The biosynthesis and maturation of proteins are primarily regulated by the endoplasmic reticulum in its physiological state. Thus, the disruption of physiological homeostasis initiates the buildup of unfolded and misfolded proteins in the endoplasmic reticulum, resulting in endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). One of the important pathways by which UPR maintains intracellular homeostasis under ERS is activating protein kinase R-like endoplasmic reticulum kinase (PERK). The activation of the PERK pathway stimulates eukaryotic translation initiation factor 2 subunit-α (eIF2α) phosphorylation and the selective translation of active transcription factor 4 (ATF4), and PERK induces cell apoptosis by directly binding to the promoter of pro-apoptotic transcription factor C/EBP homologous protein (CHOP). This signaling pathway is also one of the important mechanisms by which UPR participates in the regulation of hematological malignancies and immune cells in a tumor microenvironment. This article provides an overview of advancements in research into the PERK-eIF2α-ATF4-CHOP signaling pathway in hematological malignancies and the potential therapeutic benefits of targeting this signaling pathway.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Aim To investigate the effect of CDR132L(miR-132 antisense oligonucleotide)on vascular remode-ling and function in mice with hypertension and hyperlipidemia,and explore its possible mechanism.Methods A total of 30 8-week-old male C57BL/6 mice were randomly divided into three groups:control group,model group and CDR132L group,with 10 mice in each group.The control group received with a standard diet while the model group and CDR132L group received N-nitro-L-arginine methyl ester(L-NAME)and high-fat diet to induce hypertension and hyperlip-idemia.The CDR132L group was administered with intraperitoneal injection of CDR132L at a dose of 20 mg/kg once weekly for six consecutive weeks,whereas the control group and the model group were given intraperitoneal injection of an equivalent volume of normal saline.The tail-cuff method was utilized for blood pressure measurement,blood lipid and glucose levels were assayed by an automatic biochemical analyzer,the thoracic aorta structure was observed by HE staining,endothelium-dependent relaxation of the thoracic aorta was evaluated by the vascular ring test,the expression level of miR-132 in the thoracic aorta was measured by qPCR,the protein expression levels of Gab1 and endothelial nitric oxide synthase(eNOS)in the thoracic aorta were determined by Western blot.Results Compared with the control group,the model group demonstrated notable rises in systolic and diastolic blood pressure,serum triglyceride,total cholesterol lev-els,and body weight.Moreover,the intima of thoracic aorta and the thickness of vascular wall was uneven,the smooth muscle cells of the tunica media were arranged irregularly,with a large amount of fat deposition in the vascular wall,and the endothelium-dependent relaxation response of thoracic aorta was decreased(P＜0.05).The expression level of miR-132 in the thoracic aorta was significantly increased(P＜0.05),while the expression level of Gabl and eNOS protein was markedly decreased(P＜0.05).Compared with the model group,the CDR132L group showed no significant differences in systolic and diastolic blood pressure,serum triglyceride and total cholesterol levels,as well as body weight(P＞0.05).However,the CDR132L group exhibited a complete and smooth intima of the thoracic aorta with minimal intravascular lipid deposition,the thickness of the vascular wall was uniform,the smooth muscle cells of the tunica media were arranged order-ly,accompanied by enhanced endothelium-dependent relaxation response of the thoracic aorta(P＜0.05).The expression level of miR-132 in the thoracic aorta was significantly decreased(P＜0.05),while the expression levels of Gab1 and eNOS protein were significantly increased(P＜0.05).Conclusion CDR132L can improve vascular remodeling and endothelium-dependent relaxation in hypertensive and hyperlipidemia mice,which may be related to the decrease of miR-132 expression level and the up-regulation of Gab1 and eNOS protein expression levels in the thoracic aorta.