Progress of electromagnetic navigation bronchoscopy in diagnosis and treatment of pulmonary nodules / 实用医学杂志

With the popularity of low-dose computed tomography(LDCT)in physical examination and the widespread concern of people about lung diseases after COVID-19 outbreak,the detection rate of pulmonary nodules in the population has increased year by year.The clinical cases of early lung cancer and multiple primary lung cancer are increasing,and the necessity of personalized treatment tailored to the diverse detection of pulmonary nodules is highlighted in the diagnosis and treatment process of pulmonary nodules.However,chest CT and traditional bron-choscopy not only have insufficient accuracy in preoperative localization of pulmonary nodules and the diagnosis of benign and malignant pulmonary nodules,but also have significant limitations in the diagnosis and treatment of patients who cannot undergo surgery.The emergence of electromagnetic navigation bronchoscopy(ENB)has greatly solved this problem and further improves the diagnosis and treatment process of pulmonary nodules.ENB is a new technology that relies on electromagnetic positioning technology to locate,biopsy,and minimally invasive treatment of pulmonary nodules through bronchoscopy.In this review,we mainly summarize the application and latest progress of ENB in the diagnosis and treatment of pulmonary nodules.

Expression and in vitro activity of a neutralizing antibody against West Nile virus that reduces antibody-dependent enhancement / 中华微生物学和免疫学杂志

Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.

Advancements in the Diagnosis and Treatment of Rare Kidney Diseases / 罕见病研究

Rare kidney diseases constitute a significant factor leading to kidney failure with many having a hereditary basis. The incidence of inherited disorders contributing to adult chronic kidney disease is lower compared to that in children; however, up to 10% of adult patients with chronic kidney disease are affected by a single-gene pathogenic variant. Over the past decade, sequencing technologies have become widely utilized in clinical settings, undergoing continuous iterations and updates to enhance the diagnosis of rare kidney diseases. Simultaneously, the field confronts numerous challenges, particularly in the development and application of novel therapeutic drugs. In an era crucial development, China is set to publish rare disease catalogs in 2018 and 2023, a move that holds the promise of comprehensively advancing the diagnosis, treatment, and research of rare kidney diseases in the country.

Using Liquid Chromatography-Tandem Mass Spectrometry in Detecting Plasma Lyso-GL3 Levels in Patients with Fabry Disease and the Association Analysis of Phenotype-Genotype of the Disease / 罕见病研究

ObjectiveUsing the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the plasma level of Lyso-GL3 in patients with Fabry disease and to analyze the clinical application of the method.MethodsThirty-nine patients with a genetic diagnosis of Fabry disease were included, and plasma levels of Lyso-GL3 were measured by LC-MS/MS analysis, and detailed clinical information of the patients was obtained including: α-galactosidase A activity, genetic variants, quantification of urine protein, mean arterial pressure, and estimation of glomerular filtration rate, and the differences in the levels of Lyso-GL3 in different clinical phenotypes and genotypes were statistically analyzed, as well as the association with clinical indicators.ResultsLyso-GL3 showed good linearity within 0.7856-400 ng/mL(r=0.9992).Further analysis of 39 Fabry disease patients diagnosed in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine showed a median Lyso-GL3 concentration of 23.6 ng/mL(4.3-92.9 ng/mL); Lyso-GL3 levels were significantly higher in patients with both the frameshift and the splicing mutations, as well as in patients with the nonsense mutations, than in patients with the missense mutations (median value 119.7 ng/mL vs. 11.9 ng/mL, P=0.006, and median value 97.0 ng/mL vs. 11.9 ng/mL, P=0.015, respectively). Whereas, association analysis revealed that Lyso-GL3 was not significantly associated with urinary protein, mean arterial pressure and estimated glomerular filtration rate.ConclusionsThe using of LC-MS/MS to quantify plasma Lyso-GL showed significant differences in Lyso-GL3 concentrations between classical and atypical phenotypes, suggesting that plasma Lyso-GL3 may help with clinical phenotypes. However, Lyso-GL3 levels is found to be overlapped between genotypes. No significant linear correlation was found between Lyso-GL3 and renal clinical indicators, suggesting the urgent need in finding a more accurate tool to assess renal involvement and prognosis in patients with Fabry disease.

