1.Progress and challenges of functionalized bacterial encapsulation: A novel biotechnology for next-generation biotherapeutics.
Ying ZHANG ; Yuwei WU ; Xinyu ZHAO ; Qinghua YE ; Lulu CAO ; Ming LIU ; Bao GAO ; Qinya NIU ; Nuo CHEN ; Zixuan DUAN ; Yu DING ; Juan WANG ; Moutong CHEN ; Ying LI ; Qingping WU
Acta Pharmaceutica Sinica B 2025;15(10):5167-5191
The disturbance of the human microbiota influences the occurrence and progression of many diseases. Live therapeutic bacteria, with their genetic manipulability, anaerobic tendencies, and immunomodulatory properties, are emerging as promising therapeutic agents. However, their clinical applications face challenges in maintaining activity and achieving precise spatiotemporal release, particularly in the harsh gastrointestinal environment. This review highlights the innovative bacterial functionalized encapsulation strategies developed through advances in physicochemical and biological techniques. We comprehensively review how bacterial encapsulation strategies can be used to provide physical barriers and enhanced adhesion properties to live microorganisms, while introducing superior material properties to live bacteria. In addition, this review outlines how bacterial surface coating can facilitate targeted delivery and precise spatiotemporal release of live bacteria. Furthermore, it elucidates their potential applications for treating different diseases, along with critical perspectives on challenges in clinical translation. This review comprehensively analyzes the connection between functionalized bacterial encapsulation and innovative biomedical applications, providing a theoretical reference for the development of next-generation bacterial therapies.
2.Pathogenicity and Transcriptomic Profiling Revealed Activation of Apoptosis and Pyroptosis in Brain of Mice Infected with the Beta Variant of SARS-CoV-2.
Han LI ; Bao Ying HUANG ; Gao Qian ZHANG ; Fei YE ; Li ZHAO ; Wei Bang HUO ; Zhong Xian ZHANG ; Wen WANG ; Wen Ling WANG ; Xiao Ling SHEN ; Chang Cheng WU ; Wen Jie TAN
Biomedical and Environmental Sciences 2025;38(9):1082-1094
OBJECTIVE:
Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection frequently develop central nervous system damage, yet the mechanisms driving this pathology remain unclear. This study investigated the primary pathways and key factors underlying brain tissue damage induced by the SARS-CoV-2 beta variant (lineage B.1.351).
METHODS:
K18-hACE2 and C57BL/6 mice were intranasally infected with the SARS-CoV-2 beta variant. Viral replication, pathological phenotypes, and brain transcriptomes were analyzed. Gene Ontology (GO) analysis was performed to identify altered pathways. Expression changes of host genes were verified using reverse transcription-quantitative polymerase chain reaction and Western blot.
RESULTS:
Pathological alterations were observed in the lungs of both mouse strains. However, only K18-hACE2 mice exhibited elevated viral RNA loads and infectious titers in the brain at 3 days post-infection, accompanied by neuropathological injury and weight loss. GO analysis of infected K18-hACE2 brain tissue revealed significant dysregulation of genes associated with innate immunity and antiviral defense responses, including type I interferons, pro-inflammatory cytokines, Toll-like receptor signaling components, and interferon-stimulated genes. Neuroinflammation was evident, alongside activation of apoptotic and pyroptotic pathways. Furthermore, altered neural cell marker expression suggested viral-induced neuroglial activation, resulting in caspase 4 and lipocalin 2 release and disruption of neuronal molecular networks.
CONCLUSION
These findings elucidate mechanisms of neuropathogenicity associated with the SARS-CoV-2 beta variant and highlight therapeutic targets to mitigate COVID-19-related neurological dysfunction.
