MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation

BACKGROUND: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. RESULTS: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. CONCLUSIONS: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.

Clinical significance of serum microRNA-146a and inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment

Abstract Objective This study aimed to investigate the clinical significance of serum microRNA-146a and pro-inflammatory factors in children with Mycoplasma pneumoniae pneumonia after azithromycin treatment. microRNA-146a is known to regulate inflammatory responses, and excessive inflammation is a primary characteristic of MPP. Methods Children with MPP received conventional symptomatic therapy along with intravenous administration of azithromycin for one week. Serum levels of microRNA-146a and pro-inflammatory factors were measured using RT-qPCR and ELISA kits, respectively. The correlation between microRNA-146a and pro-inflammatory factors was analyzed by the Pearson method. Pulmonary function indexes were assessed using a pulmonary function analyzer, and their correlation with microRNA-146a and pro-inflammatory factors after treatment was evaluated. Children with MPP were divided into effective and ineffective treatment groups, and the clinical significance of microRNA-146a and pro-inflammatory factors was evaluated using receiver operating characteristic curves and logistic multivariate regression analysis. Results Serum microRNA-146a was downregulated in children with MPP but upregulated after azithromycin treatment, contrasting with the trend observed for pro-inflammatory factors. MicroRNA-146a showed a negative correlation with pro-inflammatory cytokines. Pulmonary function parameters were initially reduced in children with MPP, but increased after treatment, showing positive/inverse associations with microRNA-146a and pro-inflammatory factors. Higher microRNA-146a and lower pro-inflammatory factors predicted better efficacy of azithromycin treatment. MicroRNA-146a, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) were identified as independent factors influencing treatment efficacy. Conclusion Azithromycin treatment in children with MPP upregulates microRNA-146a, downregulates pro-inflammatory factors, and effectively improves pulmonary function.

Identification and Analysis of SND1 as an Oncogene and Prognostic Biomarker for Lung Adenocarcinoma / 中国肺癌杂志

BACKGROUND@#Transcription factor (TF) can bind specific sequences that either promotes or represses the transcription of target genes, and exerts important effects on tumorigenesis, migration, invasion. Staphylococcal nuclease-containing structural domain 1 (SND1), which is a transcriptional co-activator, is considered as a promising target for tumor therapy. However, its role in lung adenocarcinoma (LUAD) remains unclear. This study aims to explore the role of SND1 in LUAD.@*METHODS@#Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) database was obtained to explore the association between SND1 and the prognosis, as well as the immune cell infiltration, and subcellular localization in LUAD tissues. Furthermore, the functional role of SND1 in LUAD was verified in vitro. EdU assay, CCK-8 assay, flow cytometry, scratch assay, Transwell assay and Western blot were performed.@*RESULTS@#SND1 was found to be upregulated and high expression of SND1 is correlated with poor prognosis of LUAD patients. In addition, SND1 was predominantly present in the cytoplasm of LUAD cells. Enrichment analysis showed that SND1 was closely associated with the cell cycle, as well as DNA replication, and chromosome segregation. Immune infiltration analysis showed that SND1 was closely associated with various immune cell populations, including T cells, B cells, cytotoxic cells and dendritic cells. In vitro studies demonstrated that silencing of SND1 inhibited cell proliferation, invasion and migration of LUAD cells. Besides, cell cycle was blocked at G1 phase by down-regulating SND1.@*CONCLUSIONS@#SND1 might be an important prognostic biomarker of LUAD and may promote LUAD cells proliferation and migration.

Advances on BTB protein ubiquitination mediated plant development and stress response / 生物工程学报

The BTB (broad-complex, tramtrack, and bric-à-brac) domain is a highly conserved protein interaction motif in eukaryotes. They are widely involved in transcriptional regulation, protein degradation and other processes. Recently, an increasing number of studies have shown that these genes play important roles in plant growth and development, biotic and abiotic stress processes. Here, we summarize the advances of these proteins ubiquitination-mediated development and abiotic stress responses in plants based on the protein structure, which may facilitate the study of this type of gene in plants.

