Research progress of nitrobenzoyl sesquiterpenoids as marine characteristic natural products / 药学学报

Sesquiterpenoids are widely found in nature, while nitrobenzoyl sesquiterpenoids are relatively rare. Twelve natural nitrobenzoyl sesquiterpenoids were all derived from marine Aspergillus fungi, which are typical natural products with marine characteristics. These natural products exhibit good antitumor, antiviral, and inhibition of osteoclast differentiation activity, especially in the treatment of osteoclast-related diseases, showing good medicinal development value. This article reviews the natural product sources, chemical structure, chemical synthesis, biosynthesis, bioactivity, and pharmacological mechanisms of nitrobenzoyl sesquiterpenoids and predicts and discusses their absorption, distribution, metabolism, excretion, toxicity (ADME/T), and drug-likeness, providing a comprehensive understanding of the natural products of nitrobenzoyl sesquiterpenoids from marine sources and their potential for pharmaceutical development.

Effects of Zishen Yutai Pills on in vitro Fertilization-Embryo Transfer Outcomes in Patients with Diminished Ovarian Reserve: A Prospective, Open-Labeled, Randomized and Controlled Study / 中国结合医学杂志

OBJECTIVE@#To explore the effects of Zishen Yutai Pills (ZYPs) on the quality of oocytes and embryos, as well as pregnancy outcomes in patients with diminished ovarian reserve (DOR) receiving in vitro fertilization-embryo transfer (IVF-ET). The possible mechanisms, involving the regulation of bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9), were also investigated.@*METHODS@#A total of 120 patients with DOR who underwent their IVF-ET cycle were randomly allocated to 2 groups in a 1:1 ratio. The patients in the treatment group (60 cases) received ZYPs from the mid-luteal phase of the former menstrual cycle by using gonadotropin-releasing hormone (GnRH) antagonist protocol. The patients in the control group (60 cases) received the same protocol but without ZYPs. The primary outcomes were the number of oocytes retrieved and high-quality embryos. Secondary outcomes included other oocyte or embryo indices as well as pregnancy outcomes. Adverse events were assessed by comparison of the incidence of ectopic pregnancy, pregnancy complications, pregnancy loss, and preterm birth. Contents of BMP15 and GDF9 in the follicle fluids (FF) were also quantified with enzyme-linked immunosorbent assay.@*RESULTS@#Compared with the control group, the numbers of oocytes retrieved and high-quality embryos were significantly increased in the ZYPs group (both P<0.05). After treatment with ZYPs, a significant regulation of serum sex hormones was observed, including progesterone and estradiol. Both hormones were up-regulated compared with the control group (P=0.014 and 0.008), respectively. No significant differences were observed with regard to pregnancy outcomes including implantation rates, biochemical pregnancy rates, clinical pregnancy rates, live birth rates, and pregnancy loss rates (all P>0.05). The administration of ZYPs did not increase the incidence of adverse events. The expressions of BMP15 and GDF9 in the ZYPs group were significantly up-regulated compared with the control group (both P<0.05).@*CONCLUSIONS@#ZYPs exhibited beneficial effects in DOR patients undergoing IVF-ET, resulting in increments of oocytes and embryos, and up-regulation of BMP15 and GDF9 expressions in the FF. However, the effects of ZYPs on pregnancy outcomes should be assessed in clinical trials with larger sample sizes (Trial reqistration No. ChiCTR2100048441).

Clinicopathological features and prognostic factors of patients with lung metastasis of stage Ⅰa~Ⅲb cervical cancer / 中华肿瘤杂志

Objective: To investigate the clinicopathological features and prognostic factors of lung metastasis in patients with cervical cancer after treatment. Methods: The clinicopathological data of 191 patients with lung metastasis of stage Ⅰa-Ⅲb cervical cancer (FIGO 2009 stage) treated in Sichuan Cancer Hospital from January 2007 to December 2020 were analyzed retrospectively. Kaplan Meier method and Log rank test were used for survival analysis, and Cox regression model was used for prognostic factors analysis. Results: Among 191 patients with lung metastasis of cervical cancer, pulmonary metastasis was found in 134 patients (70.2%) during follow-up examination, and 57 patients (29.8%) had clinical symptoms (cough, chest pain, shortness of breath, hemoptysis, and fever). The time from the initial treatment of cervical cancer to the discovery of lung metastasis was 1-144 months in the whole group, with a median time of 19 months. Univariate analysis of the prognosis of lung metastasis after treatment of cervical cancer showed that the diameter of cervical tumor, lymph node metastasis, positive surgical margin, disease-free interval after treatment of cervical cancer, whether it is accompanied by other metastasis, the number, location and maximum diameter of lung metastasis, and the treatment method after lung metastasis are related to the prognosis of patients with lung metastasis of cervical cancer. Multivariate analysis showed that the number of lung metastases and other site metastases in addition to lung metastases were independent factors affecting the prognosis of patients with lung metastases of cervical cancer (P<0.05). Conclusions: For patients with cervical cancer, attention should be paid to chest CT examination during follow-up to guard against the possibility of lung metastasis after treatment. Besides lung metastasis, other site metastasis and the number of lung metastasis are independent factors affecting the prognosis of patients with lung metastasis of cervical cancer. For patients with lung metastasis after treatment of cervical cancer, surgical treatment is an effective treatment. It is necessary to strictly grasp the surgical indications, and some patients can achieve long-term survival. For patients with lung metastasis of cervical cancer who are not suitable for resection of lung metastasis, the remedial treatment of chemotherapy with or without radiotherapy is still a recommended choice.

