The effect of social determinants of health on severity of microbial keratitis presentation at a tertiary eye care hospital in Southern India

Purpose: Understanding the association between social determinants of health (SDoHs) and microbial keratitis (MK) can inform underlying risk for patients and identify risk factors associated with worse disease, such as presenting visual acuity (VA) and time to initial presentation. Methods: This was a cross?sectional study was conducted with patients presenting with MK to the cornea clinic at a tertiary care hospital in Madurai, India. Patient demographics, SDoH survey responses, geographic pollution, and clinical features at presentation were collected. Descriptive statistics, univariate analysis, multi?variable linear regression models, and Poisson regression models were utilized. Results: There were 51 patients evaluated. The mean age was 51.2 years (SD = 13.3); 33.3% were female and 55% did not visit a vision center (VC) prior to presenting to the clinic. The median presenting logarithm of the minimum angle of resolution (logMAR) VA was 1.1 [Snellen 20/240, inter?quartile range (IQR) = 20/80 to 20/4000]. The median time to presentation was 7 days (IQR = 4.5 to 10). The average particulate matter 2.5 (PM2.5) concentration, a measure of air pollution, for the districts from which the patients traveled was 24.3 ?g/m3 (SD = 1.6). Age? and sex?adjusted linear regression and Poisson regression results showed that higher levels of PM2.5 were associated with 0.28 worse presenting logMAR VA (Snellen 2.8 lines, P = 0.002). Patients who did not visit a VC had a 100% longer time to presentation compared to those who did (incidence rate ratio = 2.0, 95% confidence interval = 1.3–3.0, P = 0.001). Conclusion: Patient SDoH and environmental exposures can impact MK presentation. Understanding SDoH is important for public health and policy implications to mitigate eye health disparities in India.

Current status and progress on the application of ventricular assist device / 器官移植

At present, heart transplantation is the most effective treatment for end-stage heart failure. Nevertheless, the shortage of donors is becoming an increasingly severe challenge. In recent years, rapid development of mechanical circulatory support technologies has provided multiple therapeutic options for patients with end-stage heart failure. As an important mechanical circulatory support device, ventricular assist device (VAD) are divided into durable VAD (dVAD) and temporary VAD (tVAD) according to the duration of assistance. dVAD shows application potential in bridging heart transplantation, destination therapy and bridge to decision. With technological progress and experience accumulation in clinical application, VAD is evolving towards the direction of more biocompatible, lighter, more bionic and intelligent. In this article, the development of VAD, application status at home and abroad and the overall application of VAD in our hospital were reviewed, aiming to provide reference for promoting the clinical application of VAD in China.

Tumor immune checkpoint therapy and the drug delivery strategies / 药学学报

Tumor immune checkpoint therapy is a clinical treatment strategy developed based on the new principle of the inhibition of negative immune regulation. In this article, the tumor immune checkpoint therapy and the drug delivery strategies were reviewed, mainly including immunity and tumor therapy, tumor immune checkpoint therapy and its mechanism of action, clinical application of tumor immune checkpoint therapy and therapeutic drugs, immune resistance of programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PDL1) treatment and countermeasures, drug delivery strategies for tumor immune checkpoint therapeutic agents, etc. As a revolutionary new immunotherapy strategy, tumor immune checkpoint therapy has shown obvious superior therapeutic efficacy in a variety types of tumor. However, tumor immune checkpoint therapy is also faced with a big challenge, namely, immunotherapy resistance. With the discovery of new mechanism, the continuous development of new therapeutic drugs and delivery strategies, tumor immune checkpoint therapy is expected to further improve the clinical efficacy of tumor.

Xueshuantong improves cerebral microcirculation disorder: action mechanism based on network pharmacology and experimental validation / 药学学报

