Problems and thoughts in clinical safety evaluation of traditional Chinese medicine / 中国中药杂志

Amid the modernization and internationalization of traditional Chinese medicine(TCM), the safety of TCM has attracted much attention. At the moment, the government, scientific research teams, and pharmaceutical enterprises have made great efforts to explore methods and techniques for clinical safety evaluation of TCM. Although considerable achievements have been made, there are still many problems, such as the non-standard terms of adverse reactions of TCM, unclear evaluation indicators, unreasonable judgment methods, lack of evaluation models, out-of-date evaluation standards, and unsound reporting systems. Therefore, it is urgent to further deepen the research mode and method of clinical safety evaluation of TCM. Based on the current national requirements for the life-cycle management of drugs, this study focused on the problems in the five dimensions of clinical safety evaluation of TCM, including normative terms, evaluation modes, judgment methods, evaluation standards, and reporting systems, and proposed suggestions on the development of a life-cycle clinical safety evaluation method that conformed to the characteristics of TCM, hoping to provide a reference for future research.

Evaluation methods of clinical efficacy of traditional Chinese medicine / 中国中药杂志

Clinical efficacy is the basis for the development of traditional Chinese medicine(TCM), and the evaluation of clinical efficacy of TCM has always been the focus of attention. The technical and methodological difficulties in the evaluation process often restrict the generation of high-level evidence. Therefore, methodological research should be deepened and innovative practice should be carried out to study the application of scientific research methods in the evaluation of the advantages of TCM. After more than ten years of development, the clinical efficacy evaluation of TCM, on the basis of the initially classic placebo randomized controlled trials, has successively carried out a series of meaningful attempts and explorations in N-of-1 trials, cohort studies, case-control studies, cross-sectional studies, real world studies, narrative medicine studies, systematic evaluation, and other aspects, laying the foundation for the transformation of TCM from "experience" to "evidence". This paper focused on the clinical efficacy evaluation of TCM, summarized the main connotation and development status of efficacy evaluation indicators, standards, and methods, and put forward corresponding countermeasures and suggestions for the problems of indicator selection, standard formulation, and methodology optimization in the research process. It is clear that scientific and objective evaluation of the efficacy of TCM is an urgent problem to be solved at present.

Clinical Characteristics of Children with Hemophagocytic Syndrome with Different EB Virus DNA Loads / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of hemophagocytic syndrome (HLH) children with different EB virus (EBV) DNA loads, and to explore the relationship between differential indicators and prognosis.@*METHODS@#Clinical data of 73 children with HLH treated in our hospital from January 2015 to April 2022 were collected. According to EBV DNA loads, the children were divided into negative group (≤5×102 copies/ml), low load group (>5×102-<5×105 copies/ml) and high load group (≥5×105copies/ml）. The clinical symptoms and laboratory indexes of the three groups were compared, and the ROC curve was used to determine the best cut-off value of the different indexes. Cox regression model was used to analyze the independent risk factors affecting the prognosis of children, and to analyze the survival of children in each group.@*RESULTS@#The proportion of female children, the swelling rate of liver and spleen lymph nodes and the involvement rate of blood, liver, circulation and central nervous system in the high load group were higher than those in the negative group. The incidence of disseminated intravascular coagulation(DIC) and central nervous system(CNS) involvement in the high load group were higher than those in the low load group. The liver swelling rate and circulatory system involvement rate in the low load group were higher than those in the negative group(P<0.05). PLT counts in the high load group were significantly lower than those in the negative group, and the levels of GGT, TBIL, CK-MB, LDH, TG, SF, and organ involvement were significantly higher than those in the negative group. The levels of CK, LDH, SF and the number of organ involvement in the high load group were significantly higher than those in the low load group. The levels of GGT and TBIL in low load group were significantly higher than those in negative group. In terms of treatment, the proportion of blood purification therapy in the high and low load group was significantly higher than that in the negative group(P<0.01). ROC curve analysis showed that the best cut-off values of PLT, LDH, TG and SF were 49.5, 1139, 3.12 and 1812, respectively. The appellate laboratory indicators were dichotomized according to the cut-off value, and the differential clinical symptoms were included in the Cox regression model. Univariate analysis showed that LDH>1139 U/L, SF>1812 μg/L, dysfunction of central nervous system, number of organ damage, DIC and no blood purification therapy were the risk factors affecting the prognosis of children (P<0.05); Multivariate analysis shows that PLT≤49.5×109/L and dysfunction of central nervous system were risk factors affecting the prognosis of children (P<0.05). Survival analysis showed that there was no significant difference in the survival rate among the three groups.@*CONCLUSION@#The incidence of adverse prognostic factors in children with HLH in the EBV-DNA high load group is higher, and there is no significant difference in the survival rate of the three groups after blood purification therapy. Therefore, early identification and application of blood purification therapy is of great significance for children with HLH in the high load group.

