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Abstract Bovine viral diarrhea virus (BVDV) belongs to the genus Pestivirus within the family Flaviviridae. Mitophagy plays important roles in virus-host interactions. Here, we provide evidence that non-cytopathic (NCP) BVDV shifts the balance of mitochondrial dynamics toward fission and induces mitophagy to inhibit innate immune responses. Mechanistically, NCP BVDV triggers the translocation of dynamin-related protein (Drp1) to mitochondria and stimulates its phosphorylation at Ser616, leading to mitochondrial fission. In parallel, NCP BVDV-induced complete mitophagy via Parkin-dependent pathway contributes to eliminating damaged mitochondria to inhibit MAVS- and mtDNA-cGAS-mediated innate immunity responses, mtROS-mediated inflammatory responses and apoptosis initiation. Importantly, we demonstrate that the LIR motif of ERNS is essential for mitophagy induction. In conclusion, this study is the first to show that NCP BVDV-induced mitophagy plays a central role in promoting cell survival and inhibiting innate immune responses in vitro.

Background: Acute respiratory distress syndrome (ARDS) is a fatal outcome of severe sepsis. Machine learning models are helpful for accurately predicting ARDS in patients with sepsis at an early stage. Objective: We aim to develop a machine-learning model for predicting ARDS in patients with sepsis in the intensive care unit (ICU). Methods: The initial clinical data of patients with sepsis admitted to the hospital (including population characteristics, clinical diagnosis, complications, and laboratory tests) were used to predict ARDS, and screen out the crucial variables. After comparing eight different algorithms, namely, XG boost, logistic regression, light GBM, random forest, Gaussian NB, complement NB, support vector machine (SVM), and K nearest neighbors (KNN), rebuilding a prediction model with the best one. When remodeling with the best algorithm, 10% was randomly selected to test, and the remaining was trained for cross-validation. Using the area under the curve (AUC), sensitivity, accuracy, specificity, positive and negative predictive value, F1 score, kappa value, and clinical decision curve to evaluate the model's performance. Eventually, the application in the model illustrated by the SHAP package. Results: Ten critical features were screened utilizing the lasso method, namely, PaO2/PAO2, A-aDO2, PO2(T), CRP, gender, PO2, RDW, MCH, SG, and chlorine. The prior ranking of variables demonstrated that PaO2/PAO2 was the most significant variable. Among the eight algorithms, the performance of the Gaussian NB algorithm was significantly better than that of the others. After remodeling with the best algorithm, the AUC in the training and validation sets were 0.777 and 0.770, respectively, and the algorithm performed well in the test set (AUC = 0.781, accuracy = 78.6%, sensitivity = 82.4%, F1 score = 0.824). A comparison of the overlap factors with those of previous models revealed that the model we developed performs better. Conclusion: Sepsis-associated ARDS can be accurately predicted early via a machine learning model based on existing clinical data. These findings are helpful for accurate identification and improvement of the prognosis in patients with sepsis-associated ARDS.

Abstract Objectives The clinical features of aseptic meningitis associated with amoxicillin are unknown. The main objective of this study was to investigate the clinical characteristics of amoxicillin-induced aseptic meningitis (AIAM) and provide a reference for clinical diagnosis and treatment. Methods AIAM-related studies were collected by searching the relevant databases from inception to October 31, 2022. Results AIAM usually occurred 3 h to 7 days after amoxicillin administration in 13 males and 9 females. Twenty-one patients (95.5%) had recurrent AIAM with a total of 62 episodes. Fever (19 cases, 86.4%) and headache (18 cases, 81.8%) were the most common symptoms. Typical cerebrospinal fluid (CSF) findings were leukocytosis (100%) with lymphocytic predominance (14 cases, 63.6%), elevated protein (20 cases, 90.1%), normal glucose (21 cases, 95.5%) and negative culture (21 cases, 100%). Brain magnetic resonance imaging showed mild meningeal enhancement in one patient. The symptoms resolved mainly within 1–4 days after drug discontinuation in all patients. Conclusion Clinical attention should be given to the adverse effects of AIAM. The medication history of patients with suspected meningitis should be investigated to avoid unnecessary examination and antibiotic treatment.