Current status of diagnosis and treatment of chronic lymphocytic leukemia in China: A national multicenter survey research / 中华血液学杂志

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.

Multi-disciplinary open comprehensive training program in improving the post competency of medical imaging students / 中华医学教育探索杂志

Objective:To evaluate the teaching effect of multi-disciplinary integrated training program on the open comprehensive training room to improve the post competency of medical imaging students.Methods:A total of 122 residential students of five-year medical imaging from Batch 2014 of The First Affiliated Hospital of Chengdu Medical College were divided into experimental group and control group. The experimental group carried out the multi-disciplinary open comprehensive training program, and the control group carried out open-ended exercises. The comprehensive discipline theory examination, assessment of clinical thinking and comprehensive skill appraisal, and satisfaction questionnaire results were compared between the two groups. SPSS 23.0 was used for t test. Results:①Comprehensive discipline theory examination scores were higher in experimental group than the control group [(80.33±3.70) vs. (74.56±5.09)], with statistical differences ( P<0.05). ②Experimental group scored higher in clinical thinking and comprehensive skills than the control group did, and the difference was statistically significant [(87.58±3.15) vs. (74.52±3.66), P<0.05]. ③The questionnaire investigation showed that the experimental group students did better in improving autonomous learning ability, expression ability, the team cooperation ability, the ability to find and fix problems and the degree of self-esteem than control group, with statistically significant differences ( P<0.05). Conclusion:The multi-disciplinary open comprehensive training program has a good effect on optimizing the open-ended exercises. Students' knowledge of multi-disciplinary comprehensive theoretical knowledge and imaging skills have been improved, and the ability of teamwork, problem-solving ability, self-learning ability and innovation ability required by the core competence of the profession have been developed and improved, which meets the modern medical treatment of education "to create an educational platform of medical education collaboration and multi-disciplinary integration, and to cultivate students' innovative and autonomous learning."

Clinical research progress on drugs for non-alcoholic steatohepatitis treatment / 药学学报

Nonalcoholic steatohepatitis (NASH) is the leading chronic liver disease worldwide. NASH is commonly associated with metabolic risk factors, including obesity, hypertension, and diabetes. Hepatic glucose and lipid metabolism disorder, bile acid toxicity, oxidative stress, inflammation, fibrosis, intestinal dysbacteriosis, and susceptibility gene variation are involved in the pathogenesis of NASH. Drug development for NASH has been slow, this article focuses on the clinical research and development of several promising NASH drugs and their mechanisms, such as drugs targeting gut-liver axis, improving metabolism, inhibiting inflammation and fibrosis.

Effects of the national centralized drug procurement policy on drug availability and the structure of hospital drug use / 中国药房

OBJECTIVE To analyze the effects of the national centralized drug procurement （NCDP） policy on drug availability and the structure of drug use in public hospitals. METHODS Using hypoglycemic， lipid-lowering， antiviral drugs， and psychiatric drugs for the treatment of mental illness and depression as objects， the interrupted time series model was used to quantitatively evaluate the changes in consumption sum of drugs， consumption amount and daily cost of the target drugs in national sample hospitals as well as the changes in per capita medication frequency， outpatient prescription amount， and medical insurance surplus of target drugs in a third grade class A hospital before and after the implementation of NCDP policy. RESULTS After the implementation of the NCDP policy， the volume for the four bid-winning drugs increased significantly （P＜0.01 for the remaining three categories except for hypoglycemic drugs）， but DDDc （P＜0.01） and the amount of related drugs （P＜0.001） decreased significantly. The volume for the non-winning drugs （except for lipid-lowering drugs） decreased significantly （P＜0.05）， and DDDc also decreased significantly （P＜0.05 for other 3 categories except for psychiatric drugs）； the volume （P＜0.01） and DDDc （P＜0.01 only for psychiatric drugs） for alternative drugs all increased except for antiviral drugs. The structure of drug use for different drugs was affected differently by the NCDP policy，and that of hypoglycemic drugs was affected obviously； the proportion of alternative drugs increased after centralized procurement. The outpatient prescription amount of each hospital significantly decreased after centralized procurement，and the decrease in the cost paid by the patients using lipid-lowering and antiviral drugs related to centralized procurement was greater than 0.60； the remaining medical insurance amount for bid-winning drugs was approximately 1.252 5 million yuan. CONCLUSIONS NCDP policy effectively alleviates the burden of medical expenditure and also drives the structure changes of drug use such as the substitution of generic drugs for original drugs， the growth of the volume of alternative drugs.

