Navafenterol, a new drug for the treatment of chronic obstructive airway disease / 中国临床药理学与治疗学

Navafenterol is a new compound with both muscarinic receptor antagonist and β2 receptor agonist effects in a single molecule, who is being developed for the treatment of chronic obstructive airway disease such as chronic obstructive pulmonary disease and asthma. These pilot clinical studies found that it can significantly improve lung function and symptoms, and is safe and well tolerated. Common treatment emergent adverse events include headache, nasopharyngitis, and dizziness. It may become a next-generation bronchodilator for chronic obstructive airway disease. This review introduced the prospective of Navafenterol.

Risk factors of central compartment lymph node metastasis in stage T 1a solitary papillary thyroid carcinoma / 肿瘤研究与临床

Objective:To investigate the correlation of central compartment lymph node metastasis(CLNM) in stage T 1a solitary papillary thyroid carcinoma (PTC) with the clinicopathological characteristics, sonographic features and the number of lymph node dissection, and to analyze the risk factors of CLNM. Methods:The data of 218 patients with stage T 1a solitary PTC who underwent thyroid cancer surgery from January 2017 to May 2021 in Tangshan Union Medical College Hospital were retrospectively analyzed. All patients were divided into CLNM positive group and CLNM negative group according to CLNM. The age, gender, preoperative sonographic features, pathological type, the number of lymph node dissection and the number of metastasis were recorded. Logistic regression was used to analyze the risk factors of CLNM. Results:Among 218 patients, there were 71 cases (32.6%) in CLNM positive group and 147 cases (67.4%) in CLNM negative group. There were statistically significant differences in age, tumor diameter, capsular invasion in thyroid or not, tumor blood supply or not, and the number of lymph node dissection between two groups (all P < 0.05). There were no statistically significant differences in gender, clear tumor boundary or not, tumor shape, tumor aspect ratio, calcification, nodular goiter and Hashimoto's thyroiditis or not (all P > 0.05). Multivariate binary logistic regression analysis showed that age < 55 years ( OR = 2.995, 95% CI 1.228-7.307), capsular invasion in thyroid ( OR = 5.297, 95% CI 2.494-11.248) and the number of lymph node dissection ≥6 ( OR = 4.085, 95% CI 2.059-8.104) were independent risk factors of CLNM (all P < 0.05). Conclusions:Patients with stage T 1a solitary PTC, age < 55 years and capsular invasion in thyroid are prone to CLNM; sufficient number of lymph node dissection can get more accurate CLNM rate.

Acoustic analysis of an articulation assessment and training system / 中华物理医学与康复杂志

Objective:To compare the differences in important parameters between the articulation assessment and training system of intelligently extracted speech with those from the Praat acoustic software and those manually extracted.Methods:The speech of thirty-two normal subjects was captured using the intelligent articulation assessment and training system and using Praat acoustic software. The former analyzed the mean fundamental frequencies (mF0s), the first formant peaks (F1s) and the second formant peak (F2s) of the sustained vowels /a/, /i/ and /u/. The speech parameters collected by the traditional Praat software were extracted and analyzed by professionals. The two tools′ consistency in terms of these important acoustic parameters was analyzed.Results:The results with all 32 subjects when retested returned ICC values above 0.9 with all three vowels with the exception of mF0 for /u/ (ICC=0.75), indicating excellent retest reliability for the articulation assessment and training system. The ICC values also indicated excellent consistency between the two kinds of software in analyzing mF0, F1 and F2 of the three vowels. The mF0, F1, F2, FCR, VAI, tongue spacing, VSA, and mandibular spacing of all three vowels were mostly distributed within the 95% confidence interval of the data points in Bland-Altman plots, indicating the high accuracy of both acoustic analysis systems in speech measurement. The mean fundamental frequency values of the male long vowels /a/, /i/ and /u/ were all significantly lower than for the female long versions.Conclusions:The retest reliability of the articulation assessment and training system was good, and the results of the articulation check in the natural state were in good consistency compared to the Praat check and were interchangeable in the articulation check.