Traditional Chinese Medicine Intervention in Acute Pancreatitis Based on TLR4 Signaling Pathway： A Review / 中国实验方剂学杂志

Acute pancreatitis （AP） is one of the most clinically common acute digestive disorders characterized by quick onset，rapid progression，severe condition，and high mortality. If the disease is not timely intervened in the early stage，it can develop into severe AP in the later stage，which damages the long-term quality of life and brings serious economic burden to patients and their families. However， the pathogenesis of this disease is complex and has not been fully explained. The generation and development of AP is closely related to many signaling pathways. Among them，Toll-like receptor 4（TLR4），as a transmembrane signal transduction receptor，can mediate immune response and inflammatory response，and play a key role in the occurrence and development of AP. Traditional Chinese medicine（TCM）can regulate the TLR4 signaling pathway with multiple targets，multiple effects，and multiple administration methods to inhibit inflammatory response，and effectively intervene in the progression of AP， which has gradually become a new craze for preventing and treating AP. Many studies have shown that TCM has obvious advantages in the prevention and treatment of AP. It can effectively treat AP by regulating TLR4 signaling pathway，strengthening immune resistance and defense，and inhibiting inflammatory response. Despite of the research progress，there is still a lack of comprehensive review on TCM regulation of TLR4 signaling pathway in the treatment of AP. Therefore，the literature on TCM regulation of TLR4 signaling pathway published in recent years was systematically reviewed and elaborated，aiming to provide new ideas for the treatment of AP and further drug development.

Advancements in the Diagnosis and Treatment of Rare Kidney Diseases / 罕见病研究

Rare kidney diseases constitute a significant factor leading to kidney failure with many having a hereditary basis. The incidence of inherited disorders contributing to adult chronic kidney disease is lower compared to that in children; however, up to 10% of adult patients with chronic kidney disease are affected by a single-gene pathogenic variant. Over the past decade, sequencing technologies have become widely utilized in clinical settings, undergoing continuous iterations and updates to enhance the diagnosis of rare kidney diseases. Simultaneously, the field confronts numerous challenges, particularly in the development and application of novel therapeutic drugs. In an era crucial development, China is set to publish rare disease catalogs in 2018 and 2023, a move that holds the promise of comprehensively advancing the diagnosis, treatment, and research of rare kidney diseases in the country.

Using Liquid Chromatography-Tandem Mass Spectrometry in Detecting Plasma Lyso-GL3 Levels in Patients with Fabry Disease and the Association Analysis of Phenotype-Genotype of the Disease / 罕见病研究

ObjectiveUsing the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the plasma level of Lyso-GL3 in patients with Fabry disease and to analyze the clinical application of the method.MethodsThirty-nine patients with a genetic diagnosis of Fabry disease were included, and plasma levels of Lyso-GL3 were measured by LC-MS/MS analysis, and detailed clinical information of the patients was obtained including: α-galactosidase A activity, genetic variants, quantification of urine protein, mean arterial pressure, and estimation of glomerular filtration rate, and the differences in the levels of Lyso-GL3 in different clinical phenotypes and genotypes were statistically analyzed, as well as the association with clinical indicators.ResultsLyso-GL3 showed good linearity within 0.7856-400 ng/mL(r=0.9992).Further analysis of 39 Fabry disease patients diagnosed in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine showed a median Lyso-GL3 concentration of 23.6 ng/mL(4.3-92.9 ng/mL); Lyso-GL3 levels were significantly higher in patients with both the frameshift and the splicing mutations, as well as in patients with the nonsense mutations, than in patients with the missense mutations (median value 119.7 ng/mL vs. 11.9 ng/mL, P=0.006, and median value 97.0 ng/mL vs. 11.9 ng/mL, P=0.015, respectively). Whereas, association analysis revealed that Lyso-GL3 was not significantly associated with urinary protein, mean arterial pressure and estimated glomerular filtration rate.ConclusionsThe using of LC-MS/MS to quantify plasma Lyso-GL showed significant differences in Lyso-GL3 concentrations between classical and atypical phenotypes, suggesting that plasma Lyso-GL3 may help with clinical phenotypes. However, Lyso-GL3 levels is found to be overlapped between genotypes. No significant linear correlation was found between Lyso-GL3 and renal clinical indicators, suggesting the urgent need in finding a more accurate tool to assess renal involvement and prognosis in patients with Fabry disease.

Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine (version 2024) / 中华创伤杂志

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Gene mutation profiles and clinicopathological features of patients with non-small cell lung cancer harboring KRAS G12C mutation: a single-center retrospective study / 中华病理学杂志

Objective: To accurately screen non-small cell lung cancer (NSCLC) patients with KRAS G12C mutation and to evaluate their clinicopathological features, prognostic factors and current treatment status. Methods: A total of 19 410 NSCLC cases diagnosed at the Department of Pathology of Shanghai Chest Hospital, Shanghai, China from January 2018 to September 2021 were retrospectively reviewed, and the cases with KRAS gene mutation detected by next-generation sequencing were included. The clinicopathological and genetic mutation data of these cases were collected and analyzed. Results: A total of 1 633 (8.4%) NSCLC patients carried a KRAS gene mutation, among whom G12C was the most frequent (468 cases, 28.7%) mutant subtype. The mutation was more commonly found in males (414/468, 88.5%), patients with a history of smoking (308/468, 65.8%), and patients with a pathological type of invasive adenocarcinoma (231/468, 49.4%). The most common co-mutated genes in KRAS G12C mutant NSCLC were TP53 (52.4%, 245/468), STK11 (18.6%, 87/468) and ATM (13.2%, 62/468). The proportion of PD-L1 expression (≥1%) in KRAS G12C mutant NSCLC was significantly higher than that in patients without G12C mutation [64.3% (90/140) vs. 56.1% (193/344), P=0.014]. Immune checkpoint inhibitors (ICIs) treatment significantly prolonged progression-free survival (PFS) in NSCLC patients (10.0 months vs. 5.0 months, P=0.011). However, combination of chemotherapy and ICIs with anti-angiogenesis inhibitors or multi-target inhibitors did not significantly improve PFS in patients with KRAS G12C mutant NSCLC (P>0.05). Patients with KRAS G12C mutation NSCLC treated with ICIs and KRAS G12C patients with TP53 mutation had significantly longer median PFS than those with STK11 mutation (9.0 months vs. 4.3 months, P=0.012). Conclusions: Patients with KRAS G12C mutant NSCLC have relatively higher levels of PD-L1 expression and can benefit from ICIs treatment. The feasibility of chemotherapy, ICIs therapy and their combination needs further investigation.

TRPV4-induced Neurofilament Injury Contributes to Memory Impairment after High Intensity and Low Frequency Noise Exposures / 生物医学与环境科学（英文）