This study is to explore the mechanism of Xueshuantong improving cerebral microcirculation disorder through the combination of network pharmacology and experimental validation in vivo. Structural formulas of main Panax notoginseng saponins, including notoginsenoside R1, and ginsenoside Rg1, Re, Rb1 and Rd were obtained from Pubchem website and their potential targets were predicted by Swiss Target Prediction database. Potential molecular targets of brain microcirculation disorder were acquired from OMIM and GeneCards database. The overlapped molecular targets between the drug and disease were analyzed. Protein interaction analysis and topology maps were constructed through the STRING online analysis platform and Cytoscape software. Core action targets were selected. GO function and KEGG pathway were analyzed by DAVID database. Immunohistochemical method was used to examine the expression of platelet endothelial cell adhesion molecule-1 (CD31) in the ischemic cortex of middle cerebral artery occlusion and reperfusion (MCAO/R) rats. The levels of mRNA and protein expressions of core action targets in MCAO/R model rats′ brain microvessels were verified by RT-qPCR and Western blot. Based on network pharmacology, 242 targets of Xueshuantong, 425 targets of brain microcirculation disorder, and 35 overlapped targets were obtained. The potential key targets of Xueshuantong, protein kinase B (AKT1), vascular endothelial growth factor A (VEGFA), caspase 3 (CASP3), matrix metallopeptidase 9 (MMP-9), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), signal transducer and activator of transcription 3 (STAT3) involved in the alleviation of cerebral microcirculation disorder were obtained by setting degree and betweenness centrality as screening parameters. Xueshuantong at the dose of 48 mg·kg-1 was shown to significantly improve the injury of neurological behaviors, as well as the density and morphology of microvessels of MCAO/R model rats. Xueshuantong could down-regulate the mRNA levels of AKT1, MMP-9, and STAT3, increase the protein expression levels of CD31, phosphorylated AKT and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and the ratio of B-cell lymphoma 2/Bcl-2-associated X (Bcl-2/Bax), but decrease the protein expression levels of MMP-9, cleaved caspase-3 and phosphorylated STAT3. In summary, Xueshuantong could improve ischemic cerebral microcirculation disorder and thereby reduce nerve damage in ischemia-reperfusion rats by regulating signaling pathways related with PI3K, AKT, MMP-9, STAT3 and caspase-3 in microvessels. The study strictly adhered to all ethical protocols that experimental animals should follow in the course of medical research.

Effect evaluation of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: Using propensity score matching method(PSM) to investigate the clinical effect of surgical plus radio(chemo)therapy and non-surgery chemoradiotherapy treatment strategies for advanced tonsillar squamous cell carcinoma. Methods: A retrospective analysis was conducted on the clinical data of 324 patients diagnosed with advanced tonsillar squamous cell carcinoma and treated in Peking Union Medical College Hospital from 2000 to 2018, confirmed by pathology and without distant metastasis. Survival analysis was performed using Kaplan-Meier estimates, the Cox proportional hazards model, and propensity score matching(PSM). Results: Of the 324 patients, 102 were treated with non-surgery chemoradiotherapy treatment strategies and 222 with surgical plus radio(chemo)therapy treatment. Cox multivariate analysis showed that the non-surgery treatment group had a favorable prognosis than the surgical treatment group, however, these outcomes were not significantly different [overall survival(OS): adjusted Hazard Ratios(aHR): 0.92, 95% confidence interval(CI): 0.60-1.42; disease-specific survival(DSS): aHR: 0.71, 95%CI: 0.43-1.20; disease-free survival(DFS): aHR: 0.82, 95%CI: 0.53-1.28]. The new patient cohort consisted of 102 subpairs after PSM. There were no significant differences between two groups(OS: aHR: 0.85, 95%CI: 0.51-1.40; DSS: aHR: 0.62, 95%CI: 0.35-1.11; DFS: aHR: 0.80, 95%CI: 0.49-1.33). Conclusion: Our findings indicate that patients with non-surgical treatment do not have significantly better survival outcomes compared to surgical treatment group, while non-surgical treatment has advantages in improving the quality of life of patients, so comprehensive treatment based on radiotherapy and chemotherapy may be recommended for advanced tonsillar squamous cell carcinoma.

Interpretation and comparison of international guidelines for salivary gland malignancy in 2021 / 中华口腔医学杂志

In order to provide evidence-based recommendations on the management of salivary gland malignancy (SGM), the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN) formulated and updated SGM clinical practice guidelines respectively in 2021.The two guidelines are interpreted and compared in this article from six perspectives including preoperative evaluations, surgical diagnostic and therapeutic procedures, appropriate radiotherapy techniques, the role of systemic therapy, follow-up evaluations and recurrent-metastatic diseases' management of SGM, which has guiding significance for diagnosis and treatment of SGM in China.