Background: Thrombotic microangiopathy (TMA) is a rare side effect of interferon-beta (IFN-β) therapy. The clinical characteristics of IFN-β-induced TMA are unknown. Objectives: To explore the clinical characteristics of IFN-β-induced TMA and provide reference for the prevention of TMA. Design: Articles on IFN-β-induced TMA were collected by searching the literature in relevant Chinese and English databases from inception to 31 July 2023. Methods: Data in the articles were extracted and analyzed retrospectively. Results: Forty-seven patients, with a median age of 41 years (range 22, 66), were included in the analysis. The median time to the diagnosis of IFN-β-induced TMA was 8 years (range 0.1–30) after administration. The main clinical symptoms were neurological symptoms (51.1%), hypertension (78.7%), dyspnea (19.1%), edema (19.1%), asthenia/fatigue (19.1%), and digestive symptoms (17.0%). Most patients presented with hemolytic anemia (76.6%), thrombocytopenia (63.8%), and acute kidney injury (70.2%). All patients stopped IFN-β and received plasma exchange therapy (53.2%), systemic steroids (46.8%), antihypertensive therapy (46.8%), eculizumab (12.8%), and rituximab (12.8%). Kidney damage was not completely reversible; 40.4% of patients achieved renal function and hematology remission, 27.7% developed chronic kidney disease, 25.5% developed end-stage renal disease, and 2.1% died. Conclusion: IFN-β-induced TMA is a rare but serious complication that can be life-threatening. It may occur after many years of IFN-β therapy, and patients taking IFN-β should be monitored for symptoms such as headache and hypertension.

Abstract Background Increased acid sphingomyelinase (ASMase) activity is associated with insulin resistance and cardiac dysfunction. However, the effects of ASMase on diabetic cardiomyopathy (DCM) and the molecular mechanism(s) underlying remain to be elucidated. We here investigated whether ASMase caused DCM through NADPH oxidase 4-mediated apoptosis. Methods and results We used pharmacological and genetic approaches coupled with study of murine and cell line samples to reveal the mechanisms initiated by ASMase in diabetic hearts. The protein expression and activity of ASMase were upregulated, meanwhile ceramide accumulation was increased in the myocardium of HFD mice. Inhibition of ASMase with imipramine (20 mg Kg−1 d−1) or siRNA reduced cardiomyocyte apoptosis, fibrosis, and mitigated cardiac hypertrophy and cardiac dysfunction in HFD mice. The similar effects were observed in cardiomyocytes treated with high glucose (HG, 30 mmol L−1) + palmitic acid (PA, 100 μmol L−1) or C16 ceramide (CER, 20 μmol L−1). Interestingly, the cardioprotective effect of ASMase inhibition was not accompanied by reduced ceramide accumulation, indicating a ceramide-independent manner. The mechanism may involve activated NADPH oxidase 4 (NOX4), increased ROS generation and triggered apoptosis. Suppression of NOX4 with apocynin prevented HG + PA and CER incubation induced Nppb and Myh7 pro-hypertrophic gene expression, ROS production and apoptosis in H9c2 cells. Furthermore, cardiomyocyte-specific ASMase knockout (ASMaseMyh6KO) restored HFD-induced cardiac dysfunction, remodeling, and apoptosis, whereas NOX4 protein expression was downregulated. Conclusions These results demonstrated that HFD-mediated activation of cardiomyocyte ASMase could increase NOX4 expression, which may stimulate oxidative stress, apoptosis, and then cause metabolic cardiomyopathy.

Computing resource measurement and computing routing are essential technologies in the computing first network (CFN), serving as its foundational elements. This paper introduces a Software Defined Computing First Network (SD-CFN) architecture. Building upon this framework, a Dynamic-Static Integrated Computing Resource Measurement Mechanism (DCRMM) is proposed, incorporating methods such as the entropy weight method and K-Means clustering. The DCRMM algorithm outperforms the Maximum-closest Static Algorithm (MSA) and Maximum Closest Dynamic Algorithm (MDA) in terms of node stability, node utilization, and node matching accuracy. Additionally, a Reinforcement Learning and Software Defined Computing First Networking Routing (RSCR) algorithm is presented as a software-defined computing routing solution within the SD-CFN. RSCR introduces a knowledge plane responsible for computing routing calculations. It comprehensively considers factors such as link latency, available bandwidth, and packet loss rate. Simulation experiments conducted on the GÉANT topology demonstrate that RSCR outperforms the OSPF algorithm in terms of link latency, packet loss rate, and throughput. DCRMM and RSCR offer innovative solutions for computing resource measurement and computing routing in computing first networks.

