Assessing the effectiveness and safety of surufatinib versus everolimus or sunitinib in advanced neuroendocrine neoplasms: insights from a real-world, retrospective cohort study using propensity score and inverse probability treatment weighting analysis.

Background: While surufatinib, sunitinib, and everolimus have shown efficacy for advanced neuroendocrine neoplasms (NENs) in randomized controlled trials (RCTs), direct comparisons in a real-world setting remain unexplored. This gap highlights the clinical need to understand their comparative effectiveness and safety within the diverse Chinese population. Addressing this, our study provides insights into the real-world performance of these therapies, aiming to inform treatment selection and improve patient outcomes. Methods: A retrospective, observational study was conducted at Fudan University Shanghai Cancer Center, including patients with advanced NENs treated with surufatinib, sunitinib, or everolimus between July 2020 and April 2023. Eligibility criteria focused on histologically confirmed, locally advanced, unresectable, or metastatic NENs, with patients having received at least one month of targeted therapy. We employed inverse probability weighting (IPW) with the propensity score (PS) matching to adjust for the bias of baseline characteristics. The assessment of covariates included age, sex, performance status, primary tumor site, functional status, genetic mutations, tumor differentiation, Ki67 index, tumor grade, metastasis site, and previous therapies. The primary outcome was progression-free survival (PFS), and secondary outcomes included objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results: The study enrolled 123, 56, and 68 locally advanced or metastatic NEN patients treated with surufatinib, sunitinib, and everolimus, respectively. Before adjusting for confounding factors, surufatinib was used less frequently as a first-line treatment compared to sunitinib and everolimus in pancreatic NENs (pNENs) (11.1% vs. 22.1%, P=0.057). Significant differences were noted in prior treatments and tumor characteristics between surufatinib and everolimus groups in extrapancreatic NENs (epNENs) (P<0.05). Post-IPW, these disparities were resolved (P>0.05). Surufatinib demonstrated superior median PFS (mPFS) in both pancreatic [8.30 vs. 6.33 months, hazard ratio (HR) 0.592, P<0.001] and epNENs (8.73 vs. 3.70 months, HR 0.608, P<0.001) compared to everolimus or sunitinib. Notably, male gender (HR 1.75, P=0.001), functional status (HR 2.09, P=0.01), Ki67 index >20% (HR 12.7, P=0.004), previous somatostatin analogue (SSA) treatment (HR 1.73, P=0.001), germline mutation (HR 5.62, P<0.001), poor differentiation (HR 7.45, P<0.001), liver metastasis (HR 1.72, P=0.001) and multiple treatment lines (HR 1.62 for 2nd line, P=0.04; HR 1.88 for ≥3rd line, P=0.01) were identified as negative prognostic factors for PFS. Conversely, dose adjustment (HR 0.63, P=0.009) and treatment with surufatinib (HR 0.58 for pNEN, P<0.001; HR 0.62 for epNEN, P=0.002) were correlated with longer PFS. Conclusions: In a real-world Chinese cohort, surufatinib significantly outperformed sunitinib and everolimus in prolonging PFS among advanced NEN patients, with identifiable clinical features impacting survival, and conclusions regarding superiority should be interpreted with caution due to the retrospective design. Our findings underscore the need for prospective studies to further validate these results and explore additional predictive biomarkers for personalized treatment strategies.

Cadaveric feasibility study of modified contralateral C7 nerve transfer for targeted functional recovery in hemiplegic upper extremity.

BACKGROUND: Contralateral cervical seventh (cC7) nerve to C7 transfer has been proven effective for treating spastic upper limb. However, for those whose major impairment is not in the C7 area, cC7 nerve transfer to other nerve(s) may achieve a better outcome. The aim of this study was to explore the optimal surgical approach for transferring cC7 to one or two nerves by cadaveric study and to discuss the possible applications for hemiplegic patients. METHODS: Modified cC7 transfer to one (five procedures) or two nonadjacent (three procedures) nerve roots was proposed, and success rates of direct coaptation through two surgical approaches were compared: the superficial surface of longus colli (sLC) and the deep surface of longus colli (dLC) approaches. The length, diameter and distance of relevant nerves were also measured in 25 cadavers. RESULTS: Compared with the sLC approach, the distance of the dLC approach was 1.1 ± 0.3 cm shorter. The success rates for the sLC and dLC approaches were as follows, respectively: cC7-C5 surgery, 94% and reached 98%; cC7-C6 surgery, 54% and 96%; cC7-C7 surgery, 42% and 94%; cC7-C8 surgery, 34% and 94%; cC7-T1 surgery, 24% and 62%; cC7-C5C7 surgery, 74% and 98%; cC7-C6C8 surgery, 54% and 98%. cC7-C7T1 surgery, 42% and 88%. CONCLUSIONS: The dLC approach greatly improved direct coaptation rate for cC7 nerve transfer. The modified cC7 nerve transfer procedures are technically feasible for further application in clinic.

