ADAR1 regulates vascular remodeling in hypoxic pulmonary hypertension through N1-methyladenosine modification of circCDK17

Pulmonary hypertension (PH) is an extremely malignant pulmonary vascular disease of unknown etiology. ADAR1 is an RNA editing enzyme that converts adenosine in RNA to inosine, thereby affecting RNA expression. However, the role of ADAR1 in PH development remains unclear. In the present study, we investigated the biological role and molecular mechanism of ADAR1 in PH pulmonary vascular remodeling. Overexpression of ADAR1 aggravated PH progression and promoted the proliferation of pulmonary artery smooth muscle cells (PASMCs). Conversely, inhibition of ADAR1 produced opposite effects. High-throughput whole transcriptome sequencing showed that ADAR1 was an important regulator of circRNAs in PH. CircCDK17 level was significantly lowered in the serum of PH patients. The effects of ADAR1 on cell cycle progression and proliferation were mediated by circCDK17. ADAR1 affects the stability of circCDK17 by mediating A-to-I modification at the A5 and A293 sites of circCDK17 to prevent it from m1A modification. We demonstrate for the first time that ADAR1 contributes to the PH development, at least partially, through m1A modification of circCDK17 and the subsequent PASMCs proliferation. Our study provides a novel therapeutic strategy for treatment of PH and the evidence for circCDK17 as a potential novel marker for the diagnosis of this disease.

Clinical study on the diagnosis of early keratoconus based on ocular morphological parameters with different corneal diameters / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the diagnostic value of ocular morphological parameters under different corneal diameters for early keratoconus.METHODS: A retrospective case-control study. A total of 201 patients(201 eyes)who were treated in our hospital from January 2019 to March 2022 were included. They were divided into 135 cases(135 eyes)in the control group(patients with history of refractive error)and 66 cases(66 eyes)in the subclinical keratoconus group. The Pentacam anterior segment analyzer was used to determine the horizontal central curvature of corneal posterior surface(Kf), posterior vertical central curvature of corneal posterior surface(Ks), average curvature of corneal posterior surface(Km), Posterior I-S ratio, corneal posterior surface height after the thinnest point(PE at the thinnest point), maximum posterior elevation from best fit sphere(MPE from BFS), maximum posterior elevation from best fit toric ellipsoid(MPE from BFTE), posterior asphericity asymmetry index(AAI), thinnest point thickness of the cornea(TCT), central corneal thickness(CCT), depressed corneal thickness(DCT), pachymetric progression index average(PPIavg), Ambrósio relational thickness maximum(ARTmax)and Belin D value. The differences of each parameter between the two groups were analyzed. Receiver operating characteristic(ROC)curves were analyzed to determine the best diagnosis point. The control group was further divided into groups according to the corneal diameter: corneal diameter ≤11.0mm, 11.1mm≤ corneal diameter ≤11.5mm, 11.6mm≤ corneal diameter ≤12.0mm, corneal diameter ≥12.1mm. The differences of each parameter among these groups were compared. Pearson correlation analysis was used to analyze the correlation between corneal diameter and other parameters.RESULTS: There were significant differences in posterior I-S ratio, PE at the thinnest point, MPE from BFS, MPE from BFTE, posterior AAI, TCT, DCT, PPIavg, ARTmax, Belin D value between the subclinical keratoconus group and the control group(P<0.05). Sensitive index of Pentacam to diagnosis subclinical keratoconus were Belin D value, posterior I-S ratio, PPIavg, posterior AAI and MPE from BFTE(AUC≥0.9). In the control group, there was no significant difference in posterior I-S ratio, MPE from BFTE, posterior AAI, TCT, CCT, and DCT among different corneal diameter groups (P>0.05), and there was no significant correlation with corneal diameter(all P>0.05).CONCLUSION: The Belin D value, posterior I-S ratio, PPIavg, posterior AAI, MPE from BFTE obtained by Pentacam are sensitive indicators for the diagnosis of early keratoconus, among which posterior I-S ratio, posterior AAI, MPE from BFTE are less affected by corneal diameter. They play an important role in the early diagnosis of keratoconus under different corneal diameters.

