Efficacy and safety of interventional therapy combined with drug injection under bronchoscope in the treatment of central non-small cell lung cancer / 中国临床药理学与治疗学

AIM: To evaluate the efficacy and safety of interventional therapy combined with tumor drug injection under bronchoscope for central non-small cell lung cancer (NSCLC). METHODS: Sixty-four patients who met the test admission criteria were randomly assigned to the experimental group and the control group according to the ratio of 1:1, and were given bronchoscopic interventional therapy combined with local drug injection of recombinant human endostatin combined with platinum-containing dual-drug chemotherapy and platinum-containing dual-drug alone, respectively. The curative efficiency and safety of the two groups were compared. RESULTS: Compared with the control group, the KPS score, dyspnea grading were significantly improved (P<0.05). The effective rate of the test group was 78.12%, which was higher than 37.5% in the control group, the difference between the two groups was significant (P<0.05). Moreover, there was also a significant difference in the 1-year survival rate between the experimental group and the control group (P<0.05). CONCLUSION: The treatment of central NSCLC by interventional therapy combined with tumor drug injection through fiberoptic bronchoscope has obvious clinical efficacy, which can effectively alleviate the clinical symptoms and improve the quality of life of patients. There is no significant difference in adverse reactions between the two groups, and is worthy of popularization and application.

Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Long non-coding RNA alpha-2-macroglobulin antisense RNA 1 regulating oxidized low density lipoprotein-induced human brain microvascular endothelial cell damage by targeting microRNA-106b-5p / 解剖学报

Objective To investigate the effect of long non-coding RNA (lncRNA) alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) targeting microRNA (miR) -106b-5p on oxidized low-density lipoprotein (ox-LDL) -induced injury of human brain microvascular endothelial cells. Methods Human brain microvascular endothelial cells (ox-LDL group) were induced by ox-LDL, normal cultured cells were control group (Ctrl); A2M-AS1 overexpression (pcDNAA2M-AS1 group), empty vector (pcDNA group), miR-106b-5p inhibitor (anti-miR-106b-5p group), negative control (anti-miR-NC group), pcDNA-A2M-AS1 with control mimic NC (miR-NC group), pcDNA-A2M-AS1 with miR-106b-5p mimic (miR-106b-5p mimics group) were transfected into cells and treated with ox-LDL, n = 9. Real-time PCR was used to detect the expression levels of A2M-AS1 and miR-106b-5p; Kits were used to detect malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT)); Flow cytometry and TUNEL detected apoptosis; Dual luciferase reporter gene assay detected A2M-AS1 and miR-106b-5p targeting; Western blotting detected Bcl-2 and Bax protein expression. Results Compared with the Ctrl group, the expression level of A2M-AS1 in the ox-LDL group decreased, and the activity of SOD and CAT and the protein level of Bcl-2 decreased (P<0.05), while the expression level of miR-106b-5p and the level of MDA increased (P<0.05), and the rate of apoptosis and the protein level of Bax increased (P<0.05). Overexpressing A2M-AS1 or interfering with miR-106b-5p decreased the MDA level, apoptosis rate and Bax protein level after ox-LDL-induced cells, and increased SOD, CAT activity and Bcl-2 protein level (P<0.05). A2M-AS1 targeted miR-106b-5p; upregulation of miR-106b-5p reversed the effect of overexpressed lncRNA A2M-AS1 on ox-LDL-induced injury of human brain microvascular endothelial cells (P < 0.05). Conclusion A2M-AS1 attenuates ox-LDL-induced injury of human brain microvascular endothelial cells by targeting miR-106b-5p.