Research progress of biomimetic nano drug delivery system in nervous system disease / 药学学报

Brain delivery of drugs remains challenging due to the presence of the blood-brain barrier (BBB). With advances in nanotechnology and biotechnology, new possibilities for brain-targeted drug delivery have emerged. Biomimetic nano drug delivery systems with high brain-targeting and BBB-penetrating capabilities, along with good biocompatibility and safety, can enable 'invisible' drug delivery. In this review, five different types of biomimetic strategies are presented and their research progress in central nervous system disorders is reviewed. Finally, the challenges and future prospects for biomimetic nano drug delivery systems in intracerebral drug delivery are summarized.

Anti-aging and mechanism of 2-O-cinnamic acid magnolol / 药学学报

Magnolol, a hydroquinone containing an allyl side chain, is one of the major active components of magnolia for antioxidation and anti-aging. To enhance the anti-aging activity and improve the intramolecular hydrogen bonding of magnolol, magnolol was reacted with cinnamic acid to obtain 2-O-cinnamic acid magnolol by esterification. The anti-aging activity of magnolol 2-O-cinnamate was investigated based on Caenorhabditis elegans model. The results showed that 2-O-cinnamic acid magnolol can reduce lipofuscin accumulation in the nematode body, and the effect is better than that of magnolol. 2-O-Cinnamic acid magnolol can extend nematode lifespan, reduce ROS levels in nematodes during normal aging and oxidative stress and improve nematode stress resistance under heat stress and oxidative stress. 2-O-Cinnamic acid magnolol could induce DAF-16 translocation from the cytoplasm to the nucleus and upregulate the expression of the sod-3 gene encoding superoxide dismutase in the nematode TJ356 expressing DAF-16 fused with GFP. 2-O-Cinnamic acid magnolol did not improve the survival rate of hsp-16.2 gene deficient nematodes under oxidative stress, indicating that 2-O-cinnamic acid magnolol improves stress resistance of nematodes under oxidative stress may be associated with sod-3 and hsp-16.2. Moreover, 2-O-cinnamic acid magnolol did not extend the lifespan of daf-16 and age-1 mutants, indicating that age-1 and daf-16 are required for 2-O-cinnamic acid magnolol to delay aging. It showed that magnolol 2-O-cinnamic acid has the potential to improve antioxidant capacity and delay aging, and the mechanism may be related to the insulin/insulin-like growth factor signaling pathway.

Colonoscopy follow-up in patients with simultaneous multiple primary colorectal cancer and patients with sporadic colorectal cancer: a matched-pair study / 中华消化杂志

Objective:To investigate the incidences of metachronous advanced adenoma (MAA) in patients with simultaneous multiple primary colorectal cancer (CRC) and patients with sporadic CRC.Methods:From January 1, 2008 to September 30, 2022, at Beijing Shijitan Hospital, Capital Medical University, CRC patients who underwent surgery and 3 years follow-up with endoscopy were enrolled. The patients completed colonoscopy at least 2 times during follow-up in 6 to 36 months after surgery, and the interval between the 2 times colonoscopies was over 6 months. Clinical data including age, gender, and tumor location, stage, pathological features, combined underlying diseases, preoperative carcinoembryonic antigen, hemoglobin and other laboratory results, baseline colonoscopy results, and detection of MAA were collected. According to age (±2 years old), gender, location of primary lesion and stage of tumor, patients with simultaneous CRC or sporadic CRC were matched at 1∶1 ratio by propensity score matching. The cumulative risks of MAA in patients with simultaneous multiple primary CRC and patients with sporadic CRC were calculated. Cox proportional hazard regression was used to analyze the influencing factors in the occurrence of MAA.Results:A total of 814 CRC patients were enrolled and matched. After paired matching, there were 36 cases of simultaneous multiple primary CRC (78 lesions) and 78 cases of sporadic CRC (78 lesions). The cumulative incidences of MAA at 1, 2 and 3 years of simultaneous CRC group were 11.1%(4/36), 22.2%(8/36) and 33.3%(12/36), respectively. The cumulative incidences of MAA at 1-, 2- and 3-year of sporadic CRC group were 3.8%(3/78), 12.8%(10/78) and 20.5%(16/78), respectively.Simultaneous CRC was correlated with an increase in the 3-year cumulative incidence of MAA ( HR=4.163, 95% confidence interval(95% CI) 1.032 to 4.721, P=0.047). Especially in left-sided CRC, the risk of MAA in simultaneous CRC increased ( HR=7.186, 95% CI 1.602 to 20.787, P=0.010). The results of multivariate cox-regression analysis indicated that detection of simultaneous advanced adenoma at baseline endoscopy was an independent risk factor of MAA ( HR=3.175, 95% CI 1.411 to 7.142, P=0.005). Conclusion:Colouoscopy follow-up should be strengthened in patients with simultaneous multiple primary CRC and simultaneous advanced adenomas.

