The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective To provide an effective strategy for the prevention and treatment of radiation-induced infections by preparing platelet membrane-modified catalase/silica nanoparticles(PCNP)capable of targeting leukocytes.Methods PCNP and catalase/silica nanoparticles(CNP)were prepared by using platelet membrane,catalase(CAT)and silica,and its biological safety was preliminarily evaluated with cell survival test,hemolysis test and acute toxicity test in mice after tail vein administration;The culture medium,FITC labeled(FITC+)PCNP and FITC labeled(FITC+)CNP were co-incubated with human peripheral blood B lymphocytes(AHH-1)and mouse monocyte macrophages(RAW264.7),respectively.Thus,there were control group,FITC+PCNP group and FITC+CNP group of AHH-1 and RAW264.7 cells.Laser confocal microscopy was used to observe the intracellular fluorescence intensity of PCNP to evaluate the leukocytes targeting function.AHH-1 cells were divided into control,irradiation,platelet membrane,CNP(100 μg/mL)and PCNP(100 μg/mL)groups.After corresponding co-incubation,the cell media were exposed to6 Gy Co60 γ irradiation.The generation of reactive oxygen species(ROS)and cell apoptosis were measured to determine the effect of nanoparticles on reducing radiation injury of leukocytes.Twenty C57BL/6 male mice(weighing 18～20 g)were randomly divided into irradiation group(n=10)and 10 mg/kg PCNP group(n=10).In 2 h after corresponding agents were injected into the mice through tail vein,the mice received whole-body irradiation of 5 Gy Co60 γ ray,and then in 2 h later,they were given intraperitoneal injection of multidrug resistant Acinetobacter baumannii(MDR-AB).The infection inhibitory effect of PCNP after irradiation was evaluated by detecting the bacterial load in main organs.Results The hydration particle of PCNP is 91.3 nm in size,and does not exhibit significant cytotoxicity or hemolytic toxicity at concentrations＜400 μg/mL.Intravenous injection of 20 mg/kg PCNP resulted in normal increase in the body weight but no obvious pathological changes in the major organs such as the heart,liver,spleen,lungs,and kidneys.In AHH-1 and RAW264.7 cells,PCNP showed significant advantages in targeting compared to the FITC+CNP group[(15.45±3.48)%vs(9.33±2.03)%,P＜0.01;(11.25±2.08)%vs(7.06±0.71)%,P＜0.001].PCNP also effectively reduced the generation of ROS[(22.73±3.71)%vs(60.90±9.08)%,P＜0.001]and apoptotic rate[(9.84±0.92)%vs(38.96±3.62)%,P＜0.001]in AHH-1 cells.In in vitro study,bacterial colonization after irradiation showed that there was significantly less MDR-AB colonies in the spleen of mice intervened with PCNP than those of the irradiation group[(17.50±1.38)×104 vs(13.20±2.29)×106 CFU/g,P＜0.001].Conclusion PCNP can effectively inhibit the complications of radiation infection in mice,which is due to its direct protective effect on leukocytes.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Rheumatoid arthritis (RA) is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium. Currently, treatment options focus on either reducing inflammation or inhibiting synovial hyperplasia. However, these modalities are unsatisfactory in achieving the desired therapeutic outcomes. Halofuginone hydrobromide (HF), an herbal active ingredient, has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation. However, HF's medical efficacy is limited due to its poor water solubility, short half-life (t _1/2), and non-target toxicity. In the current study, by using the advantages of nanotechnology, we presented a novel dual-targeted nanocomplex, termed HA-M@P@HF NPs, which consisted of a hyaluronic acid (HA)-modified hybrid membrane (M)-camouflaged poly lactic-co-glycolic acid (PLGA) nanosystem for HF delivery. These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA (HFLS-RA). In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflammation and synovial hyperplasia, safeguarding against bone destruction in rats with adjuvant-induced arthritis (AIA). Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA, thereby offering a promising therapeutic strategy for RA.