OBJECTIVE@#Exposure to high intensity, low frequency noise (HI-LFN) causes vibroacoustic disease (VAD), with memory deficit as a primary non-auditory symptomatic effect of VAD. However, the underlying mechanism of the memory deficit is unknown. This study aimed to characterize potential mechanisms involving morphological changes of neurons and nerve fibers in the hippocampus, after exposure to HI-LFN.@*METHODS@#Adult wild-type and transient receptor potential vanilloid subtype 4 knockout (TRPV4-/-) mice were used for construction of the HI-LFN injury model. The new object recognition task and the Morris water maze test were used to measure the memory of these animals. Hemoxylin and eosin and immunofluorescence staining were used to examine morphological changes of the hippocampus after exposure to HI-LFN.@*RESULTS@#The expression of TRPV4 was significantly upregulated in the hippocampus after HI-LFN exposure. Furthermore, memory deficits correlated with lower densities of neurons and neurofilament-positive nerve fibers in the cornu ammonis 1 (CA1) and dentate gyrus (DG) hippocampal areas in wild-type mice. However, TRPV4-/- mice showed better performance in memory tests and more integrated neurofilament-positive nerve fibers in the CA1 and DG areas after HI-LFN exposure.@*CONCLUSION@#TRPV4 up-regulation induced neurofilament positive nerve fiber injury in the hippocampus, which was a possible mechanism for memory impairment and cognitive decline resulting from HI-LFN exposure. Together, these results identified a promising therapeutic target for treating cognitive dysfunction in VAD patients.

Clinical study of using basement membrane biological products in pelvic floor reconstruction during pelvic exenteration / 中华胃肠外科杂志

Objective: To investigate the value of reconstruction of pelvic floor with biological products to prevent and treat empty pelvic syndrome after pelvic exenteration (PE) for locally advanced or recurrent rectal cancer. Methods: This was a descriptive study of data of 56 patients with locally advanced or locally recurrent rectal cancer without or with limited extra-pelvic metastases who had undergone PE and pelvic floor reconstruction using basement membrane biologic products to separate the abdominal and pelvic cavities in the Department of Anorectal Surgery of the Second Affiliated Hospital of Naval Military Medical University from November 2021 to May 2022. The extent of surgery was divided into two categories: mainly inside the pelvis (41 patients) and including pelvic wall resection (15 patients). In all procedures, basement membrane biologic products were used to reconstruct the pelvic floor and separate the abdominal and pelvic cavities. The procedures included a transperitoneal approach, in which biologic products were used to cover the retroperitoneal defect and the pelvic entrance from the Treitz ligament to the sacral promontory and sutured to the lateral peritoneum, the peritoneal margin of the retained organs in the anterior pelvis, or the pubic arch and pubic symphysis; and a sacrococcygeal approach in which biologic products were used to reconstruct the defect in the pelvic muscle-sacral plane. Variables assessed included patients' baseline information (including sex, age, history of preoperative radiotherapy, recurrence or primary, and extra-pelvic metastases), surgery-related variables (including extent of organ resection, operative time, intraoperative bleeding, and tissue restoration), post-operative recovery (time to recovery of bowel function and time to recovery from empty pelvic syndrome), complications, and findings on follow-up. Postoperative complications were graded using the Clavien-Dindo classification. Results: The median age of the 41 patients whose surgery was mainly inside the pelvis was 57 (31-82) years. The patients comprised 25 men and 16 women. Of these 41 patients, 23 had locally advanced disease and 18 had locally recurrent disease; 32 had a history of chemotherapy/immunotherapy/targeted therapy and 24 of radiation therapy. Among these patients, the median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to resolution of empty pelvic syndrome were 440 (240-1020) minutes, 650 (200-4000) ml, 3 (1-9) days, and 14 (5-105) days, respectively. As for postoperative complications, 37 patients had Clavien-Dindo < grade III and four had ≥ grade III complications. One patient died of multiple organ failure 7 days after surgery, two underwent second surgeries because of massive bleeding from their pelvic floor wounds, and one was successfully resuscitated from respiratory failure. In contrast, the median age of the 15 patients whose procedure included combined pelvic and pelvic wall resection was 61 (43-76) years, they comprised eight men and seven women, four had locally advanced disease and 11 had locally recurrent disease. All had a history of chemotherapy/ immunotherapy and 13 had a history of radiation therapy. The median operative time, median intraoperative bleeding, median time to recovery of bowel function, and median time to relief of empty pelvic syndrome were 600 (360-960) minutes, 1600 (400-4000) ml, 3 (2-7) days, and 68 (7-120) days, respectively, in this subgroup of patients. Twelve of these patients had Clavien-Dindo < grade III and three had ≥ grade III postoperative complications. Follow-up was until 31 October 2022 or death; the median follow-up time was 9 (5-12) months. One patient in this group died 3 months after surgery because of rapid tumor progression. The remaining 54 patients have survived to date and no local recurrences have been detected at the surgical site. Conclusion: The use of basement membrane biologic products for pelvic floor reconstruction and separation of the abdominal and pelvic cavities during PE for locally advanced or recurrent rectal cancer is safe, effective, and feasible. It improves the perioperative safety of PE and warrants more implementation.