Alterations in nasal microbiota of patients with amyotrophic lateral sclerosis / 中华医学杂志(英文版)

BACKGROUND@#Links between alterations in gut microbiota composition and amyotrophic lateral sclerosis (ALS) have previously been reported. This study aimed to examine the microbiota in the nasal cavity of ALS.@*METHODS@#Sixty-six ALS patients and 40 healthy caregivers who live in close proximity with patients were enrolled. High throughput metagenomic sequencing of the 16S ribosomal deoxyribonucleic acid (rDNA) gene V3-V4 region of nasal microbiota was used to characterize the alpha and beta diversity and relative abundance of bacterial taxa, predict function, and conduct correlation analysis between specific taxa and clinical features.@*RESULTS@#The nasal microbiome of ALS patients showed lower alpha diversity than that of corresponding healthy family members. Genera Gaiella , Sphingomonas , Polaribacter _1, Lachnospiraceae _NK4A136_group, Klebsiella , and Alistipes were differentially enriched in ALS patients compared to controls. Nasal microbiota composition in ALS patients significantly differed from that in healthy subjects (unweighted UniFrac P = 0.001), while Linear discriminant analysis Effect Size (LEfSe) analysis indicated that Bacteroidetes and Firmicutes dominated healthy nasal communities at the phylum level, whereas Actinobacteria was the predominant phylum and Thermoleophilia was the predominant class in ALS patients. Genus Faecalibacterium and Alistipes were positively correlated with ALS functional rating scale revised (ALSFRS-R; rs = 0.349, P = 0.020 and rs = 0.393, P = 0.008), while Prevotella -9 and Bacteroides operational taxonomic units (OTUs) were positively associated with lung function (FVC) in ALS patients ( rs = 0.304, P = 0.045, and rs = 0.300, P = 0.048, respectively). Prevotella -1 was positively correlated with white blood cell counts (WBC, rs = 0.347, P = 0.021), neutrophil percentage (Neu%, rs = 0.428, P = 0.004), and neutrophil-to-lymphocyte ratio (NLR, rs = 0.411, P = 0.006), but negatively correlated with lymphocyte percentage (Lym%, rs = -0.408, P = 0.006). In contrast, Streptococcus was negatively associated with Neu% ( rs = -0.445, P = 0.003) and NLR ( rs = -0.436, P = 0.003), while positively associated with Lym% ( rs = 0.437, P = 0.003). No significant differences in nasal microbiota richness and evenness were detected among the severe and mild ALS patients.@*CONCLUSIONS@#ALS is accompanied by altered nasal microbial community composition and diversity. The findings presented here highlight the need to understand how dysbiosis of nasal microbiota may contribute to the development of ALS.

Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial / 中华医学杂志(英文版)

BACKGROUND@#Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.@*METHODS@#This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.@*RESULTS@#At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs . placebo, 95% CI 31%-69%) and 45% (low vs . placebo, 95% CI 26%-64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator's Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310.@*CONCLUSION@#CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.

Research Analysis of SLC12A3 Gene Mutation and Molecular Mechanism in Gitelman Syndrome / 罕见病研究

ObjectiveThis study aimed at conducting retrospective analysis of the clinical symptoms and genetic mutations in 20 children with Gitelman syndrome treated at the Affiliated Children′s Hospital of Nanjing Medical University from August 2015 to November 2022 and also explored the molecular mechanism of the pathogenic high-frequency mutation D486N in the Chinese population.MethodsWe collected the clinical manifestations, growth and development status, laboratory examination results, and SLC12A3 gene variations of the patients. We distinguished the wild-type and mutant SLC12A3 genes overexpressed in human embryonic kidney 293T cells (HEK293T). We used protein immunoblotting to detect the expression level of NCC, and used immunofluorescence techniques to examine the subcellular localization of NCC. In addition, we investigated the impact of the high-frequency SLC12A3 gene mutation D486N on NCC protein expression and localization.ResultsIn the 20 patients with Gitelman syndrome, all of them had hypokalemia. We indemnified twenty-six SLC12A3 gene mutations, 13 of which are missense mutation, 1 of which synonymous mutation, 1 nonsense mutation, 4 frameshift mutation, and 7 splicing site mutation. Among them, four mutations (p.T235K, c.1096-1G > A, p.A464A, and c.2660+1_2660+2insT) were novel mutations.ConclusionsWe found the preliminary evidence that the high-frequency mutation D486N in the Chinese population affected the expression of total and membrane-bound NCC protein and influenced the membrane localization of NCC protein. The findings of this study provides experimental evidence for genetic counseling, diagnosis, and treatment of Gitelman syndrome.