Rheumatoid arthritis(RA)is a prevalent autoimmune disease characterized by chronic inflammation and excessive proliferation of the synovium.Currently,treatment options focus on either reducing inflam-mation or inhibiting synovial hyperplasia.However,these modalities are unsatisfactory in achieving the desired therapeutic outcomes.Halofuginone hydrobromide(HF),an herbal active ingredient,has demonstrated pharmacological effects of both anti-inflammation and inhibition of synovial hyperplasia proliferation.However,HF's medical efficacy is limited due to its poor water solubility,short half-life(ti/2),and non-target toxicity.In the current study,by using the advantages of nanotechnology,we presented a novel dual-targeted nanocomplex,termed HA-M@P@HF NPs,which consisted of a hyaluronic acid(HA)-modified hybrid membrane(M)-camouflaged poly lactic-co-glycolic acid(PLGA)nanosystem for HF delivery.These nanocomplexes not only overcame the limitations of HF but also achieved simultaneous targeting of inflammatory macrophages and human fibroblast-like synoviocytes-RA(HFLS-RA).In vivo experiments demonstrated that these nanocomplexes effectively suppressed immune-mediated inflam-mation and synovial hyperplasia,safeguarding against bone destruction in rats with adjuvant-induced arthritis(AIA).Remarkable anti-arthritic effects of these nanocomplexes were accomplished through promoting repolarization of M1-to-M2 macrophages and apoptosis of HFLS-RA,thereby offering a promising therapeutic strategy for RA.

Objective:To investigate the effects of different small monitor unit (MU) beam deletion optimization method in the CyberKnife treatment planning system on the calculated planned dose to brain tumors.Methods:A total of 17 patients with brain metastases treated in our hospital from June, 2021 to February, 2022 were selected for this study. A treatment plan was designed for each patient using the multiPlan system in the CyberKnife VSI system as the group without optimization. To improve the efficiency, the generated original plans should be optimized first by deleting some small MUs, forming an experience group and an optimization group for each patient. For the experience group, beams below 30 MU were deleted according to experience. For the optimization group, beams below the MU value calculated based on the second derivative method were deleted. Finally, the parameters of the two groups were statistically compared. The main evaluation parameters included the node number, the beam number, the total number of MUs, the estimated treatment duration, doses to 2% and 95% planning target volumes (PTV D2 and PTV D95), average dose to PTV ( Dmean), average dose to brain tissue ( Dmean-Brain), conformity index (CI), new conformity index (nCI), gradient index (GI), coverage, and the maximum doses to the brainstem and left and right lens ( Dmax-BS, Dmax-LL, and Dmax-RL), and the average doses to the dose shells 20 mm and 40 mm away from PTV (Shell20 and Shell40). Results:The two optimization method met the requirements for the prescription dose delivery to more than 98% PTV. There were statistical differences in the node number ( H = 7.97, P< 0.05) and estimated treatment duration ( H = 6.60, P < 0.05) among the group without MP optimization, the experience group, and the optimization group, with the estimated treatment duration and node number of the optimization group less than those of the group without MP optimization ( P < 0.05). There were no statistically significant differences in other parameters among the three groups ( P > 0.05). The PTV was moderately positively correlated with the treatment duration ( r=0.79, P < 0.01) and beam number ( r=0.78, P < 0.01) of the experience group, and was also moderately positively correlated with the treatment duration ( r=0.69, P < 0.01) and beam number ( r=0.71, P < 0.01) of the optimization group. Conclusions:For the CyberKnife planning of heads, the small MU beam deletion optimization method based on the second derivative can further shorten the treatment duration while ensuring no significant differences in the distribution of doses to organs at risk and targets. Moreover, this method is more effective in optimizing the plans for a large PTV volume.