Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Background and purpose:In recent years,domestic radiotherapy equipment and related software have made great progress,and testing the functionality and stability of the equipment and software is an essential step.This paper focused on comparing the differences in intensity-modulated radiation therapy(IMRT)plans dosimetry and organ at risk(OAR)volume calculations for common cancers between uRT-treatment planning system(TPS)and Monaco-TPS,and to evaluate the feasibility of dose calculation for Infinity linac(linear accelerator,Elekta,Sweden)using uRT-TPS.Methods:Twenty cases of rectal cancer,lung cancer,breast cancer and nasopharyngeal carcinoma were selected.The IMRT plans were completed in uRT-TPS and Monaco-TPS.The dose uniformity and conformity,mean dose,maximum dose of planning target volume(PTV)and OAR between two plans under the same prescribed dose of PTV were compared.And the pass rates of two TPS plans validated at the same linear accelerator were compared.Meanwhile,monitor units(MU),source skin distance(SSD)and the volume of OAR in uRT-TPS and Monaco-TPS were compared.Results:Wonderful plans that met the clinical requirements were obtained in uRT-TPS and Monaco-TPS.Comparable uniformity and conformability was received in PTV,and the maximum dose of PTV was reduced by 1.1 Gy for uRT-TPS(P = 0.006).For breast cancer and lung cancer,the dose in lung was lower for Monaco-TPS(P＜0.05).For nasopharyngeal carcinoma,the dose indicators that oral cavity and throat in the uRT-TPS was reduced by 9.2%and 5.1%,respectively.The verification results of absolute point dose(＜3%)and three-dimensional surface dose(＞95%)for both plans met the clinical requirements.The region of interest in uRT-TPS was smaller compared with Monaco-TPS(P＜0.05).Conclusion:A comparable IMRT plan was obtained for common tumors in uRT-TPS and Monaco-TPS.It is feasible to calculate the dose of Infinity linac using uRT-TPS.

BACKGROUND:At present,the biological functions and molecular changes of bone marrow mesenchymal stem cells in the tumor microenvironment of acute myeloid leukemia are still unclear. OBJECTIVE:To explore the changes in the biological function of bone marrow mesenchymal stem cells in acute myeloid leukemia and the role of acute myeloid leukemia conditioned medium by bioinformatics and experiment. METHODS:Differential genes were screened from GEO data sets,and enrichment analysis was performed.The protein-protein interaction network was constructed and the Hub gene was obtained.Bone marrow mesenchymal stem cells from patients with acute myeloid leukemia and healthy donors were cultured.Bone marrow mesenchymal stem cells from healthy donors were treated with acute myeloid leukemia conditioned culture solution.Each group was subjected to the adipogenic differentiation,osteogenic differentiation,staining of β-galactosidase,detection of the cell cycle,and validation of Hub genes. RESULTS AND CONCLUSION:(1)Gene expression data of bone marrow mesenchymal stem cells from acute myeloid leukemia patients and healthy donors were obtained from GSE84881,and 184 up-regulated genes and 140 down-regulated genes were screened.(2)The biological functions of enrichment mainly include cell cycle,adipocyte differentiation,cell metabolism,and MYC pathway.According to the Degree algorithm,10 up-regulated Hub genes and 10 down-regulated Hub genes were selected.(3)The cell in vitro experiment found that:compared with the control group,the surface antigen of acute myeloid leukemia mesenchymal stem cells did not change,but it showed enhanced lipid differentiation ability,weakened osteogenic differentiation ability,increased β-galactosidase positive cell number,altered cell morphology,arrested cell cycle,increased LGALS3 expression,and decreased MYC expression.Mesenchymal stem cells from healthy donors showed similar changes after being cultured in acute myeloid leukemia conditioned medium.(4)The results show that biological function of mesenchymal stem cells is altered in the acute myeloid leukemia microenvironment,which provides new insights into the interaction between mesenchymal stem cells and tumor cells.