Treatment strategy of calciphylaxis in dialysis patients / 中华肾脏病杂志

Calciphylaxis is a vascular disease caused by a combination of multiple factors, and the calcified ischemic lesion results in the severe skin damage accompanied by unbearable pain. Calciphylaxis tends to occur in patients with end-stage renal disease, and the treatment of this disease faces enormous challenges. Current treatment recommendations are mainly based on clinical experience and observational research reports, and there is still a lack of clinical practice standards or consensus for managing calciphylaxis. Therefore, this paper will review the effective treatment methods and off-label use of calciphylaxis based on literature reports, providing reference for the clinical treatment of the disease.

Clinical features of POEMS syndrome initially diagnosed as pulmonary hypertension / 中华全科医师杂志

Objective:To analyze the clinical characteristics, diagnosis and treatments of patients with POEMS syndrome initially diagnosed as pulmonary hypertension (PH).Methods:Clinical data of 7 patients who were initially diagnosed as PH and finally diagnosed as POEMS syndrome in Shanghai Pulmonary Hospital from May 2013 to November 2021 were retrospectively reviewed. Clinical manifestations, laboratory tests, echocardiography, hemodynamic findings, treatment and prognosis of patients were analyzed.Results:Seven patients, including 4 males and 3 female, aged (55±9) (44-62) years were presented with elevated pulmonary artery pressure by echocardiography at admission. Chest tightness and shortness of breath (7/7), fatigue (6/7) and lower limb edema (4/7) were the most common symptoms in the first-episode. Meanwhile, patients also presented symptoms associated with POEMS syndrome, including multiple peripheral neuropathy (7/7), multiserosal cavity effusion (6/7), organomegaly (5/7), skin changes (5/7), and endocrine lesions (4/7). Serum levels of vascular endothelial growth factor (VEGF) were significantly increased in all patients. The pulmonary arterial systolic blood pressure was (66±21)mmHg (1 mmHg=0.133 kPa) estimated by echocardiography. Six patients underwent right heart catheterization and significantly increased mean pulmonary artery pressure((35±9) mmHg) was confirmed; and their pulmonary vascular resistance was (4.00±2.10) Wood U. All patients received corresponding treatment for POEMS syndrome. The excise tolerance was improved in 5 patients after successful treatment with stable or reversed WHO functional class. One patient received hemodialysis treatment for uncontrolled POEMS. One patient died during follow-up. The echocardiography was followed up in 4 patients, and 2 of whom had a complete reversal of PH, 1 had a partial reversal, and 1 had not yet reversed.Conclusions:In patients with PH who have multisystem manifestations, such as multiple peripheral neuropathy, multiserosal cavity effusion, organomegaly and skin changes, POEMS syndrome should be considered, and proper and active treatment of POEMS may reverse PH and improve the prognosis of patients.

Risk assessment of dietary lead exposure in Shanghai residents over 15 years old / 上海预防医学

ObjectiveTo investigate the risk of dietary lead exposure in residents aged 15 years and above in Shanghai. MethodsBased on the dietary consumption survey of residents aged 15 years and above in spring 2012 and the monitoring data of food lead contamination in Shanghai from 2020 to 2021， the dietary exposure level was assessed using the point assessment method and compared with the provisional weekly tolerable intake （PTWI） to assess the exposure risk. ResultsThe overall detection rate of lead in 9 commonly consumed food categories by residents in Shanghai was 56.82%， with a total excess rate of 0.23%. The average weekly dietary lead exposure （by body weight） of residents was 2.979 4 μg·kg⁻¹. The top three dietary lead contributing factors were vegetables （30.69%）， cereals （28.88%）， and aquatic products （11.12%）. The average weekly dietary lead exposure （by body weight） of residents in urban， suburban， and rural areas were 3.282 5， 2.979 5 and 2.478 0 μg·kg⁻¹， respectively. The food with the highest contribution rate of dietary lead exposure in these regions was vegetables， with contribution rates of 33.65%， 29.69%， and 25.22%， respectively. The average weekly dietary lead exposure （by body weight） of male and female residents was 3.077 7 and 2.881 5 μg·kg⁻¹， respectively， with vegetables being the main source of dietary lead， contributing 30.03% and 31.39%， respectively. The average weekly dietary lead exposure （by body weight） of residents aged 15‒， 45‒， and ≥60 years old was 3.084 2，3.009 9 and 2.874 4 μg·kg⁻¹， respectively. The food with the highest contribution rate of dietary lead exposure in these groups was vegetables， contributing 27.12%， 32.10%， and 32.26%， respectively. ConclusionThe dietary lead exposure of Shanghai residents aged 15 years and above is at an acceptable level， and the vegetables， cereals， and aquatic products with high contribution rates need to be supervised more closely.

