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.

Analysis of global mRNA drug industrialization dynamics / 药学学报

The successful development and application of mRNA COVID-19 vaccine fully illustrated the great potential and application prospect of mRNA technology in the field of biomedicine. Currently, many companies worldwide are developing drugs and vaccines based on mRNA technology for the prevention and treatment of various diseases. It can be foreseen that with the continuous launch of mRNA drugs, commercial GMP production capacity matching them is also urgent. The optimization of production processes, intelligent manufacturing and other risk control strategies, as well as the control of industrialization costs, will help improve the core competitiveness of mRNA innovative drug development. In view of this, this article will provide an overview of the global production process of mRNA drugs and the progress of related GMP production dynamics, sort out the key chain points of the mRNA industry chain, explore the construction of the mRNA pharmaceutical enterprise value chain and the formation of core competitiveness, and provide reference and reference for the research and development of innovative mRNA drugs and high-quality development in China.

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.

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.

Imaging classification and analysis of the diagnosis and treatment of infected pancreatic necrosis:a report of 126 cases / 中华外科杂志

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ2 test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ2=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ2=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.

Pathological features and clinicopathological significance of TERT promoter mutation in breast fibroepithelial tumors without definite diagnosis / 中华病理学杂志

Objective: To investigate the pathological features and the clinicopathological significance of TERT detection in those tumors that were difficult to diagnosis. Methods: A total of 93 cases of fibroepithelial tumors without definite diagnosis were collected from the Affiliated Hospital of Qigndao University between 2013 and 2021. The clinical details such as patients' age and tumor size were collected. All slides were re-reviewed and the pathologic parameters, including stromal cellularity, stromal cell atypia, stromal cell mitoses, and stromal overgrowth were re-interpreted. Sanger sequencing was used to detect TERT promoter status, and immunohistochemistry was performed to detect TERT protein expression. The relationship between TERT promoter mutation as well as protein expression levels and the clinicopathological parameters were also analyzed. Results: The patients' ages ranged from 30 to 71 years (mean of 46 years); the tumor size ranged from 1.2 to 8.0 cm (mean 3.8 cm). These tumors showed the following morphologic features: leafy structures in the background of fibroadenoma, or moderately to severely abundant stromal cells. The interpretations of tumor border status were ambiguous in some cases. The incidence of TERT promoter mutation was high in patients of age≥50 years, tumor size≥4 cm, and stromal overgrowth at ×4 or ×10 objective, and these clinicopathologic features were in favor of diagnosis of phyllodes tumors. TERT protein expression levels was not associated with the above clinicopathologic parameters and its promoter mutation status. Conclusions: The diagnostic difficulty for the breast fibroepithelial tumors is due to the difficulty in recognition of the leafy structures or in those cases with abundant stromal cells. A comprehensive evaluation combined with morphologic characteristics and molecular parameters such as TERT promoter may be helpful for the correct diagnosis and better evaluating recurrence risk.

Hematological Neoplasms Secondary to Malignant Solid Tumors with Radiotherapy and Chemotherapy: a Clinical and Prognostic Analysis / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics, treatment and prognosis of therapy-related hematological neoplasms patients secondary to malignant solid tumors.@*METHODS@#The clinical features, treatment and prognosis of 36 hematological neoplasms patients secondary to malignant solid tumors with radiotherapy and chemotherapy in the Second Hospital of Shanxi Medical University were retrospectively analyzed.@*RESULTS@#The 36 patients with therapy-related hematological neoplasms had a median age of 60 (47-81) years, 14 were male and 22 were female. Among them, 22 cases were acute myeloid leukemia, 5 cases were acute lymphoblastic leukemia, 4 cases were multiple myeloma, 3 cases were myelodysplastic syndrome, and 2 cases were non-hodgkin's lymphoma. The median latency of malignant tumor to hematological neoplasm was 42.5 (12-120) months. The median survival time of therapy-related hematological neoplasms was 10.5 (1-83) months, and the 3-year overall survival (OS) rate was 24.3%. The therapy-related acute myeloid leukemia patients had a very poor prognosis, with a median survival of 7 (1-83) months and a 3-year OS rate of 21.4%.@*CONCLUSION@#The prognosis of therapy-related hematological neoplasms secondary to malignant solid tumors with radiotherapy and chemotherapy is poor, and individualized treatment should be implemented according to the clinical situation of patients.

Effect of ligustrazine on hypoxic-ischemic encephalopathy in neonatal rats by regulating autophagy through the PINK1/Parkin pathway / 中国当代儿科杂志

OBJECTIVES@#To study the effect of ligustrazine injection on mitophagy in neonatal rats with hypoxic-ischemic encephalopathy (HIE) and its molecular mechanism.@*METHODS@#Neonatal Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group with 8 rats, a model group with 12 rats, and a ligustrazine group with 12 rats. The rats in the model group and the ligustrazine group were used to establish a neonatal rat model of HIE by ligation of the left common carotid artery followed by hypoxia treatment, and blood vessels were exposed without any other treatment for the rats in the sham-operation group. The rats in the ligustrazine group were intraperitoneally injected with ligustrazine (20 mg/kg) daily after hypoxia-ischemia, and those in the sham-operation group and the model group were intraperitoneally injected with an equal volume of normal saline daily. Samples were collected after 7 days of treatment. Hematoxylin and eosin staining and Nissl staining were used to observe the pathological changes of neurons in brain tissue; immunohistochemical staining was used to observe the positive expression of PINK1 and Parkin in the hippocampus and cortex; TUNEL staining was used to measure neuronal apoptosis; Western blotting was used to measure the expression levels of the mitophagy pathway proteins PINK1 and Parkin and the autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (P62).@*RESULTS@#Compared with the sham-operation group, the model group had a significant reduction in the number of neurons, an increase in intercellular space, loose arrangement, lipid vacuolization, and a reduction in Nissl bodies. The increased positive expression of PINK1 and Parkin, apoptosis rate of neurons, and protein expression levels of PINK1, Parkin, Beclin1 and LC3 (P<0.05) and the decreased protein expression level of P62 in the hippocampus were also observed in the model group (P<0.05). Compared with the model group, the ligustrazine group had a significant increase in the number of neurons with ordered arrangement and an increase in Nissl bodies, significant reductions in the positive expression of PINK1 and Parkin, the apoptosis rate of neurons, and the protein expression levels of PINK1, Parkin, Beclin1, and LC3 (P<0.05), and a significant increase in the protein expression level of P62 (P<0.05).@*CONCLUSIONS@#Ligustrazine can alleviate hypoxic-ischemic brain damage and inhibit neuronal apoptosis in neonatal rats to a certain extent, possibly by inhibiting PINK1/Parkin-mediated autophagy.

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.

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.