1.Construction of ceRNA Network and Analysis of Key mRNA and Immune Function for Bladder Urothelial Carcinoma Based on Bioinformatics
Bo SHAO ; Jin WANG ; Shui WAN ; Kaixiu WU ; Shen TIAN ; Yichen DU ; Danxia CHEN ; Yuanyuan MA
Journal of Modern Laboratory Medicine 2024;39(1):29-35,66
		                        		
		                        			
		                        			Objective To construct a regulatory network of competing endogenous RNA(ceRNA)with prognostic value for bladder urothelial carcinoma(BLCA),and analyze the relationship between key messenger RNA(mRNA)and immune function.Methods The UCSC Xena database was used to download mRNA expression data from 404 BLCA patients and 28 normal individuals and key mRNAs were screened by differential analysis.ENCORI database was utilized to search microRNAs(miRNAs)that bind to key mRNAs and all long non-coding RNAs(LncRNAs)that bind to miRNAs.The expression data of miRNA and LncRNA were downloaded from TCGA database,co-expression analysis was performed to identify key mRNA with all miRNAs and miRNA with all LncRNAs,and thus key miRNAs and LncRNAs were screened out.Survival analysis was conducted based on the differences in expression levels of these key mRNAs,miRNAs,and LncRNAs between tumor patients and normal individuals,and finally a ceRNA regulatory network was constructed.The correlation between key mRNAs and immune cells,immune checkpoints(CD274,PDCD1 and CTLA4),and immune cell marker genes(IG)was analyzed using the TIMER 2.0 database.Results A total of 22 key mRNAs were screened,with the most significant difference being proline 3-hydroxylase 4(P3H4).The expression of P3H4 in patients with BLCA was high,and survival time was shorter in patients with high expression.A sum of 33 miRNAs and 14 LncRNAs were screened using the key mRNAs as the central link.Through co-expression analysis and survival analysis,hsa-miR-151a-3p and MIR100 HG were identified as the key miRNA and key LncRNA with prognostic value.The differences in the above analysis results were statistically significant(all P<0.05).Based on these findings,a ceRNA regulatory network consisting of 1 mRNA,1 miRNA,and 1 LncRNA was constructed.Immunoassay firstly revealed a significant positive correlation between double positive T cells and P3H4 expression in the tumor microenvironment of BLCA.Moreover,there were 3 types of immune cells(tumor-associated neutrophils,and tumor-associated macrophages,dendritic cells),3 immune checkpoints(CD274,PDCD1,CTLA4),and 15 IGs with significant correlation with P3H4.These differences were statistically significant(all P<0.01).Conclusion This study could help to reveal the progression mechanism of BLCA.The constructed ceRNA network and immune analysis can offer new insights into potential biological targets and immunotherapy directions for the diagnosis,treatment,and prediction of BLCA patients.
		                        		
		                        		
		                        		
		                        	
2.Application of superior iliac fascia block of inguinal ligament combined with patient controlled intravenous analgesia in elderly patients after hip arthroplasty
Fu YAO ; Yun-Hua SHUI ; Ji-Lin XIANG ; Bo YANG
China Journal of Orthopaedics and Traumatology 2024;37(5):482-487
		                        		
		                        			
		                        			Objective To compare the effect of patient-controlled intravenous analgesia(PCIA)and superior inguinal liga-ment iliac fascia block combined with PCIA after hip replacement in the elderly.Methods Total of 82 elderly patients were treated with hip arthroplasty from June 2019 to June 2021 and randomly divided into observation group and control group.There were 42 patients in control group,including 18 males and 24 females,aged from 60 to 78 years old with an average of(70.43±3.67)years old,28 femoral neck fractures and 14 femoral head necrosis,who received PCIA.The study group consist-ed of 42 cases,including 20 males and 22 females,aged from 61 to 76 years old with an average of(69.68±3.74)years old,25 femoral neck fractures and 17 femoral head necrosis,who received superior inguinal ligament iliac fascia block combined with PCIA.Pain visual analogue scale(VAS)and Ramesay sedation scores at2h,6h,12h,24h and 48 h after operation were e-valuated.In addition,the follow-up results of the total consumption of sufentanil and the total number of PCIA compressions at 48 hours after operation,the first time of landing after surgery,the time of hospital stay,the incidence of adverse reactions,the satisfaction with analgesia of two groups were observed.Results All patients were followed up for 9 to 24 months with an aver-age of(13.85±2.67)months.There was no significant difference in operation time and intraoperative bleeding between two groups(P>0.05).There was no difference in VAS between two groups at 2 hours after operation(P>0.05),and the VAS of the study group at 6 h,12 h,24 h and 48 h after operation were lower than those of the control group(P<0.05).The Ramesay seda-tion scores of the study group at 2 h,6 h and 12 h after operation were higher than those of the control group(P<0.05),and there were no differences in Ramesay score between two groups at 24 h and 48 h after operation(P>0.05).The consumption of sufentanil in the study group within 48 hours after operation was lower than that in the control group(P<0.05),and PCIA com-pression times were lower than those in the control group(P<0.05),and the time of first landing was earlier than that in the control group(P<0.05).There was no significant difference in hospital stay,adverse reaction rate,complications between two groups(P>0.05).The satisfaction of analgesia in the study group was higher than that in the control group(P<0.05).Conclu-sion Superior iliac fascia block of inguinal ligament combined with PCIA has significant analgesic and sedative effects after hip arthroplasty in the elderly.It can reduce the amount of sufentanil used and the total number of PCIA compressions,which is conducive to the early activity of patients out of bed,improve the satisfaction of analgesia.
		                        		