Post-marketing safety surveillance of sacituzumab govitecan: an observational, pharmacovigilance study leveraging FAERS database.

Background and objective: Sacituzumab govitecan (SG), the first antibody-drug conjugate targeting human trophoblast cell-surface antigen 2 (Trop-2), has been approved by the Food and Drug Administration (FDA) for the treatment of advanced or metastatic breast cancer and urothelial cancer. However, there is currently a dearth of information regarding the safety profiles of SG in a large sample cohort. The objective of the present study is to investigate SG-related adverse events (AEs) in real-world settings leveraging the FDA Adverse Event Reporting System (FAERS) database to guide the safety management of clinical medication. Methods: The FAERS database was retrospectively queried to extract reports associated with SG from April 2020 to March 2023. To identify and evaluate potential AEs in patients receiving SG, various disproportionality analyses such as reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed. Results: Overall, 2069 reports of SG as the "primary suspect" were identified. Noteworthy, SG was significantly associated with an increased risk of blood lymphatic system disorders (ROR, 7.18; 95% CI, 6.58-7.84) and hepatobiliary disorders (ROR, 2.68; 95% CI, 2.17-3.30) at the System Organ Class (SOC) level. Meanwhile, 61 significant disproportionality preferred terms (PTs) simultaneously complied with all four algorithms were adopted. Therein, anemia, thrombocytopenia, neutropenia, leukopenia, diarrhea, asthenia, alopecia, and electrolyte imbalance were consistent with the common AEs described in the clinical trials and specification of SG. Furthermore, unexpected significant AEs include colitis (ROR, 12.09; 95% CI, 9.1-16.08), heart rate increased (ROR, 5.11; 95% CI, 3.84-6.79), sepsis (ROR, 4.77; 95% CI, 3.59-6.34), cholestasis (ROR, 6.28; 95% CI, 3.48-11.36), blood bilirubin increased (ROR, 4.65; 95% CI, 2.42-8.94) and meningitis (ROR, 7.23; 95% CI, 2.71-19.29) were also be detected. The median time to onset of SG-related AEs was 14 [interquartile range (IQR), 7-52] days, with the majority occurring within the initial month of SG treatment. Conclusion: Our study validates the commonly known AEs and also found some potentially emerging safety issues related to SG in real-world clinical practice, which could provide valuable vigilance evidence for clinicians and pharmacists to manage the safety issues of SG.

Prevalence and risk factors of tuberculosis among people living with HIV/AIDS in China: a systematic review and meta-analysis.

OBJECTIVE: To estimate the prevalence and risk factors associated with tuberculosis (TB) among people living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in China. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. After the literature was screened based on the inclusion and exclusion criteria, STATA® version 17.0 software was used for the meta-analysis. The heterogeneity among study data was assessed using I2 statistics. Subgroup analysis and meta-regressions were performed to further explore the source of heterogeneity. RESULTS: A total of 5241 studies were retrieved. Of these, 44 studies were found to be eligible. The pooled prevalence of HIV/TB co-infection was 6.0%. The risk factors for HIV/TB co-infection included a low CD4+ T cell count, smoking, intravenous drug use and several other sociodemographic and clinical factors. Bacillus Calmette-Guérin (BCG) vaccination history was a protective factor. CONCLUSION: A high prevalence of TB was observed among people living with HIV/AIDS in China. Low CD4+ T cell count, smoking, and intravenous drug use were the primary risk factors for HIV/TB co-infection, whereas BCG vaccination history was a protective factor. Checking for TB should be prioritized in HIV screening and healthcare access. SYSTEMATIC REVIEW REGISTRATION: Registered on PROSPERO, Identifier: CRD42022297754.

Median Nerve Palsy in Pediatric Supracondylar Humerus Fractures Recovers Faster With Open Than Closed Reduction.