Analysis of pathogenic fungi causing tinea capitis: a single-center retrospective study / 中华皮肤科杂志

Objective:To investigate the distribution of pathogenic fungi in patients with tinea capitis diagnosed in Xijing Hospital, Air Force Medical University in the past 10 years.Methods:A total of 871 outpatients or inpatients with tinea capitis were collected from the Department of Dermatology, Xijing Hospital from January 2011 to December 2020, and their clinical data and pathogen distribution were retrospectively analyzed. Pearson chi-square test was used to analyze differences in the pathogen distribution between children and adult patients with tinea capitis.Results:Of 871 patients with tinea capitis, 588 (67.5%) were males and 283 (33.5%) were females; 21 (2.40%) were aged less than 1 year, 266 (30.50%) aged 1 - 3 years, 352 (40.40%) aged 4 - 6 years, 187 (21.50%) aged 7 - 12 years, 4 (0.50%) aged 12 - 18 years, and 41 (4.70%) were aged 18 - 74 years. A total of 705 pathogenic strains were isolated from these patients, including 599 strains of Microsporum canis (85.0%) , 52 strains of Trichophyton mentagrophytes complex (7.4%) , 27 strains of Trichophyton tonsurans (3.8%) , and 18 strains of Trichophyton violaceum (2.6%) . Among the pathogenic fungi of tinea capitis, the proportion of Trichophyton violaceum was significantly higher in adults (8.8%) than in children (2.2%, P = 0.048) . Conclusions:In the past 10 years, the patients with tinea capitis in the Department of Dermatology, Xijing Hospital were mainly children aged 1 - 6 yearswhile adults, and adult patients with tinea capitis were uncommon. The main pathogen of tinea capitis was Microsporum canis, followed by Trichophyton mentagrophytes complex.

Clinical efficacy and safety of secukinumab in the treatment of 13 cases of refractory localized pustular psoriasis / 中华皮肤科杂志

Objective:To evaluate clinical efficacy and safety of secukinumab in the treatment of patients with localized pustular psoriasis irresponsive or intolerant to conventional treatment.Methods:Clinical data were collected from 13 patients with refractory localized pustular psoriasis, who received secukinumab treatment in Department of Dermatology, Xijing Hospital from December 2019 to April 2022. Efficacy was evaluated by comparing palmoplantar pustulosis (PPP) area and severity index (PPPASI) score and physician global assessment (PGA) score in PPP patients before and after the treatment, and by comparing clinical global impression (CGI) score in patients with acrodermatitis continua of Hallopeau (ACH). Adverse events were recorded during the treatment.Results:Among the 13 patients with refractory localized pustular psoriasis, 6 were diagnosed with PPP, 3 with ACH, and 4 with PPP complicated by ACH. There were 3 males and 10 females, and their age was 33.2 ± 14.6 years. After 12-week treatment, the PPPASI score decreased from 13.88 ± 3.62 points at baseline to 6.81 ± 2.31 points in 10 patients presenting with PPP lesions, 4 achieved 75% improvement in the PPPASI score (PPPASI75), and 5 achieved PGA0/1; at the same time, 6 of the 7 patients presenting with ACH lesions achieved moderate or marked improvement in the CGI score, and 4 of the 6 patients achieved marked improvement. Two patients with PPP discontinued the treatment after 3- and 5-week treatment respectively due to poor response, and 1 patient with ACH achieved mild improvement in the CGI score after 12-week treatment. No severe adverse events were reported during the treatment. However, inflammatory follicular papules occurred in 1 patient, and eczematoid lesions occurred in another 1 patient, which both regressed after symptomatic treatment.Conclusion:Secukinumab was effective and safe in the treatment of refractory localized pustular psoriasis, and may serve as a new treatment option for refractory PPP and ACH.

