1.Targeting the chromatin structural changes of antitumor immunity
Li NIAN-NIAN ; Lun DENG-XING ; Gong NINGNING ; Meng GANG ; Du XIN-YING ; Wang HE ; Bao XIANGXIANG ; Li XIN-YANG ; Song JI-WU ; Hu KEWEI ; Li LALA ; Li SI-YING ; Liu WENBO ; Zhu WANPING ; Zhang YUNLONG ; Li JIKAI ; Yao TING ; Mou LEMING ; Han XIAOQING ; Hao FURONG ; Hu YONGCHENG ; Liu LIN ; Zhu HONGGUANG ; Wu YUYUN ; Liu BIN
Journal of Pharmaceutical Analysis 2024;14(4):460-482
Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.
2.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.
3.The Research Status of Novel Coronavirus Antibodies and Small Molecule Inhibitors
Xin WU ; Han-Jie YU ; Xiao-Juan BAO ; Yu-Zi WANG ; Zheng LI
Progress in Biochemistry and Biophysics 2024;51(4):754-771
The World Health Organization has declared that the outbreak of coronavirus disease 2019(COVID-19) is a global pandemic. As mutations occurred in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the global epidemic still needs further concern. Worryingly, the effectiveness and neutralizing activity of existing antibodies and vaccines against SARS-CoV-2 variants is declining. There is an urgent need to find an effective antiviral medication with broad-spectrum inhibitory effects on novel coronavirus mutant strains against the SARS-CoV-2 infection. Neutralizing antibodies play an important role in the prevention and treatment of COVID-19. The interaction of spike-receptor-binding domain (Spike-RBD) of SARS-CoV-2 and human angiotensin-converting enzyme 2 (ACE2) is the first and critical step of SARS-CoV-2 infection. Hence, the SARS-CoV-2 Spike-RBD is a hot target for neutralizing antibodies development. Evusheld, the combination of Tixagevimab and Cilgavimab monoclonal antibodies (mAbs) targeting Spike-RBD exhibits neutralizing activity against BA.2.12.1, BA.4 and BA.5, which could be used as pre-exposure prophylaxis against SARS-CoV-2 infection. The nucleocapsid (N) protein is a conservative and high-abundance structural protein of SARS-CoV-2. The nCoV396 monoclonal antibody, isolated from the blood of convalescent COVID-19 patients against the N protein of SARS-CoV-2. This mAb not only showed neutralizing activity but also inhibits hyperactivation of complement and lung injury induced by N protein. The mAb 3E8 targeting ACE2 showed broadly neutralizing activity against SARS-CoV-2 and D614G, B.1.1.7, B.1.351, B.1.617.1 and P.1 variants in vitro and in vivo, but did not impact the biological activity of ACE2. Compared with neutralizing antibodies, small molecule inhibitors have several advantages, such as broad-spectrum inhibitory effect, low cost, and simple administration methods. Several small-molecule inhibitors disrupt viral binding by targeting the ACE2 and N-terminal domain (NTD) of SARS-CoV-2 spike protein. Known drugs such as chloroquine and hydroxychloroquine could also block the infection of SARS-CoV-2 by interacting with residue Lys353 in the peptidase domain of ACE2. The transmembrane protease serine 2 (TMPRSS2) inhibitors Camostat mesylate and Proxalutamide inhibit infection by blocking TMPRSS2 mediates viral membrane fusion. The main protease inhibitor Paxlovid and RNA-dependent RNA polymerase inhibitor Azvudine have been approved for treatment of COVID-19 patients. This review summarizes the current research status of neutralizing antibodies and small molecule inhibitors and prospects for their application. We expect to provide more valuable information for further studies in this field.
