A robust luminescent assay for screening alkyladenine DNA glycosylase inhibitors to overcome DNA repair and temozolomide drug resistance / 药物分析学报

Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical resection.However,despite its effectiveness,at least 50％of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA lesions.Studies have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine le-sions,is overexpressed in glioblastoma tissues compared to normal tissues.Therefore,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in glio-blastomas.Herein,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic methods.As a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG inhibitor.Sunitinib restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell char-acteristics,and induced GBM cell cycle arrest.Overall,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

Study on the regular pattern of "disease-syndrome-medicine" of different diseases with the same treatment for blood stasis syndrome based on complex network similarity analysis / 国际中医中药杂志

Objective:To reveal the regular pattern characteristics of different diseases with the same treatment in the most common diseases with blood stasis syndrome; To provide reference for the clinical treatment of blood stasis syndrome and the development of new drugs.Methods:RCTs of blood stasis syndrome were retrieved from CNKI, Chongqing VIP, Wanfang Data, SinoMed, and China Medical Journal Full-text Database from the establishment of the databases to December 31, 2022. Diseases, accompanied symptoms, prescriptions and medicines were extracted. The diseases with the highest frequency among the three disease systems with the highest frequency were collected, and their medication characteristics and prescription rules were analyzed using frequency statistics and association rules Apriori algorithm. The core prescriptions of blood stasis syndrome of three kinds of diseases were excavated and their network similarity was analyzed.Results:A total of 2 052 articles were included. Stable coronary heart disease, ischemic stroke and DN were more common diseases with blood stasis syndrome. The common drugs for the three diseases were Chuanxiong Rhizoma, Carthami Flos, Persicae Semen, Angelicae Sinensis Radix. The core prescription of stable coronary heart disease was Persicae Semen- Carthami Flos- Chuanxiong Rhizoma- Angelicae Sinensis Radix- Paeoniae Radix Rubra; the core prescription of ischemic stroke is Buyang Huanwu Decoction; the core prescription of DN was Persicae Semen- Carthami Flos- Chuanxiong Rhizoma- Angelicae Sinensis Radix- Cornus Officinalis- Dioscoreae Rhizoma- Astragali Radix. The similarity between stable coronary heart disease and ischemic stroke core prescription network was 0.35, the similarity between ischemic stroke and DN core prescription network was 0.29, and the similarity between stable coronary heart disease and DN core prescription network was 0.26. Conclusions:The theory of "different diseases with the same treatment" can profoundly guide clinical practice. The core medicines of blood stasis syndrome are Persicae Semen, Carthami Flos, Angelicae Sinensis Radix, and Chuanxiong Rhizoma. On this basis, combined with different diseases and syndromes to make changes of adding and subtracting.

Study on the mechanism of Kechuan'an Oral Liquid for the treatment of asthma / 国际中医中药杂志

Objective:To explore the mechanism of Kechuan'an Oral Liquid in treating asthma based on network pharmacology; To carry out experimental verification.Methods:The effective components and targets of Kechuan'an Oral Liquid were obtained through TCMSP and literature search. The related targets of asthma were screened by GEO database, and the intersection targets of drug and disease were selected. The PPI network was constructed by STRING database, and the GO function and KEGG pathway were enriched and analyzed for key targets by DAVID database. The rats were divided into blank control group, model group and Kechuan'an Oral Liquid group according to the method of random number table. Kechuan'an Oral Liquid group received Kechuan'an Oral Liquid 12.34 ml/kg for gavage, and blank control group and model group were perfused with distilled water of the same volume for gavage, once a day for 3 days. The asthma model of rats was prepared by atomizing the mixture of acetylcholine chloride and histamine phosphate, and HE staining was used to observe the pathological changes of lung tissue; Western blot was used to detect the protein expressions of IL-6, TLR4, MyD88 and TAK1, and the network pharmacological prediction results were verified.Results:A total of 153 active components, 1 896 targets and 2 982 differentially expressed genes of Kechuan'an Oral Liquid were screened out, and 25 intersection targets of drugs and diseases were obtained. The enrichment results showed that toll-like receptor signaling pathway, TNF signaling pathway and Nod-like receptor signaling pathway were the main mechanisms of immune inflammation. Compared with the control group, the lung tissue of rats in the model group showed morphological changes such as thickening of air duct wall and infiltration of inflammatory cells, which were significantly improved in the Kechuan'an Oral Liquid group. Compared with the control group, the expressions of IL-6, TLR4, MyD88 and TAK1 in the model group significantly increased ( P<0.01), and compared with model group, the expressions of IL-6, TLR4, MyD88 and TAK1 in Kechuan'an Oral Liquid group significantly decreased ( P<0.05 or P<0.01). Conclusion:Kechuan'an Oral Liquid can inhibit toll-like receptor signaling pathway and mediate anti-inflammatory effect to treat asthma.

Association of sleep duration and risk of frailty among the elderly over 80 years old in China: a prospective cohort study / 中华预防医学杂志

Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q1, Q3) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.