Preparation and evaluation of sirolimus sustained release tablets based on mesoporous silicon loaded self-microemulsion / 药学学报

Sirolimus self-microemulsion-mesoporous silicon sustained release tablets were prepared in order to improve the dissolution of the insoluble drug sirolimus and reduce its side effects. Firstly, sirolimus self-microemulsion was prepared and cured with mesoporous silicon. Secondly, the suitable excipients were selected according to the appearance, hardness and in vitro release rate. The sustained-release tablets with hydroxypropyl methylcellulose (HPMC) as skeleton material were prepared by powder direct pressing method, and the formulation was optimized by central composite design-response surface method to investigate the drug release in vitro. Finally, the pharmacokinetics was carried out in beagle dogs using the commercial sirolimus tablets as references. The final formulation of sustained-release tablets is as follows: 162 mg of sirolimus self-microemulsion-mesoporous silica (1∶1, w/w), 80 mg of HPMC K4M and 80 mg of carboxymethyl starch sodium, the microcrystalline cellulose is 168 mg. The results of in vitro release test showed that the self-made sustained-release tablets released slowly within 12 h, which conformed to the Ritger-Peppas model. The in vivo test results showed that compared with the commercial sirolimus tablets, the Cmax of the sustained-release tablets decreased by 49.47%, the Tmax of the sustained-release tablets was prolonged by 5.1 times, and the relative bioavailability was 105.81%. Sirolimus self-microemulsion-mesoporous silicon sustained-release tablets have good sustained-release effects in vitro and in vivo, which provides a reference for the solubilization of other insoluble drugs and the research and development of sustained-release preparations. Animal experiments and welfare processes were reviewed and approved by the Animal Ethics Committee of the 900TH Hospital of the Joint Logistics support Force.

Risk assessment of dietary exposure to 3-monochloropropane-1,2-diol esters in infant formula powders in Shanghai / 环境与职业医学

Background Chloropropanol esters (MCPDE) have attracted much attention in recent years as a kind of new contaminant found in various refined oils. The pollution of 3-monochloropropane-1,2-diol esters (3-MCPDE) is the most prominent. 3-MCPDE is hydrolyzed in organisms to 3-monochloropropane-1,2-diol which has been shown to have reproductive toxicity, nephrotoxicity, and potential carcinogenicity. Infant formula powders can be polluted by 3-MCPDE when refined edible oils are added during production. Objective To assess the risk of exposure to 3-MCPDE related to the consumption of infant formula powders for children aged 0-3 years in Shanghai market using the food consumption data and the data of 3-MCPDE contamination in these foods. Methods Gas chromatography-mass spectrometry was used to determine 3-MCPDE in 133 samples of infant formula powders in Shanghai. Using a multistage stratified random sampling method, a total of 807 infants and toddlers aged 0-3 years were randomly selected from each district/rural/town in Shanghai, including 208 children aged 0-6 months, 276 children aged 6-12 months, and 323 children aged 12-36 months. The food consumption data was investigated using food frequency questionnaire (FFQ) distributed by combining telephone inquiries and face-to-face interviews among guardians. Population's probability distributions of 3-MCPDE exposure were assessed by @Risk 7.5 software and Monte Carlo simulation algorithm. According to the dietary intake assessment model and the tolerable daily intake (TDI) of 3-MCPDE of 2.00 μg·(kg·d)−1 proposed by the European Food Safety Authority (ESFA), a risk assessment of exposure to 3-MCPDE was conducted for infants and toddlers aged 0 to 3 years old in Shanghai who consumed 3-MCPDE via infant formula powders. Results The average concentration of 3-MCPDE in 133 samples of infant formula powders was 0.115 mg·kg−1 with a positive rate of 100.00%. Among different types of formula powders, infant formula powders for infants of 0-6 months had the highest concentrations of 3-MCPDE and fat [0.136 mg·kg−1 and 25.2 g (per 100 g sample) in average respectively]. There was a positive correlation between fat concentration and 3-MCPDE concentration in the samples (r=0.438, P<0.05). The average consumption of infant formula powders of 807 infants aged 0-3 years was 88.3 g·d−1. Among all investigated age groups, the average consumption of infant formula powders by infants aged 0-6, 6-12, and 12-36 months was 87.7, 98.3, and 80.1 g·d−1 respectively. The dietary exposure to 3-MCPDE from infant formula powders of infants aged 0-3 years averaged 0.83 μg·(kg·d)−1 for general intake level or valued 1.44 μg·(kg·d)−1 using the 95 percentile for high intake level. Exposure decreased with increasing age and was highest in infants 0-6 months of age, whose general and high intake levels were 1.41 and 2.34 μg·(kg·d)−1, respectively. The risk population defined with the exposure higher than the TDI proposed by EFSA were proportioned to be 13.90% and 0.50% in infants aged 0-6 months and 6-12 months respectively, indicating a risk that cannot be ignored, and no risk in infants aged 12-36 months. Conclusion Among the investigated infants aged 0-3 years in Shanghai, those aged 0-6 months are at a high risk of exposure to 3-MCPDE. In view of the sensitivity of infants to pollutant exposure, the risk of exposure to 3-MCPDE should be highly concerned.