		                        		
		                        		
		                        	
3.Treatment of infection after spinal internal fixation
Shi-Bo HUANG ; Ji-Gong WU ; Shui-Lin SHAO ; Jing SUN ; You-Ping TAO
Journal of Regional Anatomy and Operative Surgery 2024;33(5):451-454
		                        		
		                        			
		                        			Objective To explore the treatment of infection after spinal internal fixation.Methods The clinical data of 6 patients with infection after spinal internal fixation in our hospital were analyzed retrospectively.The bacterial culture and drug susceptibility testing were performed to identify the pathogenic bacteria and sensitive antibiotics.Moxifloxacin and/or vancomycin were used empirically for anti-infective therapies first,and then sensitive antibiotics were used according to the results of bacterial culture and drug susceptibility testing.At the same time,imaging examination was performed to determine the infection site and internal fixation,and surgical treatment was decided based on the patients'condition.After operation,the body temperature,inflammatory indexes and drainage of patients were monitored continuously,and the drainage fluid was taken for bacterial culture regularly to evaluate the therapeutic effect.Results The results of bacterial culture in 5 patients were positive and the pathogenic bacteria was staphylococcus aureus,with the susceptibility to vancomycin by susceptibility testing.Among them,1 patient was treated with vancomycin for about 8 weeks because of his advanced age,more basic diseases and high risk of operation;the other 4 patients were received surgery combined with anti-infective treatment with vancomycin for 2 to 4 weeks.One case with negative bacterial culture received surgery combined with anti-infective treatment with imipenem and moxifloxacin.The wound of all patients healed in grade A,the body temperature and inflammatory indexes returned to normal,the low back pain disappeared,and the nerve root symptoms of lower extremities were significantly improved.Conclusion Once the patients with infection after spinal internal fixation are diagnosed,the pathogenic bacterial should be identified as early as possible and sensitive antibiotics should be used.Meanwhile,the internal fixation is removed or re-implanted depending on whether it is infected.
		                        		
		                        		
		                        		
		                        	
4.Risk factors of gastrointestinal bleeding after type A aortic dissection
Shi-Si LI ; Chun-Shui LIANG ; Tian-Bo LI ; Yun ZHU ; Han-Ting LIU ; Xing-Lu WANG ; Si ZHANG ; Rui-Yan MA
Journal of Regional Anatomy and Operative Surgery 2024;33(6):497-500
		                        		
		                        			
		                        			Objective To analyze the risk factors of gastrointestinal bleeding in patients with type A aortic dissection(TAAD)after Sun's operation.Methods The clinical data of 87 patients who underwent TAAD Sun's operation in our hospital from March 2021 to June 2022 were retrospectively analyzed.They were divided into the bleeding group and the non-bleeding group according to whether there was gastrointestinal bleeding after operation.The clinical data of patients in the two groups was compared and analyzed.The binary Logistic regression analysis was used to analyze the risk factors of gastrointestinal bleeding.The clinical predictor of postoperative gastrointestinal bleeding was analyzed by receiver operating characteristic(ROC)curve.Results In this study,there were 40 cases of postoperative gastrointestinal bleeding(the bleeding group)and 47 cases of non-bleeding(the non-bleeding group).Compared with the non-bleeding group,the bleeding group had a shorter onset time,a higher proportion of patients with hypertension history,a higher preoperative creatinine abnormality rate,more intraoperative blood loss,longer postoperative mechanical ventilation time,higher postoperative infection rate,and higher poor prognosis rate,with statistically significant differences(P<0.05).There was no statistically significant difference in the gender,age,gastrointestinal diseases history,smoking history,preoperative platelets,preoperative international normalized ratio(INR),preoperative alanine aminotransferase(ALT),preoperative aspartate aminotransferase(AST),preoperative γ-glutamyl transpeptidase(GGT),preoperative dissection involving abdominal aorta,operation time,intraoperative cardiopulmonary bypass time,intraoperative circulatory arrest time,intraoperative aortic occlusion time or intraoperative blood transfusion rate.Logistic regression analysis showed that hypertension history(OR=2.468,95%CI:0.862 to 7.067,P=0.037),preoperative creatinine>105 μmol/L(OR=3.970,95%CI:1.352 to 11.659,P=0.011),long postoperative mechanical ventilation time(OR=1.015,95%CI:0.094 to 1.018,P=0.041)and postoperative infection(OR=3.435,95%CI:0.991 to 11.900,P=0.012)were the independent risk factors for postoperative gastrointestinal bleeding in TAAD patients.ROC curve showed that the postoperative mechanical ventilation time exceeding 64 hours were the clinical predictor of postoperative gastrointestinal bleeding in TAAD patients.Conclusion The prognosis of TAAD patients with postoperative gastrointestinal bleeding after Sun's operation is poor.Hypertension history,preoperative acute renal insufficiency,long postoperative mechanical ventilation time and postoperative infection are closely related to postoperative gastrointestinal bleeding in TAAD patients after operation,which should be paid more attention to,and corresponding evaluation,early identification and early intervention should be made to improve the prognosis of patients.
		                        		