Objective: Few real-world studies have shown clear association between interleukin (IL)-17 inhibitors and inflammatory bowel disease (IBD) onset. This study investigated the reporting prevalence and evaluated the clinical features and management of IL-17 inhibitor-related IBD events.Methods: We used the US FDA Adverse Event Reporting System database and retrieved data, from 2015 to 2022, on IL-17 inhibitors to identify gastrointestinal inflammatory events and conduct disproportionality analyses by estimating the reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs). Furthermore, case reports and case series, from 2015 to 30 November 2022, on IBD induced by IL-17 inhibitors were collected for retrospective analysis.Results: A total of 388 cases of primary suspected IL-17 inhibitor-associated gastrointestinal events were reported (268 IBD and 120 colitis), including 348 cases involving secukinumab (SEC), 36 cases involving ixekizumab (IXE), and 4 cases involving brodalumab (BRO). Statistically significant reporting rates of total IBD events were observed for SEC and IXE (ROR = 2.13, 95% CI [1.96-2.30] and ROR = 2.79, 95% CI [2.39-3.27], respectively), whereas BRO did not trigger a safety signal. Twenty-nine studies, which included 34 cases, showed evidence of IBD, following SEC (79.4%) and IXE (20.6%) treatment. The median age was 42 years; typical initial symptoms included diarrhea (90.9%), abdominal pain (57.6%), bloody diarrhea (51.5%), and fever (36.4%). The median time to onset of IBD symptoms was 2.9 months. Some cases were accompanied by elevated white blood cell (WBC) count (87.5%), erythrocyte sedimentation rate (ESR; 85.7%), C-reactive protein (CRP; 100%), and fecal calprotectin (FC; 100%). Cessation of IL-17 inhibitors plus treatment with corticosteroids and TNF antagonists, as either monotherapy or in combination, could lead to complete clinical remission. The median time to remission after IL-17 inhibitor discontinuation was 4 weeks.Conclusion: IL-17 inhibitor treatment is associated with exacerbation and new onset of IBD and colitis. Obtaining a detailed patient history before initiation of treatment and monitoring gastrointestinal symptoms and intestinal inflammatory biomarkers during IL-17 inhibitor treatment is important for safe use of these drugs.

ObjectiveHypoglycemia is a sporadic and serious adverse reaction of trimethoprim-sulfamethoxazole (TMP-SMX) due to its sulfonylurea-like effect. This study explored the clinical characteristics, risk factors, treatment, and prognosis of TMP-SMX-induced hypoglycemia.MethodsCase reports and series of TMP-SMX-induced hypoglycemia were systematically searched using Chinese and English databases. Primary patient and clinical information were extracted for analysis.ResultsA total of 34 patients were reported from 31 studies (16 males and 18 females). The patients had a median age of 64 years (range 0.4-91), and 75.8% had renal dysfunction. The median duration of a hypoglycemic episode was six days (range 1-20), and the median minimum glucose was 28.8 mg/dL (range 12-60). Thirty-two patients (97.0%) showed neuroglycopenic symptoms, with consciousness disturbance (30.3%) and seizure (24.2%), sweating (18.2%), confusion (15.2%), asthenia (12.1%) being the most common symptoms. Fifteen patients (44.1%) had elevated serum insulin levels, with a median of 31.8 μU/mL (range 3-115.3). C-peptide increased in 13 patients (38.2%), with a median of 7.7 ng/mL (range 2.2-20). Complete recovery from symptoms occurred in 88.2% of patients without sequelae. The duration of hypoglycemia symptoms was 8 hours to 47 days after the intervention. Interventions included discontinuation of TMP-SMX, intravenous glucose, glucagon, and octreotide.ConclusionHypoglycemia is a rare and serious adverse effect of TMP-SMX. Physicians should be aware of this potential adverse effect, especially in patients with renal insufficiency, increased drug doses, and malnutrition.

BackgroundTo investigate the distribution of microbes and drug susceptibility in patients with diabetic foot infections (DFI) and provide guidance for clinical empirical treatment and the rational selection of antibacterial drugs.MethodsRetrospective analysis of the pathogenic bacterium distribution and antimicrobial susceptibility isolated from 581 DFI patients with different Wagner grades.ResultsThe 534 positive samples included 473 cases (88.58%)) of monomicrobial infections and 61 cases (11.42%) of polymicrobial infections before antibiotic therapy. A total of 656 strains were cultivated, including 387 (58.99%) strains of gram-positive organisms (GPOs), 235 (35.82%) gram-negative bacilli (GNB), and 21 (3.20%) fungal strains. Polymicrobial infections mainly occurred in patients with Wagner grade 3-4 ulcers. GPOs were predominant in Wagner grades 1-3 (grade 1: 96.67%, grade 2: 76.52%, grade 3 62.81%), and the most common was Staphylococcus aureus (grade 1: 31.66%, grade 2: 33.04%, grade 3 35.53%). GNB were predominant in grades 4-5 (grade 4: 51.46%, grade 5:60%), and the most common GNB in Wagner grades 4-5 was Proteus (grade 4:27.88%, grade 5: 42.86%), while the most common GPO was Enterococcus (grade 4:34.48%, grade 5:25.00%). Staphylococcus (including MRSA) and Enterococcus were still highly sensitive to vancomycin, linezolid, and tigecycline. Most GNB were still highly sensitive to meropenem, tigecycline, ertapenem, and amikacin. Proteus was most sensitive to amikacin (97.14%), followed by meropenem (92%) and ertapenem (80%).ConclusionThe distribution of microbes and antimicrobial susceptibility in DFI patients varied with different Wagner grades. The most appropriate antimicrobial therapy should be selected based on the pathogen culture and antimicrobial susceptibility.