Epidemiologic and etiologic characteristics of foodborne diseases in Minhang， Shanghai 2016‒2020 / 上海预防医学

ObjectiveTo learn the epidemiological features of foodborne diseases， and to provide scientific basis for disease control. MethodsThe monitoring data of foodborne diseases in Minhang from 2016 to 2020 were analyzed. Stool or swab specimens were collected to detect salmonella， Vibrio parahaemolyticus， Escherichia coli， Shigella， Campylobacter jejuni and norovirus. ResultsThe information of15 951 foodborne disease cases and 11 176 samples were collected， with the positive rate of 12.03%.The cases with diarrhea accounted for 99.90% of the total. The cases with fever accounted for 14.70% of the total. The cases with water stool accounted for 89.70% of the total. May to October were the epidemic periods of foodborne diseases in Minhang（79.78%）. The detection rate was the highest in the 30‒39 age group and cadre staff occupation（13.53%，13.49%）. The detection rates of foodborne bacteria and virus were 5.39% （Vibrio parahaemolyticus）， 3.25% （salmonella），1.44% （norovirus）， 1.06%（Escherichia coli）， 0.56% （Campylobacter jejuni）， 0.34% （mixed infection） and 0% （Shigella）. During this 5-year period， the positive rate of Vibrio parahaemolyticus decreased significantly， while the positive rate of salmonella and Escherichia coli and Campylobacter jejuni increased significantly. The main suspected food were aquatic products （29.44%）， meat （25.80%） and fruits （10.78%）. The main processing methods of suspected food were family workshop （41.12%） and restaurants （37.55%）. The total detection rate of the cases was the highest in the canteen， reaching 20.51%. ConclusionFoodborne disease cases have a seasonal peak. The positive detection of pathogens tends to be similar year by year. The main suspected food is aquatic products. The main resources of suspected food are family workshop， restaurants， and canteen. Targeted health education， supervision and management should be taken to prevent the occurrence of foodborne diseases and the outbreak of food poisoning

Value of different Baveno Ⅶ-based criteria in screening for high-risk esophageal and gastric varices in advanced chronic liver disease / 临床肝胆病杂志

Objective To investigate the value of Baveno Ⅶ criteria versus Expanded Baveno Ⅶ criteria in screening for high-risk varices (HRV) in patients with compensated advanced chronic liver disease (cACLD). Methods A total of 146 patients with cACLD who were admitted to Beijing Shijitan Hospital, Capital Medical University, from January 2016 to December 2018 were enrolled, and according to the absence or presence of HRV based on gastroscopy, they were divided into HRV group with 68 patients and control group with 78 patients. Clinical data, liver stiffness measurement (LSM), and gastroscopy findings were analyzed, and different Baveno Ⅶ criteria were analyzed in terms of their sensitivity and specificity in the diagnosis of HRV. The Mann-Whitney U test and the McNemar test were used for comparison of continuous data between groups, and the chi-square test was used for comparison of categorical data between groups. A univariate logistic regression analysis was performed for the variables used to predict HRV, and a multivariate analysis was performed for the variables with P 20 kPa or PLT 25 kPa or PLT < 110×10 9 /L was associated with HRV (both P < 0.05). LSM and PLT had an area under the ROC curve of 0.797 (95% confidence interval [ CI ]: 0.723-0.859) and 0.789 (95% CI : 0.714-0.852), respectively, in the diagnosis of HRV. There were significant differences in the prevalence rates of esophageal and gastric varices and HRV between the patients who met Baveno Ⅶ criteria and those who did not meet such criteria ( χ 2 =23.14 and 23.14, both P < 0.001), as well as between the patients who met Expanded Baveno Ⅶ criteria and those who did not meet such criteria ( χ 2 =43.51 and 25.71, both P < 0.001). Although a higher proportion of patients were exempted from gastroscopy based on Expanded Baveno Ⅶ criteria (32.9% vs 13.7%), Baveno Ⅶ criteria had higher sensitivity (0.98 vs 0.88) and negative predictive value (0.95 vs 0.83) and could better avoid the missed diagnosis of HRV (1.0% vs 9.3%). Conclusion Baveno Ⅶ criteria are more suitable for the screening for HRV in cACLD patients in China.

