Preliminary study on the computer-based optokinetic nystagmus analyzer to detect the visual acuity of preschool children.

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.

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.

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.

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.

16O/18O- exchange internal standard preparation enhancing reliability of bio-sample natural bioactive compounds absolute quantitation.

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.

Financial development, technological innovation and urban-rural income gap: Time series evidence from China.

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.

Increasing Use of Telemedicine for Neurological Disorders During the COVID-19 Pandemic: A Mini-Review.

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.

A Novel Three-minute Game-based Cognitive Risk Screening Tool-WeChat Mini-program-based Design and Large-sample Feasibility Studies / 中国医疗器械杂志

OBJECTIVE@#To develop a novel cognitive screening tool for older adults in China.@*METHODS@#"Game-based Cognitive Assessment-3 Minute Version"(G3) was designed and developed based on WeChat mini-program. And its feasibility was analyzed.@*RESULTS@#G3 mini-program contains three one-minute mini digital games and supports users' self-assessment of cognitive functions with instant access to reports. G3 had a good correlation with Montreal Cognitive Assessment Basic (MoCA-B) with Pearson's r =0.611 (P<0.001). Among natural users aged 50 and older (71 179), the G3 initiation and completion rates were 99.55% and 92.28%, respectively. The average time to complete G3 assessments was (278.5±73.73) seconds.@*CONCLUSIONS@#The novel G3 mini-program has good feasibility and usability for older Chinese adults, and can be used for cognitive screening and home self-assessment.

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.

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.

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.

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.

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.

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.

Predictive value of pulse infusion index in the short-term prognosis of patients with sepsis-induced acute kidney injury / 中华危重病急救医学

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.

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.

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.

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.

Hybrid Distractor for Continuous Mandibular Distraction Osteogenesis.

Distraction osteogenesis (DO) is a reconstruction method for repairing bone deficiencies in the oral and maxillofacial area. Manual DO techniques have shown the functionality of the DO method for bone tissue reconstruction. The DO method can improve treatment conditions, as well as the quality of the reconstructed bone, compared with conventional techniques. Recently, continuous DO devices have been proposed to enable an automatic DO process while using a continuous force for moving the bone segment (BS). Animal studies and clinical trials have shown the successful application of continuous distractors in terms of improving DO factors, including rate and rhythm. The continuous DO technique can shorten the treatment time and enhance the quality of the regenerated tissue. However, the developed continuous distractors are yet to be used in human applications. In this study, by combining motor-driven and hydraulic techniques, a hybrid distractor is proposed. The hybrid distractor is capable of generating a continuous distraction force while controlling the position of the BS in a linear vector, with a high positioning accuracy. Results of modelling and experimental study revealed that the proposed hybrid distractor met all required factors for enabling a continuous DO procedure in humans. The proposed distractor is capable of eliminating the drawbacks of exiting techniques in terms of generating and transferring a controlled distraction force to the BS. The wireless control, as well as the small size of the device, makes this device a suitable solution for use in the reconstruction of bone defects in the maxillofacial area in humans.