A multi-center observation of the therapeutic efficacy of Bencycloquidium bromide in the treatment of seasonal allergic rhinitis with predominant symptoms of rhinorrhea / 临床耳鼻咽喉头颈外科杂志

Objective:To observe the efficacy and safety of the M receptor antagonist Bencycloquidium bromide nasal spray in treatment of seasonal allergic rhinitis with runny nose as the main symptom. Methods:From August 2021 to September 2021, 134 patients with seasonal allergic rhinitis were enrolled in the otolaryngology Outpatient Department of Peking University Third Hospital, First Affiliated Hospital of Harbin Medical University and China-Japanese Friendship Hospital of Jilin University, including 71 males and 63 females, with a median age of 38 years. TNSS score and visual analogue scale（VAS） of total nasal symptoms were observed during 2 weeks of treatment with Bencycloquidium bromide nasal spray. Results:TNSS score decreased from （8.89±3.31） on day 0 to （3.71±2.51） on day 14（P<0.001）, VAS score of nasal symptoms decreased from （24.86±7.40） on day 0 to （6.84±5.94） on day 14（P<0.001）, VAS score of rhinorrhoea decreased from （6.88±2.06） on day 0 to （1.91±1.81） on day 14（P<0.001）. Rhinoconjunctivitis quality of life questionnaire（RQLQ） score decreased from （94.63±33.35） on day 0 to （44.95±32.28） on day 14（P<0.001）. The incidence of adverse reaction was low and no serious adverse events occurred during the whole experiment. Conclusion:Bencycloquidium bromide nasal spray has significant efficacy and good safety in the treatment of seasonal allergic rhinitis.

The impact and interaction of TLR2 and IRF-5 gene polymorphisms on the susceptibility to neonatal sepsis / 中国医师杂志

Objective:To investigate the impact and interaction of Toll like receptor 2 (TLR2) and interferon regulatory factor 5 (IRF-5) gene polymorphisms on the susceptibility to neonatal sepsis.Methods:A total of 78 cases of neonatal septicemia patients admitted to Baoding Children′s Hospital from July 2018 to August 2021 were prospectively selected as the study group, and 78 cases of healthy newborns in the same period were selected as the control group. The TLR2 and IRF-5 gene polymorphisms and the levels of inflammatory markers [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)] in different genotypes of infants were compared between the two groups. We evaluated the relationship between TLR2 and IRF-5 genotypes, inflammatory markers, and susceptibility to neonatal sepsis, and analyzed the interaction between their gene polymorphisms and susceptibility to neonatal sepsis.Results:There were significant differences in the distribution of TLR2 (rs3804099) and IRF-5 (rs2004640) loci genotype and Allele frequency between the two groups (all P<0.05); The serum CRP, TNF-α, and IL-6 levels in children with TLR2 (rs3804099) genotype TT genotype [(111.12±30.87)mg/L, (77.50±20.02)pg/ml, (40.27±11.31)pg/ml] were higher than those in children with CC/CT genotype [(72.46±24.51)mg/L, (54.18±17.65)pg/ml, (28.34±9.05)pg/ml], and the differences were statistically significant (all P<0.05). The serum CRP, TNF-α, and IL-6 levels [(113.90±28.94)mg/L, TNF-α (79.84±19.82)pg/ml, IL-6 (41.05±11.49)pg/ml] in children with the IRF-5 (rs2004640) TT genotype were higher than those in children with the GG/GT genotype [(70.88±22.16)mg/L, (52.27±16.73)pg/ml, (27.96±9.75)pg/ml], and the differences were statistically significant (all P<0.05). The TT genotypes at TLR2 (rs3804099) and IRF-5 (rs2004640) loci were positively correlated with serum CRP, TNF-α, and IL-6 levels (all P<0.05); The TT genotypes at TLR2 (rs3804099) and IRF-5 (rs2004640) loci were independent risk factors for susceptibility to neonatal sepsis (all P<0.05); The TT genotype at the TLR2 (rs3804099) locus and the TT genotype at the IRF-5 (rs2004640) locus exhibited a positive interaction in susceptibility to neonatal sepsis ( OR=7.467, γ=1.728). Conclusions:TLR2 (rs3804099) TT genotype and IRF-5 (rs2004640) TT genotype significantly increase the susceptibility to neonatal sepsis, and there is a positive interaction between the two.