Under the background of scientific and technological innovation in the new era, ethical review of traditional Chinese medicine (TCM) is facing new opportunities and challenges. Focusing on how to maintain integrity and innovation in the ethical review work of TCM clinical research in TCM medical institutions, starting from the characteristics of innovation and inheritance of TCM clinical research, this paper discussed the construction of the ethical review system of TCM clinical research, key elements of attention, shortcomings and deficiencies, training and communication, etc. It is also proposed that the joint construction of a Chinese characteristic scientific and technological ethics governance system should consider the unique requirements of modern technological means for the ethical review of scientific and technological projects such as dialectical treatment, re-evaluation of prescription projects, and expansion of indications in clinical research of TCM; innovate the form of review and strengthen the process management of ethical review; scientifically, objectively and impartially evaluate the scientific nature and social value of clinical research projects in TCM; pay attention to the toxic side effects of TCM, especially compound preparations. So as to further improve the procedural norms and quality of ethical review of clinical research of TCM, protect the legitimate rights and interests and safety of subjects, and promote the development of medicine in China.

Traditionally, Tripterygium hypoglaucum (Levl.) Hutch (THH) are widely used in Chinese folk to treat rheumatoid arthritis (RA). This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota. The main components of prepared THH extract were identified by HPLC-MS. C57BL/6 mice with adjuvant-induced arthritis (AIA) were treated with THH extract by gavage for one month. THH extract significantly alleviated swollen ankle, joint cavity exudation, and articular cartilage destruction in AIA mice. The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways. THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice, featuring the increases of Bifidobacterium, Akkermansia, and Lactobacillus and the decreases of Butyricimonas, Parabacteroides, and Anaeroplasma. Furthermore, the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota. In addition, antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora. Strikingly, THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice, which validates the indispensable role of the intestinal flora. For the first time, we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway. Therefore, THH extract may serve as a microbial modulator to recover RA in clincial practice.ver RA in clincial practice.
Mice ; Animals ; Gastrointestinal Microbiome ; Tripterygium ; Myeloid Differentiation Factor 88/genetics* ; Toll-Like Receptor 4/genetics* ; Mice, Inbred C57BL ; Arthritis, Experimental/drug therapy*

OBJECTIVE To observe the toxic effects of single administration and repeated administration of Qingzi granules for 13 weeks on rats, and to evaluate their preclinical safety. METHODS For the single dose toxicity experiment, SD rats were randomly divided into two groups, vehicle control group(deionized water) and Qingzi group(18 g·kg-1), which were given in a volume of 30 mL·kg-1 per time, twice in 24 h(interval more than 4 h), and observation was performed for 14 d after administration. The toxicity reaction was evaluated through observation of body weight change and pathological anatomy. For the repeated dose toxicity experiment, juvenile SD rats(postnatal day, PND 4) were randomly divided into vehicle control group (deionized water) and low, medium and high dose of Qingzi groups(1, 2 and 4 g·kg-1). The rats were orally administered twice daily with vehicle or Qingzi for 13 weeks in a volume of 10 mL·kg-1 per time. A recovery period of 4 weeks was followed. Test items included clinical observations, body weight measurement, food intake measurement, hematology test, biochemical test, urinalysis, sex hormone level determination, cellular immune function assay, growth indexes and histopathology test. RESULTS For the single dose toxicity experiment, Qingzi granules were orally administered to SD rats without significant toxicity, and the maximum-tolerated dose was greater than 18 g·kg-1. In the repeated dose toxicity test, juvenile SD rats were given Qingzi granules by gavage and repeated administration for 13 weeks, the no observed adverse effect level was 2 g·kg-1. The target organ of toxicity was the liver and the main toxic effect was inflammatory necrosis of hepatocytes, no dose-dependent relationship. CONCLUSION No overt toxicity of Qingzi granules was observed on the tested animals within the intended clinical dosage range.

