Testicular exosomes disturb the immunosuppressive phenotype of testicular macrophages mediated by miR-155-5p in uropathogenic Escherichia coli-induced orchitis / 亚洲男科学杂志(英文版)

Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.

Optimal processing technology of Zhangbang vinegar-processed Olibanum with multi-indicator-response surface methodology and anticoagulant effect evaluation / 中国中药杂志

This study first optimized the processing technology for Zhangbang vinegar-processed Olibanum and investigated its in vitro anticoagulant activity. A multi-index-response surface methodology was used, with yield, powder yield, and the relative percentage of the content of six non-volatile components [11-keto-boswellic acid(KBA), 3-acetyl-11-keto-boswellic acid(AKBA), β-elemonic acid, α-boswellic acid(α-BA), β-boswellic acid(β-BA), and α-acetyl-boswellic acid(α-BA)] and three volatile components(octyl acetate, incensole, and incensole acetate) as evaluation indicators. Analytical hierarchy process(AHP) combined with coefficient of variation method was used to calculate the weight of each indicator and calculate the comprehensive score(OD). Furthermore, response surface methodology was used to investigate the effects of frying temperature(A), burning time(B), rice vinegar dosage(C), and steaming time(D) on the processing technology of vinegar-processed Olibanum. Vinegar-steamed Olibanum was prepared according to the optimal processing technology for in vitro anticoagulant experiments. The results showed that the weights of octyl acetate, incensole, incensole acetate, KBA, AKBA, β-elemonic acid, α-BA, β-BA, α-ABA, yield, and powder yield were 0.358 2, 0.104 5, 0.146 4, 0.032 9, 0.123 7, 0.044 4, 0.022 1, 0.042 2, 0.110 1, 0.012 2, and 0.0032, respectively. The optimal processing technology for Zhangbang vinegar-processed Olibanum was as follows. Olibanum(50 g) with a particle size of 1-5 mm was continuously stir-fried at a low heat of 150-180 ℃ until in a gel-like state, ignited for burning for 15 s, sprayed with 7.5 g of rice vinegar(15%), and steamed for 3 min without fire. Subsequently, the cover was removed, and the product was continuously stir-fried at 150-180 ℃ until in a soft lump shape, removed, cooled, and crushed. The results of the in vitro anticoagulant experiments showed that compared with the blank group, both Olibanum and vinegar-processed Olibanum significantly prolonged the activated partial thromboplastin time(APTT), thrombin time(TT), and prothrombin time(PT) of rat platelet-poor plasma(PPP), and the effect of vinegar-processed Olibanum was significantly better than that of Olibanum(P<0.05). The optimized processing technology for Zhangbang vinegar-processed Olibanum is stable, feasible, and beneficial for the further development and utilization of Olibanum slices. At the same time, using the content of volatile and non-volatile components, yield, and powder yield as indicators, and verifying through pharmacological experiments, the obtained results are more reasonable and credible, and have positive guiding significance for the clinical application of characteristic processed Olibanum products.

Platelet Removal Efficiency by Leukocyte Filter in Red Blood Cell Units at Different Storage Periods / 中山大学学报(医学科学版)

ObjectiveThe aim of this study is to investigate change of platelet count in red blood cell （RBC） units at different storage periods and explore the efficiency of platelet removal by leukocyte filter. MethodsA total of 58 RBC units were divided into four groups according to different storage periods： 1 week Group （16）， 2 weeks Group （16）， 3 weeks Group （14） and 4 weeks Group （12）. RBC units in the four groups were filtered through leukocyte filter. The RBC samples before and after filtration were obtained. The platelet count was detected by automatic blood cell counter and the efficiency of platelet removal was calculated. RBC samples before filtration were made into blood cell smears. The blood cell smears were dyed with Wright-Giemsa stain， and the morphology of platelets was observed through a microscope. ResultsThe platelet count in RBC units stored for 1， 2， 3 and 4 weeks was （286.5±62.34）×109/L， （238.0±57.37）×109/L， （193.6±56.21）×109/L and （167.8±24.76）×109/L， respectively. Platelet count in blood stored for 3 weeks （P<0.01） and 4 weeks （P <0.000 1） were significantly lower than those stored for 1 weeks. When observed in the blood smears of RBC units at different storage periods， platelets with normal morphology were distributed in clump and scattered style. The platelet removal rates of the four groups were （80.13±9.06） %， （76.41±10.13） %， （77.78±9.30） % and （70.63±9.39） %， respectively， with no significant difference （P >0.05）. ConclusionsPlatelet count in RBC units decreases gradually as the storage period increases， but most platelets still remain in RBC units of late storage periods （3 weeks and 4 weeks）. The leukocyte filter is able to remove most of the platelets， and the removal efficiency is similar among the groups.