Study on the application of model transfer technology in the extraction process of Xiao'er Xiaoji Zhike oral liquid / 药学学报

The modernization and development of traditional Chinese medicine has led to higher standards for the quality of traditional Chinese medicine products. The extraction process is a crucial component of traditional Chinese medicine production, and it directly impacts the final quality of the product. However, the currently relied upon methods for quality assurance of the extraction process, such as simple wet chemical analysis, have several limitations, including time consumption and labor intensity, and do not offer precise control of the extraction process. As a result, there is significant value in incorporating near-infrared spectroscopy (NIRS) in the production process of traditional Chinese medicine to improve the quality control of the final products. In this study, we focused on the extraction process of Xiao'er Xiaoji Zhike oral liquid (XXZOL), using near-infrared spectra collected by both a Fourier transform near-infrared spectrometer and a portable near-infrared spectrometer. We used the concentration of synephrine, a quality control index component specified by the pharmacopoeia, to achieve rapid and accurate detection in the extraction process. Moreover, we developed a model transfer method to facilitate the transfer of models between the two types of near-infrared spectrometers (analytical grade and portable), thus resolving the low resolution, poor performance, and insufficient prediction accuracy issues of portable instruments. Our findings enable the rapid screening and quality analysis of XXZOL onsite, which is significant for quality monitoring during the traditional Chinese medicine production process.

Efficacy of second session of endoscopic ultrasound-guided lauromacrogol ablation for pancreatic cystic neoplasms / 中华消化内镜杂志

Objective:To evaluate the efficacy and safety of the second session of endoscopic ultrasound-guided lauromacrogol ablation (EUS-LA) for pancreatic cystic neoplasms (PCNs).Methods:A total of 74 patients with suspected of PCNs who underwent EUS-LA in the First Medical Center of Chinese PLA General Hospital from April 2015 to December 2020 were enrolled in the study. Fifteen of them underwent the second ablation. The efficiency of EUS-LA was determined based on the change of lesion volume during the imaging follow-up, categorized into complete resolution (CR), partial resolution (PR) and stable disease (SD). The safety was determined by the complication incidence.Results:Among the 15 patients undergoing the second EUS-LA, there were 9 males and 6 females with age of 51.5±17.6 years. Thirteen patients completed imaging follow-up after the second EUS-LA, CR was achieved in 8 patients, PR in 2 patients and 3 in SD. The CR rate increased from 0 after the first ablation to 8/13 after the second ablation ( P=0.002). The median cyst diameter decreased from 22.0 mm before the second ablation to 15.0 mm after the second ablation ( Z=-2.666, P=0.008) and the median cyst volume reduced from 2 419.7 mm 3 to 1 099.5 mm 3 ( Z=-2.134, P=0.033). The complication incidence of the second ablation was 2/15, similar to that of the first ablation. Conclusion:The second ablation is effective and safe without increasing the complication incidence in patients without achieving CR after the first EUS-LA.