Treatment advice of small molecule antiviral drugs for elderly COVID-19 / 中国药理学通报

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

The therapeutic effect of Balanophora polysaccharide on acetic acid gastric ulcer in rats and its mechanism / 中国药理学通报

Aim To study the therapeutic effect of Balanophora polysaccharide(BPS)on gastric ulcer(GU)induced by acetic acid in rats and to investigateits mechanisms. Methods Sixty male SD rats were randomly divided into sham-operated group, GU model group, omeprazole positive group(3.6 mg·kg-1), and low, medium and high dose of BPS treatment groups(100, 200 and 400 mg·kg-1). The GU model group was prepared by acetic acid cautery method, and the morphology and pathological changes of ulcers were observed by visual observation combined with HE staining, and the ulcer area and inhibition rate were measured and calculated; superoxide dismutase(SOD)activity, malondialdehyde(MDA)content and glutathione peroxidase(GSH-PX)activity were measured by enzymatic assay; tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)content were detected by ELISA. The expression levels of epidermal growth factor(EGF)and epidermal growth factor receptor(EGFR)were measured by immunohistochemistry staining and Western blot. Results Compared with the sham-operated group, obvious ulcer damage was seen in the model group. Compared with the model group, the BPS-treated group showed a significant reduction in ulcer area, an increase in SOD and GSH-PX activity and EGF and EGFR expression levels, and a significant decrease in MDA, TNF-α and IL-6 content. Conclusions BPS has a therapeutic effect on GU in rats, and its mechanism may be related to the inhibition of oxidative stress, suppression of inflammatory stimuli and promotion of regenerative repair of gastric mucosa.

Advance in study of interleukin-1 family cytokines in liver diseases / 中国药理学通报

Liver disease is a serious threat to human health in the world, including hepatitis caused by various causes (fatty, alcoholic , viral and autoimmune hepatitis) , liver fibrosis and liver cancer. Interleukin-1 (IL-1) family members are involved in the inflammation of most acute and chronic liver diseases and play a key role in the progression of liver diseases. This paper reviews the research progress on the relationship between interleukin-1 family cytokines and liver diseases,discusses the key roles of IL-1 family cytokines in the occurrence and development of various liver diseases and related immune responses, and looks forward to the application prospect of IL-1 family members in drug devel¬opment and clinical treatment.

Effect of Gualou Xiebai Decoction on type II cardiorenal syndrome based on endothelial/epithelial-to-mesenchymal transition and its mechanism / 中国药理学通报

Aim To investigate the protective effects of different doses Gualou Xiebai Decoction (GXD) on type II cardiorenal syndrome (type II CRS) and explore its preliminary mechanisms. Methods The type II cardiorenal syndrome rat model was replicated by li-gating the left anterior descending coronary artery. After 10 weeks of intragastric administration, the cardiac function of the rats in each group was evaluated by echocardiography; serum were collected for biochemical testing; heart and kidney tissue samples were stained with HE and Masson to observe pathological changes. The hydroxyproline content in the heart and kidney was detected. The expression levels of endothelial/epitheli-al-to-mesenchymal transition (EndMT/EMT) related proteins in heart and kidney tissues were detecterd by immunofluorescence double staining

Empagliflozin ameliorates renal tissue damage in diabetic nephropathy mice through autophagy-lysosome pathway / 中国药理学通报

