COVID-19 associated Guillain-Barré syndrome (GBS) caused by peripheral nerve damage after SARS-CoV-2 infection is one of the most common COVID-19 related nervous system inflammatory diseases, with high incidence of respiratory failure and mortality. Positive SARS-CoV-2 RNA in cerebrospinal fluid of COVID-19 associated GBS patients has been rarely reported. This paper reports 4 patients with COVID-19 associated GBS in China who developed neurological symptoms 4-15 days after fever and were confirmed SARS-CoV-2 infection. All patients presented with progressive weakness of both lower limbs, 3 patients with autonomic dysfunction such as defecation and urination disorders, and 1 patient with polycranial neuritis and Miller-Fisher syndrome such as bilateral facial palsy, dysphagia, diplopia and ataxia. Nerve conduction velocity and F wave were abnormal in 3 patients, and motor conduction pathway was abnormal in 1 patient. Anti-ganglioside antibodies were tested in 3 patients, and GD1a-IgG was positive in 1 patient. All 4 patients underwent metagenomic next-generation sequencing examination in blood and cerebrospinal fluid. SARS-CoV-2 RNA was positive in blood and cerebrospinal fluid of 3 patients, and SARS-CoV-2 RNA was positive in cerebrospinal fluid of 1 patient.

Objective To propose strategies for developing clinical predictive models,aiming to assist researchers in conducting standardized clinical prediction model studies.Methods Literature review was conducted to summarize the operational steps and content for developing clinical predictive models.Then,a methodological framework was summarized and refined through expert consultation.Results The 11-step methodological framework for developing clinical predictive models was obtained by synthesizing the experience of 456 clinical predictive modeling studies and expert consultation,and the details were analyzed and elaborated.Conclusions This study presents methodological strategies and recommendations for the development of clinical predictive models,intended to serve as a guide for researchers.

OBJECTIVE: To explore the influencing factors of prognosis in patients with sepsis-induced acute kidney injury undergoing continuous renal replacement therapy (CRRT), and to construct a mortality risk prediction model. METHODS: A retrospective research method was adopted, patients with sepsis-induced acute kidney injury who received CRRT at Fuyang People's Hospital from February 2021 to September 2023 were included in this study. Collect general information, comorbidities, vital signs, laboratory indicators, disease severity scores, treatment status, length of stay in the intensive care unit (ICU), and 28-day prognosis were collected within 24 hours of patient enrollment. The Cox regression model was used to identify the factors influencing prognosis in patients with sepsis-induced acute kidney injury, and a nomogram model was developed to predict mortality in these patients. Receiver operator characteristic curve (ROC curve), calibration curve, and Hosmer-Lemeshow test were used to validate the predictive performance of the nomogram model. RESULTS: A total of 146 patients with sepsis-induced acute kidney injury were included, of which 98 survived and 48 died (with a mortality of 32.88%) after 28 days of treatment. The blood lactic acid, interleukin-6 (IL-6), serum cystatin C, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), and proportion of mechanical ventilation in the death group were significantly higher than those in the survival group. The ICU stay was significantly longer than that in the survival group, and the glomerular filtration rate was significantly lower than that in the survival group. Cox regression analysis showed that blood lactic acid [odds ratio (OR) = 2.992, 95% confidence interval (95%CI) was 1.023-8.754], IL-6 (OR = 3.522, 95%CI was 1.039-11.929), serum cystatin C (OR = 3.999, 95%CI was 1.367-11.699), mechanical ventilation (OR = 4.133, 95%CI was 1.413-12.092), APACHE II score (OR = 5.013, 95%CI was 1.713-14.667), SOFA score (OR = 3.404, 95%CI was 1.634-9.959) were risk factors for mortality in patients with sepsis-induced acute kidney injury (all P < 0.05), glomerular filtration rate (OR = 0.294, 95%CI was 0.101-0.860) was a protective factor for mortality in patients with sepsis-induced acute kidney injury (P < 0.05). The ROC curve showed that the column chart model has a sensitivity of 80.0% (95%CI was 69.1%-89.2%) and a specificity of 89.3% (95%CI was 83.1%-95.2%) in predicting 28-day mortality in patients with acute kidney injury caused by sepsis. CONCLUSIONS Blood lactic acid, IL-6, mechanical ventilation, APACHEII score, SOFA score, glomerular filtration rate, and serum cystatin C are associated with the risk of death in patients with sepsis-induced acute kidney injury. The nomogram model could help early identification of mortality risk in these patients.
Humans ; Acute Kidney Injury/diagnosis* ; Sepsis/therapy* ; Retrospective Studies ; Prognosis ; Continuous Renal Replacement Therapy/methods* ; Nomograms ; Intensive Care Units ; ROC Curve ; Interleukin-6/blood* ; Proportional Hazards Models ; Female ; Male ; Cystatin C/blood* ; Middle Aged ; Risk Factors ; Lactic Acid/blood*