Role of ferroptosis in lung injury in a rat model of autologous orthotopic liver transplantation / 中华麻醉学杂志

Objective:To evaluate the role of ferroptosis in lung injury in a rat model of autologous orthotopic liver transplantation.Methods:Twenty-four healthy adult SPF-grade male rats, aged 8-10 weeks, weighing 230-270 g, were divided into 3 groups ( n=8 each) using the random number table method: sham operation group (S group), autologous in situ liver transplantation group (LT group) and ferroptosis inhibitor Ferrostain-1 group (LT+ Fer-1 group). In LT group and LT+ Fer-1 group, an autologous in situ liver transplantation model was developed in anesthetized animals, and Ferrostain-1 5 mg/kg was intraperitoneally injected at 30 min before surgery in LT+ Fer-1 group. The inferior vena cava blood samples were obtained at 6 h of reperfusion, then animals were sacrificed, and lung tissues were obtained. The morphology of lung tissues was examined, and the lung injury was scored. The serum malondialdehyde (MDA) concentration and contents of MDA, reduced glutathione (GSH), glutathione peroxidase4 (GPX4), and Fe 2+ in lung tissues were measured by enzyme-linked immunosorbent assay. The expression of ferritin heavy chain 1 (FTH1) and solute carrier family 7 member 11 recombinant protein (SLC7A11) was determined by Western blot. Results:Compared with S group, the lung injury, serum MDA concentration, and contents of MDA and Fe 2+ were significantly increased, the contents of GSH and GPX4 were decreased, and the expression of FTH1 and SLC7A11 was down-regulated in LT group ( P<0.05). Compared with LT group, the lung injury, serum MDA concentration, and contents of MDA and Fe 2+ were significantly decreased, the contents of GSH and GPX4 were increased, and the expression of FTH1 and SLC7A11 was up-regulated in LT+ Fer-1 group ( P< 0.05). Conclusions:Ferroptosis is involved in the pathophysiology of lung injury in a rat model of autologous orthotopic liver transplantation.

Analysis of therapeutic effects of step-up versus step-jump strategies in treatment of infected pancreatic necrosis / 中华肝胆外科杂志

Objective:To compare the safety and efficacy of the " step-up approach" versus the " step-jump approach" in treatment of infected pancreatic necrosis (IPN).Method:The clinical data of IPN patients who underwent step-up strategy or step-jump strategy treatment at the Department of Pancreatic and Biliary Surgery of the First Affiliated Hospital of Harbin Medical University from December 2018 to November 2022 were analyzed retrospectively. Propensity score matching (PSM) was done based on the nearest neighbor matching method (1: 1 ratio). After matching the baseline data (the caliper value was 0.01), a total of 62 patients with IPN were included, including 41 males and 21 females, aged (41.1±13.1) years old. Patients who were treated with the step-up strategy were included in the step-up group, while patients who were treated with the step-jump strategy were included in the step-jump group. There were 31 patients in each group after PSM, and the treatment effect of the two groups were compared.Results:Of the 62 patients with IPN, 43 received surgical intervention, and 19 were managed successfully using symptomatic anti-inflammatory treatment or percutaneous catheter drainage. The total hospitalization cost of patients in the step-jump group was significantly higher than that in the step-up group [122 000 (73 000, 179 000) yuan vs. 88 000 (46 000, 144 000) yuan, P=0.034]. The overall cure rate of IPN patients in the step-jump group was 93.5%(29/31). The 2 patients who died had type Ⅲ IPN. In the IPN patients in the step-up group were all cured, and the overall cure rate was 100%(31/31), with no death. There were no statistical differences between the two groups in the rates of death, postoperative complications, residual infection, debridement ≥2 times, and positive bacterial culture in blood or drainage fluid (all P>0.05). A total of 19.4% (12/62) patients had postoperative complications, including 4 patients with abdominal bleeding, 3 patients with new organ dysfunction, 2 patients with gastrointestinal bleeding, 2 patients with gastrointestinal fistula, and 1 patient with venous thrombosis in both lower limbs. Conclusion:Both the step-up treatment strategy and the step-jump treatment strategy were safe and effective for treatment of IPN patients.