Animals
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COVID-19/genetics*
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Mice
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Brain/metabolism*
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Apoptosis
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Mice, Inbred C57BL
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SARS-CoV-2/physiology*
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Pyroptosis
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Gene Expression Profiling
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Transcriptome
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Male
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Female
3.Analysis on genetic etiology of disorders of sex development using whole exome sequencing
Liu-Jiao WU ; Chan-Chan JIN ; Shu ZHU ; Wen-Ming HUANG ; Jian-Hong YE ; Tao LYU ; Bao-Sheng ZHU ; Jing HE
Medical Journal of Chinese People's Liberation Army 2024;49(5):495-503
Objective To elucidate the molecular genetic etiology of patients with disorders of sex development(DSD)using whole exome sequencing(WES),thereby enhancing our understanding of the underlying mechanisms of sexual development abnormalities.Methods Retrospective analysis was conducted on clinical data of 60 DSD patients diagnosed in the First People's Hospital of Yunnan Province between March 2008 and August 2021,with an additional family study for one proband.Genomic DNA was extracted from patients for WES analysis.Single nucleotide polymorphism(SNP)and insertions/deletion(InDel)tests were identified using SAMtools software in conjunction with established SNP and InDel databases.Copy number variations(CNVs)at the exon level were detected using ExomeDepth,while the potential pathogenicity of mutations was predicted with PolyPhen-2,Mutation taster and PyMol software,with Sanger sequencing employed for confirmation.Results The study included 22 patients with 46,XX DSD and 38 with 46,XY DSD.Among the 46,XX DSD patients,the SRY gene was detected in 14 patients.In the remaining 8 patients and a proband's families,single nucleotide site variations(SNVs)of NR5A1,PROKR2 and ANOS1 genes were identified in 2 patients,and CNVs in CYP21A2 gene were found in 4 patients.The pathogenicity of CYP21A2 EX1 Dup has been previously reported,while the remaining 3 CNVs were of uncertain significance,and no DSD-related mutations were detected in 2 patients.In the WES analysis of 46,XY DSD patients,10 pathogenic or likely pathogenic SNVs across 5 genes(SRY,AR,SRD5A2,CYP17A1,and NR5A1)were identified in 14 patients.Additionally,5 likely pathogenic CNVs involving the CYP21A2,AKR1C2,CBX2,and NR5A1 genes were detected in 5 patients,comprising 3 deletions and 2 duplications.Novel SNVs in NR5A1(c.722G>T,c.48C>G)and ANOS1 c.564A>T were identified,with no prior reports in relevant databases.The pathogenicity of CYP21A2 EX1 Dup is documented in related databases,while the remaining CNVs have not been previously reported.Conclusion The utilization of WES technology has enhanced the diagnostic potential for DSD,broadened the spectrum of known DSD-related gene mutations,and deepened our comprehension of DSD pathogenesis,offering valuable support for genetic counseling.
4.Efficacy and safety of rituximab in the treatment of pediatric myasthenia gravis
Yunong TONG ; Cuijie WEI ; Xiaoling YANG ; Taoyun JI ; Yao ZHANG ; Ye WU ; Xingzhi CHANG ; Xinhua BAO ; Yuwu JIANG ; Hui XIONG ; Yuehua ZHANG
Chinese Journal of Pediatrics 2024;62(11):1050-1055
