Epidemiological characteristics and trend prediction of pulmonary tuberculosis in Ankang City, Shaanxi Province from 2011 to 2021 / 中国热带医学

@#Abstract: Objective To analyze the epidemiological characteristics of pulmonary tuberculosis (PTB) in Ankang City from 2011 to 2021, so as to provide a scientific basis for the formulation of PTB prevention and control strategy. Methods Descriptive statistics were used to analyze the epidemiological characteristics of PTB in Ankang City from 2011 to 2021, and a time series model was established to quantitatively predict the incidence of pulmonary tuberculosis in 2023. Results The incidence rate in Ankang City showed a significant upward trend from 2011 to 2017, and a more obvious downward trend in 2017-2021 (P<0.05), and the decrease rate in 2021 was 40.36% compared with that in 2017. The proportion of etiological positivity increased from 12.5% in 2014 to over 50.00% after 2019. The incidence season was mainly concentrated in the first quarter, accounting for 28.39% of the annual incidence. High incidence areas were concentrated in the south of Ankang: Langao County, Ziyang County and Zhenping County, with 128.32/100 000, 117.07/100 000 and 110.44/100 000, respectively. Low incidence areas were located in the north of Ankang: Ningshan County, with 60.62/100 000. Farmers and students were the high incidence groups, accounting for 81.80% and 4.97% of the total cases respectively. The incidence of young children was relatively low, but cases were reported every year. The incidence rate of male was 2.39 times that of female. The age of onset increased significantly from 15 years old, and the peak incidence was in the age group of 60-<80 years old, followed by the age group of 45-<60 years old, the average annual incidence was 136.44/100 000 and 104.47/100 000, respectively. The model ARIMA(0,1,1)(0,1,1)12 predicted that the incidence of the disease generally increased from October 2022 to March 2023, then steadily decreased, and increased again in December. Conclusions The incidence of tuberculosis varies in different areas of Ankang City, and males, farmers, students and the elderly are all factors of high incidence of tuberculosis. Therefore, different prevention and control strategies should be adopted according to the characteristics of population in different areas. The number of cases in Ankang City in 2023 showed an overall downward trend, which can provide a reference for the prevention and control of PTB.

Y-box-binding protein 1 mediates sorafenib resistance via the extracellular signal regulated-protein kinase pathway in hepatoma cells / 中华肝脏病杂志

Objective: To investigate the effect and possible mechanism of Y-box-binding protein 1 (YB-1) on sorafenib resistance in hepatoma cells. Methods: Lentiviral vectors with YB-1 overexpression and knockdown were constructed, respectively, to stimulate human hepatoma cell lines (HepG2 and Huh7) alone or in combination with sorafenib.The overexpression part of the experiment was divided into four groups: overexpression control group (Lv-NC), YB-1 overexpression group (Lv-YB-1), overexpression control combined with sorafenib resistance group (Lv-NC+sorafenib), YB-1 overexpression combined with sorafenib resistance group (Lv-YB-1 + sorafenib). The knockdown part of the experiment was also divided into four groups: knockdown control group (Lv-shNC), YB-1 knockdown group (Lv-shYB-1), knockdown control combined with sorafenib resistance group (Lv-shNC + sorafenib), YB-1 knockdown combined with sorafenib resistance group (Lv-shYB-1 + sorafenib). The occurrence of cell apoptosis was detected by TUNEL. The protein expression levels of phosphorylated (p)-ERK and ERK, key proteins in the extracellular regulatory protein kinase (ERK) signaling pathway, were detected by Western blot and quantified by ImageJ software. Subcutaneous tumorigenesis experiments were performed in nude mice. The effect of YB-1 on the efficacy of sorafenib was verified in vivo. The comparison between the two sets of data was carried out by an independent sample t-test. One-way ANOVA was used for comparisons between the three groups of data above. Results: Sorafenib had accelerated the occurrence of apoptosis in hepatoma cells, while YB-1 overexpression had inhibited cell apoptosis, and at the same time also inhibited the apoptosis-accelerating impact of sorafenib. On the contrary, YB-1 knockdown accelerated cell apoptosis and amplified the induction effect of sorafenib on apoptosis. Furthermore, sorafenib resistance had down-regulated p-ERK levels (HepG2: Lv-NC 0.685 ± 0.143, Lv-NC + sorafenib 0.315 ± 0.168, P < 0.05; Huh7: Lv-NC 0.576 ± 0.078, Lv-NC + sorafenib 0.150 ± 0.131, P < 0.01), whereas YB-1 overexpression had inhibited sorafenib resistance p-ERK reduction (HepG2: Lv-NC + sorafenib 0.315 ± 0.168, Lv-YB-1 + sorafenib 0.688 ± 0.042, P < 0.05; Huh7: Lv-NC + sorafenib 0.150 ± 0.131, Lv-YB-1 + sorafenib 0.553 ± 0.041, P < 0.05). YB-1 knockdown further increased sorafenib-induced p-ERK downregulation (HepG2: Lv-shNC + sorafenib 0.911 ± 0.252, Lv-shYB-1 + sorafenib 0.500 ± 0.201, P < 0.05; Huh7: Lv-shNC + sorafenib 0.577 ± 0.082, Lv-shYB-1 + sorafenib 0.350 ± 0.143, P < 0.05), which was further verified in naked mice (Lv-shNC + sorafenib 0.812 ± 0.279, Lv-shYB-1 + sorafenib 0.352 ± 0.109, P < 0.05). Conclusion: YB-1 mediates the occurrence of sorafenib resistance via the ERK signaling pathway in hepatoma cells.