4.Clinical application of a novel separated magnetic controlled forceps assisted single-incision laparoscopic cholecystectomy
Wei XIN ; Zhenyu YANG ; Haoran LI ; Chan LI ; Peng WU ; Yao TONG ; Dongfeng DUAN ; Guoqiang BAO
Chinese Journal of Surgery 2024;62(5):406-411
Objective:To explore the application value of a novel separated magnetic-controlled forceps in transumbilical single-incision laparoscopic cholecystectomy (SILC).Methods:This is a prospective case series study. Data from patients who underwent SILC at the Department of General Surgery, the Second Affiliated Hospital of Air Force Medical University from March to August 2023 were prospectively collected, based on inclusion and exclusion criteria. All patients underwent cholecystectomy assisted by a novel separated magnetic-controlled forceps. Surgical time, intraoperative blood loss, the need for additional incisions during surgery, and the length of hospital stay were recorded to assess surgical difficulty and effectiveness. Postoperative pain scores and complications were documented to evaluate the safety of the procedure. The collaboration experience of the surgeon and assistant was evaluated using a 5-point Likert scale to assess the feasibility of this surgical approach. Informed consent was obtained from all patients in accordance with medical ethical regulations. Patients were followed up through outpatient visits or telephone calls, with follow-up at 7 days and 1 month after surgery, and evaluation of incisional scar healing and completion of satisfaction questionnaires. Follow-up was conducted until September 30, 2023.Results:A total of 45 patients were included in the study,including 19 males and 26 females,aged (42.7±4.2)years(range:32 to 61 years). The difficulty of the operation was evaluated as grade 1 or 2 in 38 cases(84.4%) and grade 3 in 7 cases(15.6%). Operation time was (37.3±5.3) minutes(range: 25 to 80 minutes),and intraoperative blood loss( M(IQR)) was 17.8(35.0) ml (range:10 to 60 ml). All surgical procedures proceeded smoothly without intraoperative incidents, and the overall satisfaction of the surgeon and assistants was high. All patients underwent successful day surgery management and were discharged within 48 hours of hospitalization. The postoperative pain scores at 1, 7, and 30 days were 3 (4), 1 (3), and 0 (2), respectively. The follow-up time was 5.0(2.2) weeks (range: 3 to 7 weeks), with no occurrence of grade 3 to 4 adverse reactions, and the patients were satisfied with the cosmetic effect of the umbilical incision. Conclusions:The novel separated magnetic-controlled forceps can be applied in transumbilical SILC. It has the advantages of convenient operation, and patients are satisfied with the surgical results.
5.Clinical application of a novel separated magnetic controlled forceps assisted single-incision laparoscopic cholecystectomy
Wei XIN ; Zhenyu YANG ; Haoran LI ; Chan LI ; Peng WU ; Yao TONG ; Dongfeng DUAN ; Guoqiang BAO
Chinese Journal of Surgery 2024;62(5):406-411
Objective:To explore the application value of a novel separated magnetic-controlled forceps in transumbilical single-incision laparoscopic cholecystectomy (SILC).Methods:This is a prospective case series study. Data from patients who underwent SILC at the Department of General Surgery, the Second Affiliated Hospital of Air Force Medical University from March to August 2023 were prospectively collected, based on inclusion and exclusion criteria. All patients underwent cholecystectomy assisted by a novel separated magnetic-controlled forceps. Surgical time, intraoperative blood loss, the need for additional incisions during surgery, and the length of hospital stay were recorded to assess surgical difficulty and effectiveness. Postoperative pain scores and complications were documented to evaluate the safety of the procedure. The collaboration experience of the surgeon and assistant was evaluated using a 5-point Likert scale to assess the feasibility of this surgical approach. Informed consent was obtained from all patients in accordance with medical ethical regulations. Patients were followed up through outpatient visits or telephone calls, with follow-up at 7 days and 1 month after surgery, and evaluation of incisional scar healing and completion of satisfaction questionnaires. Follow-up was conducted until September 30, 2023.Results:A total of 45 patients were included in the study,including 19 males and 26 females,aged (42.7±4.2)years(range:32 to 61 years). The difficulty of the operation was evaluated as grade 1 or 2 in 38 cases(84.4%) and grade 3 in 7 cases(15.6%). Operation time was (37.3±5.3) minutes(range: 25 to 80 minutes),and intraoperative blood loss( M(IQR)) was 17.8(35.0) ml (range:10 to 60 ml). All surgical procedures proceeded smoothly without intraoperative incidents, and the overall satisfaction of the surgeon and assistants was high. All patients underwent successful day surgery management and were discharged within 48 hours of hospitalization. The postoperative pain scores at 1, 7, and 30 days were 3 (4), 1 (3), and 0 (2), respectively. The follow-up time was 5.0(2.2) weeks (range: 3 to 7 weeks), with no occurrence of grade 3 to 4 adverse reactions, and the patients were satisfied with the cosmetic effect of the umbilical incision. Conclusions:The novel separated magnetic-controlled forceps can be applied in transumbilical SILC. It has the advantages of convenient operation, and patients are satisfied with the surgical results.