Tensor decomposition: new strategy for deciphering mechanism of precision medicine for same treatment of different diseases / 中国中药杂志

The aging society has led to a substantial increase in the number of clinical comorbidities. To meet the needs of comorbidity treatment, polypharmacy is widely used in clinical practice. However, polypharmacy has drawbacks such as treatment conflict. Same treatment of different diseases refers to treating different diseases with same treatment. Therefore, the principle of same treatment of different diseases can alleviate the problems caused by polypharmacy. Under the research background of precision medicine, it becomes possible to explore the mechanism of same treatment of different diseases and achieve its clinical application. However, drugs successfully developed in the past have revealed shortcomings in clinical use. To better interpret the mechanism of precision medicine for same treatment of different diseases, under the multi-dimensional attributes including dynamic space and time, omics was performed, and a new strategy of tensor decomposition was proposed. With the characteristics of complete data, tensor decomposition is advantageous in data mining and can fully grasp the connotation of precision treatment of different diseases with same treatment under dynamic spatiotemporal changes. This method is used for drug repositioning in some biocomputations. By taking advantage of the dimensionality reduction of tensor decomposition and integrating the dual influences of time and space, this study achieved accurate target prediction of same treatment of different diseases at each stage, and discovered the mechanism of precision medicine of same treatment for different diseases, providing scientific support for precision prescription and treatment of different diseases with same treatment in clinical practice. This study thus conducted preliminary exploration of the pharmacological mechanism of precision Chinese medicine treatment.

Rosuvastatin acts on the lymphatic system to improve atherosclerosis / 中华心血管病杂志

Objective: To investigate whether rosuvastatin acts on lymphatic system and influences lymphatic system-mediated reverse cholesterol transport to play an anti-atherosclerosis role. Methods: Forty-eight apolipoprotein E-/- mice fed a high fat diet were used to construct the atherosclerosis model. They were randomly divided into 4 groups with 12 rats in each group. They were treated with rosuvastatin, vascular endothelial growth factor-C (VEGF-C) and rosuvastatin+VEGF-C inhibitors as experimental group, and no intervention measures were given in control group. After 8 weeks, aortic plaque area, high density lipoprotein cholesterol (HDL-C) content in lymph fluid, the function of popliteal lymphatic drainage of peripheral Evans blue, and the ability of lymphatic system to transport peripheral cell membrane red fluorescent probes to label high-density lipoprotein (HDL) were detected. Subsequently, the effects of rosuvastatin on proliferation, migration and tubular function of lymphoendothelial cells and the expression of scavenger receptor class B type 1 (SR-B1) on lymphoendothelial cells at different concentrations were detected. Results: Compared with the control group, Rosuvastatin and VEGF-C could reduce the area of aortic atherosclerotic plaque (P<0.05). In addition to rosuvastatin plus VEGF-C inhibitor, the intra-aortic plaque area increased (P<0.05). Compared with the control group, Rosuvastatin could increase the content of HDL-C in lymphatic fluid (P<0.05), enhance the drainage function of lymphatic vessels, and enhance the capacity of HDL in the transport tissue fluid of lymphatic system. Compared with the control group, VEGF-C increased the content of HDL-C in mouse lymph fluid (P<0.01), enhanced the drainage function of popliteal lymphatic canal, and enhanced the ability of lymphatic system to transport HDL. With the addition of VEGF-C inhibitor on the basis of rosuvastatin, the content of HDL-C in lymph fluid was reduced, the drainage of popliteal lymphatic canal was interrupted, and the ability of lymphatic system to transport HDL was reduced. Western blotting showed that rosuvastatin increased the protein expression of SR-B1. Conclusion: Rosuvastatin can promote the proliferation, migration and tube formation of lymphatic endothelial cells. At the same time, SR-B1 expression on lymphatic endothelial cells is promoted, thus enhancing the lymphatic system mediated cholesterol reversal transport and playing the role of anti-atherosclerosis.

Construction of hiPSC-derived Excitatory Neural Network-like Tissue / 中山大学学报(医学科学版)

ObjectiveTo construct a neural network-like tissue with the potential of synaptic formation in vitro by seeding human induced pluripotent stem cell-derived neural precursor cells （hiPSC-NPCs） on decellularized optic nerve （DON）， so as to provide a promising approach for repair of nerve tissue injury. MethodsThrough directional induction and tissue engineering technology， human induced pluripotent stem cells （hiPSCs） and 3D DON scaffolds were combined to construct neural network-like tissues. Then the hiPSCs were directionally induced into human neural precursor cells （hNPCs） and neurons. Immunofluorescence staining was used to identify cell differentiation efficiency. 3D DON scaffolds were prepared. Morphology and cytocompatibility of scaffolds were identified by scanning electron microscopy and Tunnel staining. Induced hiPSC-NPCs were seeded on DON scaffolds. Immunofluorescence staining， scanning electron microscopy， transmission electron microscopy and patch clamp were used to observe the morphology and functional identification of constructed neural network tissues. Results①The results of immunofluorescence staining suggested that most of hiPSC-NPCs differentiated into neurons in vitro. We had successfully constructed a neural network dominated by neurons. ② The results of scanning electron microscopy and immunohistochemistry suggested that a neural network-like tissue with predominating excitatory neurons in vitro was successfully constructed. ③The results of immunohistochemical staining， transmission electron microscopy and patch clamp indicated that the neural network-like tissue had synaptic transmission function. ConclusionA neural network-like tissue mainly composed of excitatory neurons has been constructed by the combination of natural uniform-channel DON scaffold and hiPSC-NPCs， which has the function of synaptic transmission. This neural network plays a significant role in stem cell derived replacement therapy， and offers a promising prospect for repair of spinal cord injury （SCI） and other neural tissue injuries.