Early prediction of severe COVID-19 in patients with Sjögren's syndrome / 北京大学学报(医学版)

OBJECTIVE@#To investigate the predictive value of blood cell ratios and inflammatory markers for adverse prognosis in patients with primary Sjögren's syndrome (PSS) combined with coronavirus disease 2019 (COVID-19).@*METHODS@#We retrospectively collected clinical data from 80 patients with PSS and COVID-19 who visited the Rheumatology and Immunology Department of the First Affiliated Hospital of Nanchang University from December 2022 to February 2023. Inclusion criteria were (1) meeting the American College of Rheumatology (ACR) classification criteria for Sjögren's syndrome; (2) confirmed diagnosis of COVID-19 by real-time reverse transcription polymerase chain reaction or antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); (3) availability of necessary clinical data; (4) age > 18 years. According to the clinical classification criteria of the "Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (trial the 10th Revised Edition)", the patients were divided into the mild and severe groups. Disease activity in primary Sjögren' s syndrome was assessed using the European League Against Rheumatism (EULAR) Sjögren' s syndrome disease activity index (ESSDAI). Platelet-lymphocyte ratio (PLR), C-reactive protein-lymphocyte ratio (CLR), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and other laboratory data were compared between the two groups within 24-72 hours post-infection.@*RESULTS@#The mild group consisted of 66 cases with an average age of (51. 52±13. 16) years, and the severe group consisted of 14 cases with an average age of (52.64±10.20) years. Disease activity, CRP, platelets, PLR, and CLR were significantly higher in the severe group compared with the mild group (P < 0.05). Univariate analysis using age, disease activity, CRP, platelets, PLR, and CLR as independent variables indicated that disease activity, CRP, PLR, and CLR were correlated with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis further confirmed that PLR (OR=1.016, P < 0.05) and CLR (OR=1.504, P < 0.05) were independent risk factors for the severity of COVID-19 in the critically ill patients. Receiver operator characteristic (ROC) curve analysis showed that the area under the curve (AUC) for PLR and CLR was 0.708 (95%CI: 0.588-0.828) and 0.725 (95%CI: 0.578-0.871), respectively. The sensitivity for PLR and CLR was 0.429 and 0.803, respectively, while the highest specificity was 0.714 and 0.758, respectively. The optimal cutoff values for PLR and CLR were 166.214 and 0.870, respectively.@*CONCLUSION@#PLR and CLR, particularly the latter, may serve as simple and effective indicators for predicting the prognosis of patients with PSS and COVID-19.

Application and thinking of acupuncture therapy in comprehensive management of hypertension / 中国针灸

The theory of disease prevention with traditional Chinese medicine is introduced into the prevention of chronic diseases such as hypertension. In order to fully implement the advantages of acupuncture, the three-level prevention strategy is strengthened on the whole-process intervention with acupuncture for hypertension, including prevention before disease onset, starting intervention at the early phase, and prevention disease from exacerbating. Moreover, the comprehensive management scheme, multidisciplinary coordination and participation mechanism are investigated in the field of traditional Chinese medicine for preventive treatment of hypertension.

Effect and mechanism of tournefolic acid B on the improvement of glucose metabolism and renal function in diabetes nephropathy model mice / 中国药房

OBJECTIVE To explore the role and underlying mechanism of tournefolic acid B （TAB） on the improvement of glucose metabolism and renal function in diabetic nephropathy （DN） model mice. METHODS DN model mice were established by high-fat diet combined with streptozotocin， and then randomly divided into model group， positive control group （vitamin E， 20 mg/kg）， TAB low-dose， medium-dose and high-dose groups （1， 2， 4 mg/kg）， with 12 mice in each group； normal control group was given regular diet. Each group was given relevant medicine or normal saline intragastrically， once a day， for 4 consecutive weeks. The glucose metabolic function was estimated by fasting blood glucose， glucose tolerance test， insulin tolerance test and serum insulin concentration. The renal coefficients and biochemical indicators related to renal function [serum uric acid， blood urea nitrogen， creatinine levels， and ratio of urine microalbumin to creatinine] were detected in mice； the contents of biochemical indicators related to oxidative stress [superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， 8-hydroxydeoxyguanosine （8-OHdG）] were determined in renal tissue of mice； the pathological morphology of renal tissue was observed； the expressions of extracellular matrix （ECM） deposition related factors [transforming growth factor β1 （TGF- β1）， fibronectin （Fn）， type Ⅳ collagen （Col Ⅳ）] and protein kinase B （Akt）/nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1） pathway related proteins were determined in renal tissue of mice. RESULTS Compared with normal control group， fasting blood glucose， area under glucose tolerance curve， area under insulin tolerance curve， serum insulin content， the levels of uric acid， urea nitrogen and creatinine @qq.com and ratio of urinary microalbumin to creatinine in serum， the contents of MDA and 8-OHdG and the protein expressions of TGF-β1， Fn and Col Ⅳ were increased significantly in model group （P＜0.05）， while the contents of SOD， GSH-Px and the protein expressions of p-Akt， Nrf2， HO-1 in renal tissue were decreased significantly （P＜0.05）； the significant thickening of the basement membrane， accumulation of mesangial matrix， glomerulosclerosis and interstitial fibrosis of the renal tubules were all found. Compared with model group， above indexes of mice were all reversed significantly in TAB groups （P＜0.05）， and pathological changes were alleviated in a dose-dependent manner. CONCLUSIONS TAB can improve blood glucose metabolism and kidney function and alleviate renal tubulointerstitial fibrosis in DN model mice， the mechanism of which may be associated with activating the Akt/Nrf2/HO-1 signaling pathway and suppressing ECM deposition.