Association of Family Cohesion and Adaptability with Eating Behaviors of Preschoolers / 中山大学学报(医学科学版)

ObjectiveTo examine the current status of preschoolers' eating behaviors and investigate its correlation with family cohesion and adaptability. MethodsA cross-sectional study was conducted involving 21，954 preschoolers and their families from Pingshan District， Shenzhen， between September 2021 and December 2021. A general demographic questionnaire， the Chinese version of Family Adaptability and Cohesion Evaluation Scale Ⅱ （FACESⅡ-CV） and Chinese Preschoolers’ Eating Behavior Questionnaire （CPEBQ） were used to collect the relevant information. Multiple linear regression was used to analyze the association of family cohesion and adaptability with eating behaviors of preschoolers. ResultsTypes of family cohesion and adaptability were significantly correlated with all the 7 dimensions of preschoolers' eating behaviors， including food fussiness （R2=0.252， F=114.457， P<0.001）， food responsiveness （R2 = 0.111， F =24.973， P<0.001）， eating habit （R2= 0.304， F =139.658， P<0.001）， satiety responsiveness （R2 = 0.259， F =105.332， P<0.001）， external eating （R2 = 0.182， F =50.150， P<0.001）， emotional eating （R2 = 0.234， F =91.084， P<0.001） and initiative eating （R2 = 0.349， F =168.608， P<0.001）. After adjusting for confounding factors， our study showed that types of family cohesion and adaptability were independent predictors of preschoolers' eating behaviors （P<0.05）. ConclusionsTypes of family cohesion and adaptability have a significant predictive effect on the 7 dimensions of preschoolers' eating behaviors. Higher scores of family cohesion and adaptability imply stronger initiative eating ability and less poor dietary behaviors in preschoolers.

A prospective study on application of human umbilical cord mesenchymal stem cells combined with autologous Meek microskin transplantation in patients with extensive burns / 中华烧伤杂志

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.

Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

Study on anti-gastric cancer mechanism of Wisteria sinensis tumor based on network pharmacology, molecular docking technology and experimental verification / 中国药理学通报

To investigate the pharmacological mechanism of Wisteria sinensis tumor in the treatment of gastric cancer, using a network pharmacology and molecular docking approach, with verification of the results by experiments. Methods The main active components and corresponding targets of Wisteria sinensis tumor monocytogenes, as well as the disease targets of gastric cancer, were obtained through the network pharmacology database. The Venny 2.1.0 platform was used to take the intersection of drug and disease. The String database was used to construct target protein interaction(PPI)network for common targets, and Metascape database was used to analyze GO function enrichment KEGG pathway enrichment of related targets. The interactive network of "component-target-pathway" of Wisteria sinensis tumor on gastric cancer was constructed by Cytoscape3.7.2 software. The molecular docking of the key targets and active compunds was carried out by using Autodock Vina software. The effect of Wisteria sinensis tumor on gastric cancer was verified by in vitro cell tests. Results A total of 8 main active components, 290 drug targets and 251 gastric cancer-related targets were screened out. A total of 19 targets intersected between with drug and diseases. Seven pathways were involved in the treatment of gastric cancer by Wisteria sinensis tumor. The results of molecular docking showed that the main active components of Wisteria sinensis tumor had good binding ability with the key targets of gastric cancer. The results of in vitro experiments confirmed that, the formononetin from Wisteria sinensis tumor had certain activity on gastric cancer cells, and the formononetin could also induce apoptosis of gastric cancer SGC-7901 cells and increase the level of intracellular calcium ion. Conclusions This study preliminarily reveals the potential components and regulatory network of Wisteria sinensis tumor monocytogenes acting on gastric cancer clarified that Wisteria sinensis tumor monocytogenes has antitumor effect, and may be related to inducing apoptosis of gastric cancer SGC-7901 cells, and it provides references for the future research and clinical application.