		                        		
		                        		
		                        	
5.Study on micro wave ablation of lung tumor based on real anatomical model
Ju LIU ; Hong-Jian GAO ; Qi WANG ; Yu-Bo ZHANG ; Hui-Jing HE ; Wei-Wei WU ; Shui-Cai WU
Chinese Medical Equipment Journal 2024;45(9):27-34
		                        		
		                        			
		                        			Objective To plan microwave antenna puncture direction effectively and realize personalized preoperative simulation by exploring microwave ablation(MWV)outcomes of lung cancer based on real anatomical model.Methods Firstly,a personalized MWA simulation model consisting of the lung tissue,tumor and vascular system was constructed based on the lung CT data of real patients.Secondly,the MWA effect was simulated by coupling 2 physical fields including an electromagnetic field and a biological heat transfer field,so as to determine the volume of the ablation thermocoagulation zone and the temperature distribution of the lung tissue.Finally,the effects of the vascularized network on the ablation results were quantitatively evaluated in terms of conductivity and blood perfusion,and the ablation results were analyzed with different distances between the large vessels and the antennae(5 and 10 mm from the antennae tips)and puncture angles(large vessels parallelling or intersecting with the antennae tips).Results The vascularized network reduced the volume of the thermocoagulation zone by 0.5%to 3.7%,and blood perfusion made the ablation temperature and the volume of the thermocoagulation zone decreased significantly.The cooling effect gradually diminished with the increase of the distance between the large vessels and the antenna.With the same treatment parameters,the thermocoagulation zone formed when the large vessels paralleled with the antenna was obviously larger than that when the vessles intersected with the antenna.Conclusion Personalized MWA simulation analysis based on real CT data contributes to clarifying the temperature distribution and damage estimation close to the actual situation,which provides guidance and reference for precise treatment of the lung tumor and determination of microwave antenna puncture direction.[Chinese Medical Equipment Journal,2024,45(9):27-34]
		                        		
		                        		
		                        		
		                        	
6.Gene expression characteristics of lncRNAs and mRNAs in the sperm of asthenospermia patients
Shui-Bo SHI ; Long-Hua LUO ; Lian LIU ; Xue-Ming HUANG ; Su-Ping XIONG ; Dan-Dan SONG ; Dong-Shui LI
National Journal of Andrology 2024;30(9):782-788
		                        		
		                        			
		                        			Objective:To determine the differential expressions of long non-coding RNA(lncRNA)and messenger RNA(mRNA)in normal and asthenospermia(AS)men and analyze their biological significance in AS.Methods:We isolated and ex-tracted total RNAs from 9 normal and 9 AS sperm samples,determined the expressions of RNAs in the sperm using the DNBSEQ se-quencing platform,and analyzed their relevant functions by gene ontology enrichment(GO)and Kyoto encyclopedia of genes and ge-nomes pathway(KEGG)analyses.Results:An average of 10.64G data was generated per group,with 282 185 RNAs detected,in-cluding 107 009 lncRNAs.Among the total number of lncRNAs,15 157 were differentially expressed,2 190 upregulated and 12 967 downregulated;and among the 19 514 mRNAs,13 736 were differentially expressed,4 995 upregulated and 8 741 downregulated.Differentially expressed genes were enriched mainly in the sperm cell membrane and the pathways related to the ion channel functions,sperm development and fertilization.Conclusion:Differentially expressed lncRNAs and mRNAs can be identified by sequencing a-nalysis of AS and normal sperm.Regulation of sperm function through membrane ion channels may contribute to the development of AS,which provides a molecular basis for further research on AS.
		                        		