The Role of the JAK/STAT Signaling Pathway in Steroid-induced Necrosis of Femoral Heads in MRL/lpr Iupus Mice / 中国生物化学与分子生物学报

Osteonecrosis of femoral head (ONFH) is one of the complications of systemic lupus erythematosus (SLE), which is characterized by complex pathogenesis and difficult treatment, and is the main cause of SLE-induced disability. Previous studies have confirmed that the JAK/STAT signaling pathway is involved in the pathological process of SLE, and the activation of JAK/STAT has also been found to be related to the occurrence of ONFH. Therefore, we speculated that the JAK/STAT signaling pathway may play an important role in the occurrence and development of SLE-ONFH. 30 female MRL/lpr mice were randomly divided into three groups: the model group (Lipopolysaccharide/24 hours, twice + Methylprednisolone/24 hours, 3 times), the control group (equal amount of PBS) and the treatment group (the model group + JAK1/2 inhibitors Baricitinib/day, 6 weeks), with 10 mice in each group. The results showed that the grip value of the model group was significantly lower than that of the control group at the 4th and 6th week (P < 0. 05), and that of the treatment group was better than that of the model group at the 6th week (P < 0. 05). At the 6th week, the mice were sacrificed to take the bilateral femoral head, and the morphology and HE staining pathological changes of the femoral head were observed. The results showed that the femoral head of the control group was spherical, transparent, hard and without cartilage defects, while that of the model group was irregular, rough, gray in color and partial defects of the femoral head. The performance of the mice in the treatment group was basically similar to that in the model group. And the overall appearance of the femoral head was more irregular than that in the control group. The color was darker than that in the control group, and there was a partial defect of the femoral head, but the degree was not as serious as that in the model group. The empty bone lacuna rate in the model group and treatment group were significantly higher than that in the control group (P < 0. 05), and the empty bone lacuna rate in the treatment group was lower than that in the model group (P < 0. 05). Western blotting, ELISA and RT-qPCR were used to detect the protein expression, phosphorylation levels, mRNA expression of the JAK/STAT pathway (JAK1, JAK2, JAK3, STAT3) in local bone tissues, and the expression of IL-6 and TNF- α in serum and local tissues. The mRNA expression of IL-6, TNF-α and STAT3 in bone tissues of the model group were significantly higher than that of the control group and treatment group, and the content of serum IL-6 and TNF- α of the model group were significantly higher than that of the treatment group and control group. The cartilage catabolic metabolites ADAMTS-4, MMP-13 and JAK/STAT pathway related proteins JAK1, p-JAK1, JAK2, p-JAK2, STAT3 and pSTAT3 in the model group were significantly higher than those in the control group and treatment group. In summary, the JAK/STAT signaling pathway is involved in the pathogenesis of ONFH in MRL/lpr lupus erythematosus mice. Selective JAK1/2 inhibitors can effectively inhibit ONFH inflammation, improve bone structures and joint functions, and may become an effective therapeutic drug for SLE ONFH.

The Role of Wnt/β-catenin Signaling Pathway in Vascular Remodeling in Bleomycin-induced Systemic Sclerosis Mouse Model / 中国生物化学与分子生物学报

Systemic sclerosis (SSc) is a chronic autoimmune disease that can involve multiple organs throughout the body. It is characterized by extensive vascular disease and fibrosis of the skin and internal organs, but its mechanism is still unclear. Studies have confirmed that the Wnt pathway is involved in SSc fibrosis, but its pathological role in vascular lesions has not been reported. In this study, the bleomycin (BLM)-induced SSc mouse model was used to investigate the role of Wnt pathway in SSc cutaneous vascular lesions. Eighteen BALB/C mice were randomly divided into control, model and treatment groups. The control group of mice was injected with PBS 100 μL/d. The model group was injected with BLM 100 μL/d at a concentration of 1 mg/mL. The treatment group of mice received injection of BLM 100 μL as the model group of mice and retroperitoneal injection of iCRT3 (Wnt and beta-catenin inhibitors) 5 mg/kg/d. Mice were sacrificed on day 28. The thickness of dorsal dermis and epidermis in the model group induced by BLM was significantly higher than that in the control group (P <0. 05). The skin appendages such as sebaceous glands and hair follicles in the model group were significantly reduced. At the same time, the thickness of fat layer became thinner and surrounded by fibrous tissue, and the collagen deposition in the model group was higher than that in the control group. It was identified at the histological level by immunohistochemical staining that α-SMA expression in model group and treatment group α-SMA is highly expressed in skin tissues, and the positive expression of α-SMA around blood vessels was significantly higher than that in the control group. In addition, the expression of IL-6 and IL-17 in serum of model group was significantly higher than that in control group (P<0. 05), and the expression of IL-6 and IL-17 in serum of treatment group was significantly lower than that in model group (P<0. 05). Furthermore, q-PCR analysis showed that the mRNA levels of β-catenin in the skin microvessels of the mice were higher in the model and the treatment groups as compared with the control group. The protein levels of Wnt5A, β-catenin, α-SMA and col1A1 were analyzed by Western blotting and results showed that the levels of fibrosis-related proteins, α-SMA and col1A1, were increased in the model group injected with BLM as compared with the control group (P<0. 05), whereas iCRT3 treatment attenuated the upregulation of α-SMA and col1A1 induced by BLM in the treatment group (P<0. 05). The levels of Wnt pathway-related proteins β-catenin and Wnt5A were significantly increased in the model group as compared with the control (P<0. 05). This study suggests that BLM can successfully induce the skin phenotype of mice with systemic sclerosis. Abnormal activation of Wnt signaling pathway is involved in BLM-induced skin microangiopathy in mice with scleroderma, and the specific Wnt pathway inhibitor iCRT3 can reduce BLM-induced scleroderma. The expression of α-SMA and col1A1 proteins in mouse skin microvessels can improve the microvascular lesions of mouse skin. Inhibition of Wnt pathway may directly or indirectly down-regulate the abnormal expression of cytokines IL-6 and IL-17, and interfere with BLM-induced progression of vascular lesions in mice.