Let ′Rare Disease′ Been Seen: Delving into the Building up of Resource and Information Service in Medical Libraries for Rare Diseases / 罕见病研究

With the development of the diagnosis and treatment for rare diseases and the promotion of the construction of ′Double First-Class′ Universities in China, the libraries of medical schools have to make full use of their strengths to better face new challenges in discipline construction proactively. This article refers to resource and information service practices related to the rare disease carried out by medical libraries in China and in other countries; explores the possibilities of building up the resource and information in the future, aiming at improving the awareness of rare diseases among medical students, researchers, and the general public. The article also focuses on the need for strengthening the support for teaching and research into rare diseases, hoping to contribute to the overall improvement of the diagnosis, treatment, and educational research in rare diseases in China.

Analysis of chemical constituents and components absorbed into plasma of Ardisia crenata based on UPLC-QE-HF-MS/MS / 中国药房

OBJECTIVE To analyze the chemical constituents and components absorbed into plasma of the extract of Ardisia crenata and to elucidate its possible pharmacodynamic material basis. METHODS Overall， 12 rats were randomly assigned to the blank group （n＝6） and A. crenata group （n＝6） by the paired comparison method. The drug was administered once daily in the morning and afternoon for three days. Serum samples were prepared from serum after redosing on 4th day. The UPLC-QE-HF-MS/ MS was used to analyze and identify the chemical constituents in A. crenata extract and serum samples. Compound Discoverer 3.0 was employed for retention time correction， peak identification， and peak extraction. According to the secondary mass spectrometry information， the Thermo mzCloud online and Thermo mzVault local databases， referring to the relevant literature and control quality spectrum information were used to preliminarily identify the chemical constituents and components absorbed into plasma of A. crenata. RESULTS A total of 34 compounds were identified from the extract of A. crenata， mainly coumarins， flavonoids， organic acids， amino acids， including bergenin， quercetin， gallic acid， L-pyroglutamic acid， etc. Besides， 5 components absorbed into plasma were identified from serum samples: L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid. CONCLUSIONS L-pyroglutamic acid， syringic acid， bergenin， cinnabar root saponin A， and mycophenolic acid may act as the pharmacodynamic material basis of A. crenata.

Clinical application of Mimics software system to three-dimensional reconstruction to guide thoracoscopic anatomic pulmonary segmentectomy / 中国胸心血管外科临床杂志

@#Objective    To investigate the clinical effect of 3D computed tomography bronchial bronchography and angiography (3D-CTBA) and guidance of thoracoscopic anatomic pulmonary segmentectomy by Mimics software system. Methods    A retrospective analysis was performed on patients who underwent thoracoscopic segmentectomy in the Department of Thoracic Surgery of Affiliated People's Hospital of Jiangsu University from June 2020 to December 2022. The patients who underwent preoperative 3D-CTBA using Materiaise's interactive medical image control system (Mimics) were selected as an observation group, and the patients who did not receive 3D-CTBA were selected as a control group. The relevant clinical indicators were compared between the two groups. Results    A total of 59 patients were included, including 29 males and 30 females, aged 25-79 years. There were 37 patients in the observation group, and 22 patients in the control group. The operation time (163.0±48.7 min vs. 188.8±43.0 min, P=0.044), intraoperative blood loss [10.0 (10.0, 20.0) mL vs. 20.0 (20.0, 35.0) mL, P<0.001], and preoperative puncture localization rate (5.4% vs. 31.8%, P=0.019) in the observation group were better than those in the control group. There was no statistically significant difference in the thoracic tube placement time, thoracic fluid drainage volume, number of intraoperative closure nail bin, postoperative hospital stay, or postoperative air leakage incidence (P>0.05) between the two groups. Conclusion    For patients who need to undergo anatomical pulmonary segmentectomy, using Mimics software to produce 3D-CTBA before surgery can help accurately identify pulmonary arteriovenous anatomy, reduce surgical time and intraoperative blood loss, help to determine the location of nodules and reduce invasive localization before surgery, and alleviate patients' pain, which is worthy of clinical promotion.

