Chloroplast genome resolution and phylogenetic analysis of Ardisia crispa var. amplifolia and Ardisia crispa var. dielsii / 药学学报

italic>Ardisia crispa (Thunb.) A. DC. is a traditional Miao medicinal herb with significant therapeutic effects in the treatment of sore throat, tonsillitis, edema of nephritis and bruising and rheumatism, etc. Ardisia crispa var. amplifolia and Ardisia crispa var. dielsii are varieties of A. crispa. A. crispa var. amplifolia and A. crispa var. dielsii are controversial in terms of species evolutionary relationships and taxonomic identification. In this study, we sequenced the whole genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii chloroplasts using Illumina platform, assembled, annotated and characterized them, compared the structural features and degree of variation among chloroplast genomes using bioinformatics methods, and also downloaded constructing phylogenetic trees to analyze the phylogenetic relationships of chloroplasts in Primulaceae and Myrsinaceae using whole genome sequence information. The results showed that the complete chloroplast genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii were 156 749 bp and 156 748 bp in length, with 132 genes annotated, including 87 protein-coding genes; the codon preference of A/U was greater than that of G/C; The differences in the coding regions of rps15 and rpoB genes in the comparative genome analysis can be used as loci for molecular identification of the two species; the differences in the coding regions of ycf1, ycf2, rpoC1, ycf3, petD and rpl16 genes in the chloroplast genome compared with those of the same genus can be used as loci for identification of the genus. In the phylogenetic results, A. crispa var. amplifolia and A. crispa var. dielsii were clustered together with 100% support, indicating that they are closely related. In this research, we analyzed the chloroplast genome structure and phylogenetic relationships of A. crispa var. amplifolia and A. crispa var. dielsii, providing an important theoretical basis for their molecular identification, genetic variation, breeding and phylogenetic analysis.

Efficacy and safety of levetiracetam versus valproic acid in the treatment of pediatric epilepsy：a meta analysis / 中国药房

OBJECTIVE To compare the efficacy and safety of levetiracetam versus valproic acid in the treatment of pediatric epilepsy， and to provide evidence-based reference. METHODS The databases including CNKI， VIP， China Biomedical Literature Database， Wanfang data， PubMed， Embase and Cochrane Library were searched for the RCTs about levetiracetam （trial group） and valproic acid （control group） were collected from the inception to October 1st， 2021. After literature screening and data extraction， the quality of included literature was evaluated using the bias risk assessment tool recommended by Cochrane system evaluator manual 5.1.0 and RevMan 5.3 software were used for meta-analysis， sensitivity analysis and bias risk analysis. RESULTS A total of 33 RCTs were included， involving 3 116 patients in total. The results of the meta-analysis showed that the effective rate of trial group was significantly higher than control group [RR＝1.06， 95%CI （1.02， 1.11）， P＝0.003]. The subgroup analysis according to different courses of treatment showed that there was no statistical significance in the effective rate between 2 groups after 1 and 3 months of treatment （P＞0.05）； after 6 months of treatment， the effective rate of trial group was significantly higher than that of control group （P＜0.05）. The incidence of adverse drug reaction in trial group was significantly lower than control group [RR＝0.50， 95%CI （0.41， 0.61）， P＜0.000 01]； among specific adverse drug reactions， the incidence of nausea and vomiting in trial group was significantly lower than control group （P＜0.05）； but there was no statistical significance in the incidence of rash， drowsiness， abnormal mood， loss of appetite， dizziness or headache （P＞0.05）. Results of sensitivity analysis showed that study results were stable and reliable. Results of publication bias analysis showed that there was little possibility of publication bias in this study. CONCLUSIONS The short-term efficacy （1， 3 months） of LEV is similar to that of VPA in the treatment of pediatric epilepsy， but long-term efficacy （6 months） of LEV is better than that of VPA； moreover， LEV shows better safety in digestive system.