Relationship between the pelvic bone marrow dose-volume parameters and acute hematologic toxicity in neoadjuvant pelvic intensity-modulated radiotherapy for local advance rectal cancer / 中华放射医学与防护杂志

Objective:To analyze the correlation between the volume of irradiated pelvic bone marrow and acute hematologic toxicity (HT), in order to provide clinical data to reduce the risk of acute HT and optimize the radiotherapy plan.Methods:From October 2017 to May 2019, 41 LARC patients who received neoadjuvant concurrent chemoradiotherapy (CCRT) were retrospectively reviewed in our center. All patients were treated with 5-field intensity-modulated radiotherapy (IMRT), and the prescription dose delivered to PTV was 45-50.4 Gy in 25-28 fractions. Capecitabine or 5-fluorouracil (5-FU) wasadministered daily 5 days a week during radiotherapy. Different HTswere recorded according to National Cancer Institute Common Toxicity Criteria Version 5.0 (NCI-CTC.V5.0) based on laboratory tests. The volume of PBM or each site (coxal, sacrum, femoral) receiving more than x Gy refers to as TVx, CVx, SVx, and FVx, respectively. Logistic regression was performed to evaluate the association between the volume of irradiated pelvic bone marrow and different HT. Generalized additive model (GAM) and piecewise regression were used to further analyze the possible nonlinear relationship and threshold effect between them. Results:Multivariate logistic regression analysis showed that low-dose of irradiated total pelvic bone marrow volume ( TV5) and coxal bone marrow volume ( CV5, CV10) were significantly correlated with Grade ≥2 leukopenia( P<0.05). There was a significant negative correlation between the sacrum bone marrow volume ( SV5, SV10) and Grade ≥2 leukopenia ( P<0.05). A thresholdeffect has been observed between CV10 and Grade ≥2 leukopenia by Generalized additive model (GAM) and piecewise linear regression. The threshold between CV10 and Grade ≥2 leukopenia was 575 ml, OR (95% CI) was 1.85 (1.08, 3.16). Conclusions:In neoadjuvant IMRT of rectal cancer, CV is a better predictor of acute HT induced by CCRT than TV. The irradiated volume of CV associated with acute HT was mainly low-dose levels ( CV5, CV10). The thresholds of our study ( CV10= 575 ml) could be a good reference for the optimization of the radiotherapy plan.

Review of advances in chemotherapy for thyroid cancer / 中华内分泌外科杂志

The incidence of thyroid cancer has continued to increase. Most thyroid cancer patients have good prognosis, but there are still some patients who will develop into the middle or late stage. The status of cytotoxic treatment in thyroid cancer treatment is controversial. Chemotherapy, as a classical malignant tumor treatment, has its unique significance for the special type and the special period of thyroid cancer. Chemotherapy can be an option for systemic treatment if no other treatment is available for patients of differentiated thyroid carcinoma refractory to radiodine in rapid progression and life-threatening period. For patients of anaplastic thyroid cancer in progression period, chemotherapy can be selected if there are no other treatments in clinical trials. And "Chemical therapy plus" treatment model might play an important role in thyroid treatment, because with the development of targeted drugs and immunotherapy, chemotherapy combined with other treatments can reduce the dosage of chemotherapy drugs to reduce the toxic side effect, and can improve other therapeutic effects.

Investigation on biological subtypes of depression based on diffusion tensor imaging / 四川精神卫生