6.In vitro inhibition of carnosic acid against influenza A virus infections
Hai-ying PENG ; Ze-xin LIU ; Xia YANG ; Dian QIU ; Wei-xin JIA ; Wen-bao QI ; Jian-xin CHEN ; Li WU
Acta Pharmaceutica Sinica 2023;58(2):360-370
Carnosic acid (CA) is the main phenolic diterpenoid active ingredient in plants such as rosemary and sage, and has antiviral, antioxidant, anti-inflammatory effects and so on, however, its antiviral activity against influenza virus infections was not reported. In this study, antiviral activities against influenza A virus infections of three main bioactive ingredients from rosemary, including rosmarinic acid, CA and ursolic acid, were evaluated using virus titer titration assay, and CA showed remarkable inhibition on influenza H5N1 replication in A549 cells. The antiviral activity of CA was further confirmed and its mechanism of action was investigated using the indirect immunofluorescence assay (IFA), Western blot and real-time fluorescence quantification polymerase chain reaction (qRT-PCR). The results showed that the 50% effective concentration (EC50) of CA against influenza H5N1 in A549 cells and MDCK cells were 4.30 and 3.64 μmol·L-1, respectively. Meanwhile, CA also showed inhibition on influenza virus 2009panH1N1 (EC50: 10.1 μmol·L-1) and H3N2 (EC50: 12.8 μmol·L-1) replications in A549 cells. Mechanistic studies showed that antiviral activity of CA is related to its induction of heme oxygenase-1 (HO-1) in A549 cells and suppression on production of reactive oxygen in H5N1-infected cells.
7.Pathogenesis and staging treatment for non-specific low back pain based on the meridian sinew theory.
Jia-Xin SHI ; Bao-Qiang DONG ; Zheng ZOU ; Xi WU
Chinese Acupuncture & Moxibustion 2023;43(3):336-340
Based on the physiological and pathological characteristics of meridian sinew theory, the staging treatment of non-specific low back pain (NLBP) is explored to provide the reference of clinical practice. The twelve meridian sinews of the human body communicate with the bones and joints of the whole body, which governs the movement, body protection and defense, and meridian regulation. Physiologically, the meridian sinew maintains the functions of the lumbar region. In pathology, the meridian sinew may encounter stasis and pain, contraction and spasm or "transverse collateral" formation. According to the pathological staging of meridian sinew disorders, the progress of NLBP is divided into 3 phases and the corresponding treatments are provided. Mild stimulation and rapid analgesia is suggested to promote tissue repair at the early phase; muscle spasm is relieved to adjust muscular status at the middle phase; and the "cord-like" muscle foci is removed at the later phase of the disease.
Humans
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Low Back Pain
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Meridians
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Pain Management
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Analgesia
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Lumbosacral Region
8.A case of pulmonary aspergillus infection in underground coal mine workers.
Cheng Xia WANG ; Lu QIU ; Xin Shu WU ; Hong Xiang ZHANG ; Zhen Bao XU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(3):228-230
The underground environment is dark and humid, and it is easy to breed pathogenic microorganisms. A lump in the right lung of a coal mine underground transport worker was found druing occupational health examination. CT examination showed that the lump was located in the posterior segment of the upper lobe of the right lung, with point strip calcification, liquefaction necrosis, and proximal bronchial stenosis and occlusion. MRI examination FS-T(2)WI and DWI showed "target sign", annular low signal around the central high signal, and low mixed signal around the periphery, and annular high signal in the isosignal lesions on T(1)WI. Then the pulmonary aspergillus infection was confirmed by pathology.