Value of red blood cell distribution width in evaluating the severity of illness of novel coronavirus Delta variant / 中华危重病急救医学

Objective:To explore the value of red blood cell distribution width (RDW) in evaluating the severity of patients infected with novel coronavirus Delta variant.Methods:A total of 28 patients infected with novel coronavirus Delta variant in designated hospital treated by the First Affiliated Hospital of Xi'an Jiaotong University medical team from December 2021 to January 2022 were enrolled (23 cases of common type, 4 severe and 1 critical cases). The detailed clinical data of patients was collected. Then, Pearson's correlation analysis was used to identify the blood examination indexes which affected the arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2). According to the median standard deviation of red blood cell distribution width (RDW-SD, 42.5 fL), 28 patients were divided into low RDW-SD group (≤ 42.5 fL, 16 cases) and high RDW-SD group (> 42.5 fL, 12 cases), and the immune related indexes of the two groups were compared. Receiver operator characteristic curve (ROC) was drawn to evaluate the predictive value of RDW-SD on the severity of illness of coronavirus disease 2019 (COVID-19). Results:Correlation analysis showed that RDW-SD was the only index related to PaO 2 and PaCO 2 on the first day of admission, which was negative correlation with PaO 2 ( r = -0.379, P = 0.047) and positive correlation with PaCO 2 ( r = 0.509, P = 0.006). The results of effects of different clinical characteristics on RDW-SD level showed that there was no statistically significant difference in RDW-SD between groups with different clinical characteristics (including male/female, ≥ 65 years old/< 65 years old, having/without hypertension, having/without diabetes, smoking/not smoking, having/without hyperpyrexia, with/without fever for 3 days, with/without respiratory symptoms, with/without digestive symptoms). It was suggested that RDW-SD be relatively stable and not affected by the patient's baseline level. The percentage of B cells in low RDW-SD group was higher than that in high RDW-SD group (23.01±3.01 vs. 15.34±5.34, P < 0.05), immunoglobulin G (IgG) level in low RDW-SD group was lower than that in high RDW-SD group (g/L: 11.43±3.20 vs. 15.42±1.54, P < 0.05). The area under ROC curve (AUC) of RDW-SD in evaluating severe cases was 0.83 [95% confidence interval (95% CI) was 0.59-1.06], which was close to multilobularinltration, hypo-lymphocytosis, bacterial coinfection, smoking history, hyper-tension and age (MuL BSTA score; AUC = 0.82, 95% CI was 0.51-1.12) and better than British Thoracic Society's modified pneumonia score (CURB-65 score; AUC = 0.70, 95% CI was 0.50-0.91). Conclusion:RDW-SD has significant evaluative effect on the severity of COVID-19 patients with Delta variants.

Content determination of ginsenoside Rb1, cinnamic acid, paeoniflorin and berberine in Wenxin Formula based on UPLC-MS/MS MRM mode / 国际中医中药杂志

Objective:To establish a qualitative and quantitative analysis method of ginsenoside Rb1, cinnamic acid, paeoniflorin and berberine in Wenxin formula based on UPLC-MS/MS MRM model so as to provide a rapid and accurate evaluation method for the research and development of new drugs.Methods:Adopting Waters ACQUITY UPLCTM HSS T3 (2.1 mm×100 mm, 1.8 μm) and gradient elution was performed by mobile methanol-0.03% formic acid water. chromatographic column was used with electrospray ionization source in the scanning mode of multiple reactive ion monitoring (MRM) for ion separation and screening. The retention time and the relative abundance ratio (qualitative ion pairs/quantitative ion pairs) was used for qualitative analysis, while quantitative ion pairs was used for quantitative analysis.Results:The four components tested in Wenxin Formula have been qualitatively detected and showed a good linear relationship, the method showed accuracy, precision, repeatability, and stability, the recovery rate was 96.24%-104.19% and RSD was 1.29%-3.30%. Conclusion:The established method is simple, accurate, rapid and sensitive, which is reliable for the qualitative and quantitative study of the four main components in Wenxin Formula.

Herbal textual analysis of Caryophylli flos / 国际中医中药杂志

The ancient herbal books, and literatures were reviewed, and the textual research and origin of Caryophylli flos were explored from the differences between Caryophylli flos and Caryophylli fructus, the alias of Caryophylli flos and Caryophylli fructus, the origin and introduction of Caryophylli flos, and its efficacy and indications. The results indicated that Caryophylli flos and Caryophylli fructus were different from each other in terms of synonyms, chemical components and pharmacological effects. Caryophylli flos was brought to China as a spice in the Wei, Jin, Southern and Northern Dynasties, and the efficacy of Caryophylli flos was almost same in ancient and modern time. Caryophylli flos is widely used in digestive and dental diseases, and Caryophylli flos is also one of the seven natural spices, which can be used for food preservation.

