BACKGROUND:Rev-erbα is involved in the regulation of inflammation,but pharmacological activation of Rev-erbα increases the risk for cardiovascular diseases.To reduce the relevant risk,an exploration on SR9009,a Rev-erbα agonist,combined with other drugs to relieve inflammation in skeletal myoblasts was conducted,laying the theoretical foundation for the treatment of inflammation-associated skeletal muscle atrophy. OBJECTIVE:To investigate the relationship of SR9009,indolepropionic acid and nuclear factor-κB signaling pathways in lipopolysaccharide-induced C2C12 myoblasts. METHODS:(1)C2C12 myoblasts were induced to differentiate in the presence of lipopolysaccharide(1 μg/mL).RNA-seq and KEGG pathway analysis were used to study signaling pathways.(2)C2C12 myoblast viability was assessed using the cell counting kit-8 assay to determine optimal concentrations of indolepropionic acid.Subsequently,cells were categorized into control group,lipopolysaccharide(1 μg/mL)group,SR9009(10 μmol/L)+lipopolysaccharide group,indolepropionic acid(80μmol/L)+lipopolysaccharide group,and SR9009+indolepropionic acid+lipopolysaccharide group.ELISA was employed to measure protein expression levels of interleukin-6 in the cultured supernatant.Real-time quantitative PCR were employed to measure mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Western blot assay were employed to measure protein expression levels of NF-κB p65 and p-NF-κB p65.(3)After Rev-erbα was knocked down by siRNA,knockdown efficiency was assessed by RT-qPCR.And mRNA levels of interleukin-6 and tumor necrosis factor α were also measured. RESULTS AND CONCLUSION:Compared with the blank control group,lipopolysaccharide time-dependently inhibited myofibroblast fusion to form myotubes,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were elevated,and the level of interleukin-6 in the cell supernatant was significantly increased.The results of KEGG pathway showed that the nuclear factor-κB signaling pathway was activated by lipopolysaccharide.Indolepropionic acid exhibited significant suppression of C2C12 myoblasts viability when its concentration exceeded 80 μmol/L.Indolepropionic acid and SR9009 inhibited the activation of NF-κB signaling pathway,thereby played an anti-inflammatory role,and suppressed the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.Compared with the lipopolysaccharide group,the ratio of p-NF-κB p65/NF-κB p65 protein expression were downregulated.SR9009 combined with indolepropionic acid notably reduced lipopolysaccharide-induced inflammation,further downregulated the mRNA expression levels of interleukin-6,tumor necrosis factor α,TLR4 and CD14.The ratio of p-NF-κB p65/NF-κB p65 protein expression was significantly lower than that in the SR9009+lipopolysaccharide group or indolepropionic acid+lipopolysaccharide group.Rev-erbα increases time-dependently with lipopolysaccharide induction.The knockdown efficiency of Rev-erbα by siRNA reached over 58%,and lipopolysaccharide was added after Rev-erbα was successfully knocked down.Compared with the lipopolysaccharide group,the mRNA expression levels of interleukin-6 and tumor necrosis factor α were significantly up-regulated.These results conclude that Rev-erbα may act as a promising pharmacological target to reduce inflammation.SR9009 targeted activation of Rev-erbα combined with indolepropionic acid significantly inhibits the nuclear factor-κB signaling pathway and attenuates the inflammatory response of C2C12 myofibroblasts.Moreover,the combined anti-inflammatory effect is superior to that of the intervention alone.

The unmet clinical needs of patients with rare diseases persist.Many rare diseases lack effec-tive treatments,and drug development for rare diseases faces greater challenges than that for common multiple diseases.In recent years,the concept of"patient-centered"drug development has been widely adopted.The Center for Drug Evaluation(CDE)of the National Medical Products Administration has successively issued a series of relevant guiding principles,such as the Technical Guidelines for the Implementation of Patient-Centered Clinical Trials,to promote a"patient-centered"drug development model.The implementation of the"patient-centered"approach in rare disease drug research and development,with a focus on patient perspectives and ac-tive engagement,can effectively facilitate a comprehensive understanding of rare diseases and patient needs among drug research and development enterprises,researchers,and regulatory agencies.This approach also en-hances the accuracy and efficiency of rare disease drug research and development.The CDE will continue to pri-oritize the integration of the"patient-centered"concept into rare disease drug research and development,effec-tively enhance the involvement of rare patients in the drug research and development process,and leverage the guiding role of patients'perspectives on drug research and development.