Short-term efficacy of venetoclax combined with azacitidine in acute myeloid leukemia: a single-institution experience / 中华血液学杂志

Objective: To explore the safety and short-term efficacy of venetoclax combined with azacitidine (Ven+AZA) in previously untreated patients unfit for standard chemotherapy and patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) in China. Methods: A retrospective study was conducted in 60 previously untreated patients unfit for standard chemotherapy and patients with R/R AML who received Ven+ AZA (venetoclax, 100 mg D1, 200 mg D2, 400 mg D3-28; azacitidine, 75 mg/m(2) D1- 7) at the Peking University Institute of Hematology from June 1, 2019 to May 31, 2021. The incidence of adverse events, complete remission (CR) /CR with incomplete hematological recovery (CRi) rate, objective remission rate (ORR) , and minimal residual disease (MRD) status in patients with different risk stratification and gene subtypes were analyzed. Results: The median age of the patients was 54 (18-77) years, 33 (55.0%) were males, and the median follow-up time was 4.8 (1.4-26.3) months. Among the 60 patients, 24 (40.0%) were previously untreated patients unfit for standard chemotherapy, and 36 (60.0%) were R/R patients. The median mumber cycles of Ven+AZA in the two groups were both 1 (1-5) . According to the prognostic risk stratification of the National Comprehensive Cancer Network, it was divided into 8 cases of favorable-risk, 2 cases of intermediate risk, and 14 cases of poor-risk. In previously untreated patients unfit for standard chemotherapy, after the first cycle of Ven+AZA, 17/24 (70.8%) cases achieved CR/CRi, 3/24 (12.5%) achieved partial remission (PR) , and the ORR was 83.3%. Among them, nine patients received a second cycle chemotherapy and two received a third cycle. Among CR/CRi patients, 8/17 (47.1%) achieved MRD negativity after two cycles of therapy. In the R/R group, after the first cycle of Ven+AZA, 21/36 (58.3%) cases achieved CR/CRi (7/21 achieved MRD negativity) , 3 achieved PR, and the ORR was 66.7%. Among R/R patients, 12 were treated for more than two cycles. There were no new CR/CRi patients after the second treatment cycle, and 14 cases (66.7%) achieved MRD negativity. According to the time from CR to hematological recurrence, the R/R group was divided into 12 cases in the favorable-risk group (CR to hematological recurrence ≥18 months) and 24 in the poor-risk group (CR to hematological recurrence<18 months, no remission after one cycle of therapy, and no remission after two or more cycles of therapy) . Eleven of 24 (45.8%) cases achieved CR/CRi after one cycle of Ven+AZA in the poor-risk R/R group, and 10 of 12 (83.3%) achieved CR/CRi in the favorable-risk R/R group, which was significantly superior to the poor-risk group (P=0.031) . After one cycle of treatment, 13 patients with IDH1/2 mutations and 4 that were TP53-positive all achieved CR/CRi. The CR/CRi rate of 18 patients with NPM1 mutations was 77.8%. Five patients with RUNX1-RUNX1T1 combined with KIT D816 mutation (two initial diagnoses and three recurrences) had no remission. Ven+ AZA was tolerable for AML patients. Conclusion: Ven+AZA has acceptable safety in previously untreated patients unfit for standard chemotherapy, patients with R/R AML can achieve a high response rate, and some patients can achieve MRD negativity. It is also effective in NPM1-, IDH1/IDH2-, and TP53-positive patients. The long-term efficacy remains to be observed.