Ameliorative Effect of miR-31 on Liver Injury in Type 2 Diabetic Mice / 中国生物化学与分子生物学报

Type 2 diabetes mellitus (T2DM) is a metabolic disease with an increasing incidence worldwide, which leads to damage to various tissues and organs including the liver. MiR-31 is conserved across species and closely associated with metabolic diseases, but its role in type 2 diabetic liver injury has not been elucidated. This study aimed to investigate the effect of miR-31 on liver injury in type 2 diabetes and its underlying mechanism. Four to six weeks old male FVB mice and miR-31-positive transgenic mice were randomly divided into FVB mice control group (C), FVB mice induced diabetes group (DM) and miR-31-overexpression transgenic mice induced diabetes group (31DM). After 1 week of adaptive feeding, the T2DM mouse model was induced by high-fat feeding combined with intraperitoneal injection of streptozotocin (STZ) for 6 weeks. The general condition of mice and related metabolic indicators showed that the increased food and water intake, weight loss and glucose and lipid metabolism disorders could be reversed by miR-31 in T2DM mice. HE staining and liver histological activity index (HAI) scoring results showed that miR-31 improved the inflammatory status in the liver tissue of T2DM mice and decreased the HAI score. RT-qPCR results showed that the high expression of miR-31 was accompanied by a decrease in the expression of activating transcription factor 6 (ATF6) mRNA in the liver of T2DM mice. Furthermore, Western blotting results showed that miR-31 inhibited the expression of endoplasmic reticulum stress-related proteins such as ATF6, glucoregulatory protein 78 (GRP78) and C/EBP homologous protein (CHOP) in the liver of T2DM mice. In conclusion, miR-31 may ameliorate liver injury in T2DM mice by regulating glucose and lipid metabolism disorders and insulin resistance, and inhibiting endoplasmic reticulum stress factors such as ATF6, GRP78, and CHOP.

Research progress on bone metabolism disorders associated with PCOS elucidated from endocrine hormones / 中国临床药理学与治疗学

Polycystic ovary syndrome (PCOS) is a common endocrine metabolic disease of women. Clinical studies have shown that PCOS patients are likely having abnormal bone metabolism, and with increased risk of osteoporosis. This review summarized the common pathological mechanisms for both PCOS and osteoporosis, and elucidated the research progress on PCOS-inducing bone metabolism disorders from emphasizing on the regulation of endocrine hormones including insulin, androgen, growth hormone, vitamin D, parathyroid hormone and calcitonin. It is expected that this review will shed new light on monitoring and intervention for bon health of PCOS patients.

Advances in neoadjuvant therapy of esophageal cancer involved in organ preservation / 国际肿瘤学杂志

Esophageal squamous cell carcinoma is one of the most common cancer in China, and locally advanced stage remains a heterogeneous and complex disease. Its treatments are constantly evolving. To date, radiochemotherapy and surgery are involved in the comprehensive treatment of this disease. However, because of the specifical anatomical location of esophagus, its physiological function will be impaired after surgical resection. If similar survival is obtained in esophageal cancer, an organ preserving strategy without surgery is of great significance for improving the quality of life. As a non-invasive tumor treatment method, neoadjuvant therapy plays an important role in the comprehensive treatment of preserving the esophagus. Recently, there are studies investigating the role of organ preserving strategy in the comprehensive treatment of esophageal cancer with neoadjuvant therapy, and the recognition of these advances will provide reference value for the comprehensive treatment of esophageal cancer.

Improving effect of human umbilical cord mesenchymal stem cell transplantation on depression behavior in chronic stress model mice / 解剖学报

Objective To study the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) tail vein transplantation on depressive behavior in chronic unpredictable mild stress (CUMS) model mice. Methods The third generation hUCMSCs were abtained; Sixty C57BL/6 male mice were randomly divided into the normal model group (+ normal saline), the cell group (+hUCMSCs) and the fluoxetine(flu) group (+flu), with 15 mice in each group. The depression model of CUMS mice with a 6 week duration was constructed; From the third week, hUCMSCs and normal saline were transplanted into the mice by tail vein injection, and the mice were gavaged with flu daily from the fifth week; Weight changes in each group were recorded weekly; The depression model and therapeutic effect of mice were evaluated by sucrose preference test, tail suspension test, forced swimming test and open field test; The cell changes of CAI and CA3 region in hippocampus were observed by HE staining; Transmission electron microscopy was used to detect the changes of synapses in CA3 region of hippocampus; Real-time PCR was used to detect mRNA expressions of synaphysin (SYP) and postsynaptic density protein 95 (PSD-95), which are key proteins of synaptic plasticity. Results hUCMSCs improved weight decrease in depressed mice; behavioral experiments observed that the model group mice showed depressive behavior, while the cell group and the drug group mice depression were improved; HE staining showed that, compared with the model group, cells in CA 1 and CA3 regions of the hippocampus of mice in the cell group and the group were arranged orderly and the number of cells increased; Transmission electron microscopy showed that compared with the model group, the number of synapses in the CA3 region of the hippocampus was more, the synaptic gap was narrower, and the density of synaptic spines was higher in the cell group and the drug group; More mRNA expressions of SYP and PSD-95 were detected by Real-time PCR in the cell group and the drug group than in the model group. Conclusion hUCMSCs transplatation showes antidepressant effects, which are associated with improved synaptic plasticity in the hippocampus.