Evaluation of ankle joint protection effect of parachute ankle brace on paratrooper landing / 中华劳动卫生职业病杂志

Objective: To study the protective effect of parachute ankle brace on ankle joint during simulated parachuting landing. Methods: In August 2021, 30 male paratroopers were selected as the test subjects by simple random sampling method. They jumped from the 1.5 m and 2.0 m height platforms respectively with and without parachute ankle brace, and landed on the sandy ground in a semi-squat parachute landing position. The experiment was divided into 1.5 m experimental group and control group and 2.0 m experimental group and control group. Angle sensor and surface electromyograph were used to measure and analyze the coronal tilt range of the ankle joint and the percentage of maximal voluntary contraction (MVE%) of the muscles around the ankle joint, respectively, to evaluate the protective effect of the parachute ankle brace. Results: At the same height, the tilt range of coronal plane of ankle in experimental group was significantly reduced compared with control group, and the difference was statistically significant (P<0.05). Under the same protection state, the tilt range of the coronal plane of the ankle in the 1.5 m group was significantly reduced compared with that in the 2.0 m group, and the difference was statistically significant (P<0.05). The coronal plane inclination range of the ankle in 2 m experimental group was significantly lower than that in 1.5 m control group, and the difference was statistically significant (P<0.05). Compared with 1.5 m control group, MVE% of right tibialis anterior muscle and bilateral lateral gastrocnemius decreased in 1.5 m experimental group, while MVE% of bilateral peroneus longus increased, with statistical significance (P<0.05). Compared with 2.0 m control group, the MVE% of bilateral tibialis anterior muscle and right lateral gastrocnemius decreased in 2.0 m experimental group, while the MVE% of bilateral peroneus longus increased, with statistical significance (P<0.05). The MVE% of bilateral tibialis anterior muscle, bilateral lateral gastrocnemius muscle and right peroneus longus muscle in 1.5 m experimental group decreased compared with 2.0 m experimental group, and the differences were statistically significant (P<0.05). Compared with 2.0 m control group, the MVE% of bilateral tibialis anterior muscle, right lateral gastrocnemius muscle and right peroneus longus muscle in 1.5 m control group decreased, and the differences were statistically significant (P<0.05) . Conclusion: Wearing parachute ankle brace can effectively limit the coronal plane inclination range of ankle joint, improve the stability of ankle joint and reduce the load on the muscles around ankle joint by landing. Reducing the height of the jumping platform can reduce the coronal plane incline range of the ankle and the muscle load around the ankle during landing.