BACKGROUND: Management of supracondylar humerus fractures (SCHF) with coexisting median nerve injury is controversial. Although many nerve injuries improve with the reduction and stabilization of the fracture, the speed and completeness of recovery are unclear. This study investigates median nerve recovery time using the serial examination. METHODS: A prospectively maintained database of SCHF-related nerve injuries referred to a tertiary hand therapy unit between 2017 and 2021 was interrogated. Factors related to the injury (vascularity, Gartland grade, open vs. closed fracture) and treatment (fixation modality, adequacy, timing of reduction, vascular and nerve intervention, and secondary procedures) were assessed.Primary outcomes were the motor recovery of Medical Research Council (MRC) grade 4 or 5 in flexor pollicis longus or flexor digitorum profundus (index) and detection of the 2.83 Semmes Weinstein monofilament.A retrospective clinical note review of all SCHF presenting during the same period was also conducted. RESULTS: Of 1096 SCHF, 74 (7%) had an associated median nerve palsy. Twenty-one patients [mean age 7 years (SD 1.6)] with SCHF-related median nerve injuries underwent serial examination. Nineteen (90%) were modified Gartland III or IV, and 10 (48%) were pulseless on presentation. The mean follow-up was 324 days.The mean motor recovery time was 120 days (SD 71). Four (27%) and 2 (13%) patients had not achieved MRC grade 4 by 6 months and 2 years, respectively. Only 50% attained MRC grade 5 at 2 years.When compared with closed reduction, those who underwent open reduction recovered motor function 80 days faster (mean 71 vs. 151 d, P =0.03) and sensory function 110 days faster (52 vs. 162, P =0.02). Fewer patients recovered after closed reduction (8 of 10) than open (5 of 5).Modified Gartland grade, vascular status, adequacy of reduction, and secondary surgery were not associated with recovery time. CONCLUSIONS: Median nerve recovery seems to occur slower than previously thought, is often incomplete, and is affected by treatment decisions (open vs. closed reduction). Retrospective reporting methods may overestimate median nerve recovery. LEVEL OF EVIDENCE: Level III-therapeutic.

Ocular adverse events associated with BRAF and MEK inhibitor combination therapy: a pharmacovigilance disproportionality analysis of the FDA adverse event reporting system.

BACKGROUND: BRAF and MEK inhibitor combination therapy have significantly improved the outcome of several BRAF-mutation tumors, but it also confers the risk of drug-induced ocular adverse events (oAEs). However, very few studies focused on this risk. METHODS: The United States Food and Drug Administration Adverse Event Reporting System (FAERS) data from Quarter 1-2011 to Quarter 2-2022 were searched to detect signs of oAEs of three marketed BRAF and MEK inhibitor combination therapies: vemurafenib plus cobimetinib (V + C), dabrafenib plus trametinib (D + T), and encorafenib plus binimetinib (E + B). Disproportionality analyses were performed by calculating the proportional reporting ratio (PRR), χ2 (chi-square), and reporting odds ratios (RORs) with a 95% confidence interval (CI). RESULTS: A series of oAEs were identified, including 42 preferred terms, which could be classified into 8 aspects. In addition to previously reported oAEs, several unexpected oAE signals were detected. Moreover, differences in oAE profiles were found among three combination therapies (V + C, D + T, and E + B). CONCLUSIONS: Our findings support an association between several oAEs and BRAF and MEK inhibitor combination therapies, including several new oAEs. In addition, oAEs profiles may vary across the treatment regimens. Further studies are needed to better quantify these oAEs.

Cancer cell-derived type I interferons instruct tumor monocyte polarization.

Monocytes are highly plastic immune cells that modulate antitumor immunity. Therefore, identifying factors that regulate tumor monocyte functions is critical for developing effective immunotherapies. Here, we determine that endogenous cancer cell-derived type I interferons (IFNs) control monocyte functional polarization. Guided by single-cell transcriptomic profiling of human and mouse tumors, we devise a strategy to distinguish and separate immunostimulatory from immunosuppressive tumor monocytes by surface CD88 and Sca-1 expression. Leveraging this approach, we show that cGAS-STING-regulated cancer cell-derived IFNs polarize immunostimulatory monocytes associated with anti-PD-1 immunotherapy response in mice. We also demonstrate that immunosuppressive monocytes convert into immunostimulatory monocytes upon cancer cell-intrinsic cGAS-STING activation. Consistently, we find that human cancer cells can produce type I IFNs that polarize monocytes, and our immunostimulatory monocyte gene signature is enriched in patient tumors that respond to anti-PD-1 immunotherapy. Our work exposes a role for cancer cell-derived IFNs in licensing monocyte functions that influence immunotherapy outcomes.