Analysis of dynamic image features of tear film in dry eye patients / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the image features of dynamic changes of tear film break-up after corneal fluorescein staining(FL)combined with tear film lipid layer(TFLL)dynamic changes in patients with dry eye and its value of diagnosis in dry eye. METHODS: A prospective study. A total of 66 patients(132 eyes)with dry eye admitted to our hospital during September 2019 to December 2020 were divided area break-up group(17 cases, 28 eyes), circle break-up group(20 cases, 27 eyes), line break-up group(25 cases, 28 eyes), spot break-up group(21 cases, 24 eyes)and random break-up group(20 cases, 25 eyes)according to the different fluorescein tear film break-up patterns(BUPs). The image features of tear film break-up dynamic changes and the image features of TFLL dynamic changes were compared in each group, and the differences in the first non-invasive tear film break-up time(NIBUTf), average non-invasive tear film break-up time(NIBUTav), tear meniscus height(TMH)and fluorescein staining scores were compare,RESULTS:A statistically significant differences were observed in NIBUTf among the groups of patients(P&#x003C;0.001). Except that there was no difference between spot break-up group and random break-up group(7.56±1.54s vs 8.02±1.86s, P=0.881), other groups had significant differences in pairwise comparisons(P&#x003C;0.05). There were statistically differences among the groups for NIBUTav(P&#x003C;0.001). Except that there was no difference between spot break-up group and random break-up group(9.54±2.12s vs 9.73±1.94s, P=0.997), other groups had significant differences in pairwise comparisons(P&#x003C;0.05). There was statistically difference among the groups for TMH(P&#x003C;0.001). Except that there was no difference between circle break-up group and line break-up group(0.16±0.03mm vs 0.17±0.03mm, P=0.986), there was no difference between spot break-up group and random break-up group(0.22±0.03mm vs 0.21±0.05mm, P=0.993), other groups had significant differences in pairwise comparisons(P&#x003C;0.05). There were statistically significant differences among the groups for FL scores and TFLL grading(P&#x003C;0.001).CONCLUSION:It is shown that different fluorescein BUPs intuitively reflects the tear film structure of the pathological changes according to evaluation and analysis of images feature of dynamic changes of FL tear film and TFLL combined with the results of static examination of tear film. It is helpful for clinicians to identify subtypes of dry eye, which has potential clinical value for the diagnosis and classification of dry eye.

Effect on postoperative visual quality with modified ABC design aspheric IOL implantation of cataract patients / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the visual quality of patients after modified design aspheric balance curve(ABC)with intraocular lens(IOL)implantation, and to analyze the influencing factors of clinical IOL selection and guide the patient's IOL selection plan. METHODS: A prospective case-control study was conducted in 67 patients(74 eyes)with simple cataract underwent phacoemulsification and foldable aspheric IOL implantation, and 23 eyes in the observation group were implanted with modified design IOL(HOYA Vivinex XY1 group), the control group was implanted with 51 eyes of traditional design IOL(Tecnis ZCB00 group with 27 eyes, IQ SN60WF group with 24 eyes). The uncorrected visual acuity, the best corrected visual acuity, total ocular spherical aberration(SA)and coma under different pupil diameters(3, 4, 5, 6mm), and different pupil diameters(3, 4, 5mm)were measured 1wk and 1mo after operation, the modulation transfer function(MTF)curve, objective scattering index(OSI), intraocular scattered light value Log(s)and contrast sensitivity were obtained. Statistical analysis was performed on the obtained data.RESULTS: The uncorrected visual acuity and best corrected visual acuity at 1wk and 1mo after operation in the three groups were significantly improved compared with those before operation, there was no significant difference among groups(P&#x003E;0.05). The difference of total ocular spherical aberration was statistically significant among the three groups with 5 and 6mm pupil diameter 1wk after operation(P=0.045, 0.037)and there were differences among three groups in pupil diameter of 6mm at 1mo after operation(P=0.042). Comparing the total ocular coma aberration, there were differences among the three groups at 1wk and 1mo after the operation at the pupil diameter of 5 and 6 mm(P&#x003C;0.05). With the increase of pupil diameter at 1wk and 1mo after operation, the total ocular spherical aberration in the HOYA Vivinex XY1 group was lower than that in the other two groups. The MTF values of the Vivinex XY1 group were higher than those that of the control group at each spatial frequency, there was no significant difference among groups(P&#x003E;0.05), and there were no statistical differences in objective scattering index, intraocular scattered light value Log(s)and contrast sensitivity among the three groups(P&#x003E;0.05).CONCLUSION:The improved design of the modified Vivinex IOL can reduce the total ocular spherical aberration and coma, improve the visual quality, and provide a new method for the selection of aspheric IOL.