BackgroundBeing complex and highly heterogeneous with regard to the etiology and clinical manifestations of depression， neuroimaging studies make a breakthrough for exploring the biological subtypes of depression， while the current data-driven approach for the identification of subtyping depression using structural magnetic resonance imaging （MRI） data is insufficient. ObjectiveTo explore the biological subtypes of depression using diffusion tensor imaging （DTI） and machine learning methods. MethodsA total of 127 patients with depression who attended Beijing Anding Hospital from September 2017 to August 2021 and met the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） diagnostic criteria were included， and another 80 healthy individuals matched for gender and age were recruited through advertisements in surrounding communities during the same period. DTI findings， demographic characteristics and clinical data were collected from all participants. Tract-based spatial statistics （TBSS） and the Johns Hopkins University （JHU） white matter probability maps were used to extract fractional anisotropy （FA） values of white matter tracts. A semi-supervised machine learning technique was used to identify the subtypes， and the FA values for whole brain white matter of patients and controls were compared. ResultsPatients with depression were classified into two biological subtypes. FA values in multiple tracts including corpus callosum and corona radiata of subtype I patients were smaller than those of healthy controls （P<0.01， FDR corrected）， and FA values in middle cerebellar peduncle， left superior cerebellar peduncle and left cerebral peduncle of subtype II patients were larger than those of healthy controls （P<0.01， FDR-corrected）. Baseline Hamilton Depression Scale-17 item （HAMD-17） score yielded no statistical difference between subtype I and subtype II patients （P>0.05）， while subtype I patients scored lower on HAMD-17 than subtype II patients after 12 weeks of treatment （t=2.410， P<0.05）. ConclusionDepression patients exhibit two biological subtypes with distinct patterns of white matter damage. Furthermore， the subtypes respond differently to the medication treatment. ［Funded by the National Key Research and Development Program of China （number， 2016YFC1307200）， the Scientific Research and Cultivation Program of Beijing Municipal Hospitals （number，PX2023066）， Beijing Anding Hospital， Capital Medical University （number，YJ201904， YJ201911）； www.chictr.org.cn number： ChiCTR-OOC-17012566］

Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study / 中国结合医学杂志

OBJECTIVE@#To identify specific Chinese medicines (CMs) that may benefit patients with gastroesophageal reflux disease (GERD), and explore the action mechanism.@*METHODS@#Domestic and foreign literature on the treatment of GERD with CMs was searched and selected from China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Database, and PubMed from October 1, 2011 to October 1, 2021. Data from all eligible articles were extracted to establish the database of CMs for GERD. Apriori algorithm of data mining techniques was used to analyze the rules of herbs selection and core Chinese medicine formulas were identified. A system pharmacology approach was used to explore the action mechanism of these medicines.@*RESULTS@#A total of 278 prescriptions for GERD were analyzed, including 192 CMs. Results of Apriori algorithm indicated that Evodiae Fructus and Coptidis Rhizoma were the highest confidence combination. A total of 32 active ingredients and 66 targets were screened for the treatment of GERD. Enrichment analysis showed that the mechanisms of action mainly involved pathways in cancer, fluid shear stress and atherosclerosis, advanced glycation end product (AGE), the receptor for AGE signaling pathway in diabetic complications, bladder cancer, and rheumatoid arthritis.@*CONCLUSION@#Evodiae Fructus and Coptidis Rhizoma are the core drugs in the treatment of GERD and the potential mechanism of action of these medicines includes potential target and pathways.

Advances in AAV-CRISPR/Cas9-Mediated Hemophilia A Gene Therapy --Review / 中国实验血液学杂志

Hemophilia A(HA) is an X-linked recessive bleeding disorder caused by mutations in coagulation factor VIII. Nowadays, exogenous coagulation factor replacement therapy is the main treatment. With the continuous development of gene therapy, new research directions have been provided for the treatment of hemophilia A. CRISPR-Cas9 technology was applied to select suitable target sites, and mediate the targeted knock-in and efficient expression of exogenous B-domain-deleted FⅧ variant gene through corresponding vectors for the treatment of hemophilia A.CRISPR-Cas9 technology is an emerging gene editing tool with great efficiency, safety and effectiveness, and has been widely used in hemophilia gene therapy research. This paper reviews the vector selection, construction of therapeutic genes, gene editing technology and selection of expression target sites for hemophilia A gene therapy at this stage.