Objective:To evaluate the efficacy and safety of rituximab in pediatric myasthenia gravis (MG).Methods:Case series study. The clinical manifestations, laboratory tests, treatment plans and prognosis of 27 pediatric MG patients treated with rituximab from June 2013 to June 2023 at Children′s Medical Center of Peking University First Hospital were retrospectively collected.Results:There were 5 males and 22 females in 27 MG children. The onset age was 2.1 (1.6, 4.8) years, ranging from 8 months to 11 years. The clinical classification included 20 children (74%) of ocular MG and 7 children (26%) of generalized MG. Seventeen children (63%) had positive MG-related pathogenic antibodies, including 17 children of anti-AchR antibody and 1 of them also had anti-MuSK antibody. Rituximab was used as first-line immunosuppressant in 13 children, second-line immunosuppressant in 13 children and third-line immunosuppressant in 1 child. Immunosuppressants used before rituximab including 8 children of cyclosporine, 3 children of tacrolimus, 1 child of azathioprine, 1 child of mycophenolate mofetil and 1 child of cyclosporine combined with azathioprine. Rituximab was used for at least half a year with a follow-up period of more than 12 months. At the last follow-up after rituximab treatment, all children achieved improved or above, 14 children (52%) achieved complete stable remission, 7 children (26%) achieved pharmacologic remission, 1 child (4%) achieved minimal manifestations, and 5 children (18%) improved. After rituximab treatment, 27 children all could reduce the immunomodulation therapy and shorten the course of glucocorticoid therapy, and 22 children (81%) had stopped the glucocorticoid therapy. Among the 14 children with poor efficacy of other immunosuppressants, rituximab had complete stable remission of 7 children. The most common adverse reaction was respiratory infection (4 children (15%)). Only 2 children had allergic reaction to rituximab and got better after symptomatic treatment.Conclusions:Rituximab has good efficacy and tolerance in pediatric MG. Early application of rituximab can improve the prognosis and shorten the course of glucocorticoid treatment.
5.Risk factors and survival of EBV-infected aplastic anemia patients after haploid allogeneic hematopoietic stem cell transplantation
Xin-He ZHANG ; Jia FENG ; Zheng-Wei TAN ; Yue-Chao ZHAO ; Hui-Jin HU ; Jun-Fa CHEN ; Li-Qiang WU ; Qing-Hong YU ; Di-Jiong WU ; Bao-Dong YE ; Wen-Bin LIU
Chinese Journal of Infection Control 2024;23(10):1228-1235
Objective To analyze the risk factors and survival status of Epstein-Barr virus(EBV)infection in pa-tients with aplastic anemia(AA)after haploid allogeneic hematopoietic stem cell transplantation(Haplo-HSCT).Methods Clinical data of 78 AA patients who underwent Haplo-HSCT in the hematology department of a hospital from January 1,2019 to October 31,2022 were analyzed retrospectively.The occurrence and onset time of EBV viremia,EBV-related diseases(EBV diseases),and post-transplant lymphoproliferative disorders(PTLD)were ob-served,risk factors and survival status were analyzed.Results Among the 78 patients,38 were males and 40 were females,with a median age of 33(9-56)years old;53 patients experienced EBV reactivation,with a total inci-dence of 67.9%,and the median time for EBV reactivation was 33(13,416)days after transplantation.Among pa-tients with EBV reactivation,49 cases(62.8%)were simple EBV viremia,2 cases(2.6%)were possible EBV di-seases,and 2 cases(2.6%)were already confirmed EBV diseases(PTLD).Univariate analysis showed that age 1<40 years old at the time of transplantation,umbilical cord blood infusion,occurrence of acute graft-versus-host disease(aGVHD)after transplantation,and concurrent cytomegalovirus(CMV)infection were independent risk fac-tors for EBV reactivation in AA patients after Haplo-HSCT.Multivariate analysis showed that concurrent CMV in-fection was an independent risk factor for EBV reactivation in A A patients after Haplo-HSCT(P=0.048).Ritu-ximab intervention before stem cell reinfusion was a factor affecting the duration of EBV reactivation(P<0.05).The mortality of EBV viremia,EBV diseases,and PTLD alone were 8.2%,50.0%,and 100%,respectively.The 2-year overall survival rate of patients with and without EBV reactivation were 85.3%,and 90.7%,respectively,difference was not statistically significant(P=0.897).However,patients treated with rituximab had 2-year lower survival rate than those who did not use it,with a statistically significant difference(P=0.046).Conclusion EBV reactivation is one of the serious complications in AA patients after Haplo-HSCT,which affects the prognosis and survival of patients.