Objective The perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin plus docetaxel (FLOT) was recommended by the Chinese Society of Clinical Oncology Guidelines for gastric cancer (2018 edition) for patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (class IIA). However, the economic impact of FLOT chemotherapy in China remains unclear. The analysis aimed to compare the cost-effectiveness of FLOT versus epirubicin, cisplatin plus fluorouracil or capecitabine (ECF/ECX) in patients with locally advanced resectable tumours.Design We developed a Markov model to compare the healthcare and economic outcomes of FLOT and ECF/ECX in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma. Costs were estimated from the perspective of Chinese healthcare system. Clinical and utility inputs were derived from the FLOT4 phase II/III clinical trial and published literature. Sensitivity analyses were employed to assess the robustness of our result. The annual discount rate for costs and health outcomes was set at 5%.Outcome measures The primary outcome of incremental cost-effectiveness ratios (ICERs) was calculated as the cost per quality-adjusted life years (QALYs).Results The base-case analysis found that compared with ECF/ECX, the use of FLOT chemotherapy was associated with an additional 1.08 QALYs, resulting in an ICER of US$851/QALY. One-way sensitivity analysis results suggested that the HR of overall survival and progression-free survival had the greatest impact on the ICER. Probabilistic sensitivity analysis demonstrated that FLOT was more likely to be cost-effective compared with ECF/ECX at a willingness-to-pay threshold of US$31 513/QALY.Conclusions For patients with locally advanced resectable tumours, the FLOT chemotherapy is a cost-effective treatment option compared with ECF/ECX in China.Trial registration number NCT01216644.

Background: The available evidence suggests that amoxicillin is often associated with the occurrence of Kounis syndrome (KS). The purpose of this study is to explore the clinical characteristics of KS induced by amoxicillin.Methods: We searched for case reports of amoxicillin-induced KS through Chinese and English databases from 1972 to May 2022.Results: A total of 33 patients with KS were included, including 16 patients (48.5%) receiving amoxicillin treatment and 17 patients (51.5%) receiving amoxicillin-clavulanate. The median age was 58 years (range 13–82), 75.8% were from Europe and 81.8% were male. Nearly 70% of KS patients develop symptoms within 30 min after administration. Chest pain (63.6%) and allergic reaction (75.8%) were the most common clinical manifestations. Diagnostic evaluation revealed elevated troponin (72.7%), ST-segment elevation (81.2%) and coronary artery stenosis with thrombosis (53.6%). Thirty-two (97.0%) patients recovered completely after discontinuation of amoxicillin and treatments such as steroids and antihistamines.Conclusion: KS is a rare adverse reaction of amoxicillin. Amoxicillin-induced KS should be considered when chest pain accompanied by allergic symptoms, electrocardiogram changes and or elevated levels of myocardial injury markers. Therapeutic management of KS requires simultaneous treatment of cardiac and allergic symptoms. Epinephrine should be used with caution in patients with suspected KS.