Rare diseases have a significant and profound impact on society, the economy, and the healthcare system. The path to developing drugs for rare diseases is particularly arduous. Due to the small number of patients and limited market demand, pharmaceutical companies don′t have enough incentives and resources to invest in drug research and development. Additionally, the long development cycles, high costs, and high risks have led to a number of potential therapeutic drug failures at the early stages of development. This article summarizes a series of encouraging policies adopted by the National Medical Products Administration for rare diseases, which is an important public health issue, as well as the achievements in the review and approval of rare disease drugs in recent years. These policies have accelerated the approval process. Meanwhile, the policies ensure the safety and effectiveness of drugs and offer more treatment options and hopes to patients with rare diseases. With the continuous effort at optimizing the policy environment and the advancement of research and development technologies, China′s drug regulatory authorities will continue to focus on the clinical needs of rare diseases, to implement " patient-centered " approach to drug development, inject new vitality into the research and development of drugs of rare diseases, and offer more precise and effective treatment choices for patients with rare diseases.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

OBJECTIVE To explore the influence of Zingiber officinale and processed Z. officinale on pharmacodynamic indexes and intestinal flora on gastric ulcer rats with spleen -stomach deficiency and cold type before and after processing with sand . METHODS The SD rats were randomly divided into normal group ，model group ，positive control group （Compound tianqi weitong capsule 0.45 g/kg），Z. officinale high-dose（15.0 g/kg）and low -dose（7.5 g/kg）groups，processed Z. officinale high- dose（15.0 g/kg）and low -dose（7.5 g/kg）groups，with 10 rats in each group . The rat model of gastric ulcer with spleen -stomach deficiency and cold type was established by intragastric administration of vinegar （day 1-10）and absolute ethanol （day 11）. Administration groups were given relevant liquid intragastrically ，and normal group and model group were given water intragastrically（day 5-10）. One hour after intragastric administration of absolute ethanol ，blood was taken from the femoral artery of rats ，the serum contents of motilin （MTL），gastrin（GAS），epidermal growth factor （EGF）as well as 4 items of blood coagulation [activated partial thromboplastin time （APTT），prothrombin time （PT），thrombin time （TT），fibrinogen（FIB）] were detect. The ulcer index and inhibition rate of ulcer in gastric tissue were calculated . The pathological changes of gastric tissue were observed，and the number and area of erosions were recorded . The diversity of gut microbiota in fecal samples of rats was detected . RESULTS Compared with model group ，the contents of MTL （except for processed Z. officinale low-dose group ），GAS（except for processed Z. officinale low-dose group ），EGF（except forofficinale groups） and FIB （except for Z. officinale groups），inhibitory rate of ulcer （only positive control group ）were all increased significantly （P＜0.05）. APTT（except for Z. officinale groups），PT（only processed Z. officinale high- dose group ），TT（except for Z. officinale groups），ulcer index （except for Z. officinale groups），the number （except for Z. officinale groups）and area of erosions （except for Z. officinale groups）were shortened and decreased significantly （P＜0.05）； improvement effects of processed Z. officinale were better than those of the same dose of Z. officinale on EGF ，4 items of blood coagulation（except for PT ，TT，FIB of processed Z. officinale low-dose group ），ulcer index （except for processed Z. officinale low-dose group ）and inhibitory rate of ulcer （P＜0.05）. Compared with model group ，α diversity indexes as ACE ，Shannon and Simpson of intestinal microorganisms in rats were increased significantly in processed Z. officinale group；the relative abundance of Proteobacteria was decreased significantly in processed Z. officinale group，while that of Bacteroidetes was increased significantly （P＜0.05）； the relative abundance of Limosilactobacillus was decreased significantly in Z. officinale group （P＜0.05）. CONCLUSIONS Z. officinale and processed Z. officinale can improve the symptoms of spleen -stomach deficiency and cold ，and enhance gastrointestinal function by increasing the content of GAS and MTL . Processed Z. officinale can significantly inhibit gastric ulcer of spleen -stomach deficiency and cold type ，which is related to the promotion of mucosal protection and repair ，improvement of coagulation functionand adjustment of gut microbiotadisorder .