Inhibitory effect of blue light intervention on lens-induced myopia development in guinea pigs and the mechanism of cone density change / 中华实验眼科杂志

Objective:To observe the effects of blue light intervention on the development of optical defocus-induced myopia in guinea pigs and investigate its underlying mechanisms.Methods:Forty-eight normal-grade two-week-old tricolor guinea pigs were randomly divided into a blue light group and a white light group, with 24 animals in each group.The right eye of guinea pigs was fitted with a -5.00 D lens to establish an optical defocus model as the experimental eye, while the left eye served as the control without any covering.Before the experiment and after 8-week intervention, the refractive power of guinea pigs was measured by streak retinoscopy.The anterior chamber depth, lens thickness, and axial length were measured by A-scan ultrasonography.Corneal curvature radius was determined using a keratometer.After 8-week intervention, the guinea pigs were euthanized through overanesthesia, and the right eyeballs were enucleated and the retinas were isolated.The density of S and M cone cells of the guinea pig retinal sections were observed via immunofluorescence staining.The expression of retinal retinoic acid was assessed by high-performance liquid chromatography.The expressions of retinoic acid receptor (RAR-β) in the retina and matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), and type Ⅰ collagen in the sclera were detected by real-time fluorescence quantitative PCR.Changes in scleral thickness were observed through hematoxylin-eosin staining.The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission.The study protocol was approved by the Ethics Committee of Eye and ENT Hospital of Fudan University (No.2022ETKLD10032).Results:After 8 weeks of intervention, guinea pigs in the blue light group showed (0.63±0.12)D of relative hyperopia and a deceleration of axial elongation by (0.08±0.00)mm compared with the white light group in the right eye.In the left eye, guinea pigs in the blue light group showed (0.42±0.09)D of relative hyperopia and a deceleration of axial elongation by (0.08±0.00)mm compared with the white light group.The guinea pigs in blue light group showed (1.52±0.09)D of myopia in the right eye compared with the left eye, with an increase in axial elongation of (0.06±0.00)mm.The guinea pigs in white light group showed (1.66±0.07)D of myopia in the right eye compared with the left eye, with an increase in axial elongation of (0.13±0.00)mm, and the differences were statistically significant (all at P<0.05). The density of M cone cells was lower and density of S cone cells was higher in the blue light group in the dorsal and ventral sides of the retinal sections compared with the white light group, showing statistically significant differences ( t=32.33, 52.23, 42.09, 25.02; all at P<0.05). The deceleration of myopia progression in the blue light group was strongly positively correlated with the increase in S cone cell density on the ventral side ( r=0.95, P<0.01). The expression levels of retinoic acid, RAR-β, and MMP-2 were decreased, and expression levels of TIMP-2 and type Ⅰ collagen were increased in blue light group compared with the white light group, showing statistically significant differences ( t=18.73, 7.45, 3.72, 6.19, 9.03; all at P<0.05). The scleral thickness in the blue light group was (125.0±7.8)μm, which was significantly thicker than (102.0±6.3)μm in the white light group ( t=26.93, P<0.05). Conclusions:Blue light intervention can inhibit the progression of defocus-induced myopia in guinea pigs.Refractive power changes in guinea pigs may be influenced by alterations in retinal cone cell density, retinoic acid expression, and scleral collagen expression.

Detection of aqueous humor cytokines in diabetic retinopathy and its clinical significance / 中华实验眼科杂志