Background: Mesalazine is the first-line inflammatory bowel disease (IBD) treatment. However, it can cause fatal cardiotoxicity. We aimed to analyze the clinical characteristics of mesalazine-induced cardiotoxicity and provide evidence for clinical diagnosis, treatment, and prevention.Methods: We collected Chinese and English literature on mesalazine-induced cardiotoxicity from 1970 to 2021 for retrospective analysis.Results: A total of 52 patients (40 males and 12 females) were included, with a median age of 24.5 years (range 9–62) and a median onset time of 14 days (range 2–2880). Cardiotoxicity manifested as myocarditis, pericarditis, and cardiac pericarditis. The main clinical manifestations are chest pain (82.7%), fever (46.2%), and respiratory symptoms such as dyspnea and cough (40.4%). The levels of troponin T, creatine kinase, C-reactive protein, leukocyte count, erythrocyte sedimentation rate, and other biochemical markers were significantly increased. Cardiac imaging often suggests myocardial infarction, pericardial effusion, myocardial necrosis, and other symptoms of cardiac injury. It is essential to discontinue mesalamine immediately in patients with cardiotoxicity. Although corticosteroids are a standard treatment option, the benefits remain to be determined. Re-challenge of mesalamine should be carefully considered as cardiotoxic symptoms may reoccur.Conclusion: Mesalazine may cause cardiotoxicity in patients with inflammatory bowel disease, which should be comprehensively diagnosed based on clinical manifestations, biochemical indicators, and cardiac function imaging examinations. Mesalazine should be immediately discontinued, and corticosteroids may be an effective treatment for cardiotoxicity.

ObjectiveAlthough Fanconi syndrome (FS) induced by valproate (VPA) has occasionally been reported, the detailed clinical features of the disease remain unclear. The aim of this study was to elucidate the clinical features of patients with VPA-induced FS.MethodsWe searched Chinese and English databases for all original studies, clinical reports, and case reports on VPA-induced FS published before March 2022.ResultsA total of 29 articles including 54 patients (28 males and 24 females) were included. The patients had a median age of 7 years (range 2–34 years), had severely disabled (87.0%), tube feeding (64.8%), and received an average of 1.8 medications other than VPA. The median duration of VPA treatment was 4 years (range 0.7–15.5). Pathological fractures (25.9%), unexplained fever (11.1%), muscle weakness (9.3%), and edema (9.3%) were the most common symptoms, while 18 patients were diagnosed in incidental laboratory tests. Blood tests revealed hypokalemia (69.2%), hypophosphatemia (98.0%), and hypouricemia (93.3%). Urinalysis revealed glucosuria (96.1%), proteinuria (100.0%), generalized hyperaminoaciduria (100.0 %), β2 macroglobulin (100.0%). Decreased percent total reabsorption of phosphate (%TRP) found in 94.1% of patients, and increased fractional excretion of uric acid (FEUA) were found in 100% of patients. The median time to resolution of FS after discontinuation of drug therapy was 3 months (range 0.25–18).ConclusionsThe possibility of FS needs to be considered with long-term VPA administration, especially in young, tube-fed, severely disabled patients who are co-administered with anticonvulsants. Patients receiving VPA should have regular blood and urine tests. Abnormal laboratory values returned to normal levels after VPA discontinuation.

Background: Knowledge of metformin-induced hepatotoxicity is based on case reports. The aim of this study was to investigate the clinical features of metformin-induced hepatotoxicity.Methods: We collected relevant literature on metformin-induced hepatotoxicity published from January 1994 to February 2022 by searching Chinese and English databases.Results: Thirty patients (19 males and 11 females) from 29 articles were included, with a median age of 61 years (range 29–83). The median time to onset of liver injury was 4 weeks (range 0.3–648) after metformin administration. Clinical symptoms occurred in 28 patients, including gastrointestinal reactions (56.7%), jaundice (50.0%), fatigue (36.7%), anorexia (23.3%), pruritus (13.3%), dark urine (13.3%), and clay-colored stools (10.0%). Serum alanine transaminase, aspartate transaminase, γ-glutamyl transferase, total bilirubin and alkaline phosphatase were elevated to varying degrees. Liver imaging in 26 patients showed hepatic steatosis (6 cases, 23.1%) and gallbladder wall thickening (11.5%). Liver biopsies from 13 patients showed portal phlebitis (61.5%), cholestatic hepatitis (38.5%), and parenchymal inflammation (38.5%). After metformin discontinuation, liver function returned to normal levels at a median of 6 weeks (range 2–16).Conclusions: Metformin-induced hepatotoxicity is a rare adverse reaction. Physicians and patients should be alert to metformin-induced hepatotoxicity.