Determination of 27 volatile organic compounds in exhaled breath by thermal desorption-gas chromatography-mass spectrometry / 环境与职业医学

Background Volatile organic compounds (VOCs) in exhaled breath are closely associated with respiratory diseases and are linked to various metabolic reactions in the human body. A quantitative analytical method can provide technical support for studying VOCs related to various diseases. Objective To establish a thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) method for the determination of 27 VOCs in exhaled breath. Methods VOCs in exhaled breath were collected using a Bio-VOC sampler and enriched with Tenax TA thermal desorption tubes before TD-GC-MS analysis. Standards were collected using thermal desorption tubes and optimized for thermal desorption conditions as well as chromatographic and mass spectrometric conditions: The separation of the 27 VOCs was achieved by an optimized temperature program, the improvement of sensitivity by optimizing quantitative ions, and the increase of VOCs desorption efficiency by optimizing thermal desorption time and temperature. Limit of detection, limit of quantification, accuracy, precision, and stability of the proposed method were investigated by spiking with a blank gas bag, and exhaled breath samples from 20 healthy individuals were collected for an application study of the proposed method. Results The thermal desorption temperature was 280 ℃, and desorption time was 6 min. A VF-624ms chromatographic column was selected for the separation of target substances. The initial temperature of heating program was 35 ℃, maintained for 1 min, and then increased to 100 ℃ at a heating rate of 3 ℃·min−1 for 1 min, followed by increasing to 210 ℃ at a heating rate of 28 ℃·min−1 for 5 min. A quantitative analysis was conducted with a single ion monitoring (SIM) mode. Under these conditions, the 27 VOCs showed good linear relationships in their respective concentration ranges and the correlation coefficients were higher than 0.9990. The limits of detection of the method were in the range of 0.01-0.13 nmol·mol−1, the limits of quantification were in the range of 0.02-0.44 nmol·mol−1, and the spiked recoveries were in the range of 80.1%-120.5%, with intra-batch and inter-batch precision ≤ 18.8% and 17.9% respectively. All substances can be stored at room temperature (23-28 °C) for 7 d and at 4 °C for 14 d. The proposed method was applied to exhaled breath samples from 20 subjects with detection rates≥ 80% (except for trans-2-pentene and decane) and a concentration range of 0.00-465.50 nmol·mol−1. Conclusion The established TD-GC-MS method for quantification of VOCs in exhaled breath is characterized by high sensitivity and good accuracy, and is suitable for quantitative determination of VOCs in exhaled breath, which can provide technical support for the study of exhaled breath VOCs.

Characteristics and influencing factors of hearing loss among noise-exposed workers in a large machinery maintenance enterprise / 环境与职业医学

Background The current increasing trend of new cases of occupational noise-induced deafness indicates that the hearing loss of occupational population has not been effectively controlled in China. It is of great significance to study the characteristics of hearing loss among noise-exposed workers and its related factors. Objective To investigate characteristics and influencing factors of hearing loss among occupational noise-exposed workers in a large machinery maintenance enterprise, and to provide a scientific basis to prevent and control noise-induced hearing loss. Methods A cross-sectional survey was conducted to investigate male Han occupational noise-exposed workers in a large mechanical maintenance enterprise. We acquired demographic characteristics, occupational exposure history, and individual life behavior characteristics of the workers through questionnaires, collected occupational exposure level data from annual occupational disease hazard factor surveillance reports, obtained pure tone hearing threshold test data through occupational health examinations, and estimated individual noise exposure levels using cumulative noise exposure (CNE). According to the results of pure tone air conduction hearing threshold test, the workers were divided into a hearing loss group and a normal hearing group. The chi-square test was employed to compare the occupational exposure characteristics and individual life behavior characteristics between the two groups. Additionally, the trend chi-square test was utilized to analyze the changing trends of age, length of service, CNE, and hearing loss rate within the two groups. The relationship between high-frequency hearing loss in both ears and its related influencing factors was assessed by a multiple logistic regression model. Results The M (P25, P75) of CNE for the 2531 occupational noise-exposed workers was 97.51 (95.39, 99.96) dB(A)·year. The incidence of hearing anomaly, binaural high-frequency hearing anomaly, random ear high-frequency hearing anomaly, binaural low-frequency hearing anomaly, and random ear low-frequency hearing anomaly were 22.48%, 16.59%, 22.13%, 2.77%, and 3.52%, respectively. High-frequency hearing threshold increase was the main reason for hearing anomaly (98.42%). In comparison to the CNE ≤ 97 dB(A)·year group, the 97 dB(A)·year<CNE≤ 100 dB(A)·year group and the CNE>100 dB(A)·year group experienced a 36.4% and 52.3% increase in the risk of bilateral high-frequency hearing loss, respectively. The smoking group exhibited a 43.5% elevated risk of bilateral high-frequency hearing loss when compared to the non-smoking group. Conversely, the group frequently wearing hearing protection equipment demonstrated a 23.6% lower risk of bilateral high-frequency hearing loss in comparison to the group occasionally wearing protective equipment. The data suggested that CNE＞97 dB(A)·year and smoking might be independent risk factors for bilateral high-frequency hearing loss, and frequently wearing hearing protection equipment might be an important protective factor. Conclusion Increased CNE and smoking can elevate the risk of high-frequency hearing loss, while personal hearing protection can effectively reduce the risk of hearing loss.

