facilities. A total of 120 782 valid questionnaires were collected from 144 non-psychiatric health facilities, 16 246 valid questionnaires were obtained from 41 psychiatric health facilities, and 252 cases of outstanding departments/hospitals in healthcare improvement were also collected. The average overall scoring of the 12 dimensions to assess Initiative implementation at 144 non-psychiatric health facilities was 84.4%. The overall outpatient satisfaction scoring was 91.1%, 96.7%for the inpatients. The overall inpatient satisfaction(family members inclusive) at 41 psychiatric health facilities was 93%. Areas remaining to be improved include day-surgery, telemedicine and medical social work. Compared with technical services, non-technical care should be further strengthened. The compensation, workload and work environment of the healthcare providers are still to be improved. Conclusions The implementation of the Initiative by health facilities has been greatly improved. The percentage of health facilities and patients who had positive perceptions of improved doctor-patient relationship has been increasing. Patient care experiences at public hospitals have been generally improved, and the implementation of promoting traditional Chinese Medicine practices also made progress. However, work satisfaction of healthcare providers was found to be rather low, compared to the high level of patient satisfaction.

Objective: To carry out a investigation on molecular epidemiological features of tick-borne Brucella in Xinjiang Uygur Autonomous Region (Xinjiang), and to provide a scientific basis for formulation of effective preventive and control measures. Methods: In 2016-2018, parasitic ticks (including engorged females) were collected on the body surface of livestock in 10 counties (cities) along the border of Xinjiang. The free-living ticks were collected by flagging method in Alashankou. The engorged female was placed in a breathable insect tube for spawning, each egg batch was divided into two parts: one part was tick eggs, while the second part was allowed further larval development. All ticks were identified by molecular biology (16S rRNA) identification. Tick DNA was extracted, PCR was performed based on Brucella omp22 and IS711, and amplification products were sequenced and analyzed by BLAST. Results: A total of 1 084 ticks were collected in 11 counties (cities), of them 747 were parasitic ticks (including 34 engorged females) and 337 were free-living ticks. Based on 16S rRNA identification, 1 084 ticks belonged to 4 genera and 5 species, and the proportions of Dermacentor nuttalli, Dermacentor marginatus, Haemaphysalis punctata, Hyalomma asiaticum and Rhipicephalus turanicus were 29.43% (319/1 084), 16.51% (179/1 084), 10.42%(113/1 084), 37.27% (404/1 084), and 6.37% (69/1 084), respectively. A total of 214 Brucella-positive nucleic acid samples were detected, the positive rate was 19.74%. The parasitic ticks' positive rate was 25.30% (189/747), and the free-living ticks' positive rate was 7.42% (25/337), parasitic ticks' positive rate was higher than that of free-living ticks (χ²=46.873, P < 0.05). Two Brucella melitensis nucleic acid samples were detected in 34 "engorged females-tick eggs" developmental stage, and one Brucella melitensis nucleic acid sample was detected in 22 "tick eggs-larvae" developmental stage. Conclusions Brucella is widely distributed in parasitic ticks and free-living ticks in Xinjiang border areas, and the parasitic ticks' positive rate is obviously higher than that of free-living ticks. The Brucella melitensis has potential transovarian transmission and transstadial transmission in ticks. In the prevention and control of livestock brucellosis, the work of killing ticks should be strengthened, including parasitic ticks on the body surface and free-living ticks in the environment.

Objective: To explore the viral pathogens in hospitalized children with acute respiratory tract infection in Weifang. Methods: Nasopharyngeal secretion (NPS) samples were collected from hospitalized patients with acute respiratory tract infection from July 2016 to June 2017. The NPS samples were detected for 16 respiratory virus types/subtypes including influenza A virus (FluA), influenza B virus (FluB), seasonal influenza A HlNl virus (sH1N1), parainfluenza virus types 1, 2 and 3 (PIV-1, 2, 3), respiratory syncytial virus A (RSVA), respiratory syncytial virus B (RSVB), human rhinovirus (HRV), adenovirus (ADV), human metapneumovirus (HMPV), four coronavirus sybtypes (Cov-NL63, 229E, OC43, HKUl) and human bocavirus (BoV) by multiplex reverse transcription polymerase chain reaction (RT-PCR) assays based on automatic capillary electrophoresis. Results: A total of 769 children with respiratory tract infection were enrolled, and the overall positive rate for the 16 common respiratory tract viruses was 33.68% (259/769). The positive rates were as follows: RSV (9.23%), PIV (7.93%), Flu (6.89%), HRV (4.68%), ADV (3.38%), HMPV (1.69%), CoV (0.91%), BoV (0.65%). The positive rate of viral detection showed significant differences among different age groups (χ²=8.724, P=0.033), and the highest positive rate was noted in the age group of 6 months to 1 year. The overall positive rate of viral detection showed a significant difference in terms of seasonal distribution, with a peak prevalence in winter. Conclusions RSV was the main respiratory tract virus among children in Weifang, especially in winter and spring. The distribution of viruses in children with respiratory tract infection was associated with age and season.