Aim To investigate the effeots of empagliflozin on kidney tissue and autophagy-lysosome pathway in diabetio kidney disease (DKD) mice. Methods The db/m group as the control group, the db/db mice were randomly divided into the model group and empagliflozin group. After 8 weeks of administration, the levels of 24 h urine protein (24 h-UTP), fasting blood glucose (FBG), glycosylated hemoglobin (HBAlc), total cholestérol (TC), triglycéride (TG), blood urea nitrogen (BUN), serum creatinine (Scr), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β, and monocyte chemoattractant protein-1 (MCP-1) were detected. The expression of p62, LC3B, Beclinl, Agt7, LAMP1, Bcl-2, caspase-3 and Bax in kidney tissue was measured by Western blot. The pathological changes of kidney were observed under light microscope. Results Compared with the control group, the model group showed thickening of basement membrane, increased extracellular matrix, interstitial inflammatory cell infiltration and interstitial fibrosis (P < 0. 01). Moreover, the model group had higher content of FBG, HBAlc, 24h-UTP, TC, TG, BUN, Scr, TNF-α, IL-1β, and MCP-1 (P < 0. 01), higher expression of LC3B-/LC3B- I, Beclinl, LAMP1, Agt7 and Bcl-2 (P<0. 01), and lower expression of p62, caspase-3 and Bax in rénal tissue (P < 0. 01) than those in the control group. Compared with the model group, empagliflozin alleviated the pathological injury in kidney (P < 0. 01), and the changes in the above indicators were reversed. Conclusion By irepairing autophagy-lysosomal pathway in renal tissue, empagliflozin can promote the degradation of autophagy substrates, inhibit the production of inflammatory factors and apoptosis, thereby protecting the kidney.

Clinical characteristics of epileptic seizure in neurofibromatosis type 1 in 15 cases / 中华儿科杂志

Objective: To summarize the clinical characteristics of epileptic seizure associated with neurofibromatosis type 1 (NF1). Methods: From January 2017 to July 2023 at Children's Hospital Capital Institute of Pediatrics, medical records of patients with both NF1 and epileptic seizure were reviewed in this case series study. The clinical characteristics, treatment and prognosis were analyzed retrospectively. Results: A total of 15 patients(12 boys and 3 girls) were collected. Café-au-lait macules were observed in all 15 patients. There were 6 patients with neurodevelopmental disorders and the main manifestations were intellectual disability or developmental delay. The age at the first epileptic seizure was 2.5 (1.2, 5.5) years. There were various seizure types, including generalized tonic-clonic seizures in 8 patients, focal motor seizures in 6 patients, epileptic spasm in 4 patients, tonic seizures in 1 patient, absence in 1 patient, generalized myoclonic seizure in 1 patient and focal to bilateral tonic-clonic seizure in 1 patient. Among 14 patients whose brain magnetic resonance imaging results were available, there were abnormal signals in corpus callosum, basal ganglia, thalamus or cerebellum in 6 patients, dilated ventricles of different degrees in 3 patients, blurred gray and white matter boundary in 2 patients, agenesis of corpus callosum in 1 patient and no obvious abnormalities in the other patients. Among 13 epilepsy patients, 8 were seizure-free with 1 or 2 antiseizure medications(ASM), 1 with drug resistant epilepsy was seizure-free after left temporal lobectomy, and the other 4 patients who have received 2 to 9 ASM had persistent seizures. One patient with complex febrile convulsion achieved seizure freedom after oral administration of diazepam on demand. One patient had only 1 unprovoked epileptic seizure and did not have another seizure without taking any ASM. Conclusions: The first epileptic seizure in NF1 patients usually occurs in infancy and early childhood, with the main seizure type of generalized tonic-clonic seizure and focal motor seizure. Some patients have intellectual disability or developmental delay. Most epilepsy patients achieve seizure freedom with ASM.

Neuronal Histone Methyltransferase EZH2 Regulates Neuronal Morphogenesis, Synaptic Plasticity, and Cognitive Behavior in Mice / 神经科学通报·英文版

The histone methyltransferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2)-mediated trimethylation of histone H3 lysine 27 (H3K27me3) regulates neural stem cell proliferation and fate specificity through silencing different gene sets in the central nervous system. Here, we explored the function of EZH2 in early post-mitotic neurons by generating a neuron-specific Ezh2 conditional knockout mouse line. The results showed that a lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and increased dendritic spine density. Transcriptome analysis revealed that neuronal EZH2-regulated genes are related to neuronal morphogenesis. In particular, the gene encoding p21-activated kinase 3 (Pak3) was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of the dominant negative Pak3 reversed Ezh2 knockout-induced higher dendritic spine density. Finally, the lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 acts to control multiple steps of neuronal morphogenesis during development, and has long-lasting effects on cognitive function in adult mice.