Descending necrotizing mediastinitis: a clinical analysis based on 10 years of published data in China / 口腔疾病防治

Objective@#To investigate the clinical characteristics, diagnosis, treatment, and prognosis of descending necrotizing mediastinitis (DNM) to provide a reference for the early diagnosis and timely treatment of DNM.@*Methods@#Data on DNM in China was electronically retrieved from the core databases and comprehensively reviewed from June 2012 to June 2023. The infection, pathogenic microorganisms, main symptoms, comorbidities and treatment methods of DNM were analyzed.@*Results@#The data of a total of 781 DNM patients, with an average age of (52.97 ± 5.64) years, were retrieved, including 554 males and 227 females. Odontogenic source, tonsillitis, pharyngeal abscess, sialoadenitis, upper respiratory tract infection, foreign body injury, or iatrogenic traumatic procedures are common causes. Among these, odontogenic infection is the most common source. Streptococcus sp. (n = 217) and Staphylococcus sp. (n = 82) were most isolated, followed by Klebsiella pneumoniae and Pseudomonas aeruginosa (equally n = 59). A total of 69.4% (542/781) of DNM patients recruited in this study were discovered to have various comorbidities, and more than one-third of these patients (n = 185) had diabetes. Of the broad antibiotics, carbapenem was most frequently used as treatment, and vancomycin was the most frequently coadministered. The mediastinal drainage approach varies widely, and the optimal regimen is still unknown. Seventy-two patients were treated with video-assisted thoracoscopic/mediastinoscopic surgical drainage, 22 patients were treated with percutaneous catheter drainage, 30 underwent the transcervical approach, and 40 underwent thoracotomy. A total of 617 patients who were selected underwent the appropriate combined operation for surgical drainage according to the specific location of the infected focus. The overall mortality rate of all 781 DNM patients included was 11.2%.@*Conclusion@#The most effective diagnosis and treatment of DNM is a high degree of clinical vigilance followed by prompt and adequate drainage with intensive care, including hemodynamic monitoring, nutritional support, computer tomographic scanning repeated as necessary, and combined use of systemic antibiotics.

CBCT analysis of the relative position between maxillary central incisors and alveolar bone in Southern Chinese adults / 口腔疾病防治

