Efficacy and Safety of Programmed Death 1/Programmed Death-Ligand 1 Plus Cytotoxic T-Lymphocyte-Associated Antigen 4 Inhibitors for Advanced or Metastatic Non-Small Cell Lung Cancer: A Meta-analysis Based on Randomized Controlled Trials.

BACKGROUND: This meta-analysis aims to investigate the efficacy and safety of programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) combined with cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors for patients with advanced or metastatic non-small cell lung cancer (NSCLC). METHODS: Authors conducted a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, Scopus, and Medline for randomized controlled trials comparing the prognosis and safety of PD-1/PD-L1 plus CTLA-4 inhibitors with other therapies for advanced or metastatic NSCLC. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used as effect sizes. The primary outcomes of this study were overall survival (OS) and progression-free survival. RESULTS: A total of 4943 patients diagnosed with stage III/IV advanced or metastatic NSCLC were included in the analysis of the 6 randomized controlled trials. The results showed that patients receiving dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors had a longer survival time compared with the control group (HR = 0.88, P = 0.044). However, no statistically significant difference was observed in progression-free survival (HR = 0.95, P = 0.579). Subgroup analysis revealed better OS in the interventional group for patients aged >65 years (HR = 0.88, P = 0.076), smokers (HR = 0.81, P = 0.036), and those with a tumor mutational burden (TMB) ≥20 mut/Mb (HR = 0.66, P < 0.001). Conversely, the control group demonstrated superior OS in patients with TMB <20 mut/Mb (HR = 1.14, P = 0.048). In addition, the statistical results indicated a lower incidence rate of any-grade anemia in the dual immunotherapy group compared with the control group (RR = 0.32, P = 0.04). CONCLUSIONS: This meta-analysis demonstrates the effectiveness and safety of dual immunotherapy with PD-1/PD-L1 plus CTLA-4 inhibitors for treating advanced or metastatic NSCLC. Its efficacy is influenced by certain clinical and pathological factors, such as age, smoking status, and TMB.

Investigation of disinfection failure of flexible gastrointestinal endoscope due to Burkholderia cepacia contamination in irrigation tubing.

BACKGROUND AND AIMS: This study aims to identify the cause of disinfection failure of multiple flexible gastrointestinal endoscopes and to enhance the cleaning and disinfection procedures. METHODS: Samples from endoscopy devices, surrounding objects, cleaning water, automatic sterilizer, and integrated endoscopic washing workstation in a Digestive Endoscopy Center were collected and analyzed for microbial contamination and DNA/gene contents, between May and July 2021. RESULTS: The sample analysis revealed that the sink irrigation tubing of the washing workstation was contaminated with Burkholderia cepacia. After effective disinfection measures, the B. cepacia detection in the disinfected endoscope dropped from 13.23% to 0% (p=0.041). The presence of B. cepacia was confirmed through homology search and gene sequencing. CONCLUSIONS: The primary reason for endoscope disinfection failure is the contamination of the sink irrigation tubing by the B. cepacia bacteria. These findings emphasize the need for thorough cleaning of irrigation tubings in integrated endoscopic washing workstations, which is generally neglected in routine maintanance.

Effects of magnesium sulfate combined with labetalol on inflammatory stress and pregnancy outcome of patients with gestational hypertension.

Gestational hypertension (GH) is a common disorder during pregnancy that can cause adverse pregnancy outcomes. In the present study, magnesium sulfate (MgSO4) combined with labetalol was used for clinical treatment. Randomized controlled trial was conducted in 100 patients with GH, documented in the Department of Obstetrics and Gynecology (Taicang TCM Hospital) grouped into the experimental (Expt) and control (Ctrl) groups (n=50 cases/group). The Ctrl group was treated with MgSO4, whereas the Expt group was treated with MgSO4 + labetalol. The systolic blood pressure (SBP) and diastolic blood pressure (DBP) in the Expt group were not significantly different from those in the Ctrl group (P>0.05). By contrast, the SBP and DBP were significantly lower after treatment than those before treatment in both groups (P<0.05). Whole blood viscosity, plasma viscosity and hematocrit were significantly lower in the Expt group compared with those in the Ctrl group after treatment (P<0.05). High mobility group box-1 protein, homocysteine and serum cystatin C levels in the Expt group were also markedly lower than those in the Ctrl group after treatment (P<0.05). In the Expt group, the rate of spontaneous vaginal delivery was much higher, whereas the rates of cesarean section and postpartum hemorrhage were markedly lower than those in the Ctrl group (P<0.05). The occurrence of fetal intrauterine distress, placental abruption, neonatal asphyxia, premature birth and neonatal death were also significantly lower in the Expt group than those in the Ctrl group (P<0.05). In conclusion, MgSO4 + labetalol could improve inflammatory stress and the hemodynamics of patients with GH, and may have a marked antihypertensive effect. Thus, it may improve pregnancy outcome and reduce perinatal complications.