Spatial expression of the nonsense-mediated mRNA decay factors UPF3A and UPF3B among mouse tissues / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

无义介导的信使RNA（mRNA）降解途径（nonsense-mediated mRNA decay，简称为NMD)是真核生物细胞内一种重要的基因转录后表达调控机制，它积极参与一系列细胞生理和生化过程，控制细胞命运和生命体的组织稳态。NMD的缺陷会导致人类疾病，如神经发育障碍、肿瘤发生和自身免疫疾病等。UPF3 (Up-frameshift protein 3)是一个核心的NMD因子，它最早在酵母中被发现。UPF3A和UPF3B是UPF3在生物进化到脊椎动物阶段出现的两个旁系同源物，在NMD中具有激活或抑制的作用。以往研究发现，UPF3B蛋白几乎在所有哺乳动物器官中均有表达，而UPF3A蛋白在除睾丸外的大多数哺乳动物组织中难以被检测到。解释这一现象的假说为：在NMD途径中，UPF3B具有比UPF3A更高的竞争性结合UPF2的能力，UPF3B和UPF2的结合促使UPF3A成为游离状态，而游离的UPF3A蛋白不稳定且易被降解。此假说提示UPF3A和UPF3B在NMD中存在拮抗作用。在本研究中，我们重新定量评估了UPF3A和UPF3B在野生型成年雄性和雌性小鼠的9个主要组织和生殖器官中的mRNA和蛋白表达，结果证实UPF3A在雄性生殖细胞中表达量最高。令人惊讶的是，我们发现在包括大脑和胸腺在内的大多数组织中，UPF3A与UPF3B的蛋白水平相当，而在小鼠脾、肺组织中，UPF3A表达高于UPF3B。公共基因表达数据进一步支持了上述发现。因此，我们的研究表明了UPF3A是小鼠组织中普遍表达的NMD因子。同时，该研究结果推测：在生理条件下，UPF3A和UPF3B蛋白之间不存在竞争抑制，且UPF3A在多种哺乳动物组织的稳态中发挥重要作用。

Research progress on efflux pump inhibitors of Mycobacterium tuberculosis in recent years / 药学学报

Currently, the resistance of first-line anti-tuberculosis drugs has made the prevention and treatment of tuberculosis increasingly difficult, posing a serious threat to global public health. Several studies have shown that efflux pumps are one of the important causes for bacteria to develop multi-drug resistance and extremely-drug resistance, and efflux pump inhibitors can inhibit the efflux of antibacterial drugs, thereby reducing bacterial drug resistance. Numerous natural products and synthetic compounds have been reported to possess efflux pump inhibitory activity, but they have not been applied in clinical settings because of their toxicity, pharmacokinetic properties, etc. Therefore, we summarized the efflux pump inhibitory activity, antimicrobial activity, and structure-activity relationships of reported efflux pump inhibitors against Mycobacterium tuberculosis in recent years, providing references for the development of new efflux pump inhibitors with better activity and lower toxicity.

CHESS endoscopic ruler in objective measurement of diameter of esophageal varices in liver cirrhosis and portal hypertension: a prospective multicenter study / 中华消化杂志