Acupuncture as adjuvant therapy for 32 cases of coronavirus disease 2019 / 中国针灸

OBJECTIVE@#To observe the clinical effect of acupuncture on coronavirus disease 2019 (COVID-19) based on the conventional treatment.@*METHODS@#A total of 35 patients with COVID-19 of mild or ordinary type were involved (3 cases dropped off). Acupuncture was applied on the basis of western medicine and Chinese materia medica treatment. Dazhui (GV 14), Fengchi (GB 20), Kongzui (LU 6), Hegu (LI 4), etc. were selected as the main acupoints, the supplementary acupoints and the reinforcing and reducing manipulations were selected according to syndrome differentiation. Acupuncture treatment was given once a day, 5 times a week. On day 3 and day 7 of acupuncture, relief condition of the main symptoms was observed. Before acupuncture and on day 3 and day 7 of acupuncture, efficacy evaluation scale of TCM on COVID-19 (efficacy evaluation scale) score was recorded. The effects of different intervention time of acupuncture on patients' hospitalization time were compared, the understanding of acupuncture treatment of patients discharged from hospital was recorded, the clinical efficacy and safety of acupuncture treatment were evaluated.@*RESULTS@#On day 3 and day 7 of acupuncture, the symptoms of lung system and non lung system were both relieved; the scores of efficacy evaluation scale were both decreased compared before acupuncture (P<0.05), and the efficacy evaluation scale score of day 7 of acupuncture were lower than day 3 of acupuncture (P<0.05). The average hospitalization time of patients received early acupuncture was shorter than late acupuncture (P<0.05). The total effective rate was 84.4% (27/32) on day 7 of acupuncture, which was higher than 34.4% (11/32) on day 3 of acupuncture (P<0.05). During the acupuncture treatment, there were neither adverse reactions in patients nor occupational exposures in doctors. The patients generally believed that acupuncture could promote the recovery of COVID-19 and recommended acupuncture treatment.@*CONCLUSION@#On the basis of the conventional treatment, acupuncture can effectively relieve the clinical symptoms in patients with COVID-19, early intervention of acupuncture can accelerate the recovery process. Acupuncture has good safety, clinical compliance and recognition of patients.

Period circadian clock 3 inhibits palmitic acid-induced oxidative stress and inflammatory factor secretion in podocytes / 中南大学学报(医学版)

OBJECTIVES@#High fat-induced podocyte injury is one of the important factors leading to obesity related nephropathy (ORG), but the mechanism is not clear. This study aims to explore the mechanism of period circadian clock 3 (PER3) in the oxidative stress and inflammation induced by palmitic acid (PA) in podocytes.@*METHODS@#The C57BL/6J mice were fed with chow and high-fat diet for 16 weeks. The PER3 expression in kidney tissues were detected in the normal body weight group and the obesity group. The PER3 mRNA and protein expression were detected after the podocytes were induced with different concentrations (0, 50, 150 and 300 μmol/L) of PA for 48 h. The PER3 mRNA and protein expression were detected after the podocytes were induced with 150 μmol/L PA for 0, 24, 36, and 48 h. Triglyceride (TG) levels were examined in the PA group, the adenovirus (ad)-PER3+PA group, and the siRNA-PER+PA group after the podocytes were transfected by Ad-PER3 or small interfering RNA (siRNA)-PER3 for 48 h and subsequently were induced with 150 μmol/L PA for 48 h. The differential gene expression was detected using RNA sequencing (RNA-seq) after podocytes were transfected by siRNA-PER3 (siRNA-PER3 group) and siRNA-control (siRNA-control group), respectively. The mRNA levels of nephrin, podocin, podocalyxin, podoplanin, superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), catalase (CAT), and the levels of malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-2 (IL-2) were detected after podocytes were transfected with Ad-PER3 or Ad-control for 48 h and then they were induced by 150 μmol/L PA for 48 h.@*RESULTS@#The PER3 was down-regulated in the obesity group compared with the normal body weight group (@*CONCLUSIONS@#PER3 can decrease the PA-induced oxidative stress and inflammatory factor secretion via inhibiting the lipogenesis in podocytes.