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As the core region of the "Grain to Green" Program, the Loess Plateau of Northern Shaanxi became an example with the most dramatic changes in earth surface pattern and vegetation cover. Evaluating the effectiveness of vegetation restoration is important for promoting regional ecological environment. In this study, the fractional vegetation coverage (FVC) was used as the index to analyze the changes in vegetation coverage in this area. Soil conservation service, carbon sequestration service, habitat quality, and water yield were used to characterize the regional ecosystem services (ESs). The effects of FVC on ESs were analyzed based on the bivariate spatial autocorrelation model. The trade-off synergies and spatio-temporal variations of different scales of those indices were discussed. The results showed that the FVC of the study area presented a fluctuating upward trend from 2000 to 2020, with the annual average value increasing from 31.7% to 47.1%. Carbon sequestration service and soil conservation service were increased, habitat quality was stable. Water yield increased firstly and then decreased, with an overall upward trend. The ESs changes were scale-dependent. There was an obvious synergistic relationship among ESs. There was a significant spatial dependence between FVC and ESs, with some differences in the degree of correlation. FVC had the strongest impact on soil conservation, followed by carbon sequestration service. However, the increase of vegetation coverage and water consumption of forest and grass led to the negative effect of water yield reduction. In gene-ral, FVC in the Loess Plateau of Northern Shaanxi had achieved remarkable success, and the ecological environment had been significantly improved.

Neuromuscular junction dysfunctions due to immune checkpoint inhibitors therapy: An analysis of FAERS data in the past 15 years.

Introduction: The adverse effects of neuromuscular junction dysfunctions caused by immune checkpoint inhibitor (ICI) drugs have not been thoroughly assessed in the clinics. Objective: To assess the neuromuscular junction dysfunctions in cancer patients with adverse events caused by ICI therapy by searching the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Methods: The FAERS data from January 2004 to December 2020 were collected to analyze the association between neuromuscular connection dysfunction and ICI use. Disproportionate analysis and Bayesian analysis were used to quantify the association between the neuromuscular junction dysfunctions and ICIs. The onset time and outcome of neuromuscular junction dysfunctions in different ICI regimens were also compared. Results: Out of 88,617 adverse event reports, 557 neuromuscular junction dysfunction reports (0.63%) were analyzed. Marketed ICI drugs, including ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, cemiplimab, avelumab, as well as their combinations, showed positive associations with four detection methods. Most of the adverse event reports were associated with the use of nivolumab (53.32%) and pembrolizumab (31.96%). However, nivolumab-related neuromuscular junction dysfunctions were similar with pembrolizumab (33.33% vs 33.14%, p > 0.05). The onset time of neuromuscular junction dysfunctions showed no significant difference among different ICIs (p > 0.05). Conclusions: Analysis of FAERS data identified that over 30% (32.85%) of reports of neuromuscular junction dysfunctions resulted in death. Ongoing monitoring, risk evaluations, and further comparative studies of ICIs should be considered.

Effects of fulvic acid on growth performance, serum index, gut microbiota, and metabolites of Xianju yellow chicken.

Fulvic acid (FA) is a mixture of polyphenolic acid compounds extracted from humus, peat, lignite, and aquatic environments; it is used in traditional medicine to treat digestive tract diseases. The purpose of the present study was to investigate the effect of FA on growth performance, inflammation, intestinal microbiota, and metabolites in Xianju yellow chicken. The 240 Xianju yellow chickens (age, 524 days) included were randomly categorized into 4 treatments with 6 replicates per treatment and 10 birds per replicate. Birds received a basal diet or a diet supplemented with 500, 1,000, or 1,500 mg/kg of FA, for a period of 42 days. Dietary supplementation of FA improved average daily gain (ADG) and feed conversion ratio (FCR) (P > 0.05). Compared with the control group, the serum level of TNF-α in birds supplemented with FA was significantly decreased (P < 0.05), and that of IL-2 was significantly increased after administration of 1,500 mg/kg FA (P < 0.05). Analysis of gut microbiota indicated that FA reduced the relative abundance of genus Mucispirillum, Anaerofustis, and Campylobacter, but enriched genus Lachnoclostridium, Subdoligranulum, Sphaerochaeta, Oscillibacter, and Catenibacillus among others. Untargeted metabolomic analyses revealed that FA increased 7-sulfocholic acid, but reduced the levels of Taurochenodeoxycholate-7-sulfate, LysoPC 20:4 (8Z, 11Z, 14Z, 17Z), LysoPC 18:2, Phosphocholine and other 13 metabolites in the cecum. The results demonstrated that FA may potentially have a significant positive effect on the growth performance and immune function of Xianju yellow chicken through the modulation of the gut microbiota.