6.Clinical value of"four longitudinal,two transverse planes"method of membrane anatomy in laparoscopic radical cystectomy
Dongping BAO ; Peifeng ZHONG ; Guohao WU ; Haomin LI ; Dongjiang CHEN ; Xianguo HU ; Bingquan WU ; Zheng CHEN ; Zexiong GUO ; Dongming YE ; Caiyong LAI
Journal of Modern Urology 2024;29(5):399-405
Objective To explore the clinical value of laparoscopic radical cystectomy based on fascia anatomy for bladder cancer treatment.Methods The clinical data of 51 patients with bladder cancer who underwent 3D laparoscopic radical cystectomy during Jan.2015 and Jun.2022 were retrospectively analyzed.The surgery was performed based on membrane anatomy technology along four longitudinal and two transverse planes to complete the radical cystectomy.The pelvic plexus was preserved for patients with normal preoperative sexual function.Results All surgeries were completed without conversion to open operation.The mean operation time was(502.52±108.99)min,mean intraoperative blood loss was(275.96±155.18)mL,mean postoperative drainage time was(4.14±2.41)d,and the mean postoperative hospital stay was(16.37±4.85)d.The mean number of lymph nodes removed was(17.98±11.48).The mean postoperative follow-up was(30.27±19.39)months.At the last follow-up,no Clavien ≥grade 3 complications were observed.The estimated overall survival(OS),tumor-specific survival(TSS),and recurrence-free survival(RFS)were 82.4%,92.2%,and 88.2%,respectively.The lymph node positive patients had shorter OS and RFS(60.0%,60.0%)than the lymph node negative patients(84.8%,91.3%).Among the 19 male patients who underwent radical cystectomy with pre-exposure and preservation of pelvic plexus,daytime and nocturnal continence rate were 83.3%and 72.2%,respectively,and 17 patients recovered potency within 6 months postoperatively.Conclusion Laparoscopic radical cystectomy based on fascia anatomy is safe and effective in laparoscopic radical cystectomy,with standardized surgical procedure,satisfactory oncological outcomes,little hemorrhage,few complications and fast recovery.
7.Construction of a quality evaluation system for the implementation of TCM nursing program
Yashuang SHAO ; Qian SU ; Bainü WU ; Yanan KAN ; Yunchun BAO ; Fuying YE
Chinese Journal of Nursing 2024;59(18):2244-2250
Objective To establish a scientific and systematic quality evaluation system for the implementation of TCM nursing programs,and to provide references for promoting the standardized implementation and quality improvement of TCM nursing programs.Methods From October 2023 to December 2023,a research team was set up to form the first draft of the quality evaluation system for the implementation of TCM nursing programs based on the"structure-process-results"three-dimensional quality model,by combining literature research and focus group interviews,and the quality evaluation system for the implementation of TCM nursing programs was formulated by means of Delphi expert letter consultation and analytic hierarchy process.Results 2 rounds of professional consultations resulted in an excellent recovery rate of 100%;the expert authority coefficients were 0.853 and 0.958;the Kendall harmony coefficients of expert opinions were 0.151 and 0.152,respectively.Finally,the quality evaluation system of TCM nursing program implementation was determined,including 3 first-level indicators,including structure,process and result.There are 6 secondary indicators,including system management,implementation management,quality management,effect evaluation,safety evaluation,and satisfaction evaluation.There are 18 three-level indicators,including the implementation management system of TCM nursing program and regular optimization of TCM nursing program.Conclusion The quality evaluation system for the implementation of TCM nursing programs is scientific and reliable,but its practicability needs to be tested in clinical practice.
