Objective To observe the functional changes of T lymphocytes in the spleen of rats with bone cancer pain.Methods forty-one healthy female Sprague-Dawley rats were used in this study, and were divided into blank control, PBS and Walker-256 tumor groups.Bone cancer pain model was established by inoculation of Walker 256 cancer cells into the tibial cavity.The paw withdrawal threshold (PWT), paw withdrawal thermal latency (PWL), and spontaneous pain (SP) were all measured before modelling (as base) and at 4, 6, 8, 10, 12, 14, 16, 18, and 20 days after modelling. The function of T lymphocyte proliferation, and the content of T lymphocytes and their subgroups in the spleen were detected by cell counting kit-8 method and flow cytometry, respectively, on day 20 after modelling.Results Before modellng, there were no differences of PWT, PWL, and SP between the PBS and model groups.After modelling, the PWT and SP of model group were significantly decreased on day 4, and were always lower than that of PBS group during the experiment.Statistical analysis revealed that Walker-256 cancer cell inoculation in the tibia induced a significant decrease in PWL on day 8, 10 and 12 after modellng.Compared with the control group, T lymphocyte proliferation, content of T lymphocyte (CD3) and subgroups ( CD4 and CD8) in the PBS group were not significantly decreased.However, T lymphocyte proliferation and the content of CD3 lymphocytes in the model group were significantly lower than those in the blank control group and/or PBS group.Conclusions The bone cancer pain rat model may appear obvious mechanical allodynia and spontaneous pain.Its thermal pain hyperalgesiaonly occurred in the intermediate stage of bone cancer pain. The content of T lymphocytes and its subgroups, and the function of T lymphocyte proliferation are weakened to some extent in the bone cancer pain rat model.

Objective:To observe the effects of continuous light exposure on skeletal muscle fiber type transformation and lipid metabolism, and to explore its internal relationship.Methods:Mice were randomly divided into normal light group and 24-hour continuous light group by random number table. The serum and skeletal muscle lipid content and urine 6-sulfatoxymelatonin(6-SML)level were detected by ELISA. The expression of circadian clock and lipid metabolism related genes mRNA were observed by realtime PCR. The muscle fiber type and lipid deposition were evaluated by tissue immunofluorescence as well as oil red O staining.Results:Compared with the normal light group, the level of 6-SML in urine at night decreased( P<0.05), and the expression level and rhythm of brain and muscle ARNT-like protein 1(Bmal1), circadian locomotor output cycles protein kaput(Clock), and period 2(Per2)mRNA in the skeletal muscle changed in continuous light group. In addition, the body weight, blood lipid, free fatty acid, and triglyceride contents of skeletal muscle in continuous light group increased significantly( P<0.05 or P<0.01), the expression of carnitine palmitoyltransferase 1b (Cpt1b)mRNA, the key enzyme of fatty acid oxidation, decreased significantly( P<0.05), while the expression of stearoyl-CoA desaturase(Scd1)mRNA, a lipid synthesis related gene, increased significantly( P<0.01). Further immunofluorescence analysis showed that the proportion of slow muscle fibers decreased and that of fast muscle fibers increased in continuous light group(both P<0.05). Conclusion:The process of ectopic deposition of lipid in skeletal muscle in mice induced by continuous light exposure may be related to the remodeling of skeletal muscle fibers.

Objective:To observe the effect of shift work on the stability of the circadian clock and insulin sensitivity in non-overweight/obese individuals with normal blood glucose, and explore underlying connection.Methods:Female shift working nurses in the Department of Blood Transplantation and non-shift working nurses in the Health Management Center in the First Affiliated Hospital of Zhengzhou University were divided into shift worker group (SW group) and non-shift worker group (NSW group). Serum inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α)], adipokines (adiponectin, leptin, chemerin, visfatin), and melatonin levels were measured using enzyme linked immunosorbent assay (ELISA). Realtime fluorescence quantitative PCR was performed to detect peripheral blood circadian clock genes circadian locomotor output cycles protein kaput(Clock) and brain and muscle ARNT-like protein 1(Bmal1). Cortisol and fasting insulin were measured by chemiluminescent microparticle immunoassay, and HbA 1C was measured by capillary electrophoresis. In addition, visceral fat area (VFA) was assessed with bioelectrical impedance analyzer, and mid-sleep time composite phase deviations (CPD) was calculated based on the International Physical Activity Short Questionnaire. Results:SW group had lower serum level of melatonin ( P=0.023) and higher cortisol ( P=0.001) than the NSW group, and altered mRNA expression of Clock and Bmal1 ( P=0.034, P=0.047). Fasting blood glucose and HbA 1C in the SW group, although in the normal range, had been higher than in the NSW group ( P=0.011, P=0.033). Although body mass index was normal in SW group, VFA had been higher than that of the NSW group ( P=0.010). And homeostasis model assessment for insulin resistance (HOMA-IR), IL-6, TNF-α, leptin, chemerin, and visfatin were significantly higher in the SW group than NSW group ( P=0.033, P=0.012, P=0.001, P=0.011, P=0.021, P=0.007). In addition, adjusting for body mass index and activity factors revealed a significant positive correlation between CPD and VFA ( r=0.434, P=0.049), inflammatory factors IL-6 ( r=0.514, P=0.017) and TNF-α ( r=0.700, P<0.001) and pro-inflammatory adipokines leptin ( r=0.473, P=0.030), chemerin ( r=0.439, P=0.047), visfatin ( r=0.521, P=0.015). Conclusion:Shift work can affect circadian clock, with increased visceral adiposity, pro-inflammatory adipokines, inflammatory factors and decreased insulin sensitivity in women without overweight/obese.