Investigation and analysis of concentrations of radium-226 and uranium in agricultural products around uranium tailings pond / 中国辐射卫生

@#<b>Objective</b> To investigate the radionuclide radium-226 and natural uranium content in the main agricultural products around a decommissioned uranium tailings pondand to determine the radioactivity level in the food around the tailings pond. <b>Methods</b> From 2017 to 2021, several samples of rice and beans were collected in the surrounding area of the tailings pond for five consecutive years, and the concentrations of radium-226 and natural uranium were measured by a high-purity germanium gamma spectrometer. The annual accumulated effective dose of internal exposure caused by radium-226 ingested through local standard human diet was estimated by the indirect method. <b>Results</b> The detection rate of natural uranium in rice was 96.0%, and the detection rate of radium-226 was 74.0%; the detection rate of natural uranium in beans was 96.7%, and the detection rate of radium-226 was 73.3%. The annual accumulated effective dose caused by radium-226 ingested through diet was about 170.22 μSv/a in surrounding residents. <b>Conclusion</b> The concentrations of radium-226 and natural uranium in the main agricultural products around the tailings pond are within the limit of the national standard. By comparing with the research results in related fields in China, the radiation effects caused by radium-226 ingested through dieton the residents around the tailings pond are acceptable.

Vacuoles in muscle fiber: pathological differences in various diseases / 中华神经科杂志

The vacuole in muscle fibers is a non-specific myopathological change. As a myopathological term, it occurs in several rare disorders. The vacuoles are mostly related to the autophagy of glycogen, lipids, abnormal proteins, and organelles, and a few are caused by glycogen or lipids deposition or sarcoplasmic reticulum luminal vacuolization. The vacuoles impair the structure of muscle fibers, being one of the myopathological features in various diseases. In this review, clinical features and myopathological changes of various diseases with vacuolar muscle fibers were introduced and the diagnostic value of intrafibral vacuoles was focused on. Knowing the underlying pathogenesis is required to understand these myopathological changes.

Characteristics and risk factors of local recurrence in resected pancreatic cancer / 中华普通外科杂志

Objective:To investigate the characteristics and risk factors of local recurrence in resected pancreatic cancer.Methods:The clinicopathological data of 190 patients in whom recurrent sites can be identified after radical resection of pancreatic cancer from Sep 2013 to Aug 2020 at the Cangzhou Central Hospital were retrospectively analyzed. The survival time and clinicopathological characteristics of local recurrence were compared with those of other recurrence types. Cox risk regression model was used to analyze the risk factors of local recurrence.Results:The recurrence sites were local (49 cases, 25.8%), liver (53 cases, 27.9%), lung (35 cases, 18.4%), peritoneal (25 cases, 13.2%) and multiple sites (28 cases, 14.7%). Patients mRFS and mOS were 17.8 months and 30.9 months respectively. The clinicopathological features of patients with local recurrence were compared with those of other recurrence types [tumor diameter ( P=0.023), preoperative CA199 level ( P=0.021), peripancreatic nerve plexus invasion ( P=0.031), lymphovascular invasion ( P=0.004), surgical margin state ( P<0.001) and postoperative adjuvant chemotherapy ( P=0.038)]. Tumor diameter ( P=0.018), peripancreatic nerve plexus invasion ( P=0.002) and postoperative adjuvant chemotherapy ( P=0.004) were independent factors for local recurrence in resected pancreatic cancer, and only peripancreatic nerve plexus invasion was not associated with other recurrence types. Conclusions:Local recurrence in resected pancreatic cancer has important impact on the prognosis of patients. Peripancreatic nerve plexus invasion is an independent factor affecting local recurrence.

Clinical analysis of prostate targeted biopsy guided by multiparametric magnetic resonance imaging and 68Ga-PSMA PET/CT image fusion / 中华泌尿外科杂志