Association between genetic predisposition to childhood obesity and the risk of adult ischemic heart disease in China / 中华流行病学杂志

Objective: To examine the associations of childhood obesity, assessed by genetic variations of childhood body mass index (BMI), with the risk of adult ischemic heart disease (IHD) and major coronary event (MCE). Methods: More than 69 000 participants from the China Kadoorie Biobank were genotyped. After excluding those with coronary heart disease, stroke, or cancer at baseline, a total of 64 454 participants were included in this study. Based on genome-wide significant single nucleotide polymorphisms (SNPs), childhood BMI genetic risk score were constructed for every participant and divided into quintiles, with the lowest quintile as the low genetic risk group and the highest quintile as the high genetic risk group. Cox proportional hazards regression models were used to estimate the association between genetic predisposition to childhood obesity and the risk of ischemic heart disease. Results: During a median of 10.7 years of follow-up, 7 073 incident cases of IHD and 1 845 cases of MCE were documented. After adjusting for sex, age, region, and the first ten genetic principal components, the HRs (95%CIs) for IHD and MCE in the high genetic risk group were 1.10 (1.02-1.18) and 1.10 (0.95-1.27), compared with the low genetic risk group. IHD risk increased by 4% (2%-6%) for each one standard deviation increase in genetic risk score (trend P=0.001). After further adjustment for baseline BMI, the differences between genetic risk groups were not statistically significant, but there was still a linear trend between genetic risk score and IHD risk (trend P=0.019). Conclusions: IHD risk increased with genetic predisposition to childhood obesity, suggesting that childhood obesity is an important risk factor for the development of IHD in China. As an easily identifiable feature, changes of childhood BMI should be monitored regularly to realize early intervention of IHD in adults.

The correlation of sleep duration and insomnia with low muscle mass, strength and quality in Chinese adults / 中华流行病学杂志

Objective: To explore the relationship of sleep duration and insomnia with muscle mass, strength, and quality in Chinese adults. Methods: Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of sleep duration, insomnia, and its duration with low muscle mass, handgrip strength, and muscle quality. Results: The average sleep duration of the study population was (7.4±1.5) hours. Morbidities of short sleep duration (<6 hours), long sleep duration (≥9 hours), and insomnia were 9.3%,17.4%,and 29.9%,respectively. Compared with those who slept for 7- hours, those who slept for ≥9 hours were more likely to have low muscle mass, low handgrip strength,and low arm muscle quality (AMQ), and the OR (95%CI) of low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI), low grip strength and low AMQ were 1.32 (1.18-1.48),1.26 (1.13-1.41), 1.33 (1.18-1.49) and 1.16 (1.03-1.30), respectively. Compared with participants without insomnia, insomnia patients were more likely to have low muscle mass,and the longer the duration of insomnia,the higher the risk (P for trend <0.001). Participants who reported <6 hours sleep duration and insomnia had a higher proportion of low ASMI and low TSMI,compared with those who slept for 7- hours and without insomnia, the OR (95%CI) were 1.26 (1.08-1.47) and 1.25 (1.07-1.46), respectively. Conclusions: Participants who reported ≥9 hours sleep duration were more likely to have low muscle mass,low handgrip strength,and low AMQ. Participants with insomnia had lower muscle mass, and the longer the duration of insomnia, the higher the proportion of low ASMI and low TSMI.

Spicy food consumption and risk of lip, oral cavity and pharynx cancers: a prospective cohort study of Chinese adults / 中华流行病学杂志

Objective: To explore the association of spicy food consumption and risk of lip, oral cavity, and pharynx cancers (LOCPs) in Chinese adults. Methods: Based on the baseline survey and long-term follow-up of the China Kadoorie Biobank (CKB) study, Cox proportional hazard regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95%CI) for associations between spicy food consumption and LOCPs incidence. Results: Of the 510 145 participants included at baseline, 30.1% reported daily spicy food consumption. During a mean follow-up of 10.8 (2.0) years, we documented 767 LOCPs cases. Multivariate adjusted analyses showed that the risk of LOCPs incidence decreased with the frequency of spicy food intake (trend P=0.003), with HR of 0.69 (95%CI:0.54-0.88) for daily spicy food consumers, compared with never or occasional consumers. Participants who preferred moderate pungency degrees had the lowest risk of LOCPs, with a 33%[0.67(95%CI:0.52-0.87)] reduced risk compared to those who consumed spicy food less than once per week. The later the starting age, the lower the risk (trend P=0.004). Those who started eating spicy food after 18 years old had the lowest risk of LOCPs incidence, with adjusted HR (95%CI) of 0.70(0.54-0.92). Conclusions: Spicy food intake might be associated with a decreased risk of LOCPs incidence. Such association was independent of healthy lifestyles. Advocating moderate-pungency spicy food consumption and healthy lifestyles might help prevent LOCPs.