Natural killer(NK)cells as intrinsic immune cells kill tumor cells without the need for pre-stimulation by tumor antigens.Therefore,NK cell based immunotherapy has unique advantages and has made significant progress in tumor treatment.In this article,we review the development,classification,and mechanism of NK cells as well as the applications of NK cell based immunotherapies,including immune checkpoint inhibitors,adoptive cell therapy,and NK cell adapters in tumor immunity.Thus,we elucidate the principle,current status,and developmental trend of NK cell-based anti-tumor immunotherapies to provide ideas for their development and application in the field of tumor immunotherapy.

Objective:To evaluate the efficacy and outcomes of early removal of lumen-apposing metal stent (LAMS) in the treatment of pancreatic wall-off necrosis (WON).Methods:A retrospective analysis was performed on 51 patients with WON who underwent endoscopic ultrasound (EUS)-guided transluminal drainage (ETD) and direct endoscopic necrosectomy (DEN) using LAMS at Nanjing Drum Tower Hospital from January 2018 to December 2022. Patients were divided into the early removal group (within two weeks, n=24) and the traditional removal group (after two weeks, n=27) based on the timing of LAMS removal. The short-term effects, safety and long-term outcomes of WON were compared between the two groups. Results:The technical success rate of LAMS placement in 51 patients reached 100%, and all patients underwent ETD and DEN. The median number of necrosectomy sessions in the early removal group was significantly lower than in the traditional removal group, 2.0 sessions vs 3.0 sessions and the difference was statistically significant ( P<0.05). Postoperatively, 15.7% of patients required percutaneous catheter drainage (PCD) and 5.9% required surgery, with no significant difference between the two groups. The clinical success rate and mortality rate in the early removal group were 79.2% and 8.3%, respectively, compared to 81.5% and 3.7% in the traditional removal group, with no statistically significant difference. In terms of safety, the early removal group exhibited a significantly lower rate of adverse events during stent retention with statistically significant difference (12.5% vs 37.0%, P<0.05) compared to the traditional removal group. A total of 46 patients were followed up for six months. In the early removal group, the rates of disease recurrence, need for endoscopic reintervention and occurrence of long-term complications were 20.0%, 10.0% and 20.0%, respectively. These rates did not show a significant increase compared to the traditional removal group, which were 7.7%, 3.8% and 38.5%, respectively, without significant differences between the groups. Conclusions:In the treatment of WON, early removal of LAMS is safe and effective to a certain extent. In comparison to the traditional practice of removing LAMS after two weeks, early removal does not reduce clinical success rates, nor does it increase the rates of disease-related mortality, recurrence, or long-term complications. On the contrary, it may reduce the occurrence of adverse events during stent retention and decrease the number of necrosectomy procedures subsequently.

OBJECTIVE：To reevaluate the guidelines/cons ensus，systematic review/Meta-analysis of proton pump inhibitors （PPIs）in the prevention of drug-induced gastrointestinal injury ，and to provide evidence-based reference for its clinical use. METHODS： The relevant guidelines/consensus and systematic review/Meta-analysis literatures at home and abroad were systematically reviewed ，and the re evaluation was carried out from the effectiveness ，safety and economy dimensions to analyze the current situation of clinical use of PPIs in the prevention of drug-induced gastrointestinal injury in adults and children. RESULTS ： A total of 14 clinical guidelines/consensus and 10 systematic review/Meta-analysis literatures of PPIs for the prevention of drug-related gastrointestinal injury at home and abroad were sorted out and included. In terms of effectiveness ，PPIs could prevent various drug-related gastric mucosal damage ，gastrointestinal bleeding and other damage to the digestive tract ，but PPIs had not yet obtained the indication for children in China ；PPIs were widely used in the treatment of children ’s digestive tract diseases ，which belonged to off-label medication. In terms of safety ，the common adverse reactions of PPIs included headache ，gastrointestinal symptoms，etc. There may be risks of kidney disease and fracture during long-term application. In terms of economy ，for some patients with digestive tract and cardiovascular disease risk ，the economic benefit of NSAIDs combined with PPIs were higher ； esomeprazole 20 mg and 40 mg daily were equally effective in preventing ulcer recurrence caused by NSAIDs ，but increasing the dose could not improve the preventive effect. CONCLUSIONS ：The preventive effect of PPIs on drug-induced gastrointestinal injury is supported by evidence-based evidence. It has good safety in adults and has certain economic benefits ；but it belongs to off-label drug use in children in China ，and the safety and economy still need to refer to the results of adult studies. In the future ，a number of multicenter prospective clinical studies based on Chinese pediatric population are still needed to provide more support for the prevention and treatment of drug-induced gastrointestinal injury by PPIs in children.