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OBJECTIVE: Lower limb discrepancy (LLD) was frequently observed in patients with idiopathic scoliosis (IS), potentially associated with etiopathogenesis. Although sole lifts had been proposed as a conservative treatment for IS, evidence supporting their efficacy was limited. This study aimed to assess the effects of sole lift intervention on pediatric patients with mild IS, specifically focusing on thoracolumbar/lumbar (TL/L) curvature. METHODS: Twenty patients, with an average age of 12.3 ± 3.1 years and presenting mild TL/L curve (15.6° ± 6.2°), were selected from a pool of 267 pediatric IS patients in the outpatient of our spine center from February 2023 to August 2023. Inclusion criteria comprised a main TL/L curve ranging between 10° and 40°, the lower limb positioned at the convexity of the main curve, and LLD of less than 2 cm; individuals requiring bracing or surgical intervention were excluded. Custom sole lifts were used to address the shorter lower limb with the objective of leveling the pelvis. Radiographic evaluations were conducted both before and after intervention using standing full spine posteroanterior radiographs and full leg length radiographs. Statistical analysis was undertaken to evaluate curve correction and its associations with other influencing factors. RESULTS: The mean structural and functional LLD were 7.1 ± 4.5 mm and 7.1 ± 4.1 mm, respectively. Among the 20 patients, four exhibited structural LLD greater than 10 mm. The average follow-up duration was 6.4 ± 1.9 months (range: 3-8 months). Following sole lift intervention (7.0 ± 3.0 mm), a significant reduction was observed in the TL/L curve compared to the pre-sole lifting measurements (15.6° ± 6.2° vs. 12.1° ± 7.2°, p < 0.001), as well as a notable decrease in the thoracic curve (12.2° ± 4.0° vs. 8.6° ± 6.3°, p = 0.064). Nine patients experienced a significant curve reduction of ≥5°, while eight showed a reduction between 0° and 5°; however, two patients exhibited no change in curve magnitude. Furthermore, the correction rate of the TL/L curve correlated significantly with functional LLD (r = -0.484, p = 0.030) and pelvic obliquity (r = -0.556, p = 0.011), highlighting the active pelvic compensation in maintaining balance between the spine and lower limbs. Conversely, no significant correlation was observed between curve correction and structural LLD (p > 0.05). Additionally, even after adjusting for other influencing factors, the TL/L Cobb angle remained significantly different between pre- and post-sole lifting (p = 0.037). CONCLUSION: This study confirmed the effectiveness of sole lift intervention in correcting TL/L and thoracic curves among the mild IS children with a main TL/L curve, providing a supplementary conservative treatment option for patients with the lower limb at the convexity of the main curve. Moreover, our findings underscored the active compensation of the lower limbs and the pelvis in the etiopathogenesis of IS, highlighting the importance of considering their influence in treatment strategies.
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The purpose of this study is to examine the viability, precision, and consistency of a computer-based optokinetic nystagmus analyzer (nystagmus meter) for diagnosing eyesight in preschoolers. A total of 59 subjects who could pass the log of minimum angle of resolution (LogMAR) visual acuity chart were divided into three groups by age, 4-, 5-, and 6-year-old groups, and their visual acuity was tested with nystagmus meter. The percentage of children in each age group that could be detected by nystagmus was recorded along with the differences between these groups. The correlation between the test results from the two methods was found for each age group using the correlation coefficient method. Repeated measurements were used to assess the two visual acuity values of the measured nystagmus, and the repeatability of the two measurement techniques for different age groups was compared. The overall measurability of the visual acuity detected by nystagmus was 93.22%, and the measurability of the 4-, 5-, and 6-year-old groups was 90%, 95%, and 94.74%, respectively. There was no statistically significant difference in the measurability of subjects among all age groups (P = 1.0). The outcomes of the LogMAR visual acuity chart had a negative correlation with the visual acuity measured by the nystagmus meter. The overall correlation coefficient R value was -0.80, and the correlation coefficient R value of the 4-, 5-, and 6-year-old groups was -0.79, -0.76, and -0.87, respectively. The nystagmus meter has good feasibility, accuracy, and stability in visual acuity testing and can be used for visual acuity testing in children.