Objective@#Exploring the position and bone wall thickness characteristics of the maxillary central incisors in Southern Chinese adults to provide a clinical reference for the design of immediate maxillary central incisor implantation surgery.@*Methods@#The hospital ethics committee approved the study, and the patients provided informed consent. CBCT images of 990 adult patients (aged 20-79 years) from the Stomatology Hospital (January 2018 to December 2021) were categorized based on the dental arch form and age-sex groups. Sagittal CBCT images of the maxillary central incisors were used to measure the labial and palatal bone thickness wall at 4 mm the CEJ to apical, the middle of the root, and the angle between the tooth long axis and the long axis of the alveolar process, to compare the thickness of the labial and palatal bone walls in samples of male and female patients, and to explore the relationship between the angle between the tooth long axis and the alveolar process long axis in samples of male and female patients in different age groups (20-39 years; 40-59 years; 60-79 years).@*Results@#Significant differences were found in the labiopalatine side of the alveolar bone of the maxillary incisor root position. A total of 95.8% (948/990) of the maxillary incisors were positioned more buccally, 4.1% (41/990) were positioned more midway, and 0.1% (1/990) were positioned more palatally. The thicknesses of the bone wall at the CEJ of 4 mm below the palatal side, the middle of the root, and at the apex were greater (1.82 ± 0.56 mm, 3.20 ± 1.10 mm, and 7.70 ± 2.00 mm, respectively) than those at the labial side (1.21 ± 0.32 mm, 0.89 ± 0.35 mm, and 1.86 ± 0.82 mm, respectively), with statistical significance (P<0.05). Male bone wall thickness was generally greater than female bone wall thickness (P<0.05). The angle between the long axis of male teeth and the alveolar bone was 14.77° ± 5.66°, while that of female teeth was 12.80° ± 5.70°, with a statistically significant difference (P<0.05). The angle between the long axis of teeth and the alveolar bone in the 40-59-year-old group and the 60-79-year-old group was greater than that in the 20-39-year-old group, and the difference was statistically significant (P<0.05).@*Conclusion@#A total of 95.8% of adults in South China have maxillary central incisors with root deviation toward the labial bone cortex. The thickness of the labial bone wall is much thinner than that of the labial bone wall, which is the middle of the thickness of the root. In Southern Chinese adults, the angle between the upper central incisor and the long axis of the alveolar bone in males is greater than that in females, and the degree of the angle increases with age. It is recommended to pay attention to the thickness of the bone wall around the root and the angle between the teeth before immediate implantation surgery to choose a reasonable implantation plan.

Mechanism studies underlying the alleviatory effects of isoliquiritigenin on abnormal glucolipid metabolism triggered by type 2 diabetes / 药学学报

Isoliquiritigenin (ISL) is an active chalcone compound isolated from licorice. It possesses anti-inflammatory and anti-oxidative activities. In our previous study, we uncovered a great potential of ISL in treatment of type 2 diabetes mellitus (T2DM). Therefore, this study aims to reveal the mechanism underlying the alleviatory effects of ISL on T2DM-induced glycolipid metabolism disorder. High-fat-high-sugar diet (HFD) combined with intraperitoneal injection of streptozotocin (STZ) were used to establish T2DM mice model. All animal experiments were carried out with approval of the Committee of Ethics at Beijing University of Chinese Medicine. HepG2 cells were used in in vitro experiments, and sodium palmitate (SP) was applied to establish insulin resistance (IR) model cells. The effects of ISL on body weight, fasting blood glucose levels, and pathological changes in the livers of mice were examined. Enzyme-linked immune sorbent assay (ELISA) and real-time quantitative PCR (RT-qPCR) were applied to detect the regulatory effects of ISL on key targets involved in glucolipid metabolism. Additionally, molecular docking and analytical dynamics simulation methods were used to analyze the interaction between ISL and key target protein. The results indicate that ISL significantly downregulates the transcriptional levels and inhibits the activities of key enzymes involved in gluconeogenesis, including pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and fructose-1, 6-bisphosphatase (FBP). It also downregulates the transcriptional and protein levels of hepatocyte nuclear factor 4α (HNF4α) and cAMP response element binding protein (CREB), the two transcriptional factors involved in gluconeogenesis. Thus, ISL inhibits hepatic gluconeogenesis in T2DM mice. In addition, ISL reduces total cholesterol (TC) and triglyceride (TG) levels in the livers of T2DM mice. Moreover, ISL downregulates the mRNA levels of lipogenesis genes and upregulates those of genes involved in fatty acid oxidation, lipid uptake, and lipid export. In conclusion, ISL suppresses hepatic gluconeogenesis, promotes lipolysis, and restrains lipogenesis in T2DM mice, thereby improving the abnormal glycolipid metabolism caused by T2DM.