Value of serum YKL-40 in the diagnosis of anti-MDA5-positive patients with dermatomyositis complicated with severe pulmonary injury / 北京大学学报(医学版)

OBJECTIVE@#To investigate the value of serum and bronchoalveolar lavage fluid (BALF) chitinase-3-like-1 protein (YKL-40) in the diagnosis of anti-melanoma differentiation-associated gene 5 (MDA5)-positive dermatomyositis (DM) patients complicated with serious pulmonary injury, including rapidly progressive interstitial lung disease (RP-ILD) and pulmonary infection.@*METHODS@#Anti-MDA5 antibodies positive patients with DM who were hospitalized in the Department of Rheumatology of China-Japan Friendship Hospital from 2013 to 2018 were involved in this study. Demographic information, clinical, laboratory and imaging data were retrospectively collected. ELISA was used to detect the serum and BALF levels of YKL-40. The receiver operating characteristic (ROC) curve was drawn, and the area under ROC curve (AUC) was used to evaluate the diagnostic value of serum YKL-40 for pulmonary injury.Interstitial lung disease (ILD) was confirmed by chest high-resolution CT (HRCT). RP-ILD was defined as progressive respiratory symptoms such as dyspnea and hypoxemia within 3 months, and/or deterioration of interstitial changes or appearace of new pulmonary interstitial lesions on chest HRCT. Pulmonary infection was considered as positive pathogens detected in qualified sputum, blood, bronchoalveolar lavage fluid or lung biopsy specimens.@*RESULTS@#A total of 168 anti-MDA5-positive DM patients including 108 females and 60 males were enrolled in the study. Of these patients, 154 had ILD, and 66(39.3%) of them presented RP-ILD. Seventy patients with pulmonary infection were confirmed by etiology. In the patients with RP-ILD, 39 (59.1%) of them were complicated with pulmonary infection. While only 31 cases(30.4%) had pulmonary infection in the non-RP-ILD patients. The incidence of pulmonary infection in the patients with RP-ILD was significantly higher than that of those with non-RP-ILD (P < 0.001). The serum YKL-40 levels in the RP-ILD patients with pulmonary infection were the highest compared with RP-ILD without pulmonary infection, non-RP-ILD with pulmonary infection and non-RP-ILD without pulmonary infection groups among all the patients [83 (42-142) vs. 42 (21-91) vs. 43 (24-79) vs. 38 (22-69), P < 0.01].The sensitivity, specificity and AUC of serum YKL-40 in the diagnosis of RP-ILD complicated with pulmonary infection were 75%, 67%, and 0.72, respectively. The AUC of diagnosed of anti-MDA5 positive DM patients complicated with RP-ILD and pulmonary infection was higher than that of patients complicated with only RP-ILD and only pulmonary infection (0.72 vs. 0.54 and 0.55, Z=2.10 and 2.11, P < 0.05).@*CONCLUSION@#The prognosis of anti-MDA5-positive DM patients with RP-ILD and pulmonary infection were poor. Serum YKL-40 level can be used as a helpful tool for the diagnosis of coexistence of these conditions in the patients.

Intervention Mechanism of Yishen Huayu Prescription on Glomerular Podocyte Injury in Diabetic Nephropathy Rats Based on EMT Regulated by Wnt/β-catenin Pathway / 中国实验方剂学杂志

Objective:To investigate the intervention mechanism of Yishen Huayu prescription on glomerular podocyte injury in diabetic nephropathy （DN） rats based on epithelialmesenchymal transition （EMT） regulated by Wnt/<italic>β</italic>-catenin pathway. Method:The 60 SD rats were divided into control group， model group， Wnt-C59 group （0.03 g·kg^-1 Wnt/<italic>β</italic>-catenin pathway inhibitor）， low-dose group （8 g·kg^-1）， medium-dose group （16 g·kg^-1） and high-dose group （32 g·kg^-1）. After 12 weeks， various indexes ， including general signs， serum creatinine （SCr）， blood urea nitrogen （BUN）， renal index， urinary protein， blood glucose， renal pathological changes， podocyte and expressions of glomerular basement membrane injury and podocyte injury related proteins ［nephrin， synaptopodin］， Wnt/<italic>β</italic>-catenin pathway related proteins （Wnt1， <italic>β</italic>-catenin）， podocyte EMT related protein ［<italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMA）， E-cadherin］， were compared between groups. Result:Compared with the control group， the renal tissue in the model group showed significant pathological changes， including diffuse thickening of glomerular mesangial matrix and severe foot process fusion， and a significant increase in SCr， BUN， renal indexes， urinary protein， blood glucose， Wnt1， <italic>β</italic>-catenin， and <italic>α</italic>-SMA expression levels （<italic>P</italic><0.05） as well as a significant decrease in nephrin， synaptopodin and E-cadherin expression levels（<italic>P</italic><0.05）. Compared with model group， SCr， BUN， renal index， urinary protein， blood glucose， Wnt1， <italic>β</italic>-catenin， and <italic>α</italic>-SMA expression levels in each intervention group significantly decreased （<italic>P</italic><0.05）， while the expression levels of nephrin， synaptopodin and E-cadherin significantly increased （<italic>P</italic><0.05）. Among intervention groups， the improvement of above indexes in high-dose Yishen Huayu prescription group was the most obvious （<italic>P</italic><0.05）， which was similar to the effect in Wnt-C59 group. Conclusion:Yishen Huayu prescription prevents podocyte EMT by inhibiting Wnt/<italic>β</italic>-catenin pathway， thereby repairing glomerular podocyte injury in rats with diabetic nephropathy.