Animal model-based simulation training for three emergent and urgent operations of penetrating thoracic injuries / 中华创伤杂志(英文版)

PURPOSE@#To develop animal models of penetrating thoracic injuries and to observe the effects of the animal model-based training on improving the trainees' performance for emergent and urgent thoracic surgeries.@*METHODS@#With a homemade machine, animal models of lung injuries and penetrating heart injuries were produced in porcine and used for training of chest tube drainage, urgent sternotomy, and emergent thoracotomy. Coefficient of variation of abbreviated injury scale and blood loss was calculated to judge the reproducibility of animal models. Five operation teams from basic-level hospitals (group A) and five operation teams from level III hospitals (group B) were included to be trained and tested. Testing standards for the operations were established after thorough literature review, and expert questionnaires were employed to evaluate the scientificity and feasibility of the testing standards. Tests were carried out after the training. Pre- and post-training performances were compared. Post-training survey using 7-point Likert scale was taken to evaluate the feelings of the trainees to these training approaches.@*RESULTS@#Animal models of the three kinds of penetrating chest injuries were successfully established and the coefficient of variation of abbreviated injury scale and blood loss were all less than 25%. After literature review, testing standards were established, and expert questionnaire results showed that the scientific score was 7.30 ± 1.49, and the feasibility score was 7.50 ± 0.89. Post-training performance was significantly higher in both group A and group B than pre-training performance. Post-training survey showed that all the trainees felt confident in applying the operations and were generally agreed that the training procedure were very helpful in improving operation skills for thoracic penetrating injury.@*CONCLUSIONS@#Animal model-based simulation training established in the current study could improve the trainees' performance for emergent and urgent thoracic surgeries, especially of the surgical teams from basic-level hospitals.

ANNO: A General Annotation Tool for Bilingual Clinical Note Information Extraction / 대한의료정보학회지

Objectives@#This study was conducted to develop a generalizable annotation tool for bilingual complex clinical text annotation, which led to the design and development of a clinical text annotation tool, ANNO. @*Methods@#We designed ANNO to enable human annotators to support the annotation of information in clinical documents efficiently and accurately. First, annotations for different classes (word or phrase types) can be tagged according to the type of word using the dictionary function. In addition, it is possible to evaluate and reconcile differences by comparing annotation results between human annotators. Moreover, if the regular expression set for each class is updated during annotation, it is automatically reflected in the new document. The regular expression set created by human annotators is designed such that a word tagged once is automatically labeled in new documents. @*Results@#Because ANNO is a Docker-based web application, users can use it freely without being subjected to dependency issues. Human annotators can share their annotation markups as regular expression sets with a dictionary structure, and they can cross-check their annotated corpora with each other. The dictionary-based regular expression sharing function, cross-check function for each annotator, and standardized input (Microsoft Excel) and output (extensible markup language [XML]) formats are the main features of ANNO. @*Conclusions@#With the growing need for massively annotated clinical data to support the development of machine learning models, we expect ANNO to be helpful to many researchers.

Large-scale Hospital Material Supply Chain Practice under Closed-loop Management / 中国医疗器械杂志

In the context of public health emergencies, a Hospital used the existing SPD supply chain model as a basis, research and practice proceeded simultaneously and formed a set of "three-group three-port" emergency plan by itself. The program played a positive role and effectiveness in this emergency incident, assisting the hospital to obtain a valuable experience in closed-loop management of emergency supplies. This article elaborated on how the hospital can supply materials in case of emergency medical supplies shortage after emergencies by focusing on the three groups of closed-loop working group, inventory management group, and material procurement group, and the three ports of material storage port, logistics receiving and dispatching port, and closed-loop releasing port. In the case of emergency medical supplies being in short supply after emergencies, how can hospitals ensure adequate and balanced supply of supplies; barrier-free demand information; command and dispatch without chaos and reasonable deployment; materials receiving and dispatching are efficient and distributed in an orderly manner.