Principles of extramural health care for chronic wounds in China / 中华创伤杂志(英文版)

Development of extramural health care for chronic wounds is still in its infancy in China, and thus it is urgent and vital to establish a correct concept and practicable principles. The authors reviewed recent domestic and international literature and summarized the following treatment procedures and principles for extramural health care of chronic wounds. (1) The patient needs to do self-assessment of the wound by using available simple methods; (2) The patient consults with professional physicians or nurses on wound care to define the severity and etiology of the non-healing wound; (3) Professionals evaluate the existing treatment strategies; (4) Etiological treatments are given by professionals; (5) Patients buy needed dressings via the more convenient ways from pharmacies, e-commerce platform or others; (6) Professionals provide a standardized and reasonable therapeutic plan based on the patient's wound conditions; (7) Both professionals and the patient pay attention to complications to prevent adverse outcomes; (8) Professionals strengthen the public education on wound care and integrated rehabilitation. This review expected to provide new perspectives on the therapeutic strategies for chronic wounds in an extramural setting.

Analysis of F12 gene variants and molecular mechanisms in patients with coagulation factor Ⅻ deficiency / 中华医学遗传学杂志

OBJECTIVE@#To analyze the sequence of the F12 gene and molecular mechanism for 20 patients with coagulation factor Ⅻ (FⅫ) deficiency.@*METHODS@#The patients were selected from the outpatient department of the Second Hospital of Shanxi Medical University from July 2020 to January 2022. The activity of coagulation factor Ⅷ (FⅧ:C), factor Ⅸ (FⅨ:C), factor Ⅺ (FⅪ:C) and factor Ⅻ (FⅫ:C) were determined by using a one-stage clotting assay. All exons and 5' and 3' UTR of the F12 gene were analyzed by Sanger sequencing to detect the potential variants. Bioinformatic software was used to predict the pathogenicity of the variants, conservation of amino acids, and protein models.@*RESULTS@#The FⅫ:C of the 20 patients has ranged from 0.07% to 20.10%, which was far below the reference values, whilst the other coagulation indexes were all normal. Sanger sequencing has identified genetic variants in 10 patients, including 4 with missense variants [c.820C>T (p.Arg274Cys), c.1561G>A (p.Glu521Lys), c.181T>C (p.Cys61Arg) and c.566.G>C (p.Cys189Ser)], 4 deletional variants c.303_304delCA(p.His101GlnfsX36), 1 insertional variant c.1093_1094insC (p.Lys365GlnfsX69) and 1 nonsense variant c.1763C>A (p.Ser588*). The remaining 10 patients only harbored the 46C/T variant. The heterozygous c.820C>T(p.Arg274Cys) missense variant in patient 1 and the homozygous c.1763C>A (p.Ser588*) nonsense variant in patient 2 were not included in the ClinVar and the Human Gene Mutation Database. Bioinformatic analysis predicted that both variants were pathogenic, and the corresponding amino acids are highly conserved. The protein prediction models suggested that the c.820C>T (p.Arg274Cys) variant may affect the stability of the secondary structure of FⅫ protein by disrupting the original hydrogen bonding force and truncating the side chain, leading to changes in the vital domain. c.1763C>A (p.Ser588*) may produce a truncated C-terminus which may alter the spatial conformation of the protein domain and affect the serine protease cleavage site, resulting in extremely reduced FⅫ:C.@*CONCLUSION@#Among individuals with low low FⅫ:C detected by one-stage clotting assay, 50% have harbored variants of the F12 gene, among which the c.820C>T and c.1763C>A were novel variants underlying the reduced coagulating factor FⅫ.

A Case Report of Nevus Trichilemmocysticus / 罕见病研究

This article reports a case of nevus trichilemmocysticus. The patient, a 48-year-old man, presented with multiple filiform keratoses and nodules. Physical examination identified multiple subcutaneous papules and nodules on the scalp, filiform keratoses on the face and bilateral ears, in addition to linear blackheads on trunk and limbs. The patient also exhibited hair loss and hypoplastic tooth. Histopathology revealed trichilemmal cyst. Nevus trichilemmocysticus is a rare organoid nevus. We reviewed literature in order to raise the awareness of the syndrome.