Management of Occupational Bloodborne Pathogen Exposure among Medical Personnel: a 4-Year Prospective Study.

This study examined the management of occupational bloodborne pathogen exposure at a tertiary hospital in China. This prospective study was conducted at the Zhejiang Hospital of Traditional Chinese Medicine between January 2016 and December 2019. Data on bloodborne occupational exposure management were collected. In total, 460 exposures were reported. The majority of exposures (40.2 %) were from hepatitis B virus (HBV)-positive index patients. Of the 460 cases, 453 (98.5%) exposures were reported timeously, and 371 (80.7%) cases received emergency treatment response and management. Sixty-eight personnel (93.2%) received timely prophylaxis treatment. Only 82/113 (72.6%) personnel completed the recommended follow-up period. Outsourced personnel(P = 0.002) and interns (P = 0.011) were independent follow-up factors. Although adequate compliance was achieved with timely reporting and prophylactic medication, there is room for improvement in terms of emergency treatment response and follow-up compliance. Furthermore, HBV vaccination and improved follow-up with outsourced personnel are recommended.

[Clinical Characteristics and Treatment of Blastic Plasmacytoid Dendritic Cell Neoplasm].

OBJECTIVE: To explore the clinical manifestations, diagnosis, treatment and prognosis of blastic plasmacytoid dendritic cell neoplasm(BPDCN). METHODS: The clinical features, bone marrow morphology and immunophenotyping, treatment and prognosis of 4 patients with BPDCN were analyzed retrospectively. RESULTS: 4 patients had bone marrow， spleen and lymph nodes involvement， 2 patients had skin lesions， and 3 patients had central nervous system infiltration． Tailing phenomenon of abnormally cells could be seen in bone marrow. The immunophenotyping showed that CD56, CD4 and CD123 expression was observed in 4 patients， and CD304 in 3 patients． One patient refused chemotherapy and died early. Both patients achieved complete remission after the initial treatment with DA+VP regimen, 1 of them achieved complete remission after recurrence by using the same regimen again． One patient failed to respond to reduced dose of DA+VP chemotherapy, and then achieved complete remission with venetoclax+azacitidine. CONCLUSION: The malignant cells in BPDCN patients often infiltrate bone marrow, spleen and lymph nodes, and have specical phenotypes, with poor prognosis. The treatment should take into account both myeloid and lymphatic systems. The treatment containing new drugs such as BCL-2 inhibitors combined with demethylation drugs is worth trying.

[Synergistic Mechanism of Interferon alpha-1b, Interleukin-2 and Thalidomide for Immune Regulation in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML). METHODS: Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls. RESULTS: The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of perforin and Granzyme B of NK cells in the peripheral blood of patients with hematological malignancies were lower than those of healthy controls. The level of VEGF, IL-6 and TNF-α in the peripheral plasma were higher than those of the healthy control group, and the difference was statistically significant. The level of IFN-γ was lower, and the difference was not statistically significant. The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of Granzyme B and Perforin of NK cells in peripheral blood were higher after the therapy of thalidomide combined with rhIFNα-1b for 3 months as compared with those before treatment of ITI, the level of the IFN-γ in peripheral plasma was higher while that of VEGF was lower, the difference was statistically significant; after treatment, the ratio of CD3+ CD4+ and CD3+ CD8+ lymphocytes and the level of TNF-α in peripheral blood were higher those that before treatment, IL-6 was lower, while the difference was not statistically significant. CONCLUSION: The ITI regimen can raise the ratio of CD4+/CD8+ T cells and the percentage of natural killer cells, also, can enhance the generation of perforin and granzyme B and the concentration of IFN-γ as well as inhibit the generation of VEGF, suggesting that these activities may enhance the antitumour capacity of patients with AML.