Objective:To explore clinical value of prostate target biopsy guided by multiparametric magnetic resonance imaging (mpMRI) and 68Ga-labeled prostate specific membrane antigen ligand imaging positron emission tomography/X-ray computed tomography ( 68Ga-PSMA PET/CT) image fusion. Methods:The data of 50 patients admitted to Fudan University Shanghai Cancer Center from January 2021 to February 2022 who underwent mpMRI and 68Ga-PSMA PET/CT to guide prostate biopsy were retrospectively analyzed. The median age was 70 (63-79) years, the median serum tPSA value was 8.1 (6.8-83.0) ng/ml, and the prostate volume was 45.5 (30-80) ml. 36 cases were positive by mpMRI, including PI-RADS score 3 in 5 cases, 4 score in 19 cases, 5 score in 12 cases. 32 cases were positive by 68Ga-PSMA PET/CT examination, of which 30 cases were double positive and the fusion of both imaging techniques was positive, referred to as PET/CT-MRI. The patient's mpMRI and 68Ga-PSMA PET/CT images were imported into the MIM fusion software, and the outline of the prostate and the target area were outlined respectively. When PET/CT and MRI double positive cases were biopsied, the two images were alternately fused, calibrated and locked with the real-time prostate ultrasound interface(PET/CT-MRI). Single-positive cases were guided by positive images to complete targeted biopsy, and 12-needle systematic biopsies were completed after targeted biopsy and double-negative cases. The advantages of targeted biopsy and systematic biopsy was evaluated, and the diagnostic performance (sensitivity, specificity, positive predictive value, and negative predictive value) was analyzed. Results:Among the 50 biopsy patients in this group, 31 (62%) had prostate cancer, of which 22 (44%) were CsPCa. There was no significant difference in the detection rate of prostate cancer between targeted biopsy and systematic biopsy [78.9% (30/38) and 62.0% (31/50), P=0.088], and there was no significant difference in the detection rate of CsPCa [57.9% (22/38) and 40.0% (20/50), P=0.096]. The positive rate of the biopsy needles number was significantly different [86.3% (69/80) and 19.0% (114/ 600), P<0.001]. The detection rates of prostate cancer in mpMRI positive, PET/CT positive and PET/CT-MRI positive cases were 83.3% (30/36), 90.6% (29/32) and 96.6% (29/30) respectively, the detection rates of CsPCa were 61.1% (22/36), 68.8% (22/32) and 73.3% (22/30) respectively.The sensitivity, specificity, positive predictive value and negative predictive value of mpMRI in the diagnosis of prostate cancer were 96.8%(30/31), 68.4%(13/19), 83.3%(30/36)and 92.9%(13/14), respectively.Those values in 68Ga-PSMA PET/CT were 93.5%(29/31), 84.2%(16/19), 90.6%(29/32)and 88.9%(16/18), respectively.Those values in PET/CT-MRI were 93.8%(29/31), 94.7%(18/19), 96.7%(29/30)and 90.0%(18/20), respectively. The above four indicators of mpMRI diagnosis of CsPCa were 100.0%(22/22), 50.0%(14/28), 61.1%(22/36)and 100.0%(14/14), respectively.Those indicators in 68Ga-PSMA PET/CT were 100.0%(22/22), 64.3%(18/28), 68.8%(22/32)and 100.0%(18/18), respectively.Those indicators in PET/CT-MRI was 100.0%(22/22), 71.4%(20/28), 73.2%(22/30)and 100.0%(20/20), respectively. The detection efficiency of PET/CT-MRI was better than that of mpMRI (Kappa value was 0.737, P=0.031). Conclusions:PET/CT-MRI image fusion-guided targeted prostate biopsy can effectively improve the detection efficiency of prostate cancer and clinically significant prostate cancer, and increase the positive rate.

Application of lumbar plexus-sciatic nerve block combined with low-dose Remimazolam anesthesia in elderly patients with intertrochanteric fractures / 中华老年医学杂志

Objective:To explore the value of lumbar plexus-sciatic nerve block combined with low-dose Remimazolam in elderly proximal femoral nail anti-rotation(PFNA)surgery.Methods:60 elderly patients with PFNA surgery were treated from September 2021 to March 2022 in our hospital.They were randomly divided into Propofol group receiving intravenous general anesthesia with laryngeal mask combined with Propofol(control group, n=30)and Remimazolam group with lumbar plexus-sciatic nerve block with laryngeal mask combined with low-dose Remimazolam anesthesia(experimental group, n=30). Mean arterial pressure(MAP)at different time points, heart rate, awakening quality[laryngeal mask removal time], vigilance / sedative observation(OAA / S)score at 15 min after surgery, observation time and various adverse reactions in anesthesia recovery room(in a postanaesthesia care unit, PACU), Montreal cognitive function scale(MoCA)1 day after operation, visual analog score(VAS)at different time points were compared between the two groups.Results:The levels of MAP and HR at the moments of T1, T2, T3, and T4 were lower in the observation group than in the control group(all P<0.05). The time of laryngeal mask removal was shorter in the observation group than in the control group[(8.7±1.3)min and(12.3±1.4)min, t=7.09, P<0.001]. The OAA/S scale value at 15 min after surgery was higher in the observation group than in the control group[(4.6±0.3)and(4.1±0.5), t=4.841, P<0.001]. The incidence of adverse reactions was lower in the observation group than in the control group(3.3% and 20%, χ2=4.043, P=0.044). Visual analogue scale(VAS)value at 3, 6 and 9 hour after surgery were lower in the observation group than in the control group(all P<0.05). The MoCA scores at 6 and 12 hours after operation were higher in the observation group than in the control group( P<0.05). Conclusions:Lumbar plexus-sciatic nerve block combined with low-dose Remimazolam in elderly PFNA surgery is effective and safe, which can reduce the intraoperative hemodynamic fluctuations, optimize the patient's recovery quality, facilitate the postoperative cognitive function recovery, reduce the various adverse reactions, and provide the good analgesic effect within 12 hours after operation.