Associations of sugar-sweetened beverages intake frequency with physical growth and glucolipid metabolism among children and adolescents / 环境与职业医学

Background Children and adolescents drink sugar-sweetened beverages (SSBs) frequently. Research has confirmed that SSBs associate with weight gain and overweight or obesity. However, it is unclear whether high SSBs intake associates with abnormal changes in physical growth and glucolipid metabolism before causing adverse health outcomes such as overweight and obesity. Early identification of associated health risks of overconsumption of SSBs have important public health implications. Objective To investigate the differences in physical growth and glucolipid metabolism between different SSBs intake frequency groups in normal weight children and adolescents aged 6-17 years, and to evaluate the early effects of SSBs intake on physical growth and glycolipid metabolism before causing overweight and obesity, aiming to provide a scientific basis for the prevention and control of childhood overweight and obesity and related chronic diseases, and for the formulation of policies on the control of SSBs consumption. Methods Data were from the Shanghai Diet and Health Survey (SDHS) among primary and secondary school students. The participants were normal weight children and adolescents aged 6-17 years. Propensity scores were calculated according to energy intake and physical activity factors, after stratifying by age and gender. Participants were 1:1 matched with the closest propensity scores in the high-frequency (≥1 time·d−1) and the low-frequency (≤1 time·week−1) SSBs intake groups. The outcome indicators were physical measurements such as height, weight, percent of body fat, and waist circumference, and metabolic indicators such as fasting blood glucose, total triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Body mass index (BMI) was calculated. Food frequency questionnaire was used to collect SSBs consumption in the past three months through face-to-face interview. A paired t-test was used to compare the differences in physical and glycolipid metabolic indicators between the high-frequency intake group and the low-frequency intake group of SSBs. Results A total of 431 pairs were obtained. For children and adolescents in grades 6-9, overall height (difference=2.92 cm, P=0.002), weight (difference=2.53 kg, P=0.003), and waist circumference (difference=1.34 cm, P=0.035) were higher in those who consumed SSBs ≥1 time·d−1 than in those who consumed ≤1 time·week−1. For children and adolescents in grades 10-12, overall weight (difference=2.27 kg, P=0.041) was higher in those who consumed SSBs ≥1 time·d−1 than in those who consumed ≤1 time·week−1. Over 95% of the study subjects reported blood glucose and lipid test results within the normal range; but girls in grades 1-5 who consumed SSBs ≥1 time·d−1 had a higher total cholesterol (difference=0.20 mmol·L−1, P=0.027) and low-density lipoprotein cholesterol (difference=0.19 mmol·L−1, P=0.010) than those who consumed ≤1 time·week−1; boys in grades 6-9 who consumed SSBs ≥1 time·d−1 had a lower high-density lipoprotein cholesterol (difference=-0.10 mmol·L−1, P=0.039) than those who consumed ≤1 time·week−1. Conclusion High-frequency intake of SSBs may be associated with higher total cholesterol and low-density lipoprotein cholesterol in normal weight children and adolescents in grades 1-5, and higher weight in normal weight children and adolescents in grades 6-12. There is an urgent need to educate children and adolescents about nutritional health, enhance their ability to make healthy food and beverage choices, and take early interventions to control the intake of SSBs in children.

Nutrient content of 122 kinds of retail handcrafted milk tea products in Shanghai / 环境与职业医学