Clinical Efficacy of Sheti Zhiqiu Decoction Combined with Intradermal Needling in Treatment of Allergic Rhinitis with Deficient Cold of Lung Qi Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy of Sheti Zhiqiu decoction combined with intradermal needling in treatment of allergic rhinitis （AR） of deficient cold of lung Qi syndrome and its effect on cytokines of helper T cell 17 （Th17） and regulatory T cells （Treg）. Method:A total of 105 patients with AR of deficient cold of lung Qi syndrome were randomly divided into traditional Chinese medicine （TCM） group， combination group and western medicine group， with 35 cases in each group. The TCM group was treated with Sheti Zhiqiu decoction， 1 dose a day. The combination group was treated with intradermal needling in addition to the therapy of the TCM group. The selected acupoints were Yintang， bilateral Yingxiang， Fengchi， Feishu and Zusanli. The needles were retained for 3 days before being replaced. The western medicine group was treated with mometasone furoate nasal spray， 100 μg/time at each side of the nasal cavity， <italic>qd</italic>， and desloratadine citrate tablet， 8.8 mg/time， <italic>qd</italic>. Three groups were treated for 4 weeks and followed up for 3 months. Nasal and ocular symptom scores and rhinoconjunctivitis quality of life questionnaire （RQLQ） scores of patients in three groups were observed before and after treatment. Levels of serum interleukin-17 （IL-17）， interleukin-10 （IL-10） and transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁） were measured before and after treatment. The clinical efficacy and safety were evaluated， and the disease recurrence rate was observed during the follow-up period. Result:Compared with before treatment， nasal and ocular symptom scores and total score， and RQLQ scores and total score of patients in three groups were significantly decreased after treatment （<italic>P</italic><0.01）. Compared with the TCM group and the western medicine group after treatment， except for eyes itching/foreign body sensation/red eyes score， nasal and ocular symptom scores and total score， and RQLQ scores and total score of the combination group were lower（<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with before treatment， level of serum IL-17 of patients in three groups was significantly decreased （<italic>P</italic><0.01）， while levels of IL-10 and TGF-<italic>β</italic>₁ were significantly increased after treatment （<italic>P</italic><0.01）. Compared with the TCM group and the western medicine group after treatment， level of serum IL-17 was lower， whereas levels of IL-10 and TGF-<italic>β</italic>₁ were higher in the combination group （<italic>P</italic><0.05，<italic>P</italic><0.01）. The clinical efficacy of the combination group was better than that of the TCM medicine group and the western medicine group （Z=-2.207，Z=-2.185，<italic>P</italic><0.05）. There was no significant difference in recurrence rate between combination group and the TCM group， and the recurrence rate of both groups was lower than that of the western medicine group（<italic>χ</italic>²=5.020，<italic>χ</italic>²=4.835，<italic>P</italic><0.05）. There was no significant adverse reaction during the treatment period in three groups. Conclusion:Sheti Zhiqiu decoction combined with intradermal needling is effective in treatment of patients with AR of deficient cold of lung Qi syndrome. It can significantly relieve patients' symptoms， improve patients' quality of life and reduce disease recurrence. It may play a role by regulating immune balance of Th17/Treg of patients and improving their immune function.

Prenatal diagnosis of Wolf-Hirschhorn syndrome characterized by severe fetal growth restriction in three fetuses / 中华围产医学杂志

Objective:To analyze the prenatal clinical characteristics and genetic etiology of Wolf-Hirschhorn syndrome manifested by severe fetal growth restriction (FGR).Methods:Clinical data of three pregnant women admitted to Changsha Hospital for Maternal and Child Health Care from 2018 to 2020 due to severe FGR with or without other malformations diagnosed by prenatal ultrasound were collected. Amniotic fluid samples obtained by ultrasound-guided amniocentesis were analyzed by conventional G-banding staining technique and single nucleotide polymorphism array (SNP array). Parental peripheral blood cells were collected for SNP array to verify the source of variation.Results:(1) The karyotypes of both case 1 and 2 were normal, while case 3 had an abnormal karyotype of 46,XN,der(4)(9pter→9p23::4p15.31→4qter). (2) SNP array indicated a 7.8 Mb microdeletion in 4p16.3p16.1 cytoband in case 1 and a 5.5 Mb microdeletion in 4p16.3p16.2 cytoband in case 2, which were both de novo copy number variations. Case 3 harbored a 19.88 Mb deletion in 4p16.3p15.31 and a 10.89 Mb duplication in 9p24.3p23. (3) All three fetuses were diagnosed as Wolf-Hirschhorn syndrome, and their parents chose to terminate the pregnancies after genetic counseling. Conclusions:Considering the possibility of genetic disease, invasive prenatal diagnosis is suggested when prenatal ultrasonography showed severe FGR, regardless of other malformations, to clarify the cause and guide genetic counseling.