		                        		
		                        		
		                        	
7.Serological and molecular biological analysis of RhD--: a case report
Bo SHUI ; Zhibing HOU ; Li YAO ; Wei YAN ; Jiwu HE
Chinese Journal of Blood Transfusion 2023;36(12):1162-1164
		                        		
		                        			
		                        			【Objective】 To study the blood group serology and molecular biology of patients with RhD--, so as to guide clinical blood use. 【Methods】 The EDTA-K
		                        		
		                        	
8.Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population.
Meng Fan LIU ; Rui Xia MA ; Xian Bao CAO ; Hua ZHANG ; Shui Hong ZHOU ; Wei Hong JIANG ; Yan JIANG ; Jing Wu SUN ; Qin Tai YANG ; Xue Zhong LI ; Ya Nan SUN ; Li SHI ; Min WANG ; Xi Cheng SONG ; Fu Quan CHEN ; Xiao Shu ZHANG ; Hong Quan WEI ; Shao Qing YU ; Dong Dong ZHU ; Luo BA ; Zhi Wei CAO ; Xu Ping XIAO ; Xin WEI ; Zhi Hong LIN ; Feng Hong CHEN ; Chun Guang SHAN ; Guang Ke WANG ; Jing YE ; Shen Hong QU ; Chang Qing ZHAO ; Zhen Lin WANG ; Hua Bin LI ; Feng LIU ; Xiao Bo CUI ; Sheng Nan YE ; Zheng LIU ; Yu XU ; Xiao CAI ; Wei HANG ; Ru Xin ZHANG ; Yu Lin ZHAO ; Guo Dong YU ; Guang Gang SHI ; Mei Ping LU ; Yang SHEN ; Yu Tong ZHAO ; Jia Hong PEI ; Shao Bing XIE ; Long Gang YU ; Ye Hai LIU ; Shao wei GU ; Yu Cheng YANG ; Lei CHENG ; Jian Feng LIU
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2023;58(6):579-588
		                        		
		                        			
		                        			Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
		                        		
		                        		
		                        		
		                        			Female
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Adolescent
		                        			;
		                        		
		                        			SARS-CoV-2
		                        			;
		                        		
		                        			Smell
		                        			;
		                        		
		                        			COVID-19/complications*
		                        			;
		                        		
		                        			Cross-Sectional Studies
		                        			;
		                        		
		                        			COVID-19 Vaccines
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		                        			Incidence
		                        			;
		                        		
		                        			Olfaction Disorders/etiology*
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		                        			Taste Disorders/etiology*
		                        			;
		                        		
		                        			Prognosis
		                        			
		                        		
		                        	
9.Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial.
Si Yu CAI ; Xiang GU ; Pei Jing LIU ; Rong Shan LI ; Jian Jun JIANG ; Shui Ping ZHAO ; Wei YAO ; Yi Nong JIANG ; Yue Hui YIN ; Bo YU ; Zu Yi YUAN ; Jian An WANG
Chinese Journal of Cardiology 2023;51(2):180-187
		                        		
		                        			
		                        			Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Middle Aged
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		                        			Atorvastatin/therapeutic use*
		                        			;
		                        		
		                        			Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use*
		                        			;
		                        		
		                        			Hypercholesterolemia/drug therapy*
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		                        			Cholesterol, LDL/therapeutic use*
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		                        			Anticholesteremic Agents/therapeutic use*
		                        			;
		                        		
		                        			Treatment Outcome
		                        			;
		                        		
		                        			Triglycerides
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		                        			Apolipoproteins B/therapeutic use*
		                        			;
		                        		
		                        			Double-Blind Method
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		                        			Pyrroles/therapeutic use*
		                        			
		                        		
		                        	
10.Considerations during the treatment of pemphigus vulgaris under special circumstances
Qian WANG ; Shui JIANG ; Yaru ZOU ; Hongquan CHEN ; Guanzhi CHEN ; Bo YU ; Hui ZOU ; Xin CHU
Chinese Journal of Dermatology 2023;56(11):1078-1080
		                        		
		                        			
		                        			Pemphigus vulgaris is the most common and serious type of pemphigus, and timely treatment can change its prognosis. This review comprehensively analyzes considerations in the treatment of pemphigus vulgaris during pregnancy and lactation as well as during the prevention and control of COVID-19 pandemic, including treatment particularities and comprehensive nursing care, in order to provide better guidance and treatment for patients.
		                        		
		                        		
		                        		
		                        	
            
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