Background The retail milk tea industry is in a period of rapid development, but there is little research on its nutrient content, which restricts the nutritional guidance of milk tea. Objective To determine the levels of nutrients in best-selling handcrafted milk tea in Shanghai and analyze the nutritional characteristics. Methods In 2018 and 2021, a total of 13 handcrafted milk tea brands with ≥3 branch stores in Shanghai were selected by searching for milk tea on Meituan and Ele.me food delivery platforms, and a total of 122 types of handcrafted milk tea products were collected from the top three sales [milk tea (including all sweetness levels available), milk cover tea, and fruit tea]. National standard methods were used to detect energy, protein, fat, carbohydrate, sugar, trans fatty acid, calcium, caffeine, and tea polyphenol. Results The median energy of the milk tea samples was 310 kJ (per 100 g sample). The main sources of energy were carbohydrate and fat. The levels of energy, protein, and fat in milk cover tea and milk tea were significantly higher than those in fruit tea (P＜0.05), and there was no significant difference in carbohydrate among them. The total sugar, fructose, and glucose levels in milk tea were significantly lower than those in milk cover tea and fruit tea, and the lactose level in fruit tea was significantly lower than those in milk tea and milk cover tea (P＜0.05). Themedian trans fat acid level in milk cover tea was higher than that in milk tea (P＜0.05). The median levels of caffeine and tea polyphenol were higher in milk tea than in milk cover tea (P＜0.05). The levels of energy, carbohydrate, sucrose, total sugar, and calcium in milk tea were positively correlated with the number of ingredients added (0-3) (r=0.386, 0.371, 0.238, 0.698, 0.466, respectively, P < 0.05). The levels of energy, carbohydrate, and total sugar tended to increase with increasing sweetness (P<0.05), and total sugar was mainly sucrose, followed by fructose and glucose. The total sugar levels of the samples labeled sugar free, light sugar, half sugar, less sugar, and regular sugar were 3.40 (2.20, 4.9), 4.97 (4.25, 5.97), 5.80 (4.31, 6.88), 6.59 (5.17, 8.53), and 7.96 (6.82, 9.20) g, respectively; the proportions of the samples containing more than 0.5 g of total sugar were 93.3% for sugar free milk tea, 47.4% for light sugar milk tea, and 94.0% for regular sugar milk tea; the proportion of the regular sugar samples with sugar content greater than 10 g was 18.0% (all samples with nominal sugar content were measured per 100 g). Conclusion The retail handcrafted milk tea in Shanghai is characterized by high energy, high added sugar, high fat, and low protein. It is necessary to standardize the added sugar content and sweetness labeling, strengthen the nutrition education of milk tea, and guide residents to limit its intake.

Impact of the established healthy canteens and restaurants in Shanghai on usage of oil， salt， and sugar， and on nutritional knowledge and behavior of diners / 上海预防医学

ObjectiveTo evaluate the changes of the usage of oil， salt， sugar and nutritional knowledge and behavior intervention among diners before and after the establishment of healthy canteens and restaurants in Shanghai. MethodsA comprehensive intervention was conducted through the establishment of healthy canteens and restaurants， encompassing interventions such as oil， salt， and sugar management， improvement of nutritional environment， staffing and training activities， and nutrition labeling guidance. A pre-post self-controlled study design was used to compare changes in oil， salt and sugar usage， as well as diners’ knowledge and behaviors related to nutrition and nutrition labeling， before and after the intervention. ResultsAfter intervention， the total usage of oil， salt， and sugar per meal in the canteens and restaurants decreased by 18.33%， 14.83%， and 13.66%， respectively，and all had statistically significance differences（P<0.001）. The awareness rate of "cooking oil intake"， "salt intake"， and "added sugar intake" among diners increased from 24.07% to 38.04%， 58.52% to 71.28%， and 26.85% to 45.01%， respectively. The awareness rate of "daily food types" and "weekly food types" increased from 43.07% to 56.53% and 49.52% to 64.32%， with significant differences （P<0.001）. The rate of understanding the content of nutrition labels increased from 66.91% to 76.90%， the awareness rate of nutrition labels increased from 53.59% to 69.06%， the rate of active reading of nutrition labels among diners increased from 73.38% to 81.23%， and the rate of selecting and purchasing food based on the information of nutrition labels increased from 69.27% to 77.79%， all of which were statistically significant （P<0.001）. ConclusionThe comprehensive interventions carried out through the creation of healthy canteens and restaurants have significantly impact on usage of oil， salt， and sugar， as well as on the nutritional knowledge and behaviors of diners.

Application of continuous glucose monitoring technology to evaluate the advantages of insulin degludec in the treatment of type 1 diabetes mellitus / 中国医师杂志