The influence of parent-child cohesion of primary and middle school students on externalizing problem behaviors: chain mediating effect of security and self-control / 中华行为医学与脑科学杂志

Objective:To explore the effect sense of security and self-control on parent-child cohesion and externalizing problem behaviors in primary and middle school students.Methods:A total of 1 402 primary and middle school students were investigated with the problem behavior frequency scale(PBFS), family adaptability and cohesion scale(FACES-CV), security questionnaire(SQ) and brief self-control scale(BSCS). SPSS 25.0 and PROCESS v2.16 were used for statistical analysis, and common method deviation test, Pearson correlation analysis and intermediary effect analysis were used in the analysis.Results:Parent-child cohesion of primary and middle school students was positively correlated with security and self-control ( r=0.279, 0.303, both P<0.01), which was negatively correlated with externalizing problem behaviors ( r=-0.154, P<0.01). Security was positively correlated with self-control ( r=0.567, P<0.01). Security, self-control and externalizing problem behaviors were negatively correlated ( r=-0.147, -0.250, both P<0.01). The security and self-control of primary and middle school students played a partial mediating role between parent-child cohesion and externalizing problem behaviors.The mediating effect consisted of two paths: one was parent-child cohesion-self-control-externalizing problem behaviors, the other was parent-child cohesion-security-self-control-externalizing problem behaviors. The effect values of these two paths accounted for 20.52% and 20.26% of the total effect respectively. Conclusion:Parent-child cohesion not only directly affects the externalizing problem behaviors of primary and middle school students, but also indirectly affects the externalizing problem behavior through the independent mediating effect of self-control and the chain mediation of security-self-control.

Research about clinical comprehensive evaluation methods of pediatric drugs ：taking pediatric anti-allergic drugs as an example / 中国药房

OBJEC TIVE To provide reference for clinical comprehensive evaluation of pediatric drugs in China. METHODS Taking pediatric anti-allergic drugs as an example ，the clinical comprehensive evaluation methods of pediatric drugs in medical institutions were explored from the aspects of theme selection ，evaluation content and dimension ，evaluation index ，evaluation method and evaluation result report. RESULTS & CONCLUSIONS During the clinical comprehensive evaluation of pediatric drugs，under the guidance of relevant national guidelines for clinical comprehensive evaluation ，the evaluation topics could be selected according to the three principles of importance ，relevance and evaluability ，and then an appropriate evaluation index system could be developed around the six dimensions of safety ， effectiveness， economy， suitability，accessibility and innovativeness；qualitative and quantitative data integration analysis of the drugs to be evaluated were performed. In the evaluation ， it is necessary to focus on children ’s clinical basic drug use practice and decision-making needs ，normatively，scientifically and reasonably define the core index set and standard data set required by different dimensions of evidence ，standardize the collection and use of real-world data ，and effectively combine other types of evidence to truly play its advantageous role in the clinical comprehensive evaluation of pediatric drugs in China.