BackgroundCurrent knowledge of Kounis syndrome induced by non-steroidal anti-inflammatory drugs (NSAIDs) is based on case reports. This study aimed to investigate the clinical features of Kounis syndrome.MethodsCase reports of the NSAIDs-induced Kounis syndrome were analyzed by searching Chinese and English databases from 1 January 1950 to 31 January 2022.ResultsThe median age of the 45 included patients (28 women) was 51 years (20–80 years). NSAIDs that were the most frequently involved were diclofenac (26.7%, 12/45), metamizole (15.6%, 7/45), and aspirin (13.3%, 6/45). Kounis syndrome occurred mainly within 30 min after administration, with a maximum latency of 1 month. Chest pain (75.6%, 34/45), dyspnea (33.3%, 15/45), and allergic reactions (44.4%, 20/45) were the most common clinical manifestations. Thirty patients (66.7%) had an ST-segment elevation on the electrocardiogram. Echocardiogram and coronary angiography showed abnormalities in 21 patients (75%, 21/28) and 15 patients (37.5%, 15/40). Forty-four patients (97.8%) had a good prognosis after treatment with steroids, antihistamines, and vasodilators.ConclusionThe possibility of Kounis syndrome should be considered in the presence of coronary artery disease symptoms when taking NSAIDs. Kounis syndrome can be life-threatening. It is essential to identify and treat Kounis syndrome correctly.

ObjectiveTo investigate the clinical features, treatment, and prognosis of fingolimod-associated macular edema (FAME) and to provide a reference for its rational management.MethodsFAME-related case reports were included in a pooled analysis by searching Chinese and English databases from 2010 to November 31, 2021.ResultsThe median age of 41 patients was 50 years (range, 21, 67 years), of whom 32 were women. The median time to onset of FAME was 3 m (range.03, 120), and blurred vision (17 cases) and decreased vision (13 cases) were the most common complaints. A total of 55 eyes were involved in FAME, including the left eye (14 cases), right eye (10 cases), and both eyes (15 cases), of which 46 eyes had best-corrected visual acuity close to normal (20/12-20/60) and 8 eyes had moderate to severe visual impairment (20/80-20/500). Fundus examination in 23 patients showed macular edema (11 cases). Optical coherence tomography (OCT) in 39 patients mainly showed perifoveal cysts (24 cases), ME (23 cases), and foveal thickening (19 cases). Fundus fluorescein angiography (FFA) in 18 patients showed vascular leakage (11 cases). Complete resolution of ME occurred in 50 eyes and recovery of visual acuity occurred in 45 eyes at a median time of 2 m (range 0.25, 24) after discontinuation of fingolimod or administration of topical therapy.ConclusionsMacular edema is a known complication of fingolimod. All patients using fingolimod require regular eye exams, especially those with a history of diabetes and uveitis and those undergoing cataract surgery.

Abstract Background The exact incidence, clinical features and uniform diagnostic criteria of exogenous insulin autoimmune syndrome (EIAS) are still unclear. The purpose of this study is to explore the clinical characteristics of EIAS and to provide a structural approach for clinical diagnosis, treatment and prevention. Methods The literature on EIAS in Chinese and English from 1970 to 2020 was collected for retrospective analysis. Results A total of 122 patients (33 males and 73 females) were included in the study with a median age of 67 years (range 14–86) and a median HbA1c of 7.7%. EIAS mainly occurred in type 2 diabetes mellitus patients using premixed insulin. Symptoms manifested were hypoglycemia in 86.54%, recurrent episodes of symptomatic hypoglycemia in 35.58%, nocturnal hypoglycemia along with daytime hyperglycemia in 21.15% and recurrent hypoglycemia after discontinued insulin in 64.43%. The onset of symptoms occurred at night, in the early morning or during fasting, ranging from a few days to 78 months after the administration of insulin. The mean blood glucose level during the hypoglycemic phase was 2.21 mmol/L (range 1–3.4), and the serum insulin levels were mainly ≥ 100 U/mL and were associated with low C-peptide levels (≤ 10 ng/ml). Insulin autoantibodies (IAAs) were positive in all EIAS patients. The 75-g extended oral glucose tolerance test (OGTT) mainly showed a diabetic curve. Pancreatic imaging was unremarkable. Withdrawal of insulin alone or combination of oral hypoglycemic agents or replacement of insulin formulations or with corticosteroid treatment eliminated hypoglycemia in a few days to 3 months. IAA turned negative in 6 months (median, range 1–12). No hypoglycemia episodes were observed at a median follow-up of 6 months (range 0.5–60). Conclusions EIAS is an autoimmune disease caused by insulin-binding antibodies in susceptible subjects. Insulin antibodies change glucose dynamics and could increase the incidence of hypoglycemic episodes. Detection of insulin antibodies is the diagnostic test. Changing therapeutic modalities reduced the incidence of hypoglycemic episodes.