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Nistagmo Optocinético , Nistagmo Patológico , Humanos , Pré-Escolar , Nistagmo Patológico/diagnóstico , Acuidade Visual , Testes Visuais , ComputadoresRESUMO
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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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Natural bioactive compounds (NBCs) are regarded as candidates for many medical applications widely. Due to the complicated structure and biosynthesis source, only a few NBCs were supplied with commercial isotopic labeled standards. This shortage resulted in poor quantitation reliability in bio-samples for most NBCs, considering the remarkable matrix effects. NBCs metabolism and distribution studies would be restricted consequently. Those properties played critical roles in drug discovery and development. In this study, a fast, convenient, widely adopting 16O/18O exchange reaction was optimized for stable, available, affordable NBCs 18O-labeled standards preparation. With 18O- labeled internal standard, a UPLC-MRM-based NBCs pharmacokinetics analysis strategy was formed. Pharmacokinetics of caffeic acid with Hyssopus Cuspidatus Boriss extract (SXCF) dosed mice was carried out by established strategy. Compared with traditional external standards quantitation, adapting 18O-labeled internal standards, both accuracy and precision were enhanced significantly. Thus, the platform built by this work would accelerate the pharmaceutical research with NBCs, by providing a reliable, wide-adapted, affordable, isotopic internal standard-based bio-samples NBCs absolute quantitation strategy.
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Reprodutibilidade dos Testes , Animais , Camundongos , Isótopos de Oxigênio/metabolismo , Padrões de ReferênciaRESUMO
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a highly contagious viral infection. In addition to its association with common pulmonary and gastrointestinal complications, COVID-19 is also associated with numerous neurological and neuropsychiatric conditions. This minireview aims to cover current literature addressing the application of telemedicine in neurological disorders and neuropsychiatric conditions, especially in response to the COVID-19 pandemic. This article revealed that quarantine, masking, and social distancing policies practiced during the COVID-19 pandemic involved restrictions and challenges to providing medical services, especially for patients with neurological disorders with or without COVID-19 infection. During the pandemic, both healthcare administrators and clinicians, including neurologists, have rapidly adapted or introduced telemedicine technologies for delivering specialty care. In some areas in the world, telemedicine has been successfully applied to reduce the impact imposed by COVID-19. Conclusively, this article supports the idea that telemedicine is an effective tool for providing specialized healthcare for patients with neurological conditions while adhering to social distancing or lockdown policies instituted during the COVID-19 pandemic. Government and medical/healthcare authorities, physicians and healthcare providers need to work together to expand the adoption of telemedicine applications, even after the COVID-19 crisis.
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The main purpose of the paper is to investigate the relationship between technological innovation and income inequality for China based on the financial Kuznets curve (FKC) hypothesis. The study uses time-series data from 1985 to 2019. We employ the Johansen cointegration, ARDL model and VECM Granger causality techniques to analyze the links between the variables. We also use the DOLS, FMOLS and CCR mechanisms to estimate the long-run parameters. The paper finds that the FKC is valid for China's economy in the long run. Technological innovation positively affects the urban-rural income gap, while there is an inverted-U shaped between financial development and the urban-rural income gap. The relationship between financial development and the urban-rural income gap is bi-directional causality. Technological innovation and the urban-rural income gap cause each other. Empirical results suggest a twofold policy meaning: i) to further the financial system and ii) to eliminate the adverse impacts of technological innovations on income distribution.
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Desenvolvimento Econômico , Invenções , Fatores de Tempo , Dióxido de Carbono/análise , Renda , ChinaRESUMO
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.
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Humanos , Masculino , Feminino , Antígeno B7-H1/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , China , Neoplasias Pulmonares/patologia , Mutação , Proteínas Proto-Oncogênicas p21(ras)/genética , Estudos RetrospectivosRESUMO
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.