Objective:To investigate the safety and feasibility of the CHESS endoscpic ruler (CHESS ruler), and the consistency between the measured values and the interpretation values by endoscopic physician experience.Methods:From January 2021 to January 2022, a total of 105 liver cirrhosis patients with portal hypertension were prospectively enrolled from General Hospital, Xixia Branch Hospital, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region (29 cases), and the First People′s Hospital of Yinchuan (25 cases), General Hospital of Ningxia Medical University (18 cases), Wuzhong People′s Hospital (10 cases), the Fifth People′s Hospital of Ningxia Hui Autonomous Region (10 cases), Shizuishan Second People′s Hospital (6 cases), Yinchuan Second People′s Hospital (5 cases), and Zhongwei People′s Hospital (2 cases) 8 hospitals. The clinical characteristics of all the patients, including gender, age, nationality, etiolog of liver cirrhosis, and Child-Pugh classification of liver function were recorded. A big gastroesophageal varices was defined as diameter of varices ≥5 mm. Endoscopist (associated chief physician) performed gastroscopy according to the routine gastroscopy procedures, and the diameter of the biggest esophageal varices was measured by experience and images were collected, and then objective measurement was with the CHESS ruler and images were collected. The diameter of esophageal varices of 10 randomly selected patients (random number table method) was determined by 6 endoscopists (attending physician or associated chief physician) with experience or measured by CHESS ruler. Kappa test was used to test the consistency in the diameter of esophageal varices between measured values by CHESS ruler and the interpretation values by endoscopic physician experience.Results:Among 105 liver cirrhosis patients with portal hypertension, male 65 cases and female 40 cases, aged (54.8±12.2) years old, Han nationality 82 cases, Hui nationality 21 cases and Mongolian nationality 2 cases. The etiology of liver cirrhosis included chronic hepatitis B (79 cases), alcoholic liver disease (7 cases), autoimmune hepatitis (7 cases), chronic hepatitis C (2 cases), and other etiology (10 cases). Liver function of 32 cases was Child-Pugh A, Child-Pugh B 57 cases, and Child-Pugh C 16 cases. All 105 liver cirrhosis patients with cirrhotic portal hypertension were successfully measured the diameter of gastroesophageal varices by CHESS ruler, and the success rate of application of CHESS ruler was 100.0% (105/105). The procedure time from the CHESS ruler into the body to the exit of the body after measurement was (3.50±2.55) min. No complications happened in all the patients during measurement. Among 105 liver cirrhosis patients with cirrhotic portal hypertension, 96 cases (91.4%) were recognized as big gastroesophageal varices by the endoscopists. Totally 93 cases (88.6%) were considered as big gastroesophageal varices by CHESS ruler. Eight cases were recognized as big gastroesophageal varices by the endoscopist, however not by the CHESS ruler; 5 cases were recognized as big gastroesophageal varices by the CHESS ruler, but not by the endoscopists; 4 cases were not recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler; 88 cases were recognized as big gastroesophageal varices both by the endoscopists and CHESS ruler. The missed diagnostic rate of big gastroesophageal varices by the endoscopists experience was 5.4% (5/93), and the Kappa value of consistency coefficient between the measurement by the CHESS ruler and the interpretation by endoscopists experience was 0.31 (95% confidence interval 0.03 to 0.60). The overall Kappa value of consistency coefficient by 6 endoscopists measured by CHESS ruler in big gastroesophageal varices diagnosis was 0.77 (95% confidence interval 0.61 to 0.93).Conclusion:As an objective measurement tool, CHESS ruler can make up for the deficiency of subjective judgment by endoscopists, accurately measure the diameter of gastroesophageal varices, and is highly feasible and safe.

Combining respiratory-muscle resistance training with feedback respiratory electrical stimulation improves the diaphragm and pulmonary function of stroke survivors / 中华物理医学与康复杂志