Objective To investigate the expression changes of p53 and p21 in premature ovarian failure in female rats exposed to coal burning fluorosis.Methods Ablactation 24 SD female rats were chosen to establish animal model (the model group),in fluorine 90 days were put to death.Observed the changes of the teeth of the female rats during fluorine exposure and ovarian granulosa cell premature aging change,detected fluorine contents of urine and bone,and expression of the ovarian granular cell gene p53 and p21.Results In the model group,fluorine spot tooth,the fluorine contents of urine and bone increased significantly.In the model group,there was no premature aging of ovarian granulosa cells in the low fluorine group,but with the increase of dye fluorine metering,ovarian granulosa cells became mild,moderate to severe progressive edema trends,cells morphological damaged fuzzy,and atresia follicles increased significantly,corpus luteum degraded,mature follicle significantly reduced,and the ovarian function gradually signs of premature aging presented.With the increase of dye fluoride measurement,the expression of aging gene p53 and p21 in each group gradually increased,compared with the control group,there was statistically significant difference (P＜0.05).Conclusion Premature ovarian failure caused by coal-burning fluorosis was significantly related to the expression of genes p53 and p21.

Objective To investigate the expression of Sirtuin1 (SIRT1) in brain tissue of rats with different doses of fluorosis-induced brain injury.Methods Forty-eight clean SD rats were divided into 4 groups based on body weight (90-100 g) via the random number table method:the control group (normal feed containing fluoride 4.5 mg/kg),low fluoride groups (feed containing fluoride 25.0 mg/kg),middle fluoride groups (feed containing fluoride 50.0 mg/kg),high fluoride groups (feed containing fluoride 100.0 mg&g),twelve rats in each group,half male and half female.Rats in each group drank tap water freely.Low,middle and high fluorine groups were free to eat the designated different formulations of raw coal and mixed peat baked corn feed,other feed ingredients were the same as those in control group,the rats were sacrificed at 90 d of fluorine exposure.At 7 d before the rats were sacrificed,Morris water maze and platform experiment were employed to test the ability of learning and memory in rats.Take the brain tissue and thigh long bones after the rats were sacrificed,immediately.The fluorine ion selective electrode method was used to detect urinary fluoride and fluorine content in bone in rats.The brain SIRT1 mRNA and protein expression levels were detected by Real-Time PCR and Western blotting,respectively.Results In the space exploration experiments,the mean time to first passage of platform of the rats in control group and low,middle and high fluorine groups were (9.8 ± 3.5),(15.8 ± 5.1),(22.2 ± 7.9) and (30.5 ± 8.5) s,respectively.The differences between groups were statistically significant (F =10.853,P ＜ 0.05).The number of passed through the platform of the rats in control and low,middle and high fluorine groups were (5.2 ± 2.1),(3.3 ± 1.6),(1.3 ± 1.1) and (1.2 ± 0.8) time/60 s,respectively.The differences between groups were statistically significant (F =10.105,P＜ 0.05).In the control group and low,middle and high fluoride groups,the resting time of the original platform quadrant were (30.5 ± 9.8),(22.7 ± 4.6),(13.8 ± 4.8) and (7.0 ± 2.4) s,respectively.The differences between groups were statistically significant (F =17.433,P ＜ 0.05).And the middle,high fluoride groups compared with the control group was significantly different (P ＜ 0.05).With increase of fluoride dosage,the first time to cross the platform gradually extended,the number of crossing the platform and the original platform quadrant dwell time decreased gradually,the differences between the middle,high fluoride groups and the low fluoride group were statistically significant (P ＜ 0.05).The mRNA expression of SIRT1 in control group and low,middle and high fluoride groups were 0.979 ± 0.088,0.907 ± 0.050,0.426 ± 0.073,0.219 ± 0.092,respectively.The differences between groups were statistically significant (F =136.837,P ＜ 0.05).The levels of SIRT1 protein in control group,low,middle and high fluoride groups were 1.224 ± 0.139,0.988 ± 0.096,0.581 ± 0.084 and 0.269 ± 0.066,respectively.The differences between groups were statistically significant (F =107.961,P ＜ 0.05).The levels of SIRT1 mRNA and protein were gradually decreased with increase of fluoride dose in the low,middle and high fluoride groups (P ＜ 0.05).Conclusions Fluorosis can affect the learning and memory ability of rats.SIRT1 mRNA and protein expressed in rat brain is decreased,which is more obvious with the increase of fluoride dose.