The correlation of physical activity and sedentary leisure time with low muscle mass, strength, and quality in Chinese adults / 中华流行病学杂志

Objective: To explore the relationship of physical activity and sedentary leisure time with muscle mass, strength, and quality in Chinese adults. Methods: Based on the second resurvey of China Kadoorie Biobank (CKB) in 2013-2014, logistic regression models were used to analyze the correlation of physical activity and sedentary leisure time with low muscle mass, grip strength, and muscle quality. Results: A total of 24 245 participants were included in the analysis. The average daily physical activity level was (18.3±13.8) MET-h/d, and the sedentary leisure time was (4.4±1.9) hours. We took the lowest physical activity quartile as the reference and found that the participants' physical activity was negatively correlated to low muscle mass, strength, and quality. The ORs (95%CIs) of low appendicular skeletal muscle mass index (ASMI), low total skeletal muscle mass index (TSMI), low grip strength and low arm muscle quality (AMQ) were 0.68 (0.60-0.77), 0.66 (0.58-0.75), 0.82 (0.72-0.94) and 0.84 (0.74-0.95), respectively. The subtypes of physical activity, including those related to work, transportation, housework, and leisure, also showed negative correlations with low muscle mass, strength, and quality to varying degrees. Compared with participants with the shortest sedentary leisure time, those who had the longest were more likely to have low TSMI (OR=1.13, 95%CI: 0.99-1.30). Conclusions: Physical activity was negatively correlated with a lower risk of low muscle mass and strength, while longer sedentary leisure time positively correlated with low muscle mass.

Associations of body mass index and waist circumference with hospitalization risk of kidney stones in Chinese adults / 中华流行病学杂志

Objective: To evaluate the associations of body mass index (BMI) and waist circumference with hospitalization risk of kidney stones in Chinese adults. Methods: This study used long-term follow-up data from China Kadoorie Biobank. After excluding participants with chronic kidney disease, cancer, and extreme BMI or waist circumference values at baseline, 502 096 participants were included in the present analysis. Cox proportional hazards regression models were used to estimate the associations of BMI and waist circumference with hospitalization risk of kidney stones. Results: During an average follow-up period of (10.7±2.2) years, 12 396 participants were hospitalized for the first time with kidney stones. Using the participants with BMI (kg/m2) of 20.5-22.4 as reference, the multivariable-adjusted HR (95%CI) for those with BMI of <18.5, 18.5-20.4, 22.5-23.9, 24.0-25.9, 26.0-27.9, 28.0-29.9, and ≥30.0 were 0.96 (0.87-1.05), 0.94 (0.88-1.00), 1.11 (1.05-1.17), 1.25 (1.18-1.32), 1.29 (1.21-1.37), 1.39 (1.28-1.50), and 1.54 (1.40-1.71), respectively. For every 1 kg/m2 increase in BMI, the HR of kidney stones hospitalization increased by 4% (HR=1.04, 95%CI: 1.04-1.05). Using the participants with waist circumference (cm) of 75.0-79.9 as reference, the multivariable-adjusted HR (95%CI) for those with waist circumference of <65.0, 65.0-69.9, 70.0-74.9, 80.0-84.9, 85.0-89.9, 90.0-94.9, and ≥95.0 were 0.82 (0.74-0.91), 0.85 (0.80-0.92), 0.95 (0.89-1.00), 1.16 (1.09-1.22), 1.22 (1.15-1.30), 1.28 (1.19-1.38), and 1.46 (1.35-1.58), respectively. For every 5 cm increase in waist circumference, the HR of kidney stones hospitalization increased by 9% (HR=1.09, 95%CI: 1.08-1.10). After mutually adjusting for BMI and waist circumference in the above models, the association between BMI and hospitalization risk of kidney stones disappeared. In contrast, the association between waist circumference and hospitalization risk of kidney stones remained unchanged. Conclusions: BMI and waist circumference were positively associated with hospitalization risk of kidney stones. The increased waist circumference was an independent risk factor for kidney stones among Chinese adults.