Predicting Lapatinib Dose Regimen Using Machine Learning and Deep Learning Techniques Based on a Real-World Study.

Lapatinib is used for the treatment of metastatic HER2(+) breast cancer. We aim to establish a prediction model for lapatinib dose using machine learning and deep learning techniques based on a real-world study. There were 149 breast cancer patients enrolled from July 2016 to June 2017 at Fudan University Shanghai Cancer Center. The sequential forward selection algorithm based on random forest was applied for variable selection. Twelve machine learning and deep learning algorithms were compared in terms of their predictive abilities (logistic regression, SVM, random forest, Adaboost, XGBoost, GBDT, LightGBM, CatBoost, TabNet, ANN, Super TML, and Wide&Deep). As a result, TabNet was chosen to construct the prediction model with the best performance (accuracy = 0.82 and AUC = 0.83). Afterward, four variables that strongly correlated with lapatinib dose were ranked via importance score as follows: treatment protocols, weight, number of chemotherapy treatments, and number of metastases. Finally, the confusion matrix was used to validate the model for a dose regimen of 1,250 mg lapatinib (precision = 81% and recall = 95%), and for a dose regimen of 1,000 mg lapatinib (precision = 87% and recall = 64%). To conclude, we established a deep learning model to predict lapatinib dose based on important influencing variables selected from real-world evidence, to achieve an optimal individualized dose regimen with good predictive performance.

Dosage Strategy of Linezolid According to the Trough Concentration Target and Renal Function in Chinese Critically Ill Patients.

Background: Linezolid is associated with myelosuppression, which may cause failure in optimally treating bacterial infections. The study aimed to define the pharmacokinetic/toxicodynamic (PK/TD) threshold for critically ill patients and to identify a dosing strategy for critically ill patients with renal insufficiency. Methods: The population pharmacokinetic (PK) model was developed using the NONMEM program. Logistic regression modeling was conducted to determine the toxicodynamic (TD) threshold of linezolid-induced myelosuppression. The dosing regimen was optimized based on the Monte Carlo simulation of the final model. Results: PK analysis included 127 linezolid concentrations from 83 critically ill patients at a range of 0.25-21.61 mg/L. Creatinine clearance (CrCL) was identified as the only covariate of linezolid clearance that significantly explained interindividual variability. Thirty-four (40.97%) of the 83 patients developed linezolid-associated myelosuppression. Logistic regression analysis showed that the trough concentration (Cmin) was a significant predictor of myelosuppression in critically patients, and the threshold for Cmin in predicting myelosuppression with 50% probability was 7.8 mg/L. The Kaplan-Meier plot revealed that the overall median time from the initiation of therapy to the development of myelosuppression was 12 days. Monte Carlo simulation indicated an empirical dose reduction to 600 mg every 24 h was optimal to balance the safety and efficacy in critically ill patients with CrCL of 30-60 ml/min, 450 mg every 24 h was the alternative for patients with CrCL <30 ml/min, and 600 mg every 12 h was recommended for patients with CrCL ≥60 ml/min. Conclusion: Renal function plays a significant role in linezolid PKs for critically ill patients. A dose of 600 mg every 24 h was recommended for patients with CrCL <60 ml/min to minimize linezolid-induced myelosuppression.

Clinical observation and genetic analysis of a SYNS1 family caused by novel NOG gene mutation.

OBJECTIVE: Analyze the clinical and genetic characteristics of a rare Chinese family with Multiple synostoses syndrome and identify the causative variant with the high-throughput sequencing approach. METHODS: The medical history investigation, physical examination, imaging examination, and audiological examination of the family members were performed. DNA samples were extracted from the family members. The candidate variant was identified by performing whole-exome sequencing of the proband, then verified by Sanger sequencing in the family. RESULTS: The family named HBSY-018 from Hubei province had 18 subjects in three generations, and six subjects were diagnosed with conductive or mixed hearing loss. Meanwhile, characteristic features including short philtrum, hemicylindrical nose, and hypoplastic alae nasi were noticed among those patients. Symptoms of proximal interdigital joint adhesion and inflexibility were found. The family was diagnosed as Multiple synostoses syndrome type 1 (SYNS1).The inheritance pattern of this family was autosomal dominant. A novel mutation in the NOG gene c.533G>A was identified by performing whole-exome sequencing of the proband. The substitution of cysteine encoding 178th position with tyrosine (p.Cys178Tyr) was caused by this mutation, which was conserved across species. Co-segregation of disease phenotypes was demonstrated by the family verification. CONCLUSION: The family diagnosed as SYNS1 was caused by the novel mutation (c.533G>A) of NOG. The combination of clinical diagnosis and molecular diagnosis had improved the understanding of this rare disease and provided a scientific basis for genetic counseling in the family.