Analysis of cytogenetic characteristics of 321 children with hypospadias and literature review / 中华泌尿外科杂志

Objective:To explore the cytogenetic characteristics of hypospadias in children by karyotype analysis.Methods:From June 2008 to May 2018, 45 children with hypospadias in Tianjin Children's Hospital had cytogenetic abnormalities. Their median age was 10 months(range 3 hours to 5 years old). Of the 45 cases, 20 were proximal hypospadias, 1 was middle hypospadias. All 24 cases had varying degrees of genitourinary malformations. Among them, 15 cases had unilateral or bilateral cryptorchidism, 5 cases had scrotal division, 3 cases had penile scrotal transposition, 3 cases had small penis, 3 cases had indirect inguinal hernia, 1 case had repeated urethra, 1 case had hydrocele and 1 case had concealed penis. To the other systemic malformations, there was 1 with cleft lip and palate and 1 with congenital heart disease. G-banding karyotype analysis of peripheral blood lymphocytes was performed in all 45 cases.Results:Among the 45 cases of hypospadias with abnormal karyotypes, with an abnormal rate of 14.0%, 28 cases (62.22%) had sex chromosome abnormalities, including (47, XXY), (46, XX/47, XXY), (45, X0/47, XYY), etc. Sexual inversion occurred in 8 cases (17.78%), all of which were 46, XX. There were 4 autosomal abnormalities (8.89%), including (46, XY, 9p+ ), (46, XY, 10p+ ) and (46, XY, 1q+ ). Chromosome polymorphism was found in 4 cases (8.89%), including [46, XY, inv(9)] and [46, XY, 16qh+ ], and the equilibrium translocation of 1 case (2.22%) was [45, XY, -21, -22, + t(21; 22)]. Among the 45 cases, 8 sex reversal children with (46, XX) chromosome karyotype were all proximal hypospadias.Conclusions:Children with hypospadias may be associated with chromosomal karyotype abnormalities, including sex chromosomal abnormalities, autosomal abnormalities, chromosome polymorphism and balanced translocation. Among them, sex chromosome abnormality was the most common and balanced translocation was the least.

Application of island flap and its combined flap on repairing nasal alae defects / 中华耳鼻咽喉头颈外科杂志

Objective: To evaluate the application of island flap and combined flap in one-stage reconstruction of nasal alae defects after external nasal tumor resection. Methods: Data of 11 patients with perforating or full-thickness defects of the alae after nasal tumor resection in XuanWu Hospital, Capital Medical University between June 2016 and February 2021 were analyzed retrospectively. There were 7 males and 4 females, and the ages ranged from 51 to 89 years. Island flap, island flap combined with nasolabial flap or V-Y advancement flap, and island flap combined with bilobed flap were applied according to the range of defects. Descriptive statistical method was applied to analyze the treatment effects. Results: All flaps of the 11 patients were successful survival and the incisions were primary healing. Being followed up for 5 to 59 months, the patients had satisfying appearance and ventilation function, and no tumor relapsed. Conclusion: For the patients with nasal alae defects after external nose tumor resection, selecting suitable island skin flap or combined skin flap can be used to reconstruct the ideal nasal appearance and function of the nose.

Analysis on status of follow-up testing among young HIV/AIDS students aged 15-24 in Guangdong Province，2008-2019 / 中国学校卫生

Objective@#To analyze the status of follow-up cell testing of HIV/AIDS cases among young students aged 15-24 in Guangdong Province from 2008 to 2019.@*Methods@#Using the historical database downloaded from the AIDS Comprehensive Prevention and Control Information System from January 1, 2018 to December 31, 2019, eligible newly discovered cases were screened by year and were linked with follow-up database. Joinpoint regression model and trend test were used to explore the annual changes in the follow-up and CD4 testing status, and Logistic regression was used to analyze relevant influencing factors.@*Results@#The number of infected students showed a rapid upward trend before 2015(APC=41.7，β=0.3，P<0.01), and the growth rate slowed down(APC=3.6，β=-0.3，P<0.01). The proportion of follow-up and CD4 testing completed within one year increased from 58.3% in 2008 to 93.6% in 2019, and the timely detection rate increased from 33.3% in 2008 to 86.2% in 2019. The Cochran Armitage trend test was statistically significant. Pairwise comparison test showed time trends of the idnex differed in regions and education groups (Z=4.7，8.7，9.8，P<0.01). The Pearl River Delta region, cases from other cities in the province, with precise transmission routes, from voluntary counseling and testing, and cases flowing within the province, the proportion of follow up and testing completed within one year is relatively high (P<0.05).@*Conclusion@#The growth rate of HIV/AIDS cases among young students aged 15-24 in Guangdong Province has slowed down in recent years. The route of infection, source and flow of cases affect follow-up and testing compliance. And to do a good job of referrals for off-site mobility, and explore and promote student-friendly VCT service models.