Association between tea consumption and all-cause mortality in Chinese adults / 中华流行病学杂志

Objective: To investigate the association between tea consumption and the risk of all-cause and cause-specific mortality among Chinese adults. Methods: This study was based on China Kadoorie Biobank (CKB). Tea consumption information was self-reported by participants at baseline. Death was mainly identified by linkage to the death registry system. Cox proportional hazard regression models estimated HR and 95%CI. Results: With a median follow-up of 11.1 years, there were 34 661 deaths in 438 443 participants. Compared with those who never drink tea, all-cause mortality HR(95%CI) were 0.89(0.86-0.91) and 0.92(0.88-0.95) for non-daily tea drinkers and daily tea drinkers, respectively. A statistically significant difference was found in the association of tea consumption and the risk of all-cause mortality between men and women(interaction P<0.05). The protective effect was mainly seen in men. Compared with those who never drink tea, daily tea drinkers had a reduced risk of death from ischemic heart disease, ischemic stroke, hemorrhagic stroke, cancer, respiration diseases and other causes of death, and the corresponding HR(95%CI) were 0.83(0.76-0.92), 0.82(0.69-0.97), 0.86(0.78-0.94), 1.03(0.97-1.09), 1.00(0.87-1.16), 0.84(0.78-0.90). Among never smokers and non-excessive drinkers, there was no statistically significant association between daily tea drinking and the risk of death from cancer. While smokers and excessive drinkers had an increased risk of death from cancer (interaction P<0.001). Conclusions: Tea consumers had reduced risks of all-cause mortality and partial cause-specific mortality, but not for the risk of death from cancer. On the contrary, daily tea drinkers with smoking habits and excessive alcohol drinking had an increased risk of death from cancer.

Meta analysis on acceptance rate of HIV pre-exposure prophylaxis among men who have sex with men in China / 中华预防医学杂志

Objective: To systematically evaluate the acceptance of pre-exposure prophylaxis (PrEP)among men who have sex with men (MSM) in China, so as to provide reference for the promotion of preventive drug use before human immunodeficiency virus exposure in China. Methods: By searching the databases of China national knowledge infrastructure, VIP database, Wanfan knowledge service platform, PubMed, Web of Science, Embase and The Cochrane Library with key words of "men who have sex with men" "pre-exposure prophylaxis" "PrEP" and "MSM". The literature on the willingness of Chinese MSM population to accept PrEP was systematically collected, and the data of the literature meeting the inclusion criteria were extracted for Meta analysis. Results: A total of 12 articles were selected in this study, including 6 articles in English and 6 in Chinese. The score of bias risk assessment of eligible articles was 14-18, which was more than 70% of the total score. The total number of samples was 11 269. The overall acceptance rate of PrEP was 0.77(95%CI:0.71-0.82). In subgroup analysis, the acceptance rates of different nationalities, marriage, household registration, age, education background, income, sexual orientation, sexual behavior and awareness of PrEP were statistically significant. Conclusion: In general, the acceptance rate of PrEP in MSM population is higher, but the awareness rate is low. There are differences in the acceptance rate among different groups.

Pirfenidone inhibits the polarization of M2 macrophages by down-regulating IRF4 to reduce the occurrence and development of radiation-induced lung fibrosis / 中华放射肿瘤学杂志

Objective:To explore the preventive and therapeutic effect of pirfenidone (PFD) on radiation-induced lung fibrosis (RILF) and its mechanism.Methods:40 female C57/BL6 mice were randomly divided into 4 groups: negative control group (NC), PFD treatment group (PFD), radiation treatment group (RT) and radiation plus PFD treatment group (RT+ PFD). Mice in RT and RT+ PFD groups received a single whole lung X-ray consisting of a 50 Gy dose of radiation, delivered by small animal radiation research platform (SARRP). PFD at a dose of 300 mg/kg was administered orally 2 h before irradiation for 150 d. HE and Masson staining were used to detect the infiltration of inflammatory cells and the degree of pulmonary fibrosis. Quantitative real-time PCR (qPCR) and Western blotting (WB) were adopted to detect the expression levels of M1/M2 macrophage phenotypic markers. The expression levels of arginase-1(ARG-1), chitinase 3-like protein 3(YM-1) and interferon regulatory factor-4(IRF4) of macrophages stimulated with IL-4 and IL-13 were detected by WB. In addition, immunofluorescence staining was used to detect the expression and translocation of IRF4 in macrophages among different treatment groups.Results:HE and Masson staining showed that PFD could significantly inhibit radiation-induced infiltration of inflammatory cells and fibrosis in lung tissues. The M2 macrophages and expression levels of ARG-1 and YM-1 were down-regulated in the RT+ PFD group. Cell experiments further confirmed that PFD could significantly inhibit the polarization of macrophages to M2 induced by IL-4+ IL-13, which was mainly related to the down-regulation of IRF4.Conclusion:PFD has a preventive and therapeutic effect on RILF by inhibiting IRF4 and reducing the polarization of macrophages to M2.