Effects of intensive pharmaceutical intervention led by clinical pharmacists on the risk of ischemic stroke in hypertensive patients / 中国药房

OBJECTIVE To explore the effects of intensive pharmaceutical intervention led by clinical pharmacists on hypertension patients with medium and high risk of ischemic stroke. METHODS The hypertension outpatients with medium and high risk of ischemic stroke， who were assessed by the modified Framingham stroke scale in Zhengzhou People’s Hospital from Oct. 2019 to Apr. 2020， were randomly divided into control group and intervention group， with 200 cases in each group. Patients in the control group received conventional treatment without pharmaceutical intervention； on the basis of conventional treatment， patients in the intervention group received 12-month intensive pharmaceutical intervention （grading management of compliance+ regular follow-up， involving medication education and guidance， blood glucose， blood pressure， blood lipid management and healthy life guidance） provided by clinical pharmacists. The blood glucose indexes， blood lipid indexes， blood pressure compliance rate， medication compliance， 10-year stroke risk and stroke incidence were compared between two groups at baseline and 12 months after enrollment. RESULTS After 12 months of enrollment， the level of low-density lipoprotein cholesterol （LDL-C） in intervention group was significantly lower than that in the same group at baseline， and the levels of fasting blood glucose， glycosylated hemoglobin， total cholesterol and LDL-C in intervention group were significantly lower than those in control group at the same time points （P＜0.05 or P＜0.01）. The compliance rate of blood pressure and medication compliance in intervention group were significantly higher or better than those in control group （P＜0.01）. There were 12 and 15 patients in control group and intervention group turned into low-risk ones respectively， and the proportion of high-risk patients in intervention group was significantly lower than that in control group（P＜0.01）， while the proportion of medium-risk patients was significantly higher than that in control group（P＜0.05）； the incidence of stroke in intervention group was significantly lower than that in control group （1.0% vs. 4.5%， P＜0.05）. CONCLUSIONS The pharmaceutical intensive intervention led by clinical pharmacists can reduce blood glucose and blood lipid levels of hypertensive outpatients， improve their blood pressure compliance rate and medication compliance， and help reduce the risk of stroke.

Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C / 药物分析学报

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.

Fabry disease: recent advances in precision treatment / 中华肾脏病杂志

Fabry disease is a X-linked inherited lysosomal storage disease. The pathogenesis is that mutations in the GLA gene lead to the decrease or lack of α-galactosidase A activity, followed by the accumulation of substrate and its intermediate metabolites in cells and tissues, eventually leading to multiple organ injury. The rise of specific treatment and gene technology pushes the application of precision medicine in patients with Fabry disease. As a milestone in the specific treatment of Fabry disease, enzyme replacement therapy can delay disease progression and improve quality of life, but not all carriers with GLA mutation need intervention immediately, and indeed individualized treatment is required. However, enzyme-enhanced therapy is only suitable for "amenable mutations" and has clinical application limitation. Therefore, new treatments such as substrate reduction therapy, second-generation enzyme replacement therapy, and gene therapy are already undergoing clinical trials, expected to bring new gospel to Fabry disease patients. This article will review development of precision treatment on Fabry disease, providing the basis of individualized treatment for the drug selection and prevention of side effect. The expectation is to drive future therapeutic strategies toward precision-based treatment.