Clinical characteristics analysis and nursing management strategy for patients with bleeding after pancreaticoduodenectomy / 中华胰腺病杂志

Objective:To analyze the clinical features of post-pancreaticoduodenectomy hemorrhage, and explore effective and practical nursing strategies.Methods:Clinical data of 62 patients with post-pancreaticoduodenectomy hemorrhage from Jan 2014 to Dec 2019 in the First Affiliated Hospital of Naval Medical University were retrospectively analyzed. The bleeding time, location, vital signs, accompanying symptoms and surgical treatment measures and clinical outcomes were analyzed.Results:Among the 62 cases, early (within 24 h) hemorrhage occurred in 19/62 patients (30.6%), and late hemorrhage occurred in 43/62 patients (69.4%). 36/62 patients (58.1%) had arterial bleeding; And 43/62 patients (69.4%) had abdominal hemorrhage. Grade C hemorrhage occurred in 32/62 patients (51.6%). Sentinel hemorrhage occurred in 8/62 patients (12.9%). The manifestation of hemorrhage in 42 patients was bloody fluid from abdominal drainage tube (67.7%). Hemorrhage occurred in 23 patients with pancreatic fistula(37.1%), 12 patients with abdominal infection and other complications (19.4%). Shock symptoms occurred in 41 cases (66.1%) with postoperative hemorrhage. Pancreaticoduodenectomy hemorrhage were early detected in 0.3 h and last detected in 869 h, with a median time of 192.00 (14.63, 297.00) h. 30/62 cases (48.4%) of hemorrhage patients occurred 1 hour before and after nursing shift. When hemorrhage was found, emergency treatments such as blood transfusion to maintain blood volume ( n=47, 75.8%), hemostasis ( n=35, 56.5%) and vasoactive drugs to increase blood pressure ( n=32, 51.6%) were usually given immediately. 31/62 patients (50.0%) underwent emergency secondary surgery within 4 h of hemorrhage, and 45/62 patients (72.6%) were cured by emergency surgical treatment. A written treatment pre-plan for surgical nurses was established. Conclusions:Surgical nurses should be familiar with the clinical manifestations of post-pancreaticoduodenectomy hemorrhage, and improve the alarming ability of identifying the complications of post-operative hemorrhage. The establishment of an emergency pre-plan for surgical nurses could help to treat such patients timely and effectively.

Identification and functional analysis of a novel phospholipase D2 gene mutation associated with familial systemic lupus erythematosus / 中南大学学报(医学版)

OBJECTIVES@#Systemic lupus erythematosus (SLE) is a kind of autoimmune inflammatory connective tissue disease which seriously endangers human health. Genetic factors play a key role in the pathogenesis of SLE. This study aims to investigate a novel phospholipase D2 (PLD2) mutation associated with familial SLE, and further explore the underlying mechanism of the mutation in SLE.@*METHODS@#The blood samples from a SLE patient, the patient's parents, and 147 normal controls were collected and DNA was extracted. Whole genome high-throughput sequencing was performed in the patient and her parents and the results were further analyzed by various bioinformatics methods. The wild type (wt), mutant type (mu), and negative control PLD2 plasmids were further constructed and transfected into 293 cells. The expression level of HRAS protein in 293 cells was detected by Western blotting.@*RESULTS@#In this SLE family, the female SLE patient and her mother, 1 in generation II and 1 in generation III had typical clinical manifestations of SLE, and all of them had lupus nephritis at early stage. The genetic characteristics are consistent with autosomal dominant inheritance. A novel PLD2 heterozygous mutation (c.2722C>T) was found in the patient and her mother, but not in her father and other normal controls. Compared with wtPLD2 plasmid and negative control PLD2 plasmid, the expression of HRAS in 293 cells transfected with muPLD2 plasmid was significantly up-regulated (both @*CONCLUSIONS@#PLD2 c.2722C>T mutation may be one of the pathogeny of SLE in this family.

Biochemical and genetic characteristics of 40 neonates with carnitine deficiency / 中南大学学报(医学版)

OBJECTIVES@#Primary carnitine deficiency (PCD) is a rare fatty acid metabolism disorder that can cause neonatal death. This study aims to analyze carnitine levels and detect SLC22A5 gene in newborns with carnitine deficiency, to provide a basis for early diagnosis of PCD, and to explore the relationship between carnitine in blood and SLC22A5 genotype.@*METHODS@#A total of 40 neonates with low free carnitine (C0G (p.Y251C), c.495 C>A (p.R165E), and c.1298T>C (p.M433T). We found 14 PCD patients including 2 homozygous mutations and 12 heterozygous mutations, 14 with 1 mutation, and 12 with no mutation among 40 children. The C0 concentration of children with SLC22A5 gene homozygous or complex heterozygous mutations was (4.95±1.62) μmol/L in the initial screening, and (3.90±1.33) μmol/L in the second screening. The C0 concentration of children with no mutation was (7.04±2.05) μmol/L in the initial screening, and (8.02±2.87) μmol/L in the second screening. There were significant differences between children with homozygous or compound heterozygous mutations and with no mutation in C0 concentration of the initial and the second screening (both @*CONCLUSIONS@#There are 5 new mutations which enriched the mutation spectrum of SLC22A5 gene. C0<5 μmol/L is highly correlated with SLC22A5 gene homozygous or compound heterozygous mutations. Children with truncated mutation may have lower C0 concentration than that with untruncated mutation in the initial screening.