Effects of total saponins from Trillium tschonoskii maxim on cognition impairment and mitochondrial autophagy in aging rats induced by D-Gal / 中国药理学通报

Aim To investigate the effects of total saponins from Trillium tschonoskii maxim(TST)on cognitive impairment and mitochondrial autophagy in aging rats induced by D-galactose(D-gal). Methods Male SD rats were randomly divided into normal control group,model group(D-gal,subcutaneous injection),intervention group(TST,low,medium and high dose groups by intragastric administration),with 10 rats in each group,and administered for 6 weeks. Morris water maze was used to evaluate the cognitive function. HE and Nissl staining were used to test the hippocampal and brain cortex morphology. Immunohistochemistry staining was applied to detect the localization expression of Pink1 and Parkin. Western blot was employed to detect the expressions of Pink1,Parkin,LC3-Ⅱ,p62 and Beclin1. Results Compared with the normal control group,the escape latency time was prolonged and the number of crossing platform decreased in D-gal model group(P<0.05). The number of neurons in hippocampus significantly decreased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly decreased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 were markedly reduced,while the expression of p62 was significantly raised(P<0.05). Compared with D-gal model group,the escape latency time of TST dose groups was shortened,the Times of crossing the platform was more,and the time of staying in the platform quadrant increased(P<0.05). The number of neurons in hippocampus significantly increased. The positive cells labeled by Pink1 and Parkin staining in hippocampus significantly increased. The expressions of Pink1,Parkin,LC3-Ⅱ and Beclin1 in hippocampus were apparently up-regulated,while the protein expression of p62 was evidently down-regulated(P<0.05). Conclusions TST has neuroprotective effects on the learning and memory capacities in aging rats induced by D-gal,which may be related to the increasing levels of Pink1,Parkin,LC3-Ⅱ and Beclin1 proteins and the activation of mitochondrial autophagy.

Significance of TERT promoter mutation in differential diagnosis of non-invasive inverted urothelial lesions of bladder / 中华病理学杂志

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.

GBA inhibition suppresses ovarian cancer growth, survival and receptor tyrosine kinase AXL-mediated signaling pathways

The poor outcome of advanced ovarian cancer under conventional therapy necessitates new strategies to improve therapeutic efficacy. β-glucosidase (encoded by GBA) is a lysosomal enzyme and is involved in sphingolipids metabolism. Recent studies revealed that β-glucosidase plays a role in cancer development and chemoresistance. In this work, we systematically evaluated the expression and role of GBA in ovarian cancer. Our work demonstrates that inhibition of β-glucosidase has therapeutic potential for ovarian cancer. Gene Expression Profiling Interactive Analysis database, western blot and immunohistochemistry analyses of patient samples demonstrated that GBA mRNA and protein expression levels were significantly increased in ovarian cancer compared to normal tissues. Functional studies using gainof-function and loss-of-function approaches demonstrated that GBA overexpression did not affect growth and migration but alleviated cisplatin’s efficacy in ovarian cancer cells. In addition, GBA depletion resulted in growth inhibition, apoptosis induction, and enhancement of cisplatin’s efficacy. Of note, we found that GBA inhibition specifically decreased receptor tyrosine kinase AXL level, leading to the suppression of AXL-mediated signaling pathways. Our data suggest that GBA represents a promising target to inhibit AXL signaling and overcome cisplatin resistance in ovarian cancer.

Effect study of Sonic hedgehog overexpressed hair follicle stem cells in hair follicle regeneration / 中国修复重建外科杂志