Characterization and phylogenetic analysis of the complete chloroplast genome of Lycopus europaeus / 药学学报

We intend to study the structural characteristics of Lycopus europaeus Linn. chloroplast genome and compare the evolutionary relationship of species from Lamiaceae with similar medicinal effects. The total DNA of Lycopus europaeus was sequenced using the Illumina Hiseq 4000 Sequencing platform and was assembled using NOVOplasty software. And then we annotated and analyzed the genome using the CPGAVAS2 online tool. We constructed the phylogenetic tree using the Stellera chamaejasme and Potentilla chinensis as the outgroup. The whole length of Lycopus europaeus chloroplast genome was 152 085 bp. A total of 132 genes were annotated including 88 protein-coding genes, 8 rRNA genes and 36 tRNA genes. Among them, 8 protein-coding genes (ndhB, rps7, rps12, rps19, rpl2, rpl23, ycf2, ycf15), 7 tRNA coding genes (trnM-CAU, trnL CAA, trnN-GUU, trnE-UUC, trnV-GAC, trnA-UGC, trnR-ACG) and 4 rRNA coding genes (rrn16s, rrn23s, rrn4.5s, rrn5s) are located in the IR region. There are 13 protein coding genes [rps16, rps19 (×2), atpF, rpoC1, rpl2 (×2), petB, petD, rpl16, ndhB (×2), ndhA] each contains one intron, two protein-coding genes (ycf3, clpP) each contain two introns, and 8 tRNA coding genes each contain one intron. A total of 34 SSRs were detected in the chloroplast genome of Lycopus europaeus. Phylogenetic analysis revealed that two species in the Lycopus genus, four species in the Dracocephalum genus, Glechoma longituba, two species in the Mentha genus and Prunella vulgari, in total 10 species are most related. The complete genome sequence of Lycopus europaeus was obtained and analyzed, which clarified the evolutional relationship between the species of Lycopus europaeus and in the Lamiaceae family.

Evaluation of bioceramic putty repairmen iRoot and mineral trioxide aggregate in mature permanent teeth pulpotomy / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the clinical characteristics and effectiveness of pulpotomy in mature permanent teeth with bioceramic putty repairmen iRoot and mineral trioxide aggregate (MTA).@*METHODS@#Pulpotomy was performed on mature permanent premolars and molars with carious exposures at the Department of General Dentistry of Peking University School and Hospital of Stomatology, from November 2017 to September 2019. The patients were randomly divided into 2 groups, Group iRoot (n=22) and Group MTA (n=21). In Group iRoot, bioceramic putty repairmen iRoot was used as pulp capping agent, while in Group MTA, mineral trioxide aggregate was used as pulp capping agent. All the patients had signed informed consent forms. The clinical efficacy was evaluated by clinical examinations (temperature and electrical activity test) and imaging examinations 3, 6, and 12 months after surgery. Blinding was used for the patients and evaluators, but due to the obvious differences in the properties of the two pulp capping agents, the blinding method was not used for the treatment provider (the attending physician).@*RESULTS@#There was no significant difference in gender, average age, dentition and tooth position distribution between the two groups (P>0.05). In the study, 7 cases were lost to follow-up 12 months after operation (4 cases in Group iRoot, and 3 cases in Group MTA). One case in each of the two groups had transient sensitivity at the end of the 3-month follow-up, and the pulp vitality was normal at the end of the 6-month follow-up. One case in Group iRoot showed sensitivity at the end of the 12-month follow-up. The success rates of the two groups at the end of 12-month follow-up were 100%, and the cure rates were 94.4% (Group iRoot) and 100% (Group MTA), respectively, and the difference was not statistically significant (P>0.05). No cases in Group iRoot had obvious crown discoloration, while 3 cases in Group MTA had.@*CONCLUSION@#The clinical characteristics and effectiveness of pulpotomy in mature permanent teeth with bioceramic putty repairmen iRoot were similar with MTA. Bioceramic putty repairmen iRoot is an acceptable material when used in pulpotomy of mature permanent teeth. Because it is not easy to cause tooth discoloration after treatment and is convenient to operate, bioceramic putty repairmen iRoot has a better clinical application prospect.