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Animais , Camundongos , Canais de Cátion TRPV/metabolismo , Filamentos Intermediários/metabolismo , Hipocampo/metabolismo , Neurônios/metabolismo , Transtornos da Memória/metabolismoRESUMO
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.
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Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Exenteração Pélvica , Produtos Biológicos/uso terapêutico , Diafragma da Pelve/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Resultado do TratamentoRESUMO
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.
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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.
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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.
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OBJECTIVE@#To investigate the predictive value of pulse infusion index (PPI) in the short-term prognosis of patients with sepsis-induced acute kidney injury (AKI).@*METHODS@#A retrospective cohort study was conducted. The clinical data of patients with sepsis-induced AKI admitted to intensive care unit (ICU) of the First Affiliated Hospital of Soochow University from July 2021 to December 2022 were enrolled. The basic information of the patients were collect, including age, gender, site of infection, underlying disease, mean arterial pressure (MAP) and heart rate (HR) at admission, as well as the use of mechanical ventilation and vasoactive drugs, and norepinephrine (NE) dosage. Laboratory indicators, sequential organ failure assessment (SOFA) score and PPI within 24 hours of admission were also recorded, and the patient's prognosis during ICU hospitalization was also recorded. The differences in clinical data between the patients of two groups with different prognosis were compared. Spearman correlation method was used to analyze the correlation between PPI and SOFA score. Binary multivariate Logistic regression analysis was used to screen independent risk factors for death during ICU hospitalization in sepsis patients with AKI. Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive value of PPI for the short-term prognosis of patients with sepsis-induced AKI.@*RESULTS@#A total of 102 patients with sepsis-induced AKI were enrolled, of which 70 patients in the survival group and 32 patients in the death group, with ICU mortality of 31.4. Compared with the survival group, SOFA score, HR, procalcitonin (PCT), serum creatinine (SCr), and NE dosage in the death group were significantly increased [SOFA score: 11.22±2.48 vs. 8.56±2.01, HR (bpm): 103.80±12.47 vs. 97.41±9.73, PCT (μg/L): 9.22 (5.24, 17.84) vs. 6.19 (3.86, 7.71), SCr (μmol/L): 163.2 (104.7, 307.9) vs. 125.5 (89.3, 221.0), Lac (mmol/L): 2.81 (1.95, 4.22) vs. 2.13 (1.74, 2.89), NE usage (μg×kg-1×min-1): 0.7 (0.4, 1.1) vs. 0.5 (0.2, 0.6), all P < 0.05], while PPI was significantly lower than that in survival group [0.83 (0.42, 1.55) vs. 1.70 (1.14, 2.20), P < 0.01]. Spearman correlation analysis showed that based on SOFA score, PPI was closely related to the severity of patients with sepsis-induced AKI (r = -0.328, P < 0.05). Binary multivariate Logistic regression analysis showed that PPI [odds ratio (OR) = 0.590, 95% confidence interval (95%CI) was 0.361-0.966, P = 0.002], SOFA score (OR = 1.406, 95%CI was 1.280-1.545, P < 0.001), PCT (OR = 2.061, 95%CI was 1.267-3.350, P = 0.006) were independent risk factors of the short-term prognosis of patients with sepsis-induced AKI. ROC curve analysis showed that the area under the ROC curve (AUC) of PPI for death during ICU hospitalization in patients with sepsis-induced AKI was 0.779 (95%CI was 0.686-0.855, P < 0.001), which superior to PCT (AUC = 0.677, 95%CI was 0.577-0.766, P = 0.004), and similar to SOFA score (AUC = 0.794, 95%CI was 0.703-0.868, P < 0.001). When the cut-off value of PPI was 0.72, the sensitivity was 50.0%, and the specificity was 97.1%.@*CONCLUSIONS@#PPI has a good predictive value for the short-term prognosis of patients with sepsis-induced AKI during ICU hospitalization.