Utility of ¹¹C-choline imaging as a supplement to F-18 FDG PET imaging for detection of thyroid carcinoma.

PURPOSE: We present 4 patients with thyroid carcinoma who underwent ¹¹C-choline PET/CT for the detection of their primary tumor and its metastases. Previous F-18 FDG PET had shown no abnormal tracer uptake in the lesions in 3 patients and only mild uptake in 1 patient. MATERIALS AND METHODS: Four patients aged between 24 and 59 years (2 newly diagnosed and 2 with recurrence) underwent whole-body F-18 FDG PET/CT. The patients then underwent regional ¹¹C-choline PET/CT imaging on a separate day. RESULTS: All of the lesions in 4 patients were ¹¹C-choline avid except for a few small lung metastases. The SUVmax of the lesions was 7.94 ± 4.93. ¹¹C-choline imaging detected 3 primary tumors in 4 patients, 1 tumor in the tracheal wall in 1 patient, 7 cervical lymph nodes metastases in 3 patients, and several lung metastases in 1 patient. CONCLUSIONS: ¹¹C-choline PET/CT may be a promising supplement to F-18 FDG PET/CT in the detection of thyroid carcinoma and its metastases.

Neuroprotective effect of recombinant human erythropoietin on optic nerve injury in rats.

BACKGROUND: Optic nerve injury, caused by retinal and optic nerve diseases, can eventually result in vision loss. To date, few effective treatments have been discovered to restore visual function. Previous studies showed that recombinant human erythropoietin (rhEPO) has a neuroprotective effect on the central nervous system, particularly in nerve injury. In this study, we investigated the effects of rhEPO on axonal regeneration and functional restoration following optic nerve injury. This was done by measuring the expression of growth associated protein 43 (GAP-43), a marker for neuronal regeneration, on the retina and flash-visual evoked potential (F-VEP). METHODS: Adult Wistar rats were randomly assigned to rhEPO and control (saline) groups. Optic nerve crush injury models were established and rhEPO or saline were immediately injected into the vitreous cavity. The expression of GAP-43 was detected by immunohistochemistry and the F-VEP was measured pre-injury, immediately after injury, 1 week and 2 weeks post-injury. RESULTS: No detectable staining for GAP-43 was observed in normal retina. In the control group, the level of GAP-43 expression was higher at 1 week post-injury, but decreased at 2 weeks. In the rhEPO group, the level of GAP-43 expression was notably higher at both 1 week and 2 weeks. At each time point post-injury, the expression of GAP-43 in rhEPO group was significantly higher than the control group (P < 0.05). Obvious changes in F-VEP examination were detected immediately after optic nerve injury, including significantly prolonged latency and decreased amplitude of the P1 wave. In the control group, the changes were still obvious at 1 week. The latency was decreased and the amplitude had slightly recovered to 28.23% of the normal value at 2 weeks. In rhEPO group, there was significantly more recovery than the control group at 1 week and 2 weeks post-injury (P < 0.05). The latency most close to the normal level and the amplitude had recovered to 65.51% of the normal value at 2 weeks. CONCLUSIONS: rhEPO can prolong the expression of GAP-43 and increase its intensity after optic nerve injury, thereby promoting neural repair and axonal regeneration. Under the protection of rhEPO, the conduction velocity of the optic nerve recovered significantly. Therefore, rhEPO has neuroprotective effects on the optic nerve and promotes functional restoration of the optic nerve.

[Treatment of chronic idiopathic thrombocytopenic purpura with small dose heparin: a report of 12 cases].

In order to determine the curative effect of small dose heparin for treatment of chronic idiopathic thrombocytopenic purpura (CITP), a total of 12 CITP patients, who were failed with prednisone and immunosuppressants over 6 months, had been treated with subcutaneous injection of small dose heparin. The curative effects were seen in 8 patients and there were no exacerbation of hemorrhage during the therapy. The results showed that it is effective and safe to use this treatment for CITP.