Establishment of an in vivo neutralization model based on H5N1 pseudovirus / 中华微生物学和免疫学杂志

Objective:To establish an in vivo infection model of H5N1 pseudovirus and to detect the neutralizing activity of FHA3 antibody using this model. Methods:Based on the sequence information of hemagglutinin (HA) and neuraminidase (NA) of A/Anhui/1/2005/H5N1 strain, two recombinant plasmids of pcDNA3.1-HA5 and pcDNA3.1-NA1 were constructed. The two plasmids and plasmid pNL4-3.Luc.R-E- were co-transfected into 293T cells to prepare H5N1 pseudovirus supernatant. The morphology of pseudovirus particles in the supernatant was observed by electron microscopy. MDCK cells were infected with the pseudovirus supernatant and the virus titer was detected. BALB/c mice were injected with the pseudovirus supernatant by intraperitoneal injection and subjected to bioluminescence imaging at 2, 5, 8, and 12 d after infection to detect the pseudovirus infection in vivo. The functional activity of FHA3 antibody in vivo was evaluated using the established mouse infection model. Results:The recombinant plasmids pcDNA3.1-HA5 and pcDNA3.1-NA1 were correctly constructed and could be used to prepare pseudovirus supernatants of high titer by co-transfecting 293T cells with the plasmid pNL4-3.Luc.R-E-. The virus particles were round under electron microscope. H5N1 pseudovirus-infected mice exhibits strong fluorescence signals, which were attenuated by FHA3 treatment before challenge.Conclusions:The in vivo infection model of H5N1 pseudovirus was successfully constructed and FHA3 antibody was proved to be protective against the pseudovirus infection.

Research progress in optimization of therapeutic effect of antibodies against flavivirus / 中华微生物学和免疫学杂志

Flaviviruses are a class of positive-strand RNA viruses mainly transmitted by arthropods, which can cause high mortality and morbidity worldwide. At present, there is no specific therapy. Therapeutic antibodies bring hope for the treatment of flavivirus infection, but the antibody-dependent enhancement (ADE) effect induced by flavivirus infection can lead to disease progression. The ideal therapeutic antibodies against flaviviruses should not only treat flavivirus infection, but also avoid the harm caused by ADE. Therefore, researchers have optimized some of the antibodies to seek the best therapeutic antibodies. This review briefly described the research progress and mechanism of therapeutic antibodies against flaviviruses as well as some strategies to reduce the ADE effect induced by the therapeutic antibodies.

Postoperative hypoalbuminemia in patients with acute ischemic stroke with successful recanalization by endovascular therapy: risk factors and their impact on outcomes / 国际脑血管病杂志

Objective:To investigate the risk factors of hypoalbuminemia (HA) in patients with acute ischemic stroke (AIS) caused by large vessel occlusion (LVO) after endovascular mechanical thromboectomy (EMT) and impact on outcomes.Methods:Patients first diagnosed with anterior circulation LVO-AIS and underwent emergency EMT at the Department of Acute Stroke, the Affiliated Hospital of Jining Medical University from June 1, 2020 to April 31, 2023 were retrospectively included. According to the first follow-up serum albumin examination after procedure (6-8 d), the patients were divided into HA group (<35 g/L) and non-HA group (≥35 g/L). According to the modified Rankin Scale score at 90 d after EMT, the patients were divided into a good outcome group (0-2) and a poor outcome group (3-6). Univariate and multivariate logistic analysis was used to determine independent risk factors for HA after EMT and their impact on outcomes. Results:A total of 144 patients were enrolled, including 107 males (74.30%) with a median age of 64 years (interquartile range, 56-71 years). There were 50 patients (34.72%) in the HA group and 94 (65.28%) in the non-HA group; 60 (41.67%) in the good outcome group, and 84 (58.33%) in the poor outcome group. Multivariate logistic regression analysis showed that age (odds ratio [ OR] 1.061, 95% confidence interval [ CI] 1.014-1.111; P=0.011) and pulmonary infection ( OR 5.136, 95% CI 1.917-13.760; P=0.001) were independent risk factors for HA; HA ( OR 4.345, 95% CI 1.367-13.814; P=0.013), pneumonia ( OR 5.113, 95% CI 1.217-12.528; P=0.026), and onset to reperfusion time ( OR 5.473, 95% CI 1.090-16.05; P=0.038) were independent risk factors for poor outcomes. Conclusions:Age and pulmonary infection are independent risk factors for HA in LVO-ASI patients after EMT, and HA is the independent risk factor for poor outcomes of the patients.