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To explore the occurrence time and risk factors of deep vein thrombosis (DVT) in patients with acute cerebral infarction, so as to guide clinical prevention and treatment.Methods:1 129 patients with acute cerebral infarction treated in Beijing Tiantan Hospital from May 2014 to May 2016 were selected as the research objects. According to whether DVT occurred, the patients were divided into DVT group ( n=22) and non DVT group ( n=1 107); The information was analyzed retrospectively and the occurrence time of DVT was counted. The independent risk factors of acute cerebral infarction complicated with DVT were analyzed by univariate and multivariate logistic regression. Results:The time of DVT in patients with acute cerebral infarction was 10.5 (4-14) days. Univariate analysis showed that there were significant differences in age, gender, atrial fibrillation, smoking, drinking, chronic obstructive pulmonary disease, peripheral artery disease, renal failure, anticoagulants, BMI, white blood cell, blood glucose at admission and length of stay between the DVT group and the non DVT group ( P<0.05). Multiple factors further confirmed that renal failure [odds ratio ( OR)=57.421; 95% confidence interval ( CI), 5.792-569.314)] and length of hospital stay ( OR=1.148; 95% CI: 1.071-1.232) were independent risk factors for DVT. Conclusions:The median time of DVT in patients with acute cerebral infarction was 10.5 days. Renal failure and hospital stay were independent influencing factors of DVT in patients with acute cerebral infarction. This is helpful to determine the best prevention and treatment duration of DVT in patients with acute cerebral infarction, make rational use of medical resources and formulate personalized prevention and treatment strategies.

Objective:It is yet to be clarified whether pylorus-preserving gastrectomy (PPG) for early gastric cancer will bring the risk of radical tumor resection, whether it will increase the incidence of postoperative complications, and how much is the benefit of the quality of life for patients after surgery, these issues are not clear. This meta-analysis aims to evaluate the efficacy and safety of pylorus-preserving gastrectomy (PPG) for early middle gastric cancer.Methods:The Chinese and English literatures about PPG and distal gastrectomy (DG) for early gastric cancer were searched from PubMed, Embase, The Cochrane Library, Web of Science, CNKI net and Wanfang database. Literature inclusion criteria: (1) Prospective or retrospective cohort study of PPG and DG for early middle-third gastric cancer published publicly; (2) Patients with early middle-third gastric cancer; (3) The enrolled literatures include at least one of the following outcome indicators: the efficacy indicators include gallstone, residual gastritis, bile reflux, delayed gastric emptying, dumping syndrome, reflux esophagitis and overall complication; the long-term prognostic indicators include 5-year survival rate and 5-year tumor recurrence. Literature exclusion criteria: (1) Reviews, case reports, conference summaries and other non-control studies; (2) Repeated published studies, incomplete studies and unextractable studies; (3) The depth of tumor invasion exceeding submucosa. The search time ended in July 2020. The basic information and evaluation indicators included in the article were extracted. The retrospective study was evaluated using Newcastle-Ottawa literature quality evaluation scale. The prospective randomized controlled study was evaluated using Jadad modified scale. Meta-analysis was performed using Review Manager 5.3. Publication bias was assessed using funnel map. Publication bias was tested using Egger tools.Results:A total of 717 literatures were retrieved, and 17 literatures were enrolled finally, including 2 randomized controlled trials and 15 retrospective studies. A total of 2427 patients were enrolled, including 948 in PPG group and 1479 in DG group. The meta-analysis of the efficacy indicators showed that there were significant differences in gallstones incidence (OR=0.42, 95% CI: 0.28-0.65, P<0.001), residual gastritis incidence (OR=0.50, 95% CI: 0.32-0.77, P=0.002), bile reflux incidence (OR=0.30, 95% CI: 0.20-0.45, P<0.001), delayed gastric emptying incidence (OR=2.40, 95% CI:1.67-3.45, P<0.001), and postoperative dumping syndrome incidence (OR=0.28, 95% CI: 0.15-0.51, P<0.001), while there were no significant differences in postoperative overall complications (OR=0.97, 95% CI: 0.69-1.35, P=0.840), reflux esophagitis incidence (OR=0.79, 95% CI: 0.39-1.61, P=0.520) between the two groups. The meta-analysis of the long-term prognostic indicators showed that no significant differences of 5-year survival (OR=1.02, 95% CI: 0.61-1.71, P=0.940) or 5-year tumor recurrence (OR=0.77, 95% CI: 0.36-1.68, P=0.520) were observed between the two groups. Conclusion:The incidences of gallstone, residual gastritis, dumping syndrome, bile reflux are lower after PPG in early gastric cancer, while the postoperative overall complications and long-term survival are comparable between PPG and DG, indicating that PPG is quite safe and feasible.