Objective: Vancomycin combined with β-lactams (Combo therapy) has been encouraged in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSIs) in recent years, but its efficacy and safety have not been systematically evaluated. This is a systematic review and meta-analysis to clarify the efficacy and safety of Combo therapy in patients with MRSA BSIs. Methods: Relevant articles reporting on the clinical or microbiology outcomes of Combo treatment in adult patients with MRSA bacteraemia throughout November 2019 were searched in PubMed, EMBASE and Cochrane Library databases. Summary odds ratios (ORs) or mean differences (MDs) and 95% confidence intervals (CIs) were evaluated using a fixed- or random-effects model. Results: Six articles (806 patients) consisting of one RCT and five retrospective cohort studies were included in this study. The pooled data showed that Combo therapy could significantly reduce the risk of microbiological failure (OR = 0.54, 95% CI 0.35–0.83, I2 40%, P = 0.005) and persistent bacteraemia (OR=0.48, 95% CI 0.30–0.77, I2 13%, P = 0.002), as well as shorten the duration of bacteraemia (MD = −1.06, 95% CI −1.53 to −0.60, I2 0%, P < 0.00001). In addition, it did not significantly increase the incidence of nephrotoxicity (OR = 1.17, 95% CI 0.64–2.13, I2 0%, P = 0.61). However, no significant difference was detected between the groups regarding 28/30-day mortality, MRSA-related mortality, bacteraemia relapse or length of hospitalization. Conclusions: These results demonstrate that Combo therapy clears the pathogenic bacteria of MRSA bacteraemia but does not improve the clinical prognosis. As the sample size was small and most of the studies were retrospective cohort studies with substantial heterogeneity, there is a need for further studies encompassing large-scale multicentre RCTs to validate our results.

BackgroundCephalosporins are an increasingly encountered cause of Kounis syndrome. The present study examined the clinical features of cephalosporin-induced Kounis syndrome and provided references for diagnosis, prevention, treatment, and prognosis.MethodsWe collected cephalosporin-induced Kounis syndrome case reports by searching Chinese and English databases from the establishment of the database to October 31, 2021.ResultsTwenty-five patients (17 males and eight females) were included, with a median age of 61 years (range 33–92). Cephalosporins were administered via oral, intravenous and intramuscular routes. All reactions occurred within 30 min, except in two patients. Fourteen patients experienced chest pain, 19 experienced hypotension, 16 had cutaneous reactions, 10 had respiratory symptoms, and seven had gastrointestinal symptoms. Thirteen patients had elevated troponin levels, and eight patients had elevated serum tryptase levels. The electrocardiogram showed ST-segment elevation in 13 patients, depression in four patients, and elevation and depression in six patients. Coronary angiography showed normal results in 12 patients and abnormal results in 13 patients. The skin prick test was positive for cephalosporin in three patients. Twenty-four of the 25 patients recovered after being given anti-allergic and acute coronary syndrome treatment, and there was one death.ConclusionsKounis syndrome is a serious adverse reaction to cephalosporin. Clinicians should consider Kounis syndrome in every patient receiving cephalosporin and presenting with acute chest pain or anaphylactic symptoms.

Numerous case reports of acute pancreatitis (AP) induced by olanzapine have been published. Little is, however, known about the clinical features of olanzapine-induced AP. The aim of the study was to explore the clinical characteristics of olanzapine-induced AP. We collected literature on AP cases induced by olanzapine from 1996 to April 2021 for retrospective analysis in Chinese and English. The median time to onset of olanzapine-induced acute pancreatic symptoms was 12 (range = 0.86–216) weeks in 25 patients. The clinical features of AP range from asymptomatic elevation of blood amylase/lipase levels to digestive system symptoms (abdominal pain, vomiting, and nausea) and even death in a small number of patients. Laboratory tests showed varying degrees of elevated serum amylase and lipase levels, along with high blood sugar and high triglyceride levels in some patients. Computed tomography showed acute edematous pancreatitis, acute hemorrhagic pancreatitis, and acute necrotizing pancreatitis in the patients. The patients’ symptoms were completely relieved and high triglyceride levels gradually returned to normal levels after olanzapine was stopped. Some patients with hyperglycemia still needed hypoglycemic therapy. AP is a rare adverse effect of olanzapine. Clinicians should be aware of such complications and monitor pancreatin.