Objective    To analyze the effect of carotid artery stenosis degree and intervention for carotid artery stenosis on the incidence of central nervous system complications after off-pump coronary artery bypass grafting (OPCABG) and explore the influencing factors. Methods    A total of 1 150 patients undergoing OPCABG in our hospital from June 2018 to June 2021 were selected and divided into two groups according to whether there were central nervous system complications, including a central nervous system complication group [n=61, 43 males and 18 females with a median age of 68.0 (63.0, 74.0) years] and a non-central nervous system complication group [n=1 089, 796 males and 293 females with a median age of 65.5 (59.0, 70.0) years]. The risk factors for central nervous system complications after OPCABG were analyzed. Results    Univariate analysis showed that age, smoking, hyperlipidemia, preoperative left ventricular ejection fraction, intra-aortic ballon pump (IABP), postoperative arrhythmia, postoperative thoracotomy and blood transfusion volume were associated with central nervous system complications. The incidence of central nervous system complications in patients with severe carotid artery stenosis or occlusion (11.63%) was higher than that in the non-stenosis and mild stenosis patients (4.80%) and moderate stenosis patients (4.76%) with a statistical difference (P=0.038). The intervention for carotid artery stenosis before or during the operation did not reduce the incidence of central nervous system complications after the operation (42.11% vs. 2.99%, P<0.001). Age, postoperative arrhythmia, severe unilateral or bilateral carotid artery stenosis and occlusion were independent risk factors for postoperative central nervous system complications (P<0.05). Conclusion     The age, smoking, hyperlipidemia, preoperative left ventricular ejection fraction, intraoperative use of IABP, postoperative arrhythmia, secondary thoracotomy after surgery, blood transfusion volume and OPCABG are associated with the incidence of postoperative central nervous system complications in patients. Age, postoperative arrhythmia, severe unilateral or bilateral carotid artery stenosis and occlusion are independent risk factors for postoperative central nervous system complications. In patients with severe carotid artery stenosis, preoperative treatment of the carotid artery will not reduce the incidence of central nervous system complications.

Objective To explore the influence of agricultural mechanization progress on epidemic intensity of hemorrhagic fever with renal syndrome (HFRS) so as to provide reference for prevention and control of HFRS in rural areas.Methods Data of HFRS epidemics and agricultural mechanization progress of Qingdao City and five main epidemic areas of HFRS were collected by retrospective analysis methods.Agricultural mechanization progress,time distribution,incidence rate of HFRS and capture rate of rats were compared,respectively.Risk factors were analyzed by case-control study using simple random sampling method.Cases of case group were selected from HFRS cases of Jiaonan County recovered between 2012 and 2013.The control group was healthy residents with a equal number of the case group.Residential locations,work ways,rodent infestation at work locations and in residential areas and skin injury conditions were surveyed by a household questionnaire survey.Results Agricultural machinery gross power of Qingdao City was developed from 174.76 megawatts of electricity (mwe) in 1985 to 854.00 mwe in 2015.The comprehensive mechanization degree marched from 60.0％ in 1994 to 90.2％ in 2015.HFRS incidence in Qingdao City declined from the first epidemic peak (1986) of 32.97/100 000 to the third peak (2012) of 3.54/100 000.HFRS incidence in Jiaonan,Jiaozhou,Pingdu,Laixi,Jimo cities reduced from the first epidemic peak (1985 or 1986) of 101.25/100 000,86.37/100 000,35.80/100 000,11.55/100 000,8.13/100 000 to the third peak(2012) of 14.68/100 000,4.43/100 000,2.33/100 000,6.02/100 000,3.26/100 000.The platform stage of epidemic peak in autumn and winter shortened from 4 or 5 months to 2 months.The capture rate of rats fluctuated around 2％.The infection risk of small farm implements or handwork was greater than huge mechanization (OR =0.01,P ＜ 0.01).Conclusions Agricultural mechanization changes the agricultural activity patterns to a large extent and lowers the HFRS epidemic by minimizing the risk of infection and shortening the platform stage of epidemic peak.The higher the degree of mechanization,the lower the epidemic intensity.