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-positive bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-positive bacteria from blood cultures in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:A total of 3 163 strains of Gram-positive pathogens were collected from 51 member units，and the top five bacteria were Staphylococcus aureus（ n=1 147，36.3%），coagulase-negative Staphylococci（ n=928，29.3%）， Enterococcus faecalis（ n=369，11.7%）， Enterococcus faecium（ n=296，9.4%）and alpha-hemolyticus Streptococci（ n=192，6.1%）. The detection rates of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）were 26.4%（303/1 147）and 66.7%（619/928），respectively. No glycopeptide and daptomycin-resistant Staphylococci were detected. The sensitivity rates of Staphylococcus aureus to cefpirome，rifampin，compound sulfamethoxazole，linezolid，minocycline and tigecycline were all >95.0%. Enterococcus faecium was more prevalent than Enterococcus faecalis. The resistance rates of Enterococcus faecium to vancomycin and teicoplanin were both 0.5%（2/369），and no vancomycin-resistant Enterococcus faecium was detected. The detection rate of MRSA in southern China was significantly lower than that in other regions（ χ2=14.578， P=0.002），while the detection rate of MRCNS in northern China was significantly higher than that in other regions（ χ2=15.195， P=0.002）. The detection rates of MRSA and MRCNS in provincial hospitals were higher than those in municipal hospitals（ χ2=13.519 and 12.136， P<0.001）. The detection rates of MRSA and MRCNS in economically more advanced regions（per capita GDP≥92 059 Yuan in 2022）were higher than those in economically less advanced regions（per capita GDP<92 059 Yuan）（ χ2=9.969 and 7.606， P=0.002和0.006）. Conclusions:Among the Gram-positive pathogens causing bloodstream infections in China， Staphylococci is the most common while the MRSA incidence decreases continuously with time；the detection rate of Enterococcus faecium exceeds that of Enterococcus faecalis. The overall prevalence of vancomycin-resistant Enterococci is still at a low level. The composition ratio of Gram-positive pathogens and resistant profiles varies slightly across regions of China，with the prevalence of MRSA and MRCNS being more pronounced in provincial hospitals and areas with a per capita GDP≥92 059 yuan.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

Objective:To analyze the correlation between nutritional status and frailty and sarcopenia in geriatric inpatients (GIPs) planning to receive major hepatopancreatobiliary (HPB) surgery.Methods:From December, 2020 to September, 2022, GIPs who were planning to receive major HPB surgery were recruited. Nutritional assessment was performed using nutritional risk screening 2002 (NRS-2002) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Frailty and sarcopenia assessment were performed using Fried frailty phenotype (FFP) and Asian Working Group for Sarcopenia (AWGS) 2019 consensus on sarcopenia diagnosis and treatment. The prevalence and concurrence of malnutrition, frailty and sarcopenia were investigated, and the correlation between nutritional status and frailty and sarcopenia was analyzed.Results:A total of 144 participants at the mean age of (70.10±7.44) years were included. The prevalence of nutritional risk, malnutrition, and severe malnutrition were 73.6% ( n ?=?106), 68.1% ( n ?=?98), and 34.7% ( n ?=?50) respectively. The prevalence of frailty was 20.8% ( n ?=?30) and that of sarcopenia was 35.4% ( n ?=?51). The prevalence of severe malnutrition increased significantly in older participants and the prevalence of nutritional risk, malnutrition and severe malnutrition decreased significantly with higher BMI. The prevalence was 35.4% (51/144) for concurrent sarcopenia and malnutrition, 19.4% (28/144) for frailty and malnutrition, 14.6% (21/144) for sarcopenia and weakness, and 14.6% (21/144) for sarcopenia, malnutrition, and weakness. There was a positive correlation between nutritional risk and frailty ( r = 0.603, P < 0.001). The risk of pre-frailty and frailty in the nutritional risk group was higher than that in the non-nutritional risk group ( χ 2 = 31.830, P < 0.001). The risk of pre-frailty and frailty in the malnutrition group was higher than that in the normal nutrition group ( χ 2 = 36.727, P < 0.001). Logistic regression analysis showed that the risk of frailty in patients with severe malnutrition was 12.303 times higher than that in patients with normal nutrition status (95% CI: 2.592 to 58.409, P = 0.002). The risk of sarcopenia in the nutritional risk group was higher than that in the non-nutritional risk group ( χ 2 = 13.982, P < 0.001). The risk of sarcopenia in the malnutrition group was higher than that in the normal nutrition group ( χ 2 = 37.066, P < 0.001). Conclusions:The prevalence and concurrence rate of malnutrition, frailty, and sarcopenia are high in GIPs undergoing major HPB surgery. GIPs with malnutrition are susceptible to frailty.