An Introduction of EVIDEM Framework and Its Application in Healthcare Decision Making / 中国实验方剂学杂志

Evidence and value：impact on DEcisionMaking （EVIDEM） framework was developed by EVIDEM collaboration. Its core is the combination of multiple criteria decision analysis （MCDA） model and standardized health technology assessment （HTA） report， which aims to evaluate the overall value of medical interventions. It has been tested and implemented in the real-world evaluation environments. After more than 10 years of development， EVIDEM framework has been updated to version 10， and the relevant operation manuals have been published. More than 40 countries have joined the collaboration and more than 20 countries have carried out relevant studies. The framework is constructed with patients， population and sustainability as the overall goals， combing the evidence and value， forming a relatively complete decision-making framework system composed of 2 levels， 7 dimensions and 20 criteria. The two levels include normative universal criteria and contextual criteria. The normative universal criteria， namely EVIDEM core model， is the quantitative evaluation， consisting of 5 dimensions and 13 criteria. Contextual criteria， namely contextual tools， are qualitative evaluation， consisting of 2 dimensions and 7 criteria. The specific operation steps of EVIDEM framework include selecting and constructing criteria， assigning weights， integrating and evaluating evidence， quantitative and qualitative evaluation of value， comprehensive value estimation and ranking based on value estimation. EVIDEM framework is applicable to disease diagnosis， treatment， management and other fields. Its application scope includes medical insurance reimbursement， clinical practice decision-making， drug selection and so on， which can provide a method for more systematic， transparent and scientific healthcare decision-making. At present， the framework has been introduced into the field of traditional Chinese medicine and can provide a scientific and feasible evaluation tool and methodology system for the clinical comprehensive evaluation of Chinese patent medicine.

Reliability of three dimensional CT measurement of glenoid track in patients with recurrent anterior dislocation of shoulder / 中国骨伤

OBJECTIVE@#To evaluate the reliability and repeatability of three-dimensional (3D)-CT measurement of glenoid track.@*METHODS@#Glenoid and Hill-Sachs bone defects in 60 patients with recurrent anterior dislocation of the unilateral shoulder were evaluated by 3D-CT and analyzed by three independent observers(shoulder orthopedists) according to the Di Giacomo method. These injuries were classified to formulate a surgical protocol. All the patients were repeatedly measured 1 week later. Intraclass correlation coefficient (ICC) and coefficient of variation (COV) were used for reliability analysis.@*RESULTS@#Interobserver reliability was "very good" for both measurements of glenoid diameter and glenoid bone defects, and "good" for measurements of Hill-Sachs interval. Interobserver agreement was high on the assessment of the extent of the glenoid defect, and poor on track/off track assessment of the Hill-Sachs lesion. Intraobserver reliability for measurements of glenoid diameter, glenoid defect, and Hill-Sachs interval was "very good". The COV was 4.1% for glenoid diameter, 4.4% for glenoid defect, and 21.1% for Hill-Sachs interval.@*CONCLUSION@#The reliability and reproducibility of 3D-CT measurements of glenoid bone defects are good, but the assessment of humeral head bone defects shows large variability with poor reliability.