Predictors of efficacy of corticosteroid switching from abiraterone plus prednisone to dexamethasone in patients with metastatic castration-resistant prostate cancer / 亚洲男科学杂志(英文版)

Corticosteroid switching can reverse abiraterone resistance in some patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we investigated the potential biomarkers for predicting the efficacy of corticosteroid switching during treatment with abiraterone acetate (AA). We retrospectively analyzed 101 mCRPC patients receiving corticosteroid switching from West China Hospital and Sun Yat-Sen University Cancer Center between January 2016 and December 2018. All cases received AA plus prednisone as first-line therapy during mCRPC. Primary end points were biochemical progression-free survival (bPFS) and overall survival (OS). The risk groups were defined based on multivariate analysis. A total of 42 (41.6%) and 25 (24.8%) patients achieved 30% and 50% decline in prostate-specific antigen (PSA), respectively, after corticosteroid switching. The median bPFS and median OS on AA plus dexamethasone were 4.9 (95% confidence interval [CI]: 3.7-6.0) months and 18.8 (95% CI: 16.2-30.2) months, respectively. Aldo-keto reductase family 1 member C3 (AKR1C3) expression (hazard ratio [HR]: 2.15, 95% Cl: 1.22-3.80, P = 0.008) and baseline serum alkaline phosphatase (ALP; HR: 4.95, 95% Cl: 2.40-10.19, P < 0.001) were independent predictors of efficacy before corticosteroid switching in the multivariate analysis of bPFS. Only baseline serum ALP >160 IU l-1 (HR: 3.41, 95% Cl: 1.57-7.38, P = 0.002) together with PSA level at switch ≥50 ng ml-1 (HR: 2.59, 95% Cl: 1.22-5.47, P = 0.013) independently predicted poorer OS. Based on the predictive factors in multivariate analysis, we developed two risk stratification tools to select candidates for corticosteroid switching. Detection of serum ALP level, PSA level, and tissue AKR1C3 expression in mCRPC patients could help make clinical decisions for corticosteroid switching.

A rare complication of pelvic perforation by an excessive medial slide of the helical blade after treatment of an intertrochanteric fracture with proximal femoral nail anti-rotation: A case report and literature review / 中华创伤杂志(英文版)

Intertrochanteric fractures have become a severe public health problem in elderly patients. Proximal femoral nail anti-rotation (PFNA) is a commonly used intramedullary fixation device for unstable intertrochanteric fractures. Pelvic perforation by cephalic screw is a rare complication. We reported an 84-year-old female who fell at home and sustained an intertrochanteric fracture. The patient underwent surgery with PFNA as the intramedullary fixation device. Routine postoperative examination revealed medial migration of the helical blade that eventually caused pelvic perforation. We performed a cemented total hip arthroplasty as the savage procedure. At the latest follow-up of 12 months after total hip arthroplasty, the patient had no pain or loosening of the prosthesis in the left hip. Pelvic perforation should be considered when choosing PFNA as the intramedullary fixation device, especially in patients with severe osteoporosis wherein the helical blade can be easily inserted during the operation. The lack of devices to avoid oversliding of the helical blade in PFNA is an unreported cause of this complication and should be considered in such cases.

Application of three-dimensional visualization technique in laparoscopic D3 radical resection of right colon cancer / 南方医科大学学报