Development and prospects of predicting drug polymorphs technology / 药学学报

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Comprehensive analysis of insulin products complex disulfide bonds structure by high resolution mass spectrum / 药学学报

The correct pairing of disulfide bonds maintains the correct folding mode and high-level structure formation of peptides and protein drugs, which is crucial for the quality control of products. In order to ensure that the disulfide bonds are correctly paired, disulfide bond analysis is an essential part of peptides and protein drug characterization. Mass spectrometry can be used to analyze disulfide bonds. However, insulin and its analogues have two pairs of disulfide bonds without restriction enzyme cutting site. Conventional collision-induced dissociation (CID) and high-energy induced cleavage (HCD) cannot accurately locate the complex disulfide bond. In our study, three methods were used to localize the complex disulfide, including enzyme digestion combined with key peptide fragment in source decay (ISD) fragmentation method, enzyme digestion combined with partial reduction alkylation method, intact protein source ISD and electron transfer dissociation (ETD) cleavage method, The applicability of insulin aspart, insulin lispro and insulin glargine were also investigated. This study provides a new way for the quality control of disulfide bonding mode of insulin and its analogues, and also provides a reference for the disulfide bond localization of peptides or proteins containing this complex disulfide bond.

Discussion on the Scientific Connotation of Fortifying Spleen， Resolving Phlegm and Dispelling Stasis in the Treatment of Coronary Heart Disease under the Guidance of Dysfunctional High-Density Lipoprotein / 中医杂志

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Effect and Mechanism of Chinese Medicine in Treatment of Osteoporosis / 中国实验方剂学杂志

Osteoporosis （OP） is a common bone disease affecting the quality of life and causing huge medical burden to the patients and society. The occurrence of OP is mainly caused by excessive bone resorption and insufficient bone formation， which are directly influenced by external calcium ion balance. Calcium imbalance can impair bone integrity， reduce the calcium supply to the bone， and lower the calcium content in the bone， thus triggering OP. Drugs are the main anti-OP therapy in modern medicine， which， however， may cause adverse reactions and drug dependence. Chinese medicines have good clinical effects and high safety in treating OP， being suitable for long-term use. Recent studies have shown that Chinese medicines can alleviate estrogen deficiency， regulate bone cell and calcium metabolism， which is crucial for the formation and development of OP. The transient receptor potential cation channel superfamily V members 5 and 6 （TRPV5 and TRPV6， respectively） affect bone homeostasis by mediating the transmembrane calcium ion transport in the intestine （TRPV6） and kidney （TRPV5）. Therefore， TRPV5/6 is one of the key targets to understand the anti-OP mechanisms of the effective parts of Chinese medicines， which is worthy of further study. This paper summarizes the research results about the anti-OP effects of Chinese medicines in the last two decades， especially the mechanism of regulating calcium metabolism， aiming to provide new ideas for the basic research， clinical application， and drug development of OP treatment.

Herbal Textual Research on Farfarae Flos in Famous Classical Formulas / 中国实验方剂学杂志

By consulting ancient and modern literature， the herbal textual research of Farfarae Flos has been conducted to verify the name， origin， producing area， quality evaluation， harvesting and processing methods， so as to provide reference for the development and utilization of the famous classical formulas containing Farfarae Flos. According to the research， the results showed that Farfarae Flos was first described as a medicinal material by the name of Kuandonghua in Shennong Bencaojing（《神农本草经》）， and the name was used and justified by later generations. The main origin was the folwer buds of Tussilago farfara， in addition， the flower buds of Petasites japonicus were used as medicine in ancient times. The ancient harvesting time of Farfarae Flos was mostly in the twelfth month of the lunar calendar， and the modern harvesting time is in December or before the ground freeze when the flower buds have not been excavated. Hebei， Gansu， Shaanxi are the authentic producing areas with the good quality products. Since modern times， its quality is summarized as big， fat， purple-red color， no pedicel is better. Processing method from soaking with licorice water in the Northern and Southern dynasties to stir-frying with honey water followed by micro-fire in the Ming dynasty， and gradually evolved to the modern mainstream processing method of honey processing. Based on the research results， it is suggested that the dried flower buds of T. farfara， a Compositae plant， should be selected for the development of famous classical formulas containing Farfarae Flos， and the corresponding processed products should be selected according to the specific processing requirements of the formulas， and raw products are recommended for medicinal use without indicating processing requirements.