Long-term effects of endoscopic ultrasonography-guided lauromacrogol ablation for the treatment of pancreatic cystic neoplasms: a prospective study (with video) / 中华消化内镜杂志

Objective:To determine the safety and long-term efficacy of endoscopic ultrasonography-guided lauromacrogol ablation (EUS-LA) for treatment of pancreatic cystic neoplasms (PCNs) with a larger population.Methods:From April 2015 to April 2019, 255 patients suspected of PCNs were enrolled in the First Medical Center of Chinese PLA General Hospital in the study, and 57 patients underwent EUS-LA. The effectiveness of EUS-LA was determined based on imaging volume changes. The occurrence of complications was observed and recorded.Results:Among the 57 patients who underwent EUS-LA, 38 were female and 19 were male, with the mean age of 52.0±14.6 years. The cysts were located in the head/uncinate of the pancreas in 33 patients and in the body/tail of the pancreas in 24 patients. A total of 50 patients were followed up by imaging examinations. After treated by EUS-LA, the cyst median volume sharply reduced from 11 434.1 mm 3 to 639.4 mm 3 ( Z=-5.556, P<0.01), and the median diameter decreased from 32.0 mm to 12.0 mm ( Z=-6.161, P<0.01). Postoperative imaging showed a complete resolution in 24 patients (48.0%), partial resolution in 14 patients (28.0%), and persistent cyst in 12 patients (24.0%). The total number of ablation was 69, and there were 12 patients undergoing a second ablation. The adverse events rate was 4.3% (3/69). Among the 34 patients followed up for 12 months or more, complete resolution was observed in 18 patients (52.9%), partial resolution in 9 (26.5%), and persistent cyst in 7 (20.6%). Conclusion:EUS-LA is effective and safe for the treatment of PCNs. Its effectiveness is stable after more than 12 months′ follow-up.

Value of three scoring systems in evaluating the prognosis of children with severe sepsis / 中国当代儿科杂志

OBJECTIVE@#To study the predictive value of Pediatric Age-adapted Sequential Organ Failure Assessment Score (pSOFA), Pediatric Risk of Mortality Score III (PRISM III), and Pediatric Critical Illness Score (PCIS) in children with severe sepsis.@*METHODS@#A retrospective analysis was performed for the clinical data of 193 hospitalized children with severe sepsis. According to the final outcome, these children were divided into a survival group with 151 children and a death group with 42 children. The scores of pSOFA, PRISM III, and PCIS were determined according to the worst values of each index within 24 hours after admission. The receiver operating characteristic (ROC) curve was used to analyze the efficiency of each scoring system in predicting the risk of death due to sepsis. Smooth curve fitting was used to analyze the correlation between the three scoring systems and the threshold effect of each scoring system. Decision curve analysis (DCA) was used to evaluate the application value of each scoring system.@*RESULTS@#The ROC analysis showed that PCIS and pSOFA had a similar predictive value (P=0.182) and that PRISM III and pSOFA had a similar predictive value (P=0.210), while PRISM III had a better predictive value than PCIS (P=0.045). PRISM III had the highest degree of fitting with prognosis, followed by pSOFA and PCIS. The DCA analysis showed that when the risk of death was 0.4 and 0.6 in children with severe sepsis and the three scoring systems were used as the basis for emergency intervention decision-making, pSOFA achieved the highest standardized net benefit, followed by PRISM III and PCIS.@*CONCLUSIONS@#All three scoring systems have a certain value in predicting the prognosis of children with severe sepsis, and pSOFA has a better value than PRISM III and PCIS.