Objective:To detect the concentration of various cytokines in aqueous humor of patients with diabetes retinopathy (DR) with Luminex liquid chip, and analyze the relationship between the cytokines and the occurrence and development of DR.Methods:A cross-sectional study was conducted.Sixty-three DR patients (97 eyes) treated with anti-vascular endothelial growth factor (VEGF) drugs in the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine from March 1, 2019 to December 31, 2019 were enrolled as DR group, including 38 nonproliferative DR (NPDR) eyes in NPDR group and 59 proliferative DR (PDR) eyes in PDR group, 39 eyes in photocoagulation group and 58 eyes in non-photocoagulation group.Twenty-seven patients (31 eyes) hospitalized for cataract surgery at the same time were collected as the control group.Aqueous humor was extracted during the operation, and Luminex liquid chip was used to detect the concentrations of vascular endothelial growth factor-A (VEGF-A), placental growth factor (PLGF), platelet-derived growth factor (PDGF)-AA, PDGF-BB, angiopoietin-like protein 4 (ANGPTL4), interleukin-6 (IL-6), IL-8, IL-1β, monocyte chemotactic protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α) in aqueous humor.The concentrations of various cytokines of different groups were compared, and the correlation among various aqueous humor cytokines was analyzed by Spearman rank correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of First Affiliated Hospital of Guangzhou University of Chinese Medicine (No.Y[2019]230). Written informed consent was obtained from each patient.Results:The concentrations of VEGF-A, PLGF, PDGF-AA, ANGPTL4, IL-6, IL-8, MCP-1 and ICAM-1 in DR group were significantly higher and the concentration of IL-1β was significantly lower than those of control group ( Z=-4.747, -5.164, -3.373, -8.062, -4.535, -5.954, -5.098, -3.228, -5.954, all at P<0.01). The concentrations of VEGF-A, PLGF, PDGF-AA, ANGPTL4, IL-6, IL-8 and MCP-1 of the photocoagulation and non-photocoagulation groups were higher and the concentration of IL-1β was significantly lower than those in the control group (all at P<0.017). The concentration of ICAM-1 in the photocoagulation group was significantly higher than that in the control group ( P<0.017). The concentrations of PLGF, PDGF-AA and ANGPTL4 of PDR group were higher than those of NPDR group, and the differences were statistically significant ( Z=-2.291, -3.396, -2.276, all at P<0.05). VEGF-A was positively correlated with the other cytokines except ICAM-1 ( rs=0.237-0.540, all at P<0.05). ANGPTL4 was positively correlated with the other cytokines except IL-1β ( rs=0.361-0.733, all at P<0.01). Conclusions:The occurrence and development of DR are closely related to VEGF family, PDGF family, ANGPTL family and inflammatory factors.The concentrations of PLGF, PDGF-AA and ANGPTL4 are higher in PDR eyes.There are close and complex relationships among a variety of cytokines in the eyes of DR patients.

Normative wideband absorbance measures in children: a cross-sectional study / 中华耳鼻咽喉头颈外科杂志

Objective: This study was to investigate the main characteristics and related factors of wideband absorbance (WBA) in children with normal hearing and to obtain age-specific reference range of WBA. Methods: 384 children between 0-12 years old (615 ears) who visited the Beijing Children's Hospital, Capital Medical University from October 2019 to February 2021 were enrolled, including 230 males (376 ears) and 154 females (239 ears), with totally 306 left ears and 309 right ears. Wideband tympanometry (WBT) was performed and normative WBA data were analyzed by SPSS 24.0 statistical software. Repeated measures and multivariate analysis of variance were applied to the data from 16 points at 1/3-octave frequencies (226, 324, 408, 500, 667, 841, 1 000, 1 297, 1 682, 2 000, 2 670, 3 364, 4 000, 5 339, 6 727 and 8 000 Hz) to evaluate the effects of frequency, age, external auditory canal pressures, gender and ear on WBA. Results: According to the WBT frequency-absorbance curve, the subjects were divided into seven groups: 1-month old group, 2-month old group, 3-month old group, 4-5 month old group, 6-24 month old group,>2-6 year old group and>6-12 year old group. The WBA of normal-hearing children underwent a series of developmental changes with age at both ambient pressure and tympanometric peak pressures. WBA results for 1-month group and 2-month old group exhibited a multipeaked pattern, with the peaks occurring around 2 000 and 4 897 Hz, and a notch around 3 886 Hz. WBA results for 3-month group and 4-5 month old group exhibited a single broad-peaked pattern, with the peak occurring between 2 000-4 757 Hz. The WBA of 1-month old group to 4-5 month old group decreased gradually at low frequency (226-408 Hz) and 6 727 Hz, and increased at middle to high frequency (2 670-4 000 Hz). The WBA of 6-24 month old group were significantly lower than that of 2-month old group to 4-5 month old group at all frequencies except 3 364 and 4 000 Hz. WBA results for 6-24 month old group,>2-6 year old group and>6-12 year old group exhibited a single-peaked pattern, and the peak frequency of WBA moved to the lower frequency successively. From 6-24 month old group to>6-12 year old group, the WBA gradually increased at low to middle frequencies (667-2 670 Hz) and 8 000 Hz, and decreased at middle to high frequencies (3 364-5 339 Hz). Among the 16 frequencies of all age groups, the difference between WBA under ambient pressure and tympanometric peak pressure were -0.09-0.06, and 43.75%-81.25% frequency points had statistically significant difference, which was mainly manifested in that WBA under ambient pressure were lower than that under tympanometric peak pressure at 226-1 682 Hz. There was no significant ear effect on all of the age groups. Similarly, there was no significant gender effect except for 3-month old group and 4-5 month old group. Conclusions: The WBA of normal-hearing children measured at ambient pressure and tympanometric peak pressure varied across the frequencies with age from 1 month to 12 years old, and different frequencies followed different change patterns (increase vs. decrease) in WBA. There was also significant external auditory canal pressures effect on all of the age groups. The establishment of age-specific reference range of WBA for 0-12 years old normal-hearing children in this study would be useful for clinical practice of determining normative data regarding WBT.