Monoclonal antibody targeting mu-opioid receptor attenuates morphine tolerance via enhancing morphine-induced receptor endocytosis / 药物分析学报

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.

Pharmaceutical care of patients with antithrombotic therapy after transjugular intrahepatic portal shunt / 中国临床药理学与治疗学

AIM: To explore the role of clinical pharmacist in the treatment of patients with transjugular intrahepatic portosystemic shunt. METHODS: Clinical pharmacist participated in the treatment of a patient with repeated oral bleeding after transjugular intrahepatic portal shunt followed treatment with multiple antithrombotic drugs, which assisted the physician to diagnose and adjust the antithrombotic treatment plan as well as provided the patient with whole-process pharmaceutical care and online management. RESULTS: Based on the inquiry about the patient's past and current medical history and medication consumption, the pharmacist considered that there was weak correlation between oral hemorrhage and antithrombotic drugs and advised for dentist inspection. Thereafter, the patient was diagnosed with chronic gingivitis. The dosage of warfarin was adjusted, and the pharmacists managed it online after discharge to achieve stable INR of the patient. In the later online follow-up, an abnormal increase of INR was encountered, By asking about the history of medication, it was considered that the increase in INR was related to taking amoxicillin capsules. Therefore, the pharmacist suggested to stop amoxicillin capsule and to gradually adjust the dose of warfarin to the original level to improve the treatment. CONCLUSION: The involvement of clinical pharmacists in clinical treatment facilitates comprehensive pharmaceutical care of patients, which plays a positive role in the efficacy and safety of medication therapy.

Clinical evaluation of the efficacy against helicobacter pylori by amoxicillin from volume-based procurement and potassium amoxicillin clavulanate / 中国临床药理学与治疗学

AIM: To evaluate the clinical efficacy of amoxicillin from volume-based procurement (VBP) and potassium amoxicillin clavulanate in the eradication of helicobacter pylori (Hp) infection, providing basis for the selection of treatment programs. METHODS: Data from the patients who received Hp eradication therapy from May 2021 to May 2022 were recruited from the rational drug use management system. The data from the patients treated by amoxicillin (amoxicillin 1.0 g bid + bismuth potassium citrate 220 mg bid + esomeprazole 20 mg bid + clarithromycin 0.5 g bid, for 14 days) and potassium amoxicillin clavulanate (potassium amoxicillin clavulanate 0.914 g bid + bismuth potassium citrate 220 mg bid + esomeprazole 20 mg bid + clarithromycin 0.5 g bid, for 14 days) were selected and compared. RESULTS: A total of 171 cases were collected in the group treated by Amoxicillin program, and the eradication rate was 87.8% (150/171). A total of 69 cases were collected in the group of potassium amoxicillin clavulanate, and the eradication rate was 76.8% (53/69). There was no significant difference in baseline data between the two groups (P>0.05). There was a significant difference in clinical efficacy between the two groups (P< 0.05). In addition, the cost-effectiveness ratio (C/E) of the Amoxicillin treatment program was lower than that of the potassium amoxicillin clavulanate program CONCLUSION: The clinical efficacy of VBP Amoxicillin program in eradicating Hp infection is better than that of the potassium amoxicillin clavulanate program, which is worthy of clinical recommendation.