Objective:Continuous glucose monitoring (CGM) technology is used to compare the advantages of insulin degludec (IDeg) as a basal insulin regimen compared with insulin glargine (IGlar) in the treatment of adult type 1 diabetes mellitus.Methods:30 adult patients with T1DM admitted to Heji Hospital Affiliated to Changzhi Medical College from September 2019 to December 2020 were screened. According to the random number table method, the patients were randomly divided into two groups (insulin degludec group and insulin glargine group) at a ratio of 1∶1, respectively treated with IDeg, IGlar and aspartate insulin for 12 weeks. The main outcome measures were the coefficient of variation of blood glucose (CV), mean amplitude of glycemic excursions (MAGE), time in range (TIR), time above range (TAR) and time below range (TBR). The secondary outcome measures were mean blood glucose (MBG), standard deviation of blood glucose (SD), fasting blood glucose (FPG), 2 h postprandial blood glucose (2 h BG), hemoglobin A1c (HbA 1c), means of daily differences (MOOD), and the frequency of hypoglycemic events. Results:At 12 weeks of treatment, the HbA 1c, FPG, 2 h BG, MBG, SD, CV and MAGE of insulin degludec group were lower than those of insulin glargine group, with statistically significant difference (all P<0.05). The TIR in the insulin degludec group was significantly higher than that in the insulin glargine group [73(63, 75)% vs 43(28, 63)%, P<0.001], and the TAR was lower than that in the glycerine group [25(17, 23)% vs 35(33, 64)%, P=0.003]. From the curve spectrum of blood glucose level of the two groups, the stability of blood glucose in the insulin degludec group was better than that in the insulin glargine group. After 12 weeks of treatment, 8 cases (8/15) in insulin degludec group had HbA 1c<7.0%, and 4 cases (4/15) in insulin glargine group had HbA 1c<7.0%, without statistically significant difference ( P=0.264). There were 7 cases (7/15) in the insulin degludec group and 1 case (1/15) in the insulin glargine group who achieved high quality blood glucose control, with statistically significant difference ( P=0.035). At the 12th week of outpatient follow-up, the incidence of nocturnal hypoglycemic events in insulin degludec group was significantly lower than that in insulin glargine group (4/15 vs 11/15, P=0.027). Conclusions:Compared with insulin glargine, insulin degludec can achieve higher blood glucose compliance rate, lower blood glucose level and reduce blood glucose fluctuations in patients with type 1 diabetes.

Advantages of Chinese Medicine in Treating Dominant Disease： Benign Prostatic Hyperplasia / 中国实验方剂学杂志

China Association of Chinese Medicine organized specialists in andrology of Chinese and western medicine to explore the population and treatment stage of benign prostatic hyperplasia （BPH） with Chinese medicine as the leading therapy. Chinese medicine has great advantages in the treatment of benign prostatic hyperplasia. However， it is necessary to make clear the stage when Chinese medicine or modern medical treatment can be used as the leading therapy， and the conditions under which Chinese and western medicine can be combined to achieve the best treatment efficacy. The specialists agreed Chinese medicine as the leading therapy for the treatment of BPH in the following populations or conditions： the elderly and weak patients with basic diseases， BPH symptoms， and cannot tolerate anesthesia and surgery， the patients with BPH symptoms and cannot tolerate the adverse reactions or the possible adverse reactions of western medicine； the patients with mild ［international prostatic symptom score （IPSS） ≤ 7］ or moderate lower urinary tract symptoms （IPSS ≥ 8） and the quality of life not significantly affected， the patients with bladder detrusor hypofunction， bladder dysfunction and cannot be treated surgically， or with incomplete bladder emptying after surgical treatment； the BPH patients with prostatitis as the main clinical manifestation， the patients with non-acute complications after operation. BPH is one of the dominant diseases in urology and andrology of Chinese medicine， and the symptoms， complications， and prognosis of BPH patients need to be fully considered during the clinical treatment. When Chinese medicine is taken as the leading therapy， it is essential to regularly review the serum level of prostate-specific antigen to exclude the possibility of prostate cancer， and apply Chinese medicine for full treatment course and cycle. At the same time， Chinese and western medicine can be combined to achieve the most effective， convenient， economical， and satisfactory treatment， which can carry forward the advantages of Chinese medicine in treating this disease.

Free rectus abdominis myocutaneous flap for the reconstruction of major and complex defects in the craniofacial regions after ablation of advanced sinonasal carcinomas / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the method and plausibility of using free rectus abdominis flap (FRAF) to reconstruct the major and complex defects in the craniofacial regions after ablation of advanced sinonasal carcinoma. Methods: From 2007 to 2018 at No. 980 Hospital of Joint Logistic Supportive Force of People's Liberation Army of China, 13 patients with advanced carcinoma of nasal cavity and paranasal sinuses, including 11 males and 2 females, aged from 33 to 67 years, were treated with FRAF to repair the invasion of skull base, face and orbit. Based on adequate and meticulous preoperative evaluations on patients and tumors, complete resection of tumor bulks was performed. According to the sites, characters and extents of the defects, FRAF was introduced in different ways into reconstruction of major and complex defects in the craniofacial regions after resection of advanced sinonasal carcinomas, restoring the structure and contour of the craniofacial region. Results: Complete resection of tumors was achieved in all cases. For repairing the major and complex defects resulted from tumor ablation, FRAF graft was conducted in 13 patients with advanced sinonasal carcinomas. The recipient vessels were facial artery and vein in 9 cases, superficial temporal artery and vein in 4 cases. Vascular bridging with the external jugular vein was carried out in 2 cases who underwent submandibular neck dissections, in which facial artery and vein were used as recipient vessels. Free fibular flap was used along with FRAF in a case undergone bilateral maxillectomy. Pedicled galea capitis and periosteal flap were applied simultaneously in 3 cases with dura defects at the skullbase resulted from tumor resection. All flaps used in 13 cases survived uneventfully without major complications, with successful repair of defects, reconstruction of structures and restoration of contour of craniofacial regions. Conclusion: With adequate evaluation of resectability of tumors as well as nature and extent of defects after tumor removal, FRAF transplantation is an ideal method and strategy of choice for reconstructing the major and complex defects in craniofacial regions resulted from tumor ablation of advanced sinonasal carcinomas.