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Objective:To investigate the application of cromolyn sodium combined with diclofenac sodium eye drops in allergic conjunctivitis (AC) and its effect on tear film function, interleukin-10 (IL-10), interleukin-17 (IL-17) and immunoglobulin E(IgE).Methods:From April 2018 to May 2020, 78 patients with AC collected in Liaoning Armed Police Crops Hospital were divided into control group and observation group according to the random number table method (39 cases in each group). The control group was given cromolyn sodium eye drops, and the observation group was given cromolyn sodium combined with diclofenac sodium eye drops. The efficacy, clinical symptoms, changes of signs, tear film function [tear film rupture time (BUT), Schirmer I test (SIt)], tear inflammation indicators [interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α), IL-10, IL-17], tear allergy mediators [eosinophil cationic protein (ECP), hyaluronic acid (HA), IgE] and safety.Results:The total effective rate of observation group was 100.00%, which was higher than that of control group (84.62%), with statistically significant difference ( P<0.05). After treatment, the scores of eye itching, tearing, photophobia, eye secretion, conjunctival hyperemia, conjunctival edema and blepharoconjunctival papillary follicular hyperplasia in the two groups were significantly lower than those before treatment, and the observation group was lower than the control group, with statistically significant difference (all P<0.05). The BUT in the observation group was higher than that in the control group after treatment, with statistically significant difference ( P<0.05). After treatment, the tear levels of IL-4, TNF-α, IL-10 and IL-17 in the observation group were lower than those in the control group, with statistically significant difference (all P<0.05). After treatment, the tear ECP, HA and IgE level in the observation group were lower than those in the control group, with statistically significant difference (all P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P>0.05). Conclusions:Cromolyn sodium combined with diclofenac sodium eye drops is effective in the treatment of AC, which can effectively improve the clinical symptoms and signs, promote stable tear film function, alleviate local metamorphosis and inflammation, and has good safety.

The incidence of each of the rare disease is very low. The complexity and diagnosis difficulty of the rare disease lead to the difficulties in the clinical research and development (R&D) of drugs for rare diseases. There is an urgent clinical need for the drug development of rare diseases in China. Encouraging R&D of new drugs, particularly the innovative drugs with China's own independent intellectural property is the basis for solving the predicament in drug shortage in China.. In order to further improve the efficiency of clinical R&D of drugs for rare diseases, the National Medical Products Administration (NMPA), Center for Drug Evaluation (CDE) issued Technical Guidance for Clinical Research and Development of Drugs for Rare Diseases. This is the first guidance for rare diseases in China that is drafted from the standpoint of the clinical technology research and development.The guidance is the scientifitc thinking and framework for the drug developing enterprises to research and develop drugs for rare disease efficiently and appropriately by following drug developing protocols and relating to the special features of rare disease.This paper presents the concepts and rationale in the guidance for the appraisal of rare disease drug research and development.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

OBJECTIVE: To analyze the relationship between the cumulative noise exposure( CNE) and prevalence of hypertension in automotive manufacturing workers. METHODS: A total of 1 535 noise-exposed male workers with length of service ≥ 1. 0 year from automobile manufacturing industries in Guangzhou City was chosen as study subjects by convenience sampling method. The noise intensity in the workplace was measured, the CNE calculated, and the occupational health examination conducted. RESULTS: The prevalence of hypertension of the study subjects was 8. 1%( 125/1 535). The prevalence of hypertension showed an upward trend with the increase of CNE( P < 0. 01). The multivariate logistic regression analysis showed that the prevalence risk of hypertension increased with the increase of CNE after adjusting for confounding factors such as body mass index,smoking and wearing personal protective equipment in automobile manufacturing workers( P < 0. 01). CONCLUSION: There is a dose-effect relationship between prevalence of hypertension and CNE in automobile manufacturing workers who exposed to noise.