8.Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome (version 2024)
Junyu WANG ; Hai JIN ; Danfeng ZHANG ; Rutong YU ; Mingkun YU ; Yijie MA ; Yue MA ; Ning WANG ; Chunhong WANG ; Chunhui WANG ; Qing WANG ; Xinyu WANG ; Xinjun WANG ; Hengli TIAN ; Xinhua TIAN ; Yijun BAO ; Hua FENG ; Wa DA ; Liquan LYU ; Haijun REN ; Jinfang LIU ; Guodong LIU ; Chunhui LIU ; Junwen GUAN ; Rongcai JIANG ; Yiming LI ; Lihong LI ; Zhenxing LI ; Jinglian LI ; Jun YANG ; Chaohua YANG ; Xiao BU ; Xuehai WU ; Li BIE ; Binghui QIU ; Yongming ZHANG ; Qingjiu ZHANG ; Bo ZHANG ; Xiangtong ZHANG ; Rongbin CHEN ; Chao LIN ; Hu JIN ; Weiming ZHENG ; Mingliang ZHAO ; Liang ZHAO ; Rong HU ; Jixin DUAN ; Jiemin YAO ; Hechun XIA ; Ye GU ; Tao QIAN ; Suokai QIAN ; Tao XU ; Guoyi GAO ; Xiaoping TANG ; Qibing HUANG ; Rong FU ; Jun KANG ; Guobiao LIANG ; Kaiwei HAN ; Zhenmin HAN ; Shuo HAN ; Jun PU ; Lijun HENG ; Junji WEI ; Lijun HOU
Chinese Journal of Trauma 2024;40(5):385-396
Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.
9.Identification and biological characteristics of violet root rot pathogen of Pseudostellaria heterophylla in Fujian province.
Bao-Cai LIU ; Jing-Ying CHEN ; Wu-Jun ZHANG ; Ying-Zhen HUANG ; Yun-Qing ZHAO ; Jing YE
China Journal of Chinese Materia Medica 2023;48(1):45-51
Violet root rot is one of the main root diseases in the production process of Pseudostellaria heterophylla. To clarify the pathogenic species that cause the violet root rot of P. heterophylla in Fujian province, the roots and the sclerotia with violet root rot symptoms were collected from the main producing areas of P. heterophylla(Fujian province) from 2017 to 2021, and the pathogens were isolated by tissue separation method and identified by morphology and multi-gene phylogenetic analysis. Additionally, the biological characteristics of the pathogens were studied and the fungicides were determined. The results showed that 78 strains of violet root rot were isolated from the collected root samples, which belonged to one type after preliminary morphological identification. Two represen-tative strains were selected from the pathogens for multi-gene phylogenetic analysis, and they were clustered with Helicobasidium mompa together. The suitable culture conditions for the mycelium were OA medium, 25 ℃, pH 6, and ammonium oxalate as the nitrogen source. The lethal temperature of the mycelium was 50 ℃ for 10 minutes. Moreover, 99.1% propiconazole and 98.7% azoxystrobin had the optimal bacteriostatic effect, and the concentrations with the 50% bacteriostatic rate were 16.85 and 12.24 μg·mL~(-1), respectively. On the basis of the above results, the pathogen causing violet root rot of P. heterophylla in Fujian province was H. mompa. The medium type, growth temperature, pH value, nitrogen source, etc. had significant effect on the growth of mycelium.
Plant Roots
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Phylogeny
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Temperature
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Caryophyllaceae
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Nitrogen
10.The practice and exploration of the new teacher training mode of MOOC and micro-course club
Haina ZHANG ; Guangmeng XU ; Ye CHEN ; Zhongliang LIU ; Hongyan BAO ; Lixin GUO ; Wenmao LI ; Hao WU ; Qian CAO ; Yanguo QIN
Chinese Journal of Medical Education Research 2023;22(5):716-719
This study summarizes the construction background, rules and regulations and institutional settings of the MOOC and Micro-course Club in the Second Hospital of Jilin University, discusses the means of teacher training for clinical teachers, and shows the application effect of the club. At the same time, the related problems encountered in the process of club construction are summarized and reflected. The construction of MOOC and micro-course clubs is conducive to improving the information-based teaching level of clinical teachers, and also provides new inspiration and ideas for the construction of medical clubs.

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