Application of next-generation sequencing in detection of BRCA1/2 and homologous recombination repair pathway multi-genes germline mutation and correlation analysis / 中华预防医学杂志

Objective: To investigate the germline mutation status of related genes in breast cancer patients and high-risk individuals by next-generation sequencing. To analyze the correlations between homologous recombination repair (HR) pathway gene mutation status and clinicopathological characteristics of breast cancer patients. To supplement the database of breast cancer related gene mutations in Chinese population. Methods: This study is a cross-sectional study. From October 2020 to September 2021, whole blood samples were collected from 350 breast cancer patients and 49 high-risk individuals, admitted to Peking University People's Hospital and accepted genetic testing voluntarily. Germline mutations in 32 breast cancer related genes were detected by NGS. The clinicopathological characteristics, including age at the onset, family history, unilateral/bilateral tumor, Luminal typing (Luminal A subtype, Luminal B subtype, HER2-enriched subtype and triple negative breast cancer), tumor size and metastasis, were analyzed, and the correlations between HR pathway gene mutation status and clinicopathological characteristics were analyzed by Chi-squared test and Fisher's exact probability test. Results: Among 350 breast cancer patients, 64 (18.3%) cases carried gene pathogenic mutations (including pathogenic and likely pathogenic mutations), including 47 (13.4%) in BRCA1/2, 16 (4.6%) in non-BRCA1/2 genes, 1 (0.3%) in BRCA2 and FANCL. Among 49 high-risk individuals, 7 (14.3%) cases carried gene pathogenic mutations, including 6 (12.3%) in BRCA1/2 and 1 (2%) in ATM genes. BRCA1/2 pathogenic mutations were associated with age at the onset (18%, 8.7%, χ²=6.346, P=0.012), and the BRCA1/2 pathogenic mutation frequency was higher in patients diagnosed at age ≤45 years. HR pathway gene mutations (including pathogenic, likely pathogenic and uncertain significance mutations) were correlated with unilateral/bilateral tumor (49.5%, 68.4%, χ²=4.841, P=0.028) and Luminal typing (45.7%, 62.2%, 32%, 60%, χ²=12.004, P=0.007), and the HR mutation frequencies were higher in patients with bilateral tumor, Luminal B breast cancer and triple negative breast cancer (TNBC). Conclusion: The BRCA1/2 pathogenic mutation frequency in high-risk individuals is similar to that in breast cancer patients, and BRCA1/2 testing is helpful to guide breast cancer screening and prevention in high-risk individuals. Patients with early onset breast cancer, bilateral breast cancer, Luminal B breast cancer and TNBC have higher mutation frequencies of HR pathway genes, and HR pathway genes testing should be conducted as soon as possible to provide laboratory evidence for diagnosis, treatment, prognosis and risk evaluation of breast cancer.

Therapeutic value of modified multipoint drainage for biliary complications after liver transplantation / 中华消化内镜杂志

Objective:To investigate the therapeutic value of modified multipoint drainage for biliary complications after liver transplantation.Methods:A total of 125 patients treated by endoscopic retrograde cholangiopancreatography (ERCP) for biliary complications after liver transplantation in Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2018 to May 2020 were enrolled. Patients were divided into endoscopic retrograde biliary drainage (ERBD) group ( n=67, treated with multiple drainage of bile duct stent) and modified multipoint drainage group [ n=58, treated with ERBD combined with endoscopic nasobiliary drainage (ENBD)] by random number table. Modified multipoint drainage group were further randomly divided into two groups, modification group 1, 31 cases, where nasobiliary ducts were cut proximal to duodenal papilla after one week under endoscopy and modification group 2, 27 cases, where they were cut proximal to duodenal papilla after two weeks under endoscopy. The changes of serological indexes in 2 weeks after the operation in three groups were compared, and the incidence of short-term and long-term complications were analyzed. Results:The serological indexes were improved in patients at 1 d, 7 d and 14 d after ERCP, especially in modified multipoint drainage groups. Two weeks after the operation, the improvement of serological indexes in modification group 2 was better than that in modification group 1. Incidence of recent complications including cholangitis, hyperamylasinemia, and pancreatitis in the ERBD group were higher than those in modification group 1 [32.84% (22/67) VS 12.90% (4/31), 46.27% (31/67) VS 19.35% (6/31), 20.90% (14/67) VS 3.23% (1/31), all P<0.05] and modification group 2 [32.84% (22/67) VS 11.11% (3/27), 46.27% (31/67) VS 22.22% (6/27), 20.90% (14/67) VS 3.70% (1/27), all P<0.05]. ERBD group had a higher incidence of long-term complications including recurrent biliary infection and jaundice than modification group 1 [ 58.21% (39/67) VS 35.48% (11/31), P=0.036; 49.25% (33/67) VS 25.81% (8/31), P=0.027] and modification group 2 [58.21% (39/67) VS 11.11% (3/27), P<0.001; 49.25% (33/67) VS 25.93% (7/27), P=0.038]. The incidence of recurrent biliary infection in modification group 1 was higher than that in modification group 2 [35.48% (11/31) VS 11.11% (3/27), P=0.030]. Conclusion:Multiple drainage with indwelling nasal bile duct by ERCP can effectively reduce the short-term and long-term complications and improve the recovery of serological indexes for patients with biliary complications after liver transplantation. It is suggested that the nasobiliary duct should be retained for 2 weeks and then transformed into a built-in tube to continue drainage.