Objective: To investigate the clinical effect and safety of long-acting pegylated interferon-α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 μg/week) in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients, with standard-dose Peg-IFN-α-2a as positive control. Methods: This study was a multicenter, randomized, open-label, and positive-controlled phase III clinical trial. Eligible HBeAg-positive CHB patients were screened out and randomized to Peg-IFN-α-2b (Y shape, 40 kD) trial group and Peg-IFN-α-2a control group at a ratio of 2:1. The course of treatment was 48 weeks and the patients were followed up for 24 weeks after drug withdrawal. Plasma samples were collected at screening, baseline, and 12, 24, 36, 48, 60, and 72 weeks for centralized detection. COBAS® Ampliprep/COBAS® TaqMan® HBV Test was used to measure HBV DNA level by quantitative real-time PCR. Electrochemiluminescence immunoassay with Elecsys kit was used to measure HBV markers (HBsAg, anti-HBs, HBeAg, anti-HBe). Adverse events were recorded in detail. The primary outcome measure was HBeAg seroconversion rate after the 24-week follow-up, and non-inferiority was also tested. The difference in HBeAg seroconversion rate after treatment between the trial group and the control group and two-sided confidence interval (CI) were calculated, and non-inferiority was demonstrated if the lower limit of 95% CI was > -10%. The t-test, chi-square test, or rank sum test was used according to the types and features of data. Results: A total of 855 HBeAg-positive CHB patients were enrolled and 820 of them received treatment (538 in the trial group and 282 in the control group). The data of the full analysis set showed that HBeAg seroconversion rate at week 72 was 27.32% in the trial group and 22.70% in the control group with a rate difference of 4.63% (95% CI -1.54% to 10.80%, P = 0.1493). The data of the per-protocol set showed that HBeAg seroconversion rate at week 72 was 30.75% in the trial group and 27.14% in the control group with a rate difference of 3.61% (95% CI -3.87% to 11.09%, P = 0.3436). 95% CI met the non-inferiority criteria, and the trial group was non-inferior to the control group. The two groups had similar incidence rates of adverse events, serious adverse events, and common adverse events. Conclusion In Peg-IFN-α regimen for HBeAg-positive CHB patients, the new drug Peg-IFN-α-2b (Y shape, 40 kD) has comparable effect and safety to the control drug Peg-IFN-α-2a.

Objective To evaluate in vitro effects of specific small interfering RNA (siRNA)-silencing of the casitas B-lineage lymphoma b (Cbl-b)gene on immunocompetence of primary murine lymphocytes. Methods Spleens were resected from C57BL/6 mice, and splenic lymphocytes were sterily isolated and cultured in vitro. These lymphocytes were divided into 3 groups: silence group transfected with a Cbl-b-specific siRNA using the EntransterTM-R 4000 reagent, negative control group transfected with a negative control siRNA using the EntransterTM-R4000 reagent, blank control group receiving no treatment. After additional culture for 72 hours, ELISA was performed to measure levels of interferon γ(IFN-γ)and tumor necrosis factor α (TNF-α)in culture supernatants of lymphocytes. In addition, the Cbl-b gene-silenced lymphocytes were co-cultured with B16F10 melanoma cells to evaluate their immunocytotoxic effects on melanoma cells. Results Splenic lymphocytes were successfully isolated from C57BL/6 mice and cultured in vitro, and the Cbl-b-specific siRNA was also successfully transfected into the primary murine lymphocytes and effectively down-regulated the expression of Cbl-b gene in them. Compared with the negative control group and blank control group, the silence group showed significantly increased supernatant levels of IFN-γ and TNF-α(all P < 0.05). The immunocytotoxic effect of lymphocytes on melanoma cells was significantly stronger in the silence group than in the negative control group. Conclusion Cbl-b gene silencing can promote secretion of IFN-γ and TNF-α by murine lymphocytes, and enhance their immunocytotoxic effects on B16F10 melanoma cells in vitro.