Endoscopic resection for non-ampullary duodenal neuroendocrine tumors:a retrospective study / 中华消化内镜杂志

Objective To assess the diagnostic accuracy of preoperative endoscopic ultrasonography (EUS) for tumor size and invasion of non-ampullary duodenal neuroendocrine tumors (NA-DETs) and to compare the efficacy and safety of endoscopic submucosal dissection ( ESD ) and modified ESD for the treatment of NA-DETs. Methods Data of 22 patients with 22 NAD-NETs confirmed by histopathological examinations from January 2007 to January 2018 were retrospectively analyzed. ESD was performed on 13 tumors, and modified ESD was performed on 9 tumors. R0 resection rate, procedure time and incidence of procedure-related complications in the ESD group and the modified ESD group were compared. The postoperative pathological results were used as the gold standard to assess the accuracy of preoperative EUS in diagnosing tumor size and invasion of NA-DETs. Results The mean size of NA-DETs was 6. 9 ± 1. 5 mm. The accuracy in assessing the invasion depth by EUS was 95. 5％ ( 21/22 ) compared with histological results. R0 resection was achieved in 13/13 ( 100. 0％) of the ESD group and in 7/9 ( 77. 8％) of the modified ESD group (P=1. 000). The procedure time was significantly shorter in the modified ESD group than that in the ESD group ( 16. 0 ± 2. 2 min VS 29. 8 ± 4. 9 min, P<0. 001 ) . Intraoperative perforation occurred in one patient and delayed perforation occurred in one patient in the ESD group. Delayed bleeding occurred in one patient in the modified ESD group. Follow-up data were available in all cases with a mean period of 30. 0±24. 8 months. No cases of local recurrence or distant metastasis were detected in the follow-up period. Conclusion EUS can accurately assess the size and depth of NAD-NETs. Modified ESD can provide comparable clinical outcomes to ESD for NAD-NETs ≤10 mm in diameter that are confined to the submucosa.

Application of endoscope assisted curved laryngoscopy technique in transoral laryngopharyngeal minimally invasive surgery / 中华耳鼻咽喉头颈外科杂志

Objective@#To explore the possibility of endoscope assisted curved laryngoscopy technique applied in transoral laryngopharyngeal minimally invasive surgery and evaluate the advantages of this technique.@*Methods@#Eight patients with huge benign lesions in larynx and pharynx undergoing transoral microsurgery at Peking University Third Hospital between February 2016 and February 2017 were enrolled in this study.The diagnosis included cyst at the base of tongue in two patients, cysts in the epiglottis in two patients, hemangioma in two patients, multiple masses of the hypopharynx and amyloidosis in supraglottic area in one patient each.The time and exposure during surgery, occurrence rate of complication and conditions of following-up were recorded.@*Results@#The mean time of surgery was 20 min, the exposure was satisfying.There was no obvious complication after surgery.No residual or recurrent lesion was observed after 1 to 12 months follow-up(mean time 4.5 months).@*Conclusion@#The endoscope assisted curved laryngoscopy technique has advantages in shortening the time of surgery, improving exposure and reducing the rate of complication and recurrence.

Clinical efficacy analysis of submucosal tunneling endoscopic resection for upper gastrointestinal submucosal tumors / 中华消化内镜杂志

Objective To investigate the clinical efficacy and application value of submucosal tunneling endoscopic resection(STER)for upper gastrointestinal submucosal tumors(SMTs). Methods A retrospective analysis was performed on the endoscopic and clinical data of 44 cases with SMTs who received STER from January 2015 to June 2016 in Chinese PLA General Hospital. Results The rate of complete resection was 88.6%(39/44). The operating time was 60.1±30.6 min. The hospitalization time was 10.1± 3.3 days. The rate of complications was 6.8%(3/44). The diagnosis of SMTs by pathology and endoscopic ultrasonography(EUS),the size of SMTs measured by EUS and ruler after STER,and the growing direction judged by EUS and CT were consistent. Conclusion STER for SMTs has a higher complete resection rate, shorter operating time and hospitalization time, and fewer complications. EUS combined with CT is an effective method for preoperative evaluation.