ObjectiveTo investigate the association of lipid ratios with diabetes and pre-diabetes in residents aged 35-75 years in Changzhou City. MethodsA multistage whole-group random sampling method was used to survey permanent residents aged 35-75 years in Tianning and Wujin districts of Changzhou City， and the study data were obtained by questionnaires， physical examination and laboratory tests. The relationship between lipid ratios and diabetes and pre-diabetes was analyzed by dichotomous logistic regression method. ResultsThe prevalence of diabetes in the surveyed population in Changzhou was 18.69%， and the prevalence of pre-diabetes was 10.53%. In the total population， the risk of pre-diabetes was significantly increased in the highest TC/HDL-C， TG/HDL-C and LDL-C/HDL-C groups， by 68%， 93% and 38%， respectively； the risk of diabetes was also significantly increased in the highest TC/HDL-C， TG/HDL-C and LDL-C/HDL-C groups， by 105%， 149% and 78%， respectively. The risk of diabetes was also significantly increased in the highest TC/HDL-C， TG/HDL-C and LDL-C/HDL-C groups， by 105%， 149% and 78%， respectively. All three lipid ratios increased in women compared to men， leading to a stronger association with increased risk of diabetes and pre-diabetes. ConclusionLipid ratios TC/HDL-C， TG/HDL-C， and LDL-C/HDL-C were correlated with the risk of diabetes and pre-diabetes in people aged 35-75 years， with TG/HDL-C having the strongest association with diabetes and pre-diabetes， and is expected to be a key predictor for assessing the development of diabetes.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical bacterial isolates from bloodstream infections in China in 2021.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2021 to December 2021. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 11 013 bacterial strains were collected from 51 hospitals, of which 2 782 (25.3%) were Gram-positive bacteria and 8 231 (74.7%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.6%), Klebsiella pneumoniae (18.9%), Staphylococcus aureus (9.8%), coagulase-negative Staphylococci (6.3%), Pseudomonas aeruginosa (3.6%), Enterococcus faecium (3.6%), Acinetobacter baumannii (2.8%), Enterococcus faecalis (2.7%), Enterobacter cloacae (2.5%) and Klebsiella spp (2.1%). The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus aureus were 25.3% and 76.8%, respectively. No glycopeptide- and daptomycin-resistant Staphylococci was detected; more than 95.0% of Staphylococcus aureus were sensitive to ceftobiprole. No vancomycin-resistant Enterococci strains were detected. The rates of extended spectrum B-lactamase (ESBL)-producing isolated in Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were 49.6%, 25.5% and 39.0%, respectively. The prevalence rates of carbapenem-resistance in Escherichia coli and Klebsiella pneumoniae were 2.2% and 15.8%, respectively; 7.9% of carbapenem-resistant Klebsiella pneumoniae was resistant to ceftazidime/avibactam combination. Ceftobiprole demonstrated excellent activity against non-ESBL-producing Escherichia coli and Klebsiella pneumoniae. Aztreonam/avibactam was highly active against carbapenem-resistant Escherichia coli and Klebsiella pneumoniae. The prevalence rate of carbapenem-resistance in Acinetobacter baumannii was 60.0%, while polymyxin and tigecycline showed good activity against Acinetobacter baumannii (5.5% and 4.5%). The prevalence of carbapenem-resistance in Pseudomonas aeruginosa was 18.9%. Conclusions:The BRICS surveillance results in 2021 shows that the main pathogens of blood stream infection in China are gram-negative bacteria, in which Escherichia coli is the most common. The MRSA incidence shows a further decreasing trend in China and the overall prevalence of vancomycin-resistant Enterococci is low. The prevalence of Carbapenem-resistant Klebsiella pneumoniae is still on a high level, but the trend is downwards.