Impaired Sphingosine-1-Phosphate Synthesis Induces Preeclampsia by Deactivating Trophoblastic YAP (Yes-Associated Protein) Through S1PR2 (Sphingosine-1-Phosphate Receptor-2)-Induced Actin Polymerizations.

Incomplete spiral artery remodeling, caused by impaired extravillous trophoblast invasion, is a fundamental pathogenic process associated with malplacentation and the development of preeclampsia. Nevertheless, the mechanisms controlling this regulation of trophoblast invasion are largely unknown. We report that sphingosine-1-phosphate synthesis and expression is abundant in healthy trophoblast, whereas in pregnancies complicated by preeclampsia the placentae are associated with reduced sphingosine-1-phosphate and lower SPHK1 (sphingosine kinase 1) expression and activity. In vivo inhibition of sphingosine kinase 1 activity during placentation in pregnant mice led to decreased placental sphingosine-1-phosphate production and defective placentation, resulting in a preeclampsia phenotype. Moreover, sphingosine-1-phosphate increased HTR8/SVneo (immortalized human trophoblst cells) cell invasion in a Hippo-signaling-dependent transcriptional coactivator YAP (Yes-associated protein) dependent manner, which is activated by S1PR2 (sphingosine-1-phosphate receptor-2) and downstream RhoA (Ras homolog gene family, member A)/ROCK (Rho-associated protein kinase) induced actin polymerization. Mutation-based YAP-5SA (S61A, S109A, S127A, S164A, S381A) demonstrated that sphingosine-1-phosphate activation of YAP could be either dependent or independent of Hippo signaling. Together, these findings suggest a novel pathogenic pathway of preeclampsia via disrupted sphingosine-1-phosphate metabolism and signaling-induced, interrupted actin dynamics and YAP deactivation; this may lead to potential novel intervention targets for the prevention and management of preeclampsia.

Meta-analysis of risk factors associated with oxaliplatin hypersensitivity reactions in cancer patients.

This study aimed to investigate risk factors associated with oxaliplatin hypersensitivity reactions in cancer patients through a meta-analysis. A comprehensive retrieve of Chinese databases China National Knowledge Infrastructure, Wanfang Data, VIP Database and English databases PubMed, ScienceDirect, Embase and Cochrane library was conducted. The studies that meet the requirements for meta-analysis according to inclusion and exclusion criteria were screened and assessed for eligibility. Odds ratio (OR) / Weighted mean difference (WMD) and 95% confidence intervals (95% CIs) or calculable dichotomous and continuous raw data were extracted to perform meta-analysis using random effect model or fixed effect model on the basis of heterogeneity between studies through Review Manager 5.4 software. A total of 14 cross-sectional studies and 3367 cancer patients were included. Meta-analysis results showed that platinum exposure history (OR value 3.13, 95% CI 2.19-4.48, heterogeneity P = 0.26), allergy history (OR value 1.76, 95% CI 1.09-2.85, heterogeneity P = 0.61), platinum free interval (OR value 3.75, 95% CI 2.00-7.06, heterogeneity P = 0.83), dexamethasone premedication dose (OR value 0.28, 95% CI 0.13-0.58, heterogeneity P = 0.21) were significantly correlated to oxaliplatin hypersensitivity reactions. Gender, age, metastasis, combination with bevacizumab, XELOX regimen and cancer types were detected to have no statistically significant effect on oxaliplatin hypersensitivity reactions. Platinum exposure history, allergy history and long platinum-free interval are risk factors of oxaliplatin hypersensitivity reactions. High dexamethasone premedication dose is a protective factor of oxaliplatin hypersensitivity reactions.

SIRT1/PGC-1α/PPAR-γ Correlate With Hypoxia-Induced Chemoresistance in Non-Small Cell Lung Cancer.