Risk assessment of brain metastasis after prophylactic cranial irradiation for 550 limited stage small cell lung cancer patients with remission after radiochemotherapy / 中华放射肿瘤学杂志

Objective:To evaluate the risk and prognostic factors of brain metastasis (BM) after prophylactic cranial irradiation (PCI) in limited stage small cell lung cancer (LS-SCLC) patients with complete and partial remission (CR/PR) after radiochemotherapy.Methods:Baseline data of 550 patients with LS-SCLC who obtained CR/PR after chemoradiotherapy and received PCI in Zhejiang Cancer Hospital between 2002 and 2017 were collected. The risk of BM and clinical prognosis were retrospectively analyzed. The survival analysis was performed by Kaplan-Meier method. Multivariate prognostic analysis was conducted byCox models.Results:The overall BM rate after PCI was 15.6%(86/550), with 9%(4/43), 13%(7/52), and 16.5%(75/455) for stage Ⅰ, Ⅱ and Ⅲ patients, respectively. The median overall survival (OS) for the entire cohort was 27.9 months, and the 5-year OS rate was 31.0%. The OS was 24.9 and 30.2 months for patients with or without BM, and the 5-year OS rates were 8.9% and 36.1%( P<0.001). BM was an independent factor of OS ( P<0.001). Clinical staging remained the influencing factor of OS and BM-free survival ( P<0.001, P=0.027). Having tumors of ≥5 cm in diameter significantly increased the risk of BM ( P=0.034) rather than the OS ( P=0.182). The median OS of patients aged<60 years was significantly longer than those aged ≥60 years (34.9 months vs. 24.6 months, P=0.001). The median OS of patients irradiated with 2 times/d was 29.8 months, significantly longer than 24.5 months of those irradiated with 1 time/d ( P=0.013). Age, sex, radiotherapy fraction and efficacy of radiochemotherapy (CR/PR) were not associated with the incidence rate of BM (all P>0.05). Conclusions:SCLC patients with tumors of ≥5 cm in diameter may have a higher risk of developing BM after PCI. Patients aged<60 years achieve better OS compared with their counterparts aged ≥60 years.

Low-frequency pulsed electromagnetic fields promote osteoblast mineralization and maturation of rats through the PC2/sAC/PKA/CREB signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore whether the effect of low-frequency pulsed electromagnetic fields (PEMFs) in promoting osteoblast mineralization and maturation is related to the primary cilia, polycystin2 (PC2) and sAC/PKA/CREB signaling pathway.@*METHODS@#We detected the expression levels of PC2, sAC, PKA, CREB and their phosphorylated proteins in primary rat calvarial osteoblasts exposed to 50 Hz 0.6 mT PEMFs for 0, 5, 15, 30, 60, 90, and 120 min. We blocked PC2 function with amiloride hydrochloride and detected the changes in the activity of sAC/PKA/CREB signal pathway and the mineralization and maturation of the osteoblasts. These examinations were repeated in the osteoblasts after specific knockdown of PC2 via RNA interference and were the co-localization of PC2, sAC, PKA, CREB and their phosphorylated proteins with the primary cilia were using immunofluorescence staining. The expressions of PC2 and the signaling proteins of sAC/PKA/CREB pathway were detected after inhibition of primary ciliation by RNA interference.@*RESULTS@#The expression levels of PC2, sAC, p-PKA and p- CREB were significantly increased in the osteoblasts after exposure to PEMFs for different time lengths (P < 0.01). Blocking PC2 function or PC2 knockdown in the osteoblasts resulted in failure of sAC/PKA/CREB signaling pathway activation and arrest of osteoblast mineralization and maturation. PC2, sAC, p-PKA and p-CREB were localized to the entire primary cilia or its roots, but PKA and CREB were not detected in the primary cilia. After interference of the primary cilia, PEMFs exposure no longer caused increase of PC2 expression and failed to activate the sAC/PKA/CREB signaling pathway or promote osteoblast mineralization and maturation.@*CONCLUSION@#PC2, located on the surface of the primary cilia of osteoblasts, can perceive and transmit the physical signals from PEMFs and promote the mineralization and maturation of osteoblasts by activating the PC2/ sAC/PKA/CREB signaling pathway.

Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported / 中华肿瘤杂志

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

Banxia Xiexintang and Its Disassembled Prescriptions Regulate Colonic Mucosal Immunity in Young Rats with Flora Disorder / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and possible mechanism of Banxia Xiexintang and its disassembled prescriptions in regulating the flora disorder induced by mixed antibiotics in young rats. MethodSeventy male BALB/C young rats were randomly assigned into 7 groups： blank group， model group， Bifidobacterium tetralogy viable tablets （0.68 g·kg-1） group， Banxia Xiexintang （9.1 g·kg-1） group， Xinkai （3.19 g·kg-1） group， Kujiang （1.82 g·kg-1） group， and Ganbu （4.1 g·kg-1） group， with 10 rats in each group. Except the blank group， the other groups were given mixed antibiotics by gavage to induce intestinal flora disorder. After 14 days， the rats in different drug groups were administrated with corresponding drugs by gavage， and those in the blank group and model group with the same amount of normal saline once a day for 14 days. After that， fecal samples were collected aseptically for 16S rDNA sequencing of intestinal flora， and lipopolysaccharide （LPS， 10 mg·kg-1） was injected intraperitoneally to induce inflammatory reaction. The tissue morphology of colonic mucosa was observed via hematoxylin-eosin （HE） staining， and the macrophage infiltration of colonic mucosa was observed via toluidine blue staining and immunohistochemistry. The expression of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10） mRNA were determined by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the modeling changed the intestinal flora structure of the young rats （P<0.01）， damaged the colonic mucosa， reduced the macrophage infiltration， and down-regulated the mRNA levels of IL-1β， IL-6， IL-8， TNF-α， and IL-10 （P<0.01）. Compared with the model group， bifidobacterium quadruple viable tablets， Banxia Xiexintang and its disassembled prescriptions increased the diversity of intestinal flora and the relative abundance of beneficial bacteria such as Bacteroidetes and Firmicutes （P<0.01）. At the same time， they ameliorated colonic mucosal injury （P<0.05， P<0.01）， increased macrophage infiltration （P<0.05， P<0.01）， and up-regulated the mRNA levels of IL-6， IL-8， and TNF-α （P<0.01）. The mRNA level of IL-1β was up-regulated in Bifidobacterium tetralogy viable tablets， Banxia Xiexintang， Kujiang， and Ganbu groups （P<0.01）， and that of IL-10 was up-regulated in Bifidobacterium tetralogy viable tablets， Banxia Xiexintang， Xinkai， and Ganbu groups （P<0.01）. ConclusionBanxia Xiexintang and the disassembled prescriptions can adjust the intestinal flora of young rats exposed to antibiotics and protect the immune barrier of colonic mucosa after intestinal flora disorder. In particularly， the whole prescription of Banxia Xiexintang demonstrates the best performance.

Medication Regularity for Chronic Renal Failure and Underlying Mechanism Based on Data Mining， Network Pharmacology， and Molecular Docking / 中国实验方剂学杂志