Evaluation of adhesive bone conduction hearing aid in pediatric patients with unilateral congenital aural atresia / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the auditory efficacy and subjective satisfaction of adhesive bone conduction hearing aid in children with unilateral congenital aural atresia (UCAA). Methods: Ten subjects (5 males and 5 females) diagnosed with UCAA with an average age of 8.3 years old (ranged from 5 to 15) were included in Beijing Tongren Hospital, Capital Medical University from January to August 2019. The free sound field hearing threshold, word recognition score in quiet, speech reception threshold in noise and sound localization ability (results were measured by RMS error) tests were performed in unaided and aided situation, respectively. Subjective satisfaction questionnaires were also distributed to subjects. Paired t test and Wilcoxon signed rank test were used as statistical analysis methods. Results: The average hearing threshold in aided condition was improved by (21.9±4.4) dB (t=15.8，P<0.05). Speech recognition abilities were generally improved both under quiet and noise (P<0.05);however, when the binaural summation, squelch and head shadow effects were analyzed respectively, the binaural squelch effect was not statistically improved (P>0.05), while the other effects were improved in aided condition (P<0.05). In sound localization test, there was no significant difference of the RMS error value between the unaided and aided situation (P>0.05). The subjects got high satisfaction rates in three subjective questionnaires. Conclusion: The adhesive bone conduction hearing aid can provide significant audiological benefit for children with UCAA as well as raising the quality of their life.

Effect of γ-secretase inhibitor on middle ear ultrastructures in ovalbumin-mediated otitis media with effusion in rats / 中华耳鼻咽喉头颈外科杂志

Objective: To study the effect of the inhibitor of Notch signaling pathway-γ-secretase inhibitor DAPT on the ultrastructures of middle ear in the ovalbumin (OVA)-mediated allergic OME in vivo. Methods: Male Sprague-Dawley (SD) rats, weighing 250-300 g, were completely and randomly divided into three groups (5 rats, 10 ears in each group):(1)Control group(2)OME group(3)OME+DAPT group. Rats in the OME group underwent systemic and local sensitization by intraperitoneal and intratympanic injection of ovalbumin to make the model of OVA-induced OME. Rats in the control group were sensitized with PBS. On the basis of establishing the OME model, OME+DAPT group were intraperitoneal injected with DAPT (10 mg/kg) for seven consecutive days and were administered before intratympanic injection of ovalbumin. After the model was successfully established, endoscopy,H&E staining and scanning electron microscopy were used to study the histology and mucous-ciliary ultrastructures of the non-ciliated and ciliated mucosa in the middle ear of each group. One-way ANOVA and Tukey methods were used for statistical analysis. Results: H&E staining showed that the three groups had statistically significant differences in submucosal thickness both in non-ciliated and ciliated regions (non-ciliated area:(6.83±1.47)μm, (38.58±9.57)μm, (32.17±11.89)μm, respectively. F=107.9;cilia area:(26.69±3.22)μm, (30.41±6.75)μm, (26.76±4.06)μm, respectively. F=5.62,both P<0.01). The thickness of the submucosa in the non-ciliated area and the cilia area of the OME group were significantly thicker than that of control group (F=42.08 and 4.40,both P<0.05); the thickness of the non-ciliated area and the ciliated area in OME+DAPT group were reduced compared to OME group(F=1.55 and 2.77,both P<0.05). Scanning electron microscopy showed that the array of cilia on the middle ear mucosa was disorderly arranged and inversed, this phenomenon was relieved in the OME+DAPT group. The number of goblet cells in the control group, OME group, and OME+DAPT group were 9.87±1.92; 15.67±5.77; 10.33±1.99 respectively and the difference between them was statistically significant (F=11.43, P<0.01). The number of goblet cells in the OME group were significantly higher than those in the control group (F=9.00,P<0.01) and the number of goblet cells in the OME+DAPT group were decreased compared to those of OME group (F=8.41, P<0.01). Conclusions: The study demonstrates the pathological changes of the ultrastructure in middle ear in OVA-induced OME and the effect of the γ-secretase inhibitor on it. In OME group, the cilia are disorderly arranged and inversed, the number of goblet cell is increased and they are swelled which suggest the hypersecretion of the mucus. DAPT can regulate OVA-induced allergic inflammation and relieve pathological changes of ultrastructure in middle ear mucociliary transport system through alleviating submucosal inflammation, reducing the hypersecretion of goblet cell and the morphological damage of cilia through the Notch signaling pathway.