Resistance is the major cause of treatment failure and disease progression in non-small cell lung cancer (NSCLC). There is evidence that hypoxia is a key microenvironmental stress associated with resistance to cisplatin, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), and immunotherapy in solid NSCLCs. Numerous studies have contributed to delineating the mechanisms underlying drug resistance in NSCLC; nevertheless, the mechanisms involved in the resistance associated with hypoxia-induced molecular metabolic adaptations in the microenvironment of NSCLC remain unclear. Studies have highlighted the importance of posttranslational regulation of molecular mediators in the control of mitochondrial function in response to hypoxia-induced metabolic adaptations. Hypoxia can upregulate the expression of sirtuin 1 (SIRT1) in a hypoxia-inducible factor (HIF)-dependent manner. SIRT1 is a stress-dependent metabolic sensor that can deacetylate some key transcriptional factors in both metabolism dependent and independent metabolic pathways such as HIF-1α, peroxisome proliferator-activated receptor gamma (PPAR-γ), and PPAR-gamma coactivator 1-alpha (PGC-1α) to affect mitochondrial function and biogenesis, which has a role in hypoxia-induced chemoresistance in NSCLC. Moreover, SIRT1 and HIF-1α can regulate both innate and adaptive immune responses through metabolism-dependent and -independent ways. The objective of this review is to delineate a possible SIRT1/PGC-1α/PPAR-γ signaling-related molecular metabolic mechanism underlying hypoxia-induced chemotherapy resistance in the NSCLC microenvironment. Targeting hypoxia-related metabolic adaptation may be an attractive therapeutic strategy for overcoming chemoresistance in NSCLC.

Effect of 3 mg versus 6 mg pegfilgrastim on the prevention of febrile neutropenia in breast cancer patients receiving docetaxel and cyclophosphamide: a retrospective study.

BACKGROUND: An ECCOPG (Eastern China Cooperative Oncology Pharmacy Group) funded study was designed to compare the effect of 3 versus 6 mg pegfilgrastim for primary prevention of febrile neutropenia (FN) in Chinese breast cancer patients retrospectively. METHODS: Patients undergoing a docetaxel and cyclophosphamide chemotherapy regimen, followed by pegfilgrastim, for primary prevention during 2018 and 2020 were retrospectively enrolled in the present study. The patients were divided into 2 groups according to the dose of pegfilgrastim. The incidence of severe neutropenia (absolute neutrophil count <0.5×109/L), incidence of FN, and recovery time were calculated to compare the efficacy of different groups. P<0.05 was considered statistically significant. RESULTS: A total of 295 patients were enrolled, 150 in the 3 mg pegfilgrastim group and 145 in the 6 mg pegfilgrastim group. No significant differences were found in the incidence of severe neutropenia (3 vs. 6 mg, 39.3% vs. 34.5%, P=0.401) and the incidence of FN (3 vs. 6 mg, 7.3% vs. 8.3%, P=0.830). Median recovery time was 2 days for both groups (P=0.485). CONCLUSIONS: 3 mg pegfilgrastim may be effective and safe for Chinese breast cancer patients as the primary prevention for FN. Prospective studies are needed to further confirm the prophylactic effect of 3 mg pegfilgrastim.

Plasma proprotein convertase subtilisin/kexin type 9 concentration and recurrent cardiovascular events in patients with familial hypercholesterolemia.

AIMS: Familial hypercholesterolemia patients are characterized by early onset of coronary artery calcification and atherosclerosis, and high incidence of cardiovascular events. Plasma proprotein convertase subtilisin/kexin type 9 was reported to be a predictor for cardiovascular risk in the general population. However, its prognostic value for predicting recurrent cardiovascular events in familial hypercholesterolemia patients remains undetermined. METHODS: A total of 249 patients with molecularly and/or clinically (Dutch Lipid Clinic Network score > 6) defined familial hypercholesterolemia who had experienced a first cardiovascular event were consecutively included and plasma proprotein convertase subtilisin/kexin type 9 concentrations were measured by enzyme-linked immunosorbent assay. Coronary artery calcification was measured using Agatston method and coronary severity was assessed by Gensini score, respectively. All patients received standard lipid-lowering therapy and were followed-up for recurrent cardiovascular events. Univariate and multivariate regression and Cox analyses was used to calculate hazard ratios with 95% confidence interval. RESULTS: Circulating proprotein convertase subtilisin/kexin type 9 concentrations were positively associated with coronary artery calcification scores and Gensini score by both univariate and multivariate analyses. During a mean follow-up of 43 ± 19 months, 29 (11.51%) recurrent cardiovascular events occurred. Kaplan-Meier analysis showed that patients with the highest proprotein convertase subtilisin/kexin type 9 levels had the lowest event-free survival time. Multivariable Cox regression analysis revealed that proprotein convertase subtilisin/kexin type 9 was independently associated with recurrent cardiovascular events (hazard ratio: 1.45, 95% confidence interval: 1.11-1.88). The combination of proprotein convertase subtilisin/kexin type 9 to Cox prediction model led to an enhanced predictive value for recurrent cardiovascular events. CONCLUSIONS: Increased level of proprotein convertase subtilisin/kexin type 9 was a significant risk factor of atherosclerosis and independently predicted future recurrent cardiovascular events in familial hypercholesterolemia patients receiving standard lipid-lowering treatment.