ObjectiveTo clarify the medication regularity of WU Zhao-dong，a famous chief physician in traditional Chinese medicine （TCM） of Jiangxi province， and investigate the potential mechanism of potential new prescriptions against chronic renal failure （CRF）. MethodThe outpatient prescriptions of WU Zhao-dong from July 2019 to July 2021 were collected. Data mining was carried out by using the Traditional Chinese Medicine Inheritance Auxiliary Platform （V 2.5） to analyze the medication frequency and drug association and obtain potential new prescriptions. The interaction between drug targets in new prescriptions was analyzed by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP），STRING，and Kyoto Encyclopedia of Genes and Genomes（KEGG）， followed by verification by molecular docking and experiments. ResultA total of 200 prescriptions were screened out， with 217 Chinese medicinal drugs involved， and eight new potential prescriptions were derived. To be specific， Prescription 1： Armeniacae Semen Amarum-Astragali Radix-Platycodonis Radix-Angelicae Sinensis Radix-Smilacis Glabrae Rhizoma-fried Atractylodis Macrocephalae Rhizoma， Prescription 2： Saposhnikoviae Radix-Schizonepetae Herba-Kochiae Fructus-Asteris Radix et Rhizoma-Menthae Haplocalycis Herba，Prescription 3：Armeniacae Semen Amarum-Asteris Radix et Rhizoma-Platycodonis Radix-Eriobotryae Folium-prepared Ephedrae Herba， Prescription 4：Perillae Caulis-Codonopsis Radix-Coptidis Rhizoma-Pseudostellariae Radix， Prescription 5：Ecliptae Herba-Astragali Radix Praeparata Cum Melle-Dryopteridis Crassirhizomatis Rhizoma-Rosae Laevigatae Fructus-Coicis Semen-Ligustri Lucidi Fructus， Prescription 6： Lycopi Herba-Lonice Raejaponicae Caulis-Trachelospermi Caulis et Folium-Alismatis Rhizoma， Prescription 7：Scutellariae Radix-Hirudo-Paeoniae Radix Rubra-Eriobotryae Folium-Glehniae Radix， Prescription 8：Glycyrrhizae Radix et Rhizoma-Scrophulariae Radix-Chrysanthemi Indici Flos-Smilacis Glabrae Rhizoma- Serissae Herba. In Prescription 1，18 main chemical components were screened out. Eighty targets of active components of Prescription 1 were predicted， and 37 potential targets for the treatment of CRF were obtained， including interleukin （IL）-6， vascular endothelial growth factor （VEGF）， cysteinyl aspartate-specific protease-3 （Caspase-3）， nitric oxide synthase 3 （NOS3）， and hypoxia-inducible factor-1 （HIF-1）. The KEGG pathways involved in the targets of Chinese medicinal drugs and disease mainly included the signaling pathways of lipid and atherosclerosis，NF-κB， Toll-like receptors， and HIF-1. Prescription 1 significantly decreased serum creatinine and urea nitrogen， and increased the content of NO and NOS3 in renal tissues of CRF rats. ConclusionPrescription 1 shows the multi-component and multi-target characteristics of action，and its mechanism may be related to its inhibition of renal fibrosis，anti-inflammation，improvement of intestinal microecology，and improvement of renal hypoxia and ischemia.

Preparation of Rehmanniae Radix Juice for Baihe Dihuangtang Based on UPLC-Q-TOF-MS / 中国实验方剂学杂志

ObjectiveTo compare the four preparation methods of Rehmanniae Radix juice described in ancient literature and find the method that is most suitable for the preparation of Rehmanniae Radix juice used in Baihe Dihuangtang. MethodThe ancient medical books record four methods for preparing Rehmanniae Radix juice： crushing fresh Rehmanniae Radix for juice， steaming fresh Rehmanniae Radix for juice， boiling fresh Rehmanniae Radix for juice， and boiling dry Rehmanniae Radix for juice. Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS） was employed to detect the compounds in the four juice samples， followed by principal component analysis （PCA）. Result① Totally 27 compounds were identified in the juice samples， including 10 iridoid glycosides， 14 phenylethanoid glycosides， 2 phenolic acids， and 1 irisone. Among them， 15 common compounds were shared by the four juice samples， including 7 iridoid glycosides， 7 phenylethanoid glycosides， and 1 phenolic acid. ② Five common compounds in the four juice samples can be matched with the reference standards， which were catalpol， aucubin， rehmannioside D， ajugol， and purpureaside C. ③ Verbascoside and isoacteoside were not detected in the juice prepared by crushing fresh Rehmanniae Radix， while it was detected in the other three juice samples， which indicated that the two components were produced after heating rather than being the original components in fresh Rehmanniae Radix. ④ The comparison of the ion fragments demonstrated that verbascoside was produced from purpureaside C after the cleavage of the glycosidic bond and removal of a molecule of mannose. ⑤ Isoacteoside could be isomerized from verbascoside， and its relative content increased with the extension of heating time. However， the relative content of verbascoside and purpureaside C did not decrease significantly. Therefore， it was hypothesized that purpureaside C was produced from its upstream component. ConclusionThe juice prepared by crushing fresh Rehmanniae Radix has the chemical composition significantly different from the juice samples prepared with the other 3 methods， while the latter 3 juice samples had similar chemical composition. Although all the four methods can be used， it is more suitable to prepare Rehmanniae Radix juice by steaming fresh Rehmanniae Radix， boiling fresh Rehmanniae Radix， and boiling dry Rehmanniae Radix.