OBJECTIVE@#To explore the clinical value of three-dimensional (3D) visualization technique in laparoscopic D3 radical resection of right colon cancer.@*METHODS@#We retrospectively analyzed the clinical data of 73 patients with right colon cancer undergoing laparoscopic D3 radical operation in our hospital between May, 2019 and March, 2021. Among these patients, 41 underwent enhanced CT examination with 3D visualization reconstruction to guide the actual operation, and 32 underwent enhanced CT examination only before the operation (control group). In 3D visualization group, we examined the coincidence rate between the 3D visualization model and the findings in surgical exploration of the anatomy and variations of the main blood vessels, supplying vessels of the tumor, and the tumor location, and the coincidence rate between the actual surgical plan for D3 radical resection of right colon cancer and the plan formulated based on the 3D model. The operative time, estimated blood loss, unexpected injury of blood vessels, number of harvested lymph nodes, mean time of the first flatus, complications, postoperative hospital stay and postoperative drainage volume were compared between the two groups.@*RESULTS@#The operative time was significantly shorter in 3D visualization group than in the control group (P < 0.05). The volume of blood loss, proportion of unexpected injury of blood vessel, the number of harvested lymph nodes, time of the first flatus, proportion of complications, postoperative hospital stay and postoperative drainage volume did not differ significantly between the two groups (P > 0.05). In the 3D visualization group, the 3D visualization model clearly displayed the shape and direction of the colon, the location of the tumor, the anatomy and variation of the main blood vessels and the blood vessels supplying the cancer, and showed a coincidence rate of 100% with the findings by surgical exploration. The surgical plan for D3 radical resection of right colon cancer was formulated based on the 3D model also showed a coincidence rate of 100% with the actual surgical plan.@*CONCLUSION@#The 3D visualization reconstruction technique allows clear visualization the supplying arteries of the tumor and their variations to improve the efficiency, safety and accuracy of laparoscopic D3 radical resection of right colon cancer.

Ultrasound-guided percutaneous cannulation for extracorporeal membrane oxygenation in children / 中华儿科杂志

Objective: To evaluate the effectiveness and safety of ultrasound-guided percutaneous cannulation for extracorporeal membrane oxygenation (ECMO) in children. Methods: In this retrospective observational study, 66 cases who underwent non-cardiac surgery ECMO in pediatric intensive care unit (PICU) of Shanghai Children's Hospital from May 2016 to April 2021 were collected. The demographics, model of ECMO support, type and size of arteriovenous cannulas, way of catheterization and complications were recorded and summarized. Patients were divided into percutaneous cannulation group and surgical cannulation group according to catheterization strategies. The demographics, duration of cannulation and ECMO support, ECMO weaning rate and hospital survival rate were compared among two groups. χ2 and nonparametric rank sum test were used for comparison. Results: Among the 66 patients who received ECMO, 38 were male and 28 were female, with age 44.5 (12.0, 83.5) months and weight 15.0 (10.0, 25.0) kg; 21 patients underwent percutaneous cannulation, with a success rate of 95% (20 cases). Point-of-care ultrasound was performed for all percutaneous cannulation cases. The duration of percutaneous cannulation was significantly shorter than that of surgical cannulation (26.0 (23.3, 30.3) vs. 57.0 (53.8, 64.0) min, Z=6.31, P<0.001). Successful percutaneous cannulation cases were aged 70.5 (23.8, 109.5) months, and their weight was 23.2 (13.6, 37.0) kg. Ten cases were initially given veno-venous (VV) ECMO support, and 10 cases were given veno-arterial (VA) ECMO support. ECMO arterial cannulas were sized from 8 F to 17 F, and venous cannulas sized from 10 F to 19 F. For VV-ECMO, the right internal jugular and femoral veins were used as vascular access, while VA-ECMO used right internal jugular vein-femoral artery or right femoral vein-left femoral artery approach. Only one patient suffered severe complication (superior vena cava perforation). There was no catheter-related bloodstream infection. Conclusion: Ultrasound-guided percutaneous cannulation for ECMO can be performed with a high rate of success and safety in children.

Electroacupuncture at Siguan points for migraine of liver yang hyperactivity: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical effect of electroacupuncture at Siguan points and flunarizine hydrochloride capsule on migraine of liver yang hyperactivity.@*METHODS@#A total of 110 patients with migraine of liver yang hyperactivity were randomly divided into an electroacupuncture group (55 cases, 2 cases dropped off) and a western medication group (55 cases, 2 cases dropped off). In the electroacupuncture group, electroacupuncture was applied at Siguan points (Hegu [LI 4] and Taichong [LR 3]), with disperse-dense wave of 2 Hz/100 Hz in frequency and current intensity of 0.1-1 mA, 30 min each time, once a day, 5 times per week for 4 weeks. Flunarizine hydrochloride capsule was given orally in the western medication group, 10 mg a day for 4 weeks. The visual analogue scale (VAS) score and the migraine attack days were observed before and after treatment, during follow-up of 1, 3 and 6 months, and the migraine symptom score was observed before and after treatment in the two groups.@*RESULTS@#After treatment, during follow-up of 1, 3 and 6 months, the VAS scores and the migraine attack days in the two groups were decreased compared with before treatment (Ｐ<0.05), and above indexes in the electroacupuncture group were lower than the western medication group (Ｐ<0.05). After treatment, the migraine symptom scores in the two groups were decreased (Ｐ<0.05), the change in the electroacupuncture group was greater than the western medication group (Ｐ<0.05).@*CONCLUSION@#Electroacupuncture at Siguan points could effectively reduce headache intensity and migraine attack days, relieve migraine symptoms in patients with migraine of liver yang hyperactivity, and the efficacy is superior to oral flunarizine hydrochloride capsules.