Objective To investigate the clinical efficacy of warming and unblocking acupuncture in treating scapulocostal syndrome.Method Eighty patients with scapulocostal syndrome meeting the inclusion criteria were allocated by simple randomization to warming and unblocking acupuncture and conventional acupuncturegroups, 40 cases each.The warming and unblocking acupuncture group received warming and unblocking acupuncture at points Tianzong(SI11), Jianjing(GB21)and Dazhui(GV14)on the affected side and affected chest Huatuo jiaji(Ex-B2)points and uniform reinforcing-reducing acupuncture at points Quchi(LI11), Hegu(LI4)and Waiguan(TE5).The conventional acupuncture group received uniform reinforcing-reducing acupuncture at the same points as those in the warming and unblocking acupuncture group after arrival of qi.Both groupswere treated once every other day, 10 days as a course, for a total of one course.Pain severity was assessed using the Pain Visual Analogue Scale(VAS) in the two groups of patients before and after treatment.Theclinical therapeutic effects were evaluated by follow-up at one month after the completion of treatment.Result The total efficacy rate was 95.0% (38/40) in the warming andunblocking acupuncture group and 80.0% (32/40) in the conventional acupuncture group; there was a statistically significant difference (P<0.05).The PainVisual Analogue Scale(VAS) score was significantly lower in the two groups of patients after treatment than before treatment; there was a statistically significant difference (P<0.05).The VAS score was decreased more in the warming and unblocking acupuncture group after treatment and at the follow-up one month after the completion of treatment (P<0.05).Conclusion Warming and unblocking acupuncture has clinically a better therapeutic effect onscapulocostal syndrome.

Objective:To observe the analgesic effect of acupuncture and to explore its central analgesic mechanism in rheumatoid arthritis rabbits.Methods:A total of 60 flap-eared white rabbits were randomly assigned into a normal control group (n=6),a model group (n=6),a body-acupuncture group (n=24),and a buccal acupuncture group (n=24).The later 2 groups were further randomly assigned into 0,0.5,1,and 2 h subgroups,with 6 cases in each group.The rheumatoid arthritis model was established by induction of eggalbumin.In the body acupuncture group,bilateral Xiyan and Zusanli were punctured for 15 s while in the buccal acupuncture group,acupuncture was applied to Xi for 15 s,with the needle retaining for 30 min.The pain threshold was detected with PL-200,taking struggle movements of rabbits as a measurement index,response latency from irradiation to struggling movements as the rabbit's pain threshold.The contents of β-endorplhin (β-EP) and cholecystokinin-8 (CCK-8) in cerebrospinal fluid were examined by radioimmunoassay.Results:Compared with the control group,pain threshold and CCK-8 levels decreased significantly (P＜0.01) and the concentration of β-EP significantly increased (P＜0.05) in the model group.The pain threshold in the body-acupuncture group and the buccal acupuncture group at 0 and 1 h (P＜0.05 or P＜0.01) increased significantly,while the β-EP and CCK-8 contents in the bodyacupuncture group and the buccal acupuncture group were significantly higher than those in the model group (P＜0.01 or P＜0.05).Both β-EP and CCK-8 contents in the buccal acupuncture group at 0 h were significantly higher than those in the body-acupuncture group (P＜0.05).Conclusion:The analgesic effect of buccal acupuncture is superior to that of body-acupuncture.Both buccal acupuncture and body-acupuncture can effectively raise the pain threshold in acute arthritis rabbits,which is closely associated with their effects in the up-regulation of β-EP and CCK-8 contents in cerebrospinal fluid.