Objective To investigate the clinical effect of shuxuening treatment on organophosphorus pesti-cide poisoning with toxic myocarditis.Methods 60 patients with organophosphorus toxic myocarditis were selected in our hospital as the research subjects,and 60 cases were divided into two groups:observation group(n =30) and control group(n =30).Control group was given conventional treatment,treatment group was given shuxuening injec-tion 14 days on the basis of conventional treatment.After treatment,creatine kinase isoenzyme (CKMB),troponin (TNI),interleukin 6 (IL -6) and cholinesterase(ChE) were compared,and the changes of clinical symptoms were observed at the same time.Results There was no significant difference between the observation group and the control group(χ2 =0.630,P =0.730).The TNI,IL -6,CKMB could reflect the severity of myocardial injury in patients with different degrees of organic phosphorus poisoning,TNI,CK -MB,IL -6 increased with the degree of poisoning,the differences were statistically significant(F =11.863,4.512,3.774;P =0.000,0.015,0.029).After treatment for 4, 9,14 days,TnI,CK,CK -MB,levels of IL -6 in the two groups were recovered,but the recovery levels of TnI,CK -MB and IL -6 of the observation group significantly better than the control group,the differences were statistically sig-nificant(Fourth days,t =8.125,5.128,10.461;P =0.000,0.001,0.000;Ninth days,t =5.464,4.674,9.510;P =0.001,0.002,0.000,t =6.162,8.248,5.523;P =0.000,0.000,0.001).Conclusion Conventional treatment combined with shuxuening in the treatment of organophosphorus pesticide poisoning with toxic myocarditis has better therapeutic effect,it is worthy of promotion.

Objective To construct a eukaryotic expression plasmid vector encoding Cbl-b gene-specific short hairpin RNAs (shRNAs),and to evaluate its interference effect,so as to lay a foundation for further study on the role of Cbl-b in the immunotherapy of malignant melanoma.Methods According to the sequence of Cbl-b cDNA,4 pairs of shRNAs targeting the Cbl-b gene were designed and synthesized,and then inserted into the plasmid PGPU6/GFP/Neo to construct recombinant plasmids.After identification by DNA sequencing,the 4 shRNA expression vectors were cotransfected into 293T cells with the Cbl-b gene eukarytic expresson plasmid,respectively.The knockdown efficiency of these shRNA expression plasmids on Cbl-b expression was evaluated by real-time (RT) fluorescence-based quantitative PCR and Western blot at 48 hours aftert transfection.Results Sequencing analysis revealed that all the 4 pairs of shRNAs were successfully inserted into the eukarytic expression vector PGPU6/GFP/Neo.As RT-PCR and Western blot showed,all the 4 shRNA-expressing vectors could downregulate Cbl-b expession,and the NO.1 shRNA-expressing vector displayed the strongest interference effect(P ＜ 0.05).Conclusions A eukaryotic expression plasmid vector was successfully constructed for Cbl-b gene-specific shRNAs,and the most effective shRNA was selected in this study.

BACKGROUND:Papain-induced rat knee osteoarthritis is a common modeling method, which can obtain a stable osteoarthritis model.
OBJECTIVE:To observe the change of ultrastructure of chondrocytes in the early process of papain-induced rat knee osteoarthritis under transmission electron microscope.
METHODS:A total of 18 Sprague-Dawley rats were randomly divided into three groups. Two rats were considered as a normal control group, without intervention. The mixture of papain and L-cysteine was injected in right knee joint cavity of 16 rats to induce osteoarthritis models (osteoarthritis model group). Physiological saline was injected in the left side (physiological saline control group). At 1, 2, 4 and 6 weeks after injection, samples were col ected. Transmission electron microscope was used to observe the change of cartilage ultrastructure of the medial femoral condyle joint.
RESULTS AND CONCLUSION:For the normal control group and physiological saline control group, their cytoplasm contained abundant rough endoplasmic reticulum and mitochondria. After 1 week of injection,
mitochondria vacuoles and light expanded rough endoplasmic reticulum were visible. Two weeks later, lipid droplets appeared, mitochondria degeneration was distinct, vacuolization was serious and its number was reduced, and rough endoplasmic reticulum expansion was obvious. Four weeks later, lipid droplets became increased, and the number of mitochondria decreased significantly. Most of the rough endoplasmic reticula were highly expanded, and part of the rough endoplasmic reticula were dissolved and fractured. Six weeks later, a number of lipid droplets were visible in cytoplasm, most of the mitochondria disappeared, only a smal number of mitochondria existed, and most of the rough endoplasmic reticula were dissolved and fractured. These results confirmed that cartilage ultrastructure changes gradual y in the early process of papain-induced rat knee osteoarthritis under transmission electron microscope.