The pregnancy outcomes in women with gestational diabetes mellitus in one-day outpatient management with or without nutrition specialist involvement: a propensity score matching study / 中华临床营养杂志

Objective:Objective To explore the special role of nutrition specialists in the one-day-care clinic of gestational diabetes mellitus (GDM), and provide a basis for strengthening the standardized construction of one-day-care clinic.Methods:It was a retrospective observation study that the pregnant women who participated in the one-day-care clinic of GDM in our hospital without nutrition specialists in November and December 2017 were divided into control group (177 cases), and who participated in the one-day-care clinic of GDM in our hospital with nutrition specialists in January and February 2018 were divided into observation group (307 cases). The differences of pregnancy outcomes between the two groups were compared after the propensity score matching.Results:176 pairs of patients were successfully matched with a 1:1 propensity score. The incidence of macrosomia in pregnant women with GDM in the observation group (2.8%) was significantly lower than that in the control group (8.5%) ( P=0.036). There were no significant differences in the weight gain during pregnancy, the gestational week of delivery and the incidences of insulin use, hypertension during pregnancy, preeclampsia, cesarean section, premature infants, premature rupture of membranes, umbilical cord around the neck, and fetal distress between the two groups ( P>0.05). Conclusion:Nutrition specialists are indispensable in the multidisciplinary cooperation of one-day-care clinic of GDM, and they play a key role in considerably lowering the prevalence of macrosomia in GDM pregnant women.

Effect of tegafur combined with oxaliplatin on the life cycle and serum alpha-fetoprotein and carbohydrate antigen 242 levels in patients with advanced gastric cancer / 中国医师进修杂志

Objective:To investigate the effect of tegafur combined with oxaliplatin on the life cycle and serum alpha-fetoprotein (AFP) and carbohydrate antigen 242 (CA242) levels in patients with advanced gastric cancer.Methods:A total of 100 patients with advanced gastric cancer admitted to Hefei Third People′s Hospital from October 2016 to October 2019 were selected and divided into two groups according to randomization, with 50 cases in each group. The patients in the control group received calcium leucovorin and fluorouracil and oxaliplatin, and the patients in the observation group was treated with tegafur combined with oxaliplatin. The remission rate, disease control rate, median progression-free survival (PFS), median overall survival (OS), side effects and serum tumor markers AFP, CA242, carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125), carbohydrate antigen 19-9 (CA19-9), tumor growth promoting indicators vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-2, MMP-9, insulin-like growth factor-1 (IGF-1), platelet endothelial cell adhesion molecule-1 (PECAM-1), microRNA (miR) 216a, miR95, miR4286 before and after treatment of the two groups were compared.Results:The remission rate in the observation group was higher than that in the control group: 42.0%(21/50) vs. 22.0%(11/50), and the difference was statistically significant ( P<0.05). After treatment, the levels of AFP, CA242, CEA, CA125, CA19-9 in the observation group were lower than those in the control group: (15.04 ± 3.65) μg/L vs. (20.65 ± 4.17) μg/L, (20.88 ± 6.37) kU/L vs.(35.46 ± 7.33) kU/L, (8.65 ± 2.13) μg/L vs.(15.39 ± 3.25) μg/L, (26.15 ± 8.49) kU/L vs. (34.16 ± 7.50) kU/L, (22.29 ± 5.80) kU/L vs. (38.81 ± 6.79) kU/L, and the differences were statistically significant ( P<0.05). The levels of VEGF, MMP-2, MMP-9, IGF-1 and PECAM-1 in the observation group were lower than those in the control group; the level of miR216a in the observation group was higher than that in the control group, and the levels of miR95 and miR4286 were lower than those in the control group, and the differences were statistically significant ( P<0.05). The median PFS in the control group was 3.0 months, the median OS in the control group was 6.6 months, the median PFS in the observation group was 3.3 months, the median OS in the observation group was 7.0 months, and the differences were no statistically significant ( P>0.05). The incidences of myelosuppression and skin damage toxicity in the observation group were lower than those in the control group: 6.0%(3/50) vs. 24.0%(12/50), 4.0%(2/50) vs. 18.0% (9/50), and the differences were statistically significant ( P<0.05). Conclusions:Tegafur combined with oxaliplatin in the treatment of advanced gastric cancer can improve the anti-cancer effect and promote the relief of the disease, and has high safety. The mechanism may be related to the inhibition of tumor growth promotion indexes and the regulation of miR.