Radiosensitization Effect and Mechanism of Xuefu Zhuyutang on Transplanted Esophageal Carcinoma in Nude Mice / 中国实验方剂学杂志

ObjectiveTo explore the radiosensitization and underlying mechanism of Xuefu Zhuyutang on subcutaneous transplanted esophageal carcinoma. MethodThe subcutaneous xenograft model of human esophageal carcinoma ECA-109 in nude mice was induced and the model mice were divided into a model group， an irradiation group， a Xuefu Zhuyutang group， and a combination group， with six nude mice in each group. After the intervention， the transplanted tumors were removed and weighed， and the tumor inhibition rate of each group was calculated according to the formula. The protein expression of hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor A （VEGFA） was detected by immunohistochemistry （IHC）. The protein expression of mammalian target of rapamycin （mTOR）， HIF-1α， VEGFA， and vascular endothelial growth factor receptor 2 （VEGFR2） in transplanted tumors was detected by Western blot. The mRNA expression of mTOR， HIF-1α， and VEGFA in transplanted tumors was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the model group， the tumor weight decreased in the irradiation group and the Xuefu Zhuyutang group （P<0.05）， as well as the combination group （P<0.01）. Compared with the irradiation group， the combination group showed decreased tumor weight （P<0.05）， with tumor inhibition rate of 57.37%. Compared with the model group， the irradiation group， the Xuefu Zhuyutang group， and the combination group showed decreased protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. Compared with the irradiation group， the combination group showed down-regulated protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can inhibit the growth of transplanted esophageal carcinoma ECA-109 in nude mice and shows an obvious radiosensitization effect in combination with radiotherapy. The mechanism may be related to the inhibition of the mTOR/HIF-1α/VEGFA signaling pathway to improve the hypoxic state of tumors.

The Value of CD44 / 中国实验血液学杂志

OBJECTIVE@#To investigate the value of CD44@*METHODS@#Flow cytometry was used to detected the proportion of CD44@*RESULTS@#The percentage of CD44@*CONCLUSION@#HCD44

Relationship between Leukocytes Derived Microparticles and Minimal Residual Disease and Prognosis of Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To detect the relationship between leukocytes derived microparticle (CD45@*METHODS@#The expression of CD45@*RESULTS@#The percentages of CD45@*CONCLUSION@#High level of CD45

Prevalence of late-onset hypogonadism among middle-aged and elderly males in China: results from a national survey / 亚洲男科学杂志(英文版)

This study aimed to propose an operational definition of late-onset hypogonadism (LOH) that incorporates both clinical symptoms and serum testosterone measurements to evaluate the prevalence of LOH in aging males in China. A population-based sample of 6296 men aged 40 years-79 years old was enrolled from six representative provinces in China. Serum total testosterone (TT), sex hormone-binding globulin (SHBG), and luteinizing hormone (LH) were measured and free testosterone (cFT) was calculated. The Aging Males' Symptoms (AMS) scale was used to evaluate the LOH symptoms. Finally, 5078 men were included in this analysis. The TT levels did not decrease with age (P = 0.59), and had no relationship with AMS symptoms (P = 0.87 for AMS total score, P = 0.74 for ≥ 3 sexual symptoms). The cFT levels decreased significantly with age (P < 0.01) and showed a negative association with the presence of ≥ 3 sexual symptoms (P = 0.03). The overall estimated prevalence of LOH was 7.8% (395/5078) if a cFT level <210 pmol l