Humans
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Coal
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Miners
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Pneumonia
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Lung
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Aspergillosis
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Coal Mining
9.Clinical research of less invasive surfactant administration combined with nasal intermittent positive pressure ventilation in preterm infants with respiratory distress syndrome
Bao JIN ; Bin ZHOU ; Xiuhui MA ; Jiebin WU ; Yun WANG ; Xin ZHANG
Chinese Journal of Emergency Medicine 2023;32(6):748-754
Objective:To evaluate the efficacy and safety of less invasive surfactant administration (LISA) combined with nasal intermittent positive pressure ventilation (NIPPV) in the treatment of infants with respiratory distress syndrome (RDS).Methods:A prospective study was conducted on preterm infants of gestational age ≤34 weeks with RDS who were admitted to the Neonatal Intensive Care Unit of Xuzhou Central Hospital from October 2019 to November 2021. The infants were randomly assigned into the LISA+NIPPV group and the intubation-surfactant-extubation (INSURE) +nasal continuous positive airway pressure (NCPAP) group. In the LISA+NIPPV group, with the support of NIPPV, a Lisa tube was inserted through the vocal cords under direct vision with direct laryngoscope, and then pulmonary surfactant (PS) was infused into the lung. In the INSURE+NCPAP group, the patients were endotracheally intubated and infused with PS into the lung through endotracheal tube, then extubated and continued to receive NCPAP therapy (INSURE). The blood gas analysis at 1 h and 6 h after PS infusion, the adverse reactions during injection, clinical efficacy, bronchopulmonary dysplasia (BPD) and other related complications were compared between the two groups.Results:A total of 112 preterm infants with RDS were enrolled, including 58 in the LISA+NIPPV group and 54 in the INSURE+NCPAP group. The blood oxygen partial pressure (PaO 2) and PaO 2/FiO 2 (P/F) in the LISA+NIPPV group were significantly higher than those in the INSURE+NCPAP group at 1 h and 6 h after PS infusion, while carbon dioxide partial pressure (PaCO 2) were significantly lower than that in the INSURE+NCPAP group, and the differences were statistically significant (all P<0.05). The rate of tracheal intubation within 72 h (15.5% vs. 33.3%), the duration of non-invasive ventilation [ (7.5 ± 4.3) d vs.(9.9 ± 5.5) d ], total oxygen inhaling [ (10.5 ± 3.5) d vs.(13.3 ± 4.1) d ], failure rate of machine withdrawal (8.6% vs. 31.0% ), the times of apnea [7.0 (3.0-21.0) times vs. 15.0 (4.0-28.0) times ] and re-administration of PS (17.2% vs. 33.3%) in the LISA+NIPPV group were significantly lower than those in the INSURE+NCPAP group, and the differences were statistically significant ( P<0.05). The incidence of regurgitation in the LISA+NIPPV group was lower than that in the INSURE+NCPAP group (13.8% vs. 35.2%), and the difference was statistically significant ( P<0.05). There was no significant difference in the time needed for intubation between the two groups ( P>0.05). The occurrence of BPD in the LISA+NIPPV group was significantly lower than that in the INSURE+NCPAP group (10.3% vs. 25.9%), and there was no significant difference in other related complication between the two groups (all P>0.05). Conclusions:LISA combined with NIPPV in the treatment of preterm infants with RDS can effectively improve oxygenation, reduce carbon dioxide retention, reduce the mechanical ventilation rate, shorten the duration of noninvasive mechanical ventilation, and reduce the incidence of BPD.
10.Triaging patients in the outbreak of COVID-2019
Guo-Qing HUANG ; Wei-Qian ZENG ; Wen-Bo WANG ; Yan-Min SONG ; Xiao-Ye MO ; Jia LI ; Ping WU ; Ruo-Long WANG ; Fang-Yi ZHOU ; Jing WU ; Bin YI ; Zeng XIONG ; Lu ZHOU ; Fan-Qi WANG ; Yang-Jing TIAN ; Wen-Bao HU ; Xia XU ; Kai YUAN ; Xiang-Min LI ; Xin-Jian QIU ; Jian QIU ; Ai-Min WANG
Chinese Journal of Infection Control 2023;22(3):295-303
In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50%of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.

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