Establishmend of Content Determination of 5 Components and Their Content Difference Analysis in the Branch and Root of Juglans man dshurica / 中国药房

OBJECTIVE：To esta blish a method for si multaneous determination of 5 components in the branch and root of Juglans mandshurica as gallic acid ，ellagic acid ，1，6-di-O-galloyl-β-D-glucose，1，2，6-tri-O-galloyl-β-D-glucose and 1，2，3， 6-tetra-O-galloyl-β-D-glucose，and to analyze the content difference of above 5 components between the branch and root samples. METHODS：HPLC method was adopted. The determination was performed on Agilent Poroshell 120 SB-C18 column with mobile phase consisted of water （containing 0.2％ formic acid ）-acetonitrile （containing 0.2％ formic acid ）. A gradient elution was performed at a flow rate of 0.3 mL/min. The column temperature was 30 ℃ and the detection wavelength was 270 nm. The sample size was 5 μL. Independent samples t-test and partial least squares-discriminant analysis （PLS-DA）were applied for statistical analysis of 5 components. RESULTS ：The linear range of gallic acid ，ellagic acid ，1，6-di-O-galloyl-β-D-glucose，1，2， 6-tri-O-galloyl-β-D-glucose and 1，2，3，6-tetra-O-galloyl-β-D-glucose were 0.989-63.3，1.58-101，1.01-64.7，3.31-212，3.34-214 μg/mL （r≥0.997 3），respectively. RSDs of precision ，reproducibility and stability tests （12 h）were all lower than 3.2％. The average recoveries of the 5 components were 103.2％（RSD＝4.85％），99.1％（RSD＝2.80％），101.5％（RSD＝1.31％），102.9％（RSD＝ 2.73％）and 104.7％（RSD＝1.28％），respectively. The average contents of the above components in the branch of J. mandshurica were 0.296 5，0.621 1，0.562 5，3.111 7 and 3.451 3 mg/g，respectively. The average contents of above components in the root were 0.673 4，2.755 5，0.964 0，2.946 6 and 4.836 4 mg/g，respectively. The total contents of the 5 components in the branch and roo t of J. mandshurica were 8.043 2 and 12.175 9 mg/g，respectively. The contents of gallic acid ，ellagic acid and 1，6-di-O-galloyl- β-D-glucose in roots were significantly higher than those in branches （P＜0.05 or P＜0.01）. There were no significant differences in the contents of the other 2 components and the total contents of the 5 components in branches and roots （P＞0.05）. The cumulative interpretability （R 2X，R 2Y） and cumulative predictability （Q 2） of the model established by PLS-DA were 0.943，0.745，and 0.710 respectively. The model load diagram showed that the distance between the ellagic acid and the origin was the farthest ，and only variable projection importance of the content of the ellagic acid was greater than 1. CONCLUSIONS：The established method can be used for the content determination of 5 components in the branch and root of J. mandshurica . Except for 1，2，6-tri-O-galloyl-β-D-glucose，the contents of other 4 components and total contents of the 5 components in the root of J. mandshurica are higher than those of the branch. Ellagic acid is selected as the potential marker for discriminating the branch and root samples.

Early incision, decompression and screw fixation for the treatment of Lisfranc injuries with foot osteofascial compartment syndrome / 中国骨伤

OBJECTIVE@#To explore clinical effect of early incision and decompression combined with screw fixation in treating Lisfranc injury and foot osteofascial compartment syndrome.@*METHODS@#Clinical data of 5 patients with Lisfranc injury and foot osteofascial compartment syndrome were retrospective analysized from January 2017 to December 2018, including 4 males and 1 female, aged from 19 to 62 years old. All patients were suffered from closed injuries. The time from injury to treatment ranged from 1 to 14 h. According to Myerson classification, 1 patient was type A, 1 patient was type B, and 3 patients were type C. All patients were performed early incision decompression and screw fixation. Maryland foot functional scoring standard at 12 months after opertaion was used to evaluate clinical effect.@*RESULTS@#All patients were followed up for 10 to 48 months. All fractures were achieved bone union, and healing time ranged from 3 to 9 months. All metatarsal and tarsal joints were reached to anatomical reduction. No infection, osteomyelitis, loosening or breaking of internal fixation occurred. Postopertaive Maryland foot function score at 12 months was from 44 to 97, and 2 patients got excellent result, 2 good, and 1 poor.@*CONCLUSION@#Early incision and decompression with screw fixation for the treatment of Lisfranc injury and foot osteofascial compartment syndrome, which has advantages of simple opertaion, thoroughly decompression, screw fixation does not occupy space, stable decompression and fixation, and could receive satisfied clinical effect.

Age-dependent changes of total and differential white blood cell counts in children / 中华医学杂志(英文版)