Objective:To document any effect of combining respiratory-muscle resistance training with feedback respiratory electrical stimulation in rehabilitating the diaphragm function and lung function of stroke survivors.Methods:Sixty hemiplegic stroke survivors were randomly assigned to an observation group or a control group, each of 30. Both groups were given conventional rehabilitation, including respiratory-muscle resistance training. The observation group additionally received feedback respiratory electrical stimulation twice a day, six days a week for 3 weeks. Before and after the treatment, ultrasound was used to measure the end-inspiratory and end-expiratory thickness of the diaphragm. Diaphragm movement during quiet breathing and deep breathing was also observed, and the diaphragm thickening fraction was calculated. The incidence of diaphragm dysfunction on the affected and healthy sides of the two groups before and after the treatment was also analyzed and compared.Results:Diaphragm dysfunction on either side had decreased significantly more in the observation group than in the control group after the treatment. The observation group also showed significantly greater average improvement in the thickening functions and in diaphragm movement on both the affected and healthy sides during quiet breathing and deep breathing. All of the pulmonary function indicators improved significantly in both groups after the treatment, but those of the observation group were, on average, significantly better than the control group′s averages.Conclusions:Combining 3 weeks of respiratory muscle resistance training with electrical stimulation feedback can effectively increase the bilateral thickness of the diaphragm and diaphragm movement in deep breathing of hemiplegic stroke survivors. That reduces the incidence of diaphragm dysfunction.

Cost-effectiveness analysis of different screening modes for thalassemia in Hunan Province / 中华围产医学杂志

Objective:To analyze the costs and effectiveness of five common screening modes and genetic screening for thalassemia in China in order to find the optimal way and provide evidence for the implementation of thalassemia prevention and control projects in Hunan Province.Methods:From June 2020 to April 2021, 12 971 couples from 14 cities and autonomous prefectures in Hunan Province were selected as the study population. The diagnosis of thalassemia was based on the results of genetic testing. Results of routine blood test and hemoglobin electrophoresis were collected and analyzed. The efficacy of five screening modes, at the cut-off value of <80 fl or 82 fl for the mean corpuscular volume (MCV), was analyzed by positive predictive value, negative predictive value, Jorden index and cost-effectiveness ratio. Sensitivity analysis was used to assess the feasibility of genetic screening at different costs after fixing the costs of routine blood and hemoglobin electrophoresis. The five thalassemia screening models are as follows: Mode 1: The woman had a blood routine test first. If the result was positive, the spouse required a blood routine test. If both results were positive, a thalassemia gene test should be offered to the couple. Mode 2: Both husband and wife were screened by blood routine and hemoglobin electrophoresis. If one or both of them were positive, both would be tested for thalassemia gene. Mode 3: The couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing. Mode 4: The woman was screened by blood routine and hemoglobin electrophoresis. If any one of them was positive, the woman would be tested for thalassemia gene. If the gene test result was positive, the spouse should receive thalassemia gene. Mode 5: Both spouses conducted a blood routine test. If either was positive, both would conduct hemoglobin electrophoresis test. If both were positive, both spouses should receive thalassemia gene testing. Gene testing mode: The woman would be tested for thalassemia, and her spouse would have thalassemia test too if her result was positive.Results:When using MCV<80 fl as the cut-off for diagnosing thalassemia, the Youden indices of the five prenatal screening modes in Hunan Province were 0.551, 0.639, 0.898, 0.555 and 0.356, while when using MCV<82 fl as the cut-off, the Youden indices were 0.549, 0.629, 0.851, 0.548 and 0.356. When the MCV cut-off value was <80 fl, the missed diagnosis rates of the five screening modes were 44.44%, 0.00, 0.00, 18.52% and 62.96%, and the cost-effectiveness ratios were 21 709, 250 939, 76 870, 138 463 and 92 860 yuan (RMB)/couple, respectively. When the price of genetic testing was lower than 55 yuan (RMB), the cost-effectiveness ratio of genetic screening was lower than that of Mode 3.Conclusions:MCV<80 fl can be considered as the positive criteria in blood routine screening for thalassemia in Hunan Province, and the cost-effectiveness ratio of Mode 3 (the couple received blood routine tests initially. If either was positive, both should receive hemoglobin electrophoresis testing. If either was positive, both parties will conduct thalassemia gene testing) is the best. Genetic screening has certain advantages with the decreasing price.