Bonebridge implantation combined with simultaneous bilateral auricle reconstruction for bilateral congenital aural atresia / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the feasibility and safety of auricle reconstruction combined with Bonebridge implantation for bilateral aural atresia patients. Methods: A retrospective analysis was conducted for 36 cases(72 ears) who underwent Bonebridge implantation combined with bilateral auricle reconstruction from February 1, 2017 to January 15, 2020. All cases were bilateral congenital aural atresia and underwent Nagata auricle reconstruction for both sides simultaneously. Bonebridge implantations were performed during the second stage of auricle reconstruction. Results: All 36 patients healed well and had no surgical complications when discharged. The preoperative average bone conduction threshold of the patients was(8.5±5.8) dB HL and postoperative bone conduction threshold was (8.4±5.2) dB HL. There was no significant change after the implantation (P=0.724). The preoperative average air conduction threshold of was(64.9±7.4)dB HL and postoperative air conduction threshold was (24.0±5.3) dB HL, which had a significant change after the implantation (P<0.001). The hearing threshold with Bonebridge significantly decreased by 40.9 dB HL compared with the preoperative air conduction threshold(P<0.001). The speech recognition rate of monosyllable words, disyllabic words and short sentences in quiet environment increased by 62.5%, 63.5% and 72.2% respectively. The differences were statistically significant (P<0.001). The speech recognition rate of monosyllabic words, disyllabic words and short sentences in noise environment were significantly increased by 55.9%, 58.9% and 69.9% respectively (P<0.001). After a follow-up of 18.3 months in average, the hearing results were stable and the aesthetic outcomes were satisfied. One patient had implant rupture and healed after revision surgery. Conclusions: With an integrated surgical procedure, patients with bilateral congenital aural atresia can complete bilateral auricle reconstruction and hearing implantation within six months. This integrated surgical procedure is safe and efficient, with a stable hearing improvement and good appearance.

Prevalence of CYP2C19 gene mutations in patients with coronary heart disease and its biological activation effect in clopidogrel antiplatelet response / 中华心血管病杂志

Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.

Glycyrrhizic acid: a potential drug against COVID-19 / 药学学报

Pneumonia caused by SARS-CoV-2 has seriously threatened human life and health worldwide and caused a large number of deaths. Viral infection and acute inflammation are important causes of death, so it is particularly important to combine antiviral therapy with anti-inflammatory therapy. Glycyrrhizic acid, the main component of the glycyrrhizic root extract, has a wide range of pharmacological effects as well as high efficiency and low toxicity, its preparation has been widely used in the treatment of chronic hepatitis and other diseases. Glycyrrhizic acid can regulate the expression and release of a variety of cytokines and play a significant anti-inflammatory effect. At the same time, glycyrrhizic acid also showed significant inhibition towards a variety types of viruses. Therefore, the potential application of glycyrrhizic acid as COVID-19 treatment should be explored.

Application value of different operation methods in the treatment of left hepatolithiasis in special position / 国际外科学杂志