Comparsion of GV oocytes transcriptome between PCOS patients and normal ovulatory women / 吉林大学学报(医学版)

Objective: To investigate the effects of controlled ovarian stimulation (COS) on the differentially expressed genes in GV oocytes and main signal transduction pathways in the polycystic ovary syndrome (PCOS) patients and the normal ovulatory women, and to screen the key genes impacting the development of oocytes of the PCOS patients. Methods: During controll ovarian hyperstimulation with GnRH-a long protocol, 3 patients with PCOS (PCOS group) and 3 normal ovulatory women due to male infertility factor (control group) were selected. Enzyme digestion was used to islolate the granule cells. The dumped immature oocytes were collected after intracytoplasmic sperm injection (ICSI). The cDNA library was constructed and sequencing was performed in Illumina MiSeq sequencing platform and RT-PCR was used to confirm the data obtained in vivo. Results: A total of 510 024 82 sequence reads were obtained, and 8 G base sequence information were contained. A total of 63 differentially expressed genes were found by bio-informatics software, including 19 significant up-regulation genes and 44 significant down-regulation genes (Fold Change>4, FDR<0. 01). The expression levels of vascular endothelial growth (VEGF) and fatly acid dehydrogenase 1 (FADS1) mRNA in the patients in PCOS group were significantly higher than those in control groups (P

Biocompatibility of modified nano-hydroxyapatite/polyvinyl alcohol porous composite hydrogel as an artificial corneal material / 中国组织工程研究

BACKGROUND:How to improve the stability of artificial cornea in the host and reduce the complications is the current key issues to be solved.Therefore,looking for an ideal biocompatible scaffold material is still the focus of the study.OBJECTIVE:To explore the biocompatibility of nano-hydroxyapatite (nHA)/polyvinyl alcohol (PVA) porous composite hydrogel and pure PVA hydrogel as artificial corneal materials.METHODS:Inverted microscope was used to observe cell growth of rabbit corneal stromal fibroblasts when cultured with nHA/PVA composite hydrogel extract or PVA extract for 48 hours.MTT method was used to detect the relative proliferation rate of rabbit corneal stromal fibroblasts cultured with nHA/PVA composite hydrogel extract or PVA extract.Systemic toxicity,allergies,pyrogen reaction and deaths were observed in New Zealand white rabbits at 48 hours after artificial corneal implantation.ELISA and hematoxylin-eosin staining were used to detect changes in serum inflammatory factors at 4 weeks after artificial corneal implantation.Slit-lamp examination was performed to observe corneal or conjunctival hyperemia/edema and corneal neovascularization at 1-4 weeks after corneal implantation.Corneal neovascularization time and neovascularization area were detected after the two materials were implanted.RESULTS AND CONCLUSION:The cells were sparse and grew slowly at 48 hours after culture in nHA/PVA composite hydrogel or PVA extract as compared with the blank control group.The cell growth in the nHA/PVA composite hydrogel group was better than that in the PVA group.The relative cell proliferation rate was significantly decreased at different time after culture in nHA/PVA composite hydrogel or PVA extract compared with the blank control group (P ＜ 0.05),and the relative cell proliferation rate in the nHA/PVA composite hydrogel group was significantly higher than that in the PVA group (P ＜ 0.05).There were two rabbits appearing to have allergic reaction,but no one presenting with pyrogen reaction and death in the nHA/PVA composite hydrogel group;and there were two rabbits appearing to have allergic reaction,and two appearing to have pyrogen reaction,but no death in the PVA group at 48 hours after implantation.The inflammatory factor levels were increased significantly in the nHA/PVA composite hydrogel group and PVA group compared with the control group (P ＜ 0.05),and inflammatory infiltration was milder in the nHA/PVA composite hydrogel group than the PVA group at 4 weeks after implantation (P ＜ 0.05).Corneal neovascularization appeared later in the nHA/PVA composite hydrogel group than the PVA group,and the neovascularization area was also smaller in the nHA/PVA composite hydrogel group than the PVA group (P ＜ 0.05).Taken together,the biocompatibility of nHA/PVA composite hydrogel is superior to that of pure PVA when they are used as artificial cornea materials,which provides a scientific basis for artificial cornea material innovation and extensive clinical application.