Etiological diagnostic value of metagenomic next-generation sequencing in peritoneal dialysis-related peritonitis / 中华肾脏病杂志

Objective:To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis.Methods:The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared.Results:A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant ( P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria ( Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture ( Z=3.726, P<0.001). Conclusions:mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.

Clinical characteristics of 57 cases of clear cell papulosis / 中华皮肤科杂志

Objective:To analyze and summarize clinical and pathological characteristics of clear cell papulosis (CCP) .Methods:Clinical data were collected from 57 children with CCP, who were diagnosed in Department of Dermatology, Children′s Hospital of Chongqing Medical University from November 2014 to March 2022, and their clinical and pathological characteristics were analyzed.Results:Among the 57 patients, 30 were males and 27 were females; their age ranged from 6 months to 7 years and 10 months; the age at onset ranged from 1 to 74 months, and 39 (68.4%) experienced onset of disease in infancy; the course of disease ranged from 1 to 84 months. Skin lesions mainly manifested as millet- to soybean-sized roundish white macules or short bar-like white macules measuring 1 - 2 cm in length. Most patients (49 cases, 85.9%) had skin lesions less than 20 in number. The most common location of skin lesions was the lower abdomen (35 cases, 61.4%), followed in turn by chest or upper abdomen (34 cases, 59.6%), anterior axilla or armpit (17 cases, 29.8%), and vulva (11 cases, 19.3%). Short bar-like white macules predominated on the chest or upper abdomen (23/34, 65.7%) and anterior axilla or armpit (10/17), roundish white macules predominated on the lower abdomen (30/35, 85.7%), and the vulvar lesions all manifested as roundish white macules. Histopathological findings showed that slightly larger cells with abundant clear cytoplasm were scattered in or above the basal layer of the epidermis, and these cells were positive for cytokeratin 7, carcinoembryonic antigen, and periodic acid-Schiff staining.Conclusion:CCP mainly occurred in young children, roundish white macules predominated on the lower abdomen and vulva, and short bar-like white macules predominated on the chest or upper abdomen, as well as on the anterior axilla or armpit, indicating that CCP has strongly identifiable clinical features.

Analysis of the nail microbiome in patients with onychomycosis by high-throughput sequencing of 16S rDNA and internal transcribed spacer regions / 中华皮肤科杂志

Objective:To investigate differences in bacterial and fungal microbiome between infected nails and healthy nails among patients with onychomycosis.Methods:Nail scraping samples were collected from infected nails and healthy nails of 31 patients with onychomycosis, who visited Dalian Dermatosis Hospital from August 2020 to July 2021. The total DNA of nail microbiota was extracted, and the V3-V4 regions of the bacterial 16S rDNA gene and the fungal internal transcribed spacer (ITS) region were amplified and sequenced using Illumina technology. The USEARCH and mothur softwares were used for data cluster analysis to obtain the operational taxonomic units (OTUs) , Wilcoxon rank sum test was used to analyze α diversity, analysis of similarities (ANOSIM) was performed to analyze β diversity, linear discriminant analysis of effect size (LEfSe) was performed to evaluate the species difference.Results:Among the 31 patients with onychomycosis, 16 were males and 15 were females. According to the age, they were divided into young group (18 - 35 years old, 10 cases) , middle-aged group (36 - 60 years old, 11 cases) , and elderly group (over 60 years old, 10 cases) . As the α-diversity analysis revealed, the infected nail group showed significantly decreased Shannon index ( W = 290, P = 0.007) , but significantly increased Simpson index ( W = 663, P = 0.010) compared with the healthy nail group, suggesting that the diversity and evenness of bacterial communities were lower in the infected nail group than in the healthy nail group; however, there was no significant difference in the diversity of fungal communities between the infected nail group and healthy nail group. The β-diversity analysis based on the unweighted-UniFrac distance matrix showed no significant difference in the fungal or bacterial community composition between the infected nail group and healthy nail group (bacterial communities: R = 0.0052, P = 0.331; fungal communities: R = 0.0036, P = 0.337) ; the β-diversity analysis based on the weighted-UniFrac distance matrix showed significant differences in the abundance of bacterial and fungal communities between the two groups (both P = 0.001) . In terms of the species composition, the bacterial flora with significantly decreased abundance in the infected nail group compared with the healthy nail group included Bacteroidetes, Proteobacteria, Betaproteobacteria, Burkholderiales, Ralstonia, Sphingomonas and Streptococcus, while the abundance of Bacilli, Bacillales and Staphylococcus was significantly higher in the infected nail group than in the healthy nail group. Compared with the healthy nail group, the fungal flora with significantly increased abundance in the infected nail group included Eurotiomycetes, Onygenales, Leotiomycetes-ord-incertae-sedis, Arthrodermataceae, Periconia, Erysiphe, Tilletiopsis, Trichophyton, Erysiphe cruciferarum, Trichophyton rubrum, Malassezia sympodialis, while the abundance of Saccharomycetes, Saccharomycetales, Saccharomycetaceae, Dothioraceae, Candida and Alternaria was significantly lower in the infected nail group than in the healthy nail group. Conclusion:The diversity and abundance of bacterial communities significantly differed between infected nails and healthy nails among patients with onychomycosis, while only the abundance of fungal communities differed between the two groups, and perhaps there was correlations between some bacterial and fungal communities.