Objective: To evaluate the efficacy and safety of different doses of sildenafil for persistent pulmonary hypertension of the newborn (PPHN) with Bayesian random effects network meta-analysis.Methods: We searched Chinese and English databases for randomized controlled trials (RCTs) concerning sildenafil in newborns with persistent pulmonary hypertension from 1998 to December 2020.Results: Twenty-two RCTs including over 2131 patients were included. Sildenafil was administered by nasal feeding at 0.3–2 mg/kg every 4–6 h. The network meta-analysis revealed that 1.5 mg/kg of sildenafil led to a significant decrease in pulmonary artery systolic pressure (PASP) compared with 0.3 and 0.6 mg/kg (p < 0.05); 1.5 mg/kg was better than 0.3, 0.5, and 1.0 mg/kg at increasing the partial pressure of oxygen (PaO2) (p < 0.05); 1.5 mg/kg was better than 0.5, 0.6 and 1.0 mg/kg at reducing the partial pressure of carbon dioxide (PaCO2) (p < 0.05); and 1.2 mg/kg was better than 0.3, 0.5 and 1.0 mg/kg at increasing the arterial oxygen saturation (SaO2) (p < 0.05). The surface under the cumulative ranking analysis (SUCRA) results showed that 1.5 mg/kg had the best effect in reducing PASP (SUCRA = 92.0%, moderate certainty evidence) and PaCO2 (91.1%) and increasing PaO2 (SUCRA = 79.3%, moderate certainty evidence), 2.0 mg/kg had the best effect in increasing SaO2 (SUCRA = 88.6%, moderate certainty evidence) and total effective rate (SUCRA = 93.5%, low certainty of evidence)). No severe adverse effects were observed with the different doses of sildenafil.Conclusion: Different doses of sildenafil can significantly improve PPHN, and 1.5 mg/kg of sildenafil has better clinical efficacy and does not increase the probability of adverse reactions.

Objective: The was a pilot study to assess the biochemical and historical information about bariatric patients before undergoing the surgery in the aim of identifying nutritional deficiencies and their prevalence from 2015 to 2020.Methods: Clinical data of 247 patients (105 males and 142 females) were included. Vitamins, trace elements, electrolytes, albumin, globulin, hemoglobin, folate, ferritin, microalbuminuria (MAU), and parathyroid hormone (PTH) levels were determined to explore the nutritional status according to gender, age, high body mass index (BMI), and waist circumstance (WC).Results: The mean age, mean BMI, and mean WC of the candidates were 32.95 ± 10.46 years, 38.01 ± 7.11 kg/m2, and 117.04 ± 16.18 cm, respectively. The prevalence of preoperative nutritional deficiencies was 76.88% for 25 (OH) vitamin D, 19.84% for globulin, 11.74% for albumin, 11.02% for sodium, 8.33% for folic acid, 10.48% (male) and 6.34% (female) for chloride, 4.05% for calcium, 3.07% (male) and 0.70%(female) for ferritin, 11.90% for elevated PTH, and 44.96% for MAU. Males exhibited increased prevalence of globulin and MAU relative to females (P < 0.05). Older groups are more likely to exhibit albumin deficiency (P = 0.007), globulin deficiency (P = 0.003), and zinc deficiency (P = 0.015). In addition, 25 (OH) D deficiency and albumin deficiency were more common in patients with BMI ≥ 47.5 kg/m2 (P = 0.049 and 0.015, respectively). Wider WC (≥150 cm) exhibited higher rates of albumin deficiencies (P = 0.011).Conclusion: Electrolyte and nutritional deficiencies were common in patients prior to bariatric surgery in South China. Routine evaluation of electrolyte and nutritional levels should be carried out in this population.

Prostaglandin pathway plays multiple roles in various physiological and pathological conditions. The present study aimed to investigate the effect of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key enzyme in the degradation of prostaglandins, on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in mice. In this study, male C57BL/6J mice were injected intraperitoneally with LPS (10 mg/kg). SW033291, a potent small-molecule inhibitor of 15-PGDH, was used to investigate the therapeutic potential of 15-PGDH inhibition on LPS-induced AKI. We discovered that the expression of 15-PGDH protein was upregulated in kidneys of LPS-stimulated mice, and it was mainly localized in the cytoplasm of renal tubular epithelial cells in renal cortex and outer medulla. SW033291 administration improved the survival rates of mice and attenuated renal injury of mice that were challenged by LPS. Additionally, inhibition of 15-PGDH also reversed LPS-induced apoptosis of renal cells, increased expression of anti-apoptotic protein Bcl-2, and downregulated expression of Fas, caspase-3, and caspase-8. Pretreatment of SW033291 enhanced autophagy in kidney cells after LPS stimulation. Our data also showed that inhibition of 15-PGDH relieved the level of lipid peroxidation and downregulated NADPH oxidase subunits induced by LPS in mice kidneys but had no significant effect on the release of inflammatory factors, such as IL-6, IL-1β, TNF-α, and MCP-1. Our study demonstrated that inhibition of 15-PGDH could alleviate LPS-induced AKI by regulating the apoptosis, autophagy, and oxidative stress rather than inflammation in mice.