Endoscopic ultrasonography-guided lauromacrogol ablation for pancreatic cystic neoplasms: a prospective study / 中华消化内镜杂志

Objective To evaluate the safety and effectiveness of endoscopic ultrasonography (EUS)-guided ablation with lauromacrogol for pancreatic cystic neoplasms(PCNs). Methods A total of 38 patients with PCNs admitted to Chinese PLA General Hospital from April 2015 to March 2017 were prospectively enrolled to receive EUS-guided ablation with lauromacrogol. Adverse events, such as pancreatitis,fever,bleeding and abdominal pain, were monitored during and after the procedure. Patients were followed up with contrast-enhanced CT or MRI in 3 months,6 months,1 year and 2 year after ablation. Results Thirty-eight patients were enrolled in the study, and 8 of them underwent a second ablation;so, there were 46 treatments. There were 24 females and 14 males with mean age being 53.9±14.7 years. Mild acute pancreatitis occurred in 2 cases and moderate fever occurred in 1 case. The adverse events rate was 6.5%(3/46). Among the 29 patients with complete follow-up of 5 months(2-17 months), the medium tumor volume before operation was 7 564.40 mm3(301.38-87 082.87 mm3)while 542.84 mm3(0-18 202.58 mm3)after the operation(P=0.000). A total of 14 had complete remission(CR)and 8 had partial remission(PR)in 29 patients. The remission effective rate was 48.3%(14/29),40.0%(8/20)in the cysts of the head/uncinate and 66.7%(6/9)in the body/tail(P=0.353). The medium surface area of CR group seemed smaller than that of non-CR group(1 194.27 mm2VS 1 764.09 mm2, P=0.023). Conclusion EUS-guided ablation with lauromacrogol for PCNs is safe and effective. Cysts of smaller surface are more likely to be cured than larger ones.

Effects of FOXO3a on regulating mitophagy in hepatic ischemia reperfusion injury / 天津医药

Objective To investigate the effect of transcription factor FOXO3a on mitophagy in hepatic ischemia-reperfusion injury in mice. Methods A total of 30 male C57BL/6 mice were randomly divided into Sham operation group (Sham) and ischemia reperfusion (IR) 2 h, 6 h, 12 h and 24 h groups, 6 mice in each group. The mouse model of liver ischemia -reperfusion injury was established. Blood biochemical methods were used to detect changes of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). HE staining and TUNEL were used to observe the damages of liver tissue and apoptosis. Western blot assay and qRT-PCR were used to detect the expressions of transcription factor FOXO3a, mitochondrial autophagy-related protein Nix protein and its mRNA expression in each group. Mouse liver AML12 cells were treated with FOXO3a and Nix interfering RNA, and the model was established for 6 h after hypoxia for 1.5 h.These cells were divided into siRNA-NC group, FOXO3a siRNA group and Nix siRNA group. MTT assay was used to detect the viability of cells in each group. The number and distribution of autophagy in each group were observed by confocal microscopy. The expressions of FOXO3a, Nix, microtubule-associated protein LC3, apoptotic protein P62 and Caspase-3 were detected by Western blot assay. Results The levels of ALT and AST in all groups of IR were reduced, and reached the peak value at 6 h (P<0.05). HE and TUNEL results showed that liver injury and apoptosis were the most serious at 6 h after reperfusion. The expression of FOXO3a and Nix was higher in IR group than that in the Sham group, and the expression level of FOXO3a mRNA was the highest at 12 h after reperfusion, the expression of Nix mRNA was the highest at 6 h after reperfusion (P<0.05). Western blot assay showed the highest expression of FOXO3a in the reperfusion of 12 h, and the highest expression levels of Nix, Caspase-3 and LC3Ⅱin reperfusion 6 h. After interfering with the expression of FOXO3a, MTT showed a marked reduction in cell survival (P<0.05), Western blot assay showed that the expression level of FOXO3a was significantly higher in siRNA-NC group than that in FOXO3a siRNA group, and the expression levels of Nix, Caspase-3 and LC3Ⅱwere significantly lower than those of FOXO3a siRNA group. Confocal microscopy showed that the number and distribution of autophagosomes were significantly lower in siRNA-NC group than those in FOXO3a siRNA group. After interfering with the expression of Nix, MTT showed a marked increase in cell survival (P<0.05), Western blot assay showed that the expression levels of Nix, P62 and LC3Ⅱ were significantly higher in siRNA-NC group than those in Nix siRNA group. Conclusion FOXO3a can reduce the hepatic ischemia-reperfusion injury in mice, which may be related to the FOXO3a inhibition for liver cell mitophagy and apoptosis.