OBJECTIVE@#To determine the expression level of Sonic hedgehog (Shh) in the passage of hair follicle stem cells (HFSCs), analyze the effect of Shh overexpression on the proliferation activity of HFSCs, and explore the survival of HFSCs after Shh overexpression and its effect on hair follicle regeneration.@*METHODS@#Hair follicles from the normal area (H1 group) and alopecia area (H2 group) of the scalp donated by 20 female alopecia patients aged 40-50 years old were taken, and the middle part of the hair follicle was cut under the microscope to culture, and the primary HFSCs were obtained and passaged; the positive markers (CD29, CD71) and negative marker (CD34) on the surface of the fourth generation HFSCs were identified by flow cytometry. The two groups of HFSCs were transfected with Shh-overexpressed lentivirus. Flow cytometry and cell counting kit 8 assay were used to detect the cell cycle changes and cell proliferation of HFSCs before and after transfection, respectively. Then the HFSCs transfected with Shh lentivirus were transplanted subcutaneously into the back of nude mice as the experimental group, and the same amount of saline was injected as the control group. At 5 weeks after cell transplantation, the expression of Shh protein in the back skin tissue of nude mice was detected by Western blot. HE staining and immunofluorescence staining were used to compare the number of hair follicles and the survival of HFSCs between groups.@*RESULTS@#The isolated and cultured cells were fusiform and firmly attached to the wall; flow cytometry showed that CD29 and CD71 were highly expressed on the surface of the cells, while CD34 was lowly expressed, suggesting that the cultured cells were HFSCs. The results of real-time fluorescence quantitative PCR and Western blot showed that the expression levels of Shh protein and gene in the 4th, 7th, and 10th passages of cells in H1 and H2 groups decreased gradually with the prolongation of culture time in vitro. After overexpression of Shh, the proliferation activity of HFSCs in the two groups was significantly higher than that in the blank group (not transfected with lentivirus) and the negative control group (transfected with negative control lentivirus), and the proliferation activity of HFSCs in H1 group was significantly higher than that in H2 group before and after transfection, showing significant differences ( P<0.05). At 5 weeks after cell transplantation, Shh protein was stably expressed in the dorsal skin of each experimental group; the number of hair follicles and the expression levels of HFSCs markers (CD71, cytokeratin 15) in each experimental group were significantly higher than those in the control group, and the number of hair follicles and the expression levels of HFSCs markers in H1 group were significantly higher than those in H2 group, and the differences were significant ( P<0.05).@*CONCLUSION@#Lentivirus-mediated Shh can be successfully transfected into HFSCs, the proliferation activity of HFSCs significantly increase after overexpression of Shh, which can secrete and express Shh continuously and stably, and promote hair follicle regeneration by combining the advantages of stem cells and Shh.

Study on the sterilization effect of plasma jet and plasma activated water on Streptococcus mutans / 生物医学工程学杂志

To explore the effects of plasma jet (PJ) and plasma activated water (PAW) on the sterilization of Streptococcus mutans ( S. mutans) and compare the advantages and disadvantages of the two methods, so as to provide a basis for plasma treatment of dental caries and to enrich the treatment means of dental caries, an atmospheric pressure plasma excitation system was built, and the effects of PJ and PAW on the sterilization rate of S. mutans and the changes of temperature and pH during treatment were studied under different excitation voltage ( U e ) and different excitation time ( t e ). The results showed that in the PJ treatment, the difference in the survival rate of S. mutans between the treatment group and the control group was statistically significant ( P = 0.007, d=2.66) when U e = 7 kV and t e = 60 s, and complete sterilization was achieved at U e = 8 kV and t e = 120 s in the PJ treatment. In contrast, in the PAW treatment, the difference in the survival rate of S. mutans between the treatment group and the control group was statistically significant ( P = 0.029, d = 1.71) when U e = 7 kV and t e = 30 s, and complete sterilization was achieved with PAW treatment when U e = 9 kV and t e = 60 s. Results of the monitoring of temperature and pH showed that the maximum temperature rise during PJ and PAW treatment did not exceed 4.3 °C, while the pH value after PAW treatment would drop to a minimum of 3.02. In summary, the optimal sterilization parameters for PJ were U e =8 kV and 90 s < t e ≤ 120 s, while the optimal sterilization parameters for PAW were U e = 9 kV and 30 s< t e ≤ 60 s. Both treatment methods achieved non-thermal sterilization of S. mutans, where PJ required only a smaller U e to achieve complete sterilization, while at pH < 4.7, PAW only required a shorter t e to achieve complete sterilization, but its acidic environment could cause some chemical damage to the teeth. This study can provide some reference value for plasma treatment of dental caries.