Experience in treatment of cervical spondylotic radiculopathy by relaxing the sinew of hand three / 中国针灸

The clinical experience of professor

Recent advancement in targeting the KRAS-G12C mutant for cancer therapy / 药学学报

RAS, as a well-known proto-oncogene, is the most frequently mutated oncogene in human cancers, yet tremendous efforts over the past 30 years have failed to develop effective therapies for RAS-mutant cancer. Recently, specifically targeting the KRAS-G12C mutant, a frequently occurring KRAS mutation in human cancers, has shown promise in conquering KRAS-mutant cancers, and has inspired interest in this direction. We herein review the very recent progress achieved in the development of covalent inhibitors towards KRAS-G12C mutant, in combinational therapies and in proteolysis-targeting chimeras (PROTACs)-based approaches to disrupt KRAS-G12C protein. We provide insights for drug discovery against KRAS-G12C-mutated tumors and discuss the potential challenges in this field.

Advances in high-resolution mass spectrometric-based data-mining technologies for detecting and characterizing the components and metabolites of Chinese materia medica / 药学学报

Research on the material basis of Chinese materia medica (CMM) is the basis for modernization of CMM. High-resolution mass spectrometry (HRMS) has become a powerful tool for the qualitative analysis of the components of CMM. Some data-mining strategies based on high-resolution mass spectrometry, such as full-information tandem mass spectrometry scanning acquisition strategy, sequential windowed acquisition of all theoretical fragment ions, mass detect filter, characteristic ion filter, mass spectral tree similarity filter, etc. have greatly promoted the elucidation of the qualitative basis of CMM. In order to provide methods for the rapid discovery and structural characterization of components and metabolites of CMM, this review summarized the advances in HRMS-based data-mining technologies for detecting and characterizing the compounds and metabolites of CMM, which includes class compounds, all compounds and metabolites.

Oxidative stress and antioxidant defense in detoxification systems of snake venom-induced toxicity

Snakebites remain a major life-threatening event worldwide. It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. The main reason for this is a shortage of diagnostic biomarkers and lack of knowledge about pathways of venom-induced toxicity. In traditional Chinese medicine, snakebites are considered to be treated with wind, fire, and wind-fire toxin, but additional studies are required. Methods: Cases of snakebite seen at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were grouped as follows: fire toxin - including four cases of bites by Agkistrodon acutus and three bites by Trimeresurus stejnegeri - and wind-fire toxin - four cases of bites by vipers and three bites by cobras. Serum protein quantification was performed using LC-MS/MS. Differential abundance proteins (DAPs) were identified from comparison of snakebites of each snake species and healthy controls. The protein interaction network was constructed using STITCH database. Results: Principal component analysis and hierarchical clustering of 474 unique proteins exhibited protein expression profiles of wind-fire toxins that are distinct from that of fire toxins. Ninety-three DAPs were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison. GO analysis revealed that the DAPs participated in bicarbonate/oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding. Thirty DAPs directly or indirectly acted on hydrogen peroxide in the interaction network of proteins and drug compounds. The network was clustered into four groups: lipid metabolism and transport; IGF-mediated growth; oxygen transport; and innate immunity. Conclusions: Our results show that the pathways of snake venom-induced toxicity may form a protein network of antioxidant defense by regulating oxidative stress through interaction with hydrogen peroxide.(AU)

Protraction of mandibular molars through a severely atrophic edentulous space in a case of juvenile periodontitis / 대한치과교정학회지

Moving the mandibular posterior teeth into a severely atrophic edentulous space is a challenge. A carefully designed force-and-moment system that results in bodily protraction of the posterior teeth with balanced bone resorption and apposition is needed in such cases. This report describes the treatment of a 19-year-old woman with missing mandibular first molars due to juvenile periodontitis. Miniscrews were used as absolute anchorage during protraction of the mandibular second and third molars. Bodily mesial movement of the mandibular second and third molars was achieved over a distance of 11 to 17 mm after 39 months of orthodontic treatment.