Objective:To evaluate the perioperative safety of pancreaticoduodenectomy(PD)in elderly patients.Methods:Clinical data of 152 patients undergoing PD in Beijing Hospital between 2016 and 2019 were retrospectively analyzed.According to the age, patients were divided into the elderly group(age≥65 years)and the non-elderly group(age<65 years). The perioperative and postoperative parameters were compared between the two groups.Results:There was no significant difference in the operative time, intraoperative blood loss and intraoperative urine output between the elderly group and the non-elderly group(352.7±69.5)min vs.(359.0±94.4)min, (708.7±672.7) vs.(662.6±896.7)ml and(875.8±497.3)ml vs.(1010.6±568.2)ml, all P>0.05). The perioperative mortality, postoperative complications(Clavien-Dindo classification ≥ grade Ⅲ)and reoperation rate had no significant difference between elderly group and the non-elderly group(6.1% vs.1.2%, 21.2% vs.19.8%, 10.6% vs.8.1%, respectively, χ2=1.487, 0.048 and 0.272, all P>0.05). The incidences of operation-related complications, cardiovascular or cerebrovascular adverse events in elderly group were comparable to non-elderly group( P>0.05). The postoperative hospital stay had no significant difference between the elderly group and the non-elderly group[(28±19)d vs.(27±18)d, P>0.05]. Conclusions:PD is safe in elderly patients.Age is not a contraindication to pancreaticoduodenectomy.The comprehensive systemic evaluation, intraoperative delicate operation and enhanced perioperative management are necessary in the elderly patients undergoing PD.

Objective:To investigate the distribution and antimicrobial resistance profile of clinical bacteria isolated from blood culture in China.Methods:The clinical bacterial strains isolated from blood culture from member hospitals of Blood Bacterial Resistant Investigation Collaborative System (BRICS) were collected during January 2018 to December 2019. Antibiotic susceptibility tests were conducted with agar dilution or broth dilution methods recommended by US Clinical and Laboratory Standards Institute (CLSI). WHONET 5.6 was used to analyze data.Results:During the study period, 14 778 bacterial strains were collected from 50 hospitals, of which 4 117 (27.9%) were Gram-positive bacteria and 10 661(72.1%) were Gram-negative bacteria. The top 10 bacterial species were Escherichia coli (37.2%), Klebsiella pneumoniae (17.0%), Staphylococcus aureus (9.7%), coagulase-negative Staphylococci (8.7%), Pseudomonas aeruginosa (3.7%), Enterococcus faecium (3.4%), Acinetobacter baumannii(3.4%), Enterobacter cloacae (2.9%), Streptococci(2.8%) and Enterococcus faecalis (2.3%). The the prevalence of methicillin-resistant S. aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococcus were 27.4% (394/1 438) and 70.4% (905/1 285), respectively. No glycopeptide-resistant Staphylococcus was detected. More than 95% of S. aureus were sensitive to amikacin, rifampicin and SMZco. The resistance rate of E. faecium to vancomycin was 0.4% (2/504), and no vancomycin-resistant E. faecalis was detected. The ESBLs-producing rates in no carbapenem-resistance E. coli, carbapenem sensitive K. pneumoniae and Proteus were 50.4% (2 731/5 415), 24.6% (493/2001) and 35.2% (31/88), respectively. The prevalence of carbapenem-resistance in E. coli and K. pneumoniae were 1.5% (85/5 500), 20.6% (518/2 519), respectively. 8.3% (27/325) of carbapenem-resistance K. pneumoniae was resistant to ceftazidime/avibactam combination. The resistance rates of A. baumannii to polymyxin and tigecycline were 2.8% (14/501) and 3.4% (17/501) respectively, and that of P. aeruginosa to carbapenem were 18.9% (103/546). Conclusions:The surveillance results from 2018 to 2019 showed that the main pathogens of bloodstream infection in China were gram-negative bacteria, while E. coli was the most common pathogen, and ESBLs-producing strains were in majority; the MRSA incidence is getting lower in China; carbapenem-resistant E. coli keeps at a low level, while carbapenem-resistant K. pneumoniae is on the rise obviously.