Objective:To study the application value of different operation methods in the treatment of left hepatolithiasis in special position (the stone is located in the sagittal section of left portal vein and/or near the proximal end of left hepatic vein).Methods:From July 2015 to June 2018, 58 patients with left hepatolithiasis in special position in Department of General Surgery, the First People′s Hospital of Tianmen City of Hubei Province were analyzed retrospectively. According to the different operation methods, they were divided into two groups: left liver excision under laparoscopy and gallbladder incision stone group (left liver excision group, n=28) and laparoscopic left-half liver excision and bile tube excision stone removal group (left half liver excision group, n=30). The operation time, intraoperative bleeding, postopera-tive hospital stay, postoperative biliary fistula, postoperative bleeding, postoperative stone residue and stone recurrence were compared between the two groups.The measurement data with normal distributions were represented as ( Mean± SD), and comparison between groups was done using the t test. The chi-square test and Fisher precision test were used for comparison between counting data. Results:All 58 patients underwent laparoscopic surgery. Left liver excision group surgery time, in-serum bleeding, number of days hospitalized after surgery, number of postoperative bile fistula cases, number of postoperative bleeding cases were (161.53±30.56) min, (203.45±26.69) mL, (9.26±3.3. 86) days, 1 case, 1 case, left half liver excision group (153.16±42.63) min, (198.79±30.82) mL, (9.59±4.01) days 1 case, 1 case, The difference between the two groups was not statistically significant ( P>0.05). The number of postoperative stone residues was more than that of the left liver and outer leaf excision group (4 cases) than that of the left half of the liver excision group (1 case), and the number of postoperative stone recurrence cases was more than that of the latter (1 case), all of which were statistically significant ( P<0.05). The number of stone residues and stone recurrences after left liver excision group was 4 and 5 cases respectively, and the left half liver excision nurses were 1 case and 1 case, respectively, and the difference between the two was statistically significant ( P<0.05). Conclusion:For the left hepatolithiasis in special position (the stone is located in the sagittal section of the left branch of the portal vein and (or near the proximal end of the left hepatic vein in imaging), the lower abdominal left hemihepatectomy + choledocholithotomy is a safer and more effective treatment.

Irritable bowel syndrome in China: a review on the epidemiology, diagnosis, and management / 中华医学杂志(英文版)

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disease worldwide. Current guidelines of IBS are mostly based on the western populations and expected to vary in different communities. China has a large population and a vast literature is available on IBS. Due to linguistic variations in the literature, the studies are not widely known and their conclusions thus remain largely obscured to the western medical literature. In this article, we reviewed the published literatures on the investigations of IBS epidemiology, diagnosis, and management in the Chinese population and emphasized the different findings gleaned from the western publications. The detailed literature review will benefit understanding of and promote future study on IBS.

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse / 中华医学杂志(英文版)

BACKGROUND@#It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011.@*METHODS@#A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided).@*RESULTS@#The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107).@*CONCLUSIONS@#The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly.@*TRIAL REGISTRATION NUMBER@#NCT03620565, https://register.clinicaltrials.gov.

Bioinformatics analysis and expression pattern of NAC transcription factor family of Angelica dahurica var. formosana from Sichuan province / 中国中药杂志

NAC(NAM/ATAF/CUC) protein plays an important role in plant growth and development, secondary cell wall formation and stress response. In this study, based on the sequencing data of Angelica dahurica, the NAC family was systematically analyzed using bioinformatics methods and its expression pattern was analyzed. Studies showed that 75 candidate genes had been selected from the NAC transcription factor family of A. dahurica, with the protein size of 148-641, all of which were unstable hydrophilic proteins. Most NAC proteins were localized in the nucleus, and had complete NAC domain. Phylogenetic analysis of NAC family proteins of A.dahurica and Arabidopsis thaliana showed that among the 17 subfamilies, NAC members were unevenly distributed in each subfamily, indicating that the evolution of species is developing in multiple directions. Among them, ANAC063 subfamily contained no NAC sequence of A. dahurica, which might be due to the functional evolution of the species. Analysis of protein transmembrane structure and signal peptide showed that NAC transcription factor could carry out transmembrane transportation, but its signal peptide function had not been found. Expression analysis showed that most transcription factors responded to abiotic stress and hormones to varying degrees, and the effects of hormones were obvious, especially ABA and IAA. In different organs of A. dahurica, most members of the NAC family had higher expression in root phloem, followed by root xylem. This study lays a foundation for further research on the function of A. dahurica NAC transcription factor and for solving the biological problems of A. dahurica.