Objective:It is yet to be clarified whether pylorus-preserving gastrectomy (PPG) for early gastric cancer will bring the risk of radical tumor resection, whether it will increase the incidence of postoperative complications, and how much is the benefit of the quality of life for patients after surgery, these issues are not clear. This meta-analysis aims to evaluate the efficacy and safety of pylorus-preserving gastrectomy (PPG) for early middle gastric cancer.Methods:The Chinese and English literatures about PPG and distal gastrectomy (DG) for early gastric cancer were searched from PubMed, Embase, The Cochrane Library, Web of Science, CNKI net and Wanfang database. Literature inclusion criteria: (1) Prospective or retrospective cohort study of PPG and DG for early middle-third gastric cancer published publicly; (2) Patients with early middle-third gastric cancer; (3) The enrolled literatures include at least one of the following outcome indicators: the efficacy indicators include gallstone, residual gastritis, bile reflux, delayed gastric emptying, dumping syndrome, reflux esophagitis and overall complication; the long-term prognostic indicators include 5-year survival rate and 5-year tumor recurrence. Literature exclusion criteria: (1) Reviews, case reports, conference summaries and other non-control studies; (2) Repeated published studies, incomplete studies and unextractable studies; (3) The depth of tumor invasion exceeding submucosa. The search time ended in July 2020. The basic information and evaluation indicators included in the article were extracted. The retrospective study was evaluated using Newcastle-Ottawa literature quality evaluation scale. The prospective randomized controlled study was evaluated using Jadad modified scale. Meta-analysis was performed using Review Manager 5.3. Publication bias was assessed using funnel map. Publication bias was tested using Egger tools.Results:A total of 717 literatures were retrieved, and 17 literatures were enrolled finally, including 2 randomized controlled trials and 15 retrospective studies. A total of 2427 patients were enrolled, including 948 in PPG group and 1479 in DG group. The meta-analysis of the efficacy indicators showed that there were significant differences in gallstones incidence (OR=0.42, 95% CI: 0.28-0.65, P<0.001), residual gastritis incidence (OR=0.50, 95% CI: 0.32-0.77, P=0.002), bile reflux incidence (OR=0.30, 95% CI: 0.20-0.45, P<0.001), delayed gastric emptying incidence (OR=2.40, 95% CI:1.67-3.45, P<0.001), and postoperative dumping syndrome incidence (OR=0.28, 95% CI: 0.15-0.51, P<0.001), while there were no significant differences in postoperative overall complications (OR=0.97, 95% CI: 0.69-1.35, P=0.840), reflux esophagitis incidence (OR=0.79, 95% CI: 0.39-1.61, P=0.520) between the two groups. The meta-analysis of the long-term prognostic indicators showed that no significant differences of 5-year survival (OR=1.02, 95% CI: 0.61-1.71, P=0.940) or 5-year tumor recurrence (OR=0.77, 95% CI: 0.36-1.68, P=0.520) were observed between the two groups. Conclusion:The incidences of gallstone, residual gastritis, dumping syndrome, bile reflux are lower after PPG in early gastric cancer, while the postoperative overall complications and long-term survival are comparable between PPG and DG, indicating that PPG is quite safe and feasible.