BACKGROUND@#Total and differential white blood cell counts are important for the diagnostic evaluation of suspected diseases. To facilitate the interpretation of total and differential white blood cell counts in pediatric patients, the present study investigated age-dependent changes in total and differential white blood cell counts in healthy reference children.@*METHODS@#Data were obtained from the Pediatric Reference Intervals in China study (PRINCE), which aims to establish and verify pediatric reference intervals for Chinese children based on a nationwide multicenter cross-sectional study from January 2017 to December 2018. Quantile curves were calculated using the generalized additive models for location, shape, and scale method. The 2.5th, 50th, and 97.5th quantile curves were calculated for both total and differential white blood counts. Percents of stacked area charts were used to demonstrate the proportions of differential white blood cells. All statistical analyses were performed using R software.@*RESULTS@#Both 50th and 97.5th quantiles of total white blood cell count and monocyte count were highest at birth, then rapidly decreased in the first 6 months of life; relatively slow reduction continued until 2 years of age. The lymphocyte count was low during infancy and increased to its highest level at 6 months of age; it then exhibited moderate and continuous reduction until approximately 9 years of age. The pattern of neutrophil count changed with age in a manner opposite to that of lymphocyte count. Besides, there were two inter-sections of lymphocyte count and neutrophil count during infancy and at approximately 5 years of age, based on locally weighted regression (LOESS) analysis. There were no apparent age-related changes in eosinophil or basophil counts.@*CONCLUSION@#These data regarding age-related changes in total and differential white blood cell counts can be used to assess the health of pediatric patients and guide clinical decisions.

Effect of metformin on mitochondrial pathway of apoptosis and oxidative stress in cell model of nonalcoholic fatty liver disease / 中华肝脏病杂志

Objective@#To investigate the effects of metformin on mitochondrial pathway of apoptosis and oxidative stress in cell model of nonalcoholic fatty liver disease.@*Methods@#An in vitro cell model of nonalcoholic fatty liver disease was established using 0.6 mmol/L oleic acid to induce lipid accumulation in HepG2 cells. HepG2 cells were divided into control (Con) group, oleic acid (OA) group, and metformin-low (1mmol/L) and high (10mmol/L) dose group. Oil Red O stain was used to detect intracellular lipid droplet distribution. The levels of alanine aminotransferase and aspartate aminotransferase in the culture supernatant were detected by assay kits. DCFH-DA method was used to detect the reactive oxygen species of HepG2 cells. Double staining flow cytometry was used to detect the apoptosis rate of HepG2 cells. Western blot was used to detect caspase-3, B-lymphocyte lymphoma-related protein, B-cell lymphoma 2, and cytochrome c protein. One-way analysis of variance was used to compare the data between groups.@*Results@#Oleic acid-induced HepG2 cells were significantly increased with lipid droplets. Low and high-dose metformin had reduced intracellular lipid droplets accumulation. The effect of metformin in the high-dose group was more significant than that in the low-dose group. Aspartate aminotransferase and alanine aminotransferase in HepG2 cells of OA group were significantly increased, which were (43.41 ± 7.11) U/L and (29.56 ± 4.11) U/L, respectively. The intracellular aspartate aminotransferase and alanine aminotransferase were decreased significantly after the treatment with low and high-dose metformin, which were (32.44 ± 4.08)U/L, (19.31 ± 3.03) U/L, (26.00 ± 3.11) U/L and (15.11 ± 4.11) U/L, respectively and the differences were statistically significant (P < 0.05). DCFH-DA test results showed that the fluorescence intensity of reactive oxygen species in the oleic acid group was 41.21% ± 4.23%, while the fluorescence intensity of reactive oxygen species in the low and high-dose metformin groups were reduced to 27.44% ± 3.91%, and 17.55% ± 5.11%, respectively and the differences between the groups were statistically significant (P < 0.05). The results of flow cytometry analysis showed that the cell apoptosis rate of the OA group was significantly higher than that of the Con group (12.12% ± 0.72% vs. 3.04% ± 0.57%, P < 0.05).The apoptosis rate of HepG2 cells was significantly reduced after metformin treatment at low and high doses (8.71% ± 0.71%, 5.71% ± 0.61%, P < 0.05). Western blot results showed that compared with the Con group, the expressions of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 were increased in the OA group, while the B-cell lymphoma 2 were decreased (P < 0.05). The expression of B-lymphocyte lymphoma-related protein, cytochrome c, and caspase-3 protein in HepG2 cells was decreased after treatment with low and high-dose metformin, while B-cell lymphoma 2 was increased (P < 0.05).@*Conclusion@#Metformin can effectively alleviate steatosis and improve the HepG2 function in cell model of nonalcoholic fatty liver disease. The mechanism of metformin may be related to the reduction of oxidative stress injury, the regulation of protein expression related to mitochondrial apoptosis pathway and the inhibition of cell apoptosis.

Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood, Placental Size, and Risk for Fetal Growth Restriction: A Nested Case-control Study / 生物医学与环境科学（英文）

Objective@#To explore the effects of prenatal exposure to polybrominated diphenyl ethers (PBDEs) on placental size and birth outcomes.@*Methods@#Based on the perspective Wenzhou Birth Cohort, this nested case-control study included 101 fetal growth restriction (FGR) and 101 healthy newborns. Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry. The basic information of mother-newborn pairs was collected from questionnaires, whereas the placental size and birth outcomes of newborns were obtained from hospital records.@*Results@#A total of 19 brominated diphenyle ether (BDE) congeners were detected in maternal serum samples. Higher concentrations of BDE-207, -208, -209, and ∑ @*Conclusion@#A negative association was found between PBDE levels in maternal serum and placental size and birth outcomes. Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.