Efficacy and safety evaluation of the regimen containing Bedaquiline in elderly patients with drug-resistant pulmonary tuberculosis / 中华老年医学杂志

Objective:To evaluate the efficacy and adverse reactions of the regimen containing Bedaquiline in elderly patients with multi-drug resistant tuberculosis.Methods:From March 2019 to June 2022, patients with multi-drug resistant pulmonary tuberculosis admitted to Anhui Chest Hospital were randomly divided into two groups: the observation group was given a treatment containing Bedaquiline, and the control group was given a treatment without Bedaquiline.Patients were also divided into elderly patients(age ≥60 years old)and non-elderly patients(age <60 years old)according to age.Sputum culture conversion, lesion absorption and adverse reactions were compared between the observation group and the control group in general, elderly and non-elderly patients, respectively.Results:A total of 170 cases were collected, including 79 in the observation group and 91 in the control group.Sputum culture conversion: The sputum culture conversion rates of observation groups in general, non-elderly and elderly patients were better than that of control groups at the 3rd month after treatment(the general, 96.2% vs.75.8%, χ2=14.001, P<0.001; the non-elderly, 94.9% vs.82.1%, χ2=4.675, P=0.031; the elderly, 100.0% vs. 65.7%, χ2=8.771, P=0.003), and at the 6th month, the rates of overall observation group was better than that of control group(98.7% vs.92.3%, χ2=3.895, P=0.048); the rates of non-elderly and elderly observation group and control group were all greater than 90%, with no statistical significance( P>0.05). Lesion absorption: Overall and non-elderly observation groups were better than control group in lesion absorption at the 3rd month(the general, 84.8% vs.68.1%, χ2=12.962, P=0.002; the non-elderly, 88.1% vs.71.4%, χ2=9.832, P=0.007; and the 6th month(the general, 88.6% vs.76.9%, χ2=14.888, P=0.001; the non-elderly, 89.8% vs.82.1%, χ2=8.618, P=0.013). The focal absorptivity of senile observation group at the end of March and June were 75.0% and 85.0%, respectively, both better than control group, but the difference was not statistically significant( P>0.05). Adverse reactions: Overall and non-senile observation groups had longer QT interval than control groups( P<0.05), but no patients stopped bedaquiline because of this, and there was no significant difference in QT interval between the two groups( P>0.05). Conclusions:In elderly patients with multi-drug resistant pulmonary tuberculosis, early sputum culture conversion turns fast after treatment with Bedaquiline, which has good therapeutic effect, good tolerance and controllable adverse reactions.