Characteristics of intestinal flora in female patients with type 2 diabetes mellitus and coronary heart disease / 中华内分泌代谢杂志

Objective:To explore the characteristics of intestinal flora in female patients with type 2 diabetes mellitus (T2DM) with comorbid coronary heart disease.Methods:Female patients with T2DM from September 2019 to November 2020 were enrolled in this study and divided into 2 groups stratified by coronary heart disease: 22 patients with coronary heart disease(T2DM+ CHD group) and 49 patients with simple T2DM group(T2DM group). Thirty-one healthy females were selected as the normal control group(NC group). The abundance of intestinal flora, the difference in intestinal flora and its relationship with indicators such as glycosylated hemoglobin and fasting blood glucose was analyzed by the real-time fluorescent quantitative PCR detection technology in the three groups.Results:The abundance of Prevotella in the T2DM group was lower, and Roseburia inulinivorans and Faecalibacterium prausnitzii in the T2DM+ CHD group were lower, while Bacteroides and Enterococcus spp in the T2DM+ CHD group were higher compared with NC group, respectively( P<0.05). The abundance of Bacteroides and Enterococcus spp in the T2DM+ CHD group was lower than that in the T2DM group( P<0.05). Spearman correlation analysis showed that the abundance of Faecalibacterium prausnitzii and Eubacterium rectale was negatively correlated with obesity while abundance of Bacteroides and Enterococcus spp was positively correlated with HbA 1C and fasting blood glucose. The abundance of Bacteroides was positively correlated with TCH and TG(all P<0.05). Logistic regression analysis showed that Bacteroides and Enterococcus spp were independent influencing factor of the development of female patients with T2DM and CHD. Conclusion:Female T2DM and T2DM with CHD had intestinal flora imbalance, which was related to a variety of glucose and lipid metabolism indicators, and might be closely related to the occurrence of T2DM and CHD. Bacteroides and Enterococcus spp were independent influencing factors of the development of female patients with T2DM and CHD. Regulating the intestinal flora can provide ideas for the prevention and treatment of T2DM with CHD in female.

Clinical comprehensive evaluation of desloratadine in the treatment of urticaria / 中国药房

OBJECTIVE To eva luate the clinical comprehensive value of desloratadine in the treatment of urticaria. METHODS The clinical comprehensive evaluation index system based on six dimensions such as safety ，effectiveness，economy，suitability， innovation and accessibility were preliminarily determined by using the methods of literature investigation and expert investigation ； the core contents of the evaluation index system were evaluated and screened by Delphi method and analytic hierarchy process ；the importance of the index was assigned by Likert 5-level scoring method ；the evidence from various sources were collected and qualitative and quantitative integration analysis were conducted according to the clinical comprehensive evaluation index system with the help of system evaluation ，drug instructions ，expert guidelines/consensus ，adverse drug reaction monitoring report ，etc； the experts scored its clinical comprehensive value according to the clinical comprehensive evaluation evidence of each dimension of desloratadine ，combined with the weight of the clinical comprehensive evaluation index system ，the clinical comprehensive evaluation score of the tertiary indexes of desloratadine were calculated. The total clinical comprehensive evaluation score was obtained by accumulating the scores of each index ，and compared with loratadine. RESULTS This study successfully constructed the clinical comprehensive evaluation index system of desloratadine in the treatment of urticaria ，including 6 primary indexes ，13 secondary indexes and 30 tertiary indexes. The total clinical comprehensive evaluation score of desloratadine was 93.63 and that of loratadine was 70.91. CONCLUSIONS The clinical comprehensive value of desloratadine is higher than that of loratadine ，which can provide a reference basis for clinical rational drug use in medical institutions ，selection of drug use catalogue and improvement of national drug policy.

Epidemiological characteristics, diagnosis, treatment and prognosis of gallbladder cancer in China: a report of 6 159 cases / 中华消化外科杂志

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Inhibiting DNA methylation alleviates cisplatin-induced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1-PI3K/AKT pathway

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.