Exosomal miR-30a and miR-222 derived from colon cancer mesenchymal stem cells promote the tumorigenicity of colon cancer through targeting MIA3.

BACKGROUND: Multipotent mesenchymal stem cells (MSCs) derived from virus tumors have been reported to contribute to malignant cell growth, invasion, and metastasis. However, the mechanism of communication between MSCs and colon cancer cells is poorly understood. Recent studies have suggested that exosomes are an important player in crosstalk between cells and could significantly suppress the invasion ability of human cancer cells (hCCs) when transfected with a microRNA inhibitor. However, to date, no study has illuminated the miRNA changes in exosomes derived from hCC-MSCs. METHODS: Colon cancer stem cells were cultured in medium and passaged to develop fibroblast-like morphology. Exosomes were collected using ExoQuick precipitation and exosome morphology was visualized by transmission electron microscopy. Small RNA sequencing was analyzed using an Illumina HiSeq4000 analyzer, and the expression of MIA3 was assessed by real-time PCR and Western blot. The functional roles of miR-30a and miR-222 in colon cancer cells were evaluated through cell and animal experiments. RESULTS: Our results showed that the characteristics of MSC-like cells (hCC-MSCs) derived from human colon cancer stem cells were comparable to those of bone marrow-derived MSCs, including surface antigens and the ability to multi-differentiate to osteocytes and adipocytes. Furthermore, we screened the microRNA (miRNA) profiles of exosomes derived from hCC-MSCs and the corresponding parent hCC-MSCs. We found a significant enrichment in the miR-30a and miR-222 level in hCC-MSC-derived exosomes. Furthermore, in vitro and in vivo experiments demonstrated that miR-30a and miR-222 bound to their shared downstream target, MIA3, to promote the ability of colon cells to proliferate, migrate, and metastasize, thus evidencing their functional roles as oncogenic miRNAs. CONCLUSIONS: These data suggest that hCC-MSC-secreted exosomes promote colon cancer cell proliferation and metastasis through delivering miR-30a and miR-222. Subsequently, exosomal miR-30a and miR-222 simultaneously target MIA3, suppress its expression, and promote colon cell proliferation, migration, and metastasis.

Outcomes of ulnar nerve decompression for double crush syndrome.

BACKGROUND: Double crush syndrome (DCS) of the ulnar nerve, including cubital tunnel syndrome with ulnar tunnel syndrome (UTS), is uncommon. This study compares the postoperative outcomes of patients with isolated ulnar tunnel syndrome versus those with double crush syndrome of the elbow and ulnar tunnel. METHODS: This study enrolled 22 patients: 12 underwent cubital tunnel surgery and ulnar tunnel surgery (double crush group); and 10 underwent only ulnar tunnel decompression (isolated UTS group). Postoperative effect evaluation of patients in both groups after at least 2.6 years (mean, 5.1 years and 5.7 years, respectively). Statistical analysis compared postoperative function, physical examination, and patient-reported satisfaction between groups. RESULTS: In terms of postoperative grip strength, there was no difference between the postoperative states of the two groups (0.88 ± 0.04 versus 0.87 ± 0.05), while there was statistical difference in terms of the increment of the grip strength (p = 0.036); the two-point discrimination of isolated UTS group is better than the double crush group (90% versus 83.3%); double crush patients reported lower satisfaction than the UTS group (90% versus 83.3%). CONCLUSIONS: At a minimum of 2.6 years after the nerve decompression, the patients of isolated UTS group are likely to have superior grip strength increment than patients with a history of double crush surgery, and there is no big difference in the final recovery situation. The sensation and satisfaction of isolated UTS group after nerve release were better compared with patients following double crush surgery.