Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective:To observe the clinical efficacy of posterior vertebral column resection (PVCR) combined with double row nanomimetic bone column implantation and internal fixation in the treatment of stage Ⅲ Kümmell's disease plus kyphosis.Methods:A retrospective study was conducted to analyze the clinical data of the 12 patients with stage Ⅲ Kümmell's disease plus kyphosis who had been admitted to Department of Spine Surgery, Zhengzhou Orthopedic Hospital from March 2017 to September 2023. There were 2 males and 10 females, with an age of (63.4±6.4) years and a disease duration of (8.6±5.1) months. The injured segment was T 11 in 1 patient, T 12 in 5 ones, and L 1 in 6 ones. The preoperative spinal nerve injury was graded according to American Spinal Injury Association (ASIA): grade D in 5 cases and grade E in 7 cases. All the patients were treated with PVCR combined with double row nanomimetic bone column implantation and internal fixation. The operation time, intraoperative blood loss, shortening rate of the osteotomy area, complications during follow-up, and spinal nerve recovery at the last follow-up were recorded. The visual analogue scale (VAS) pain scores, Oswestry Disability Indexes (ODIs), and local kyphosis Cobb angles were compared between pre-surgery, 2 weeks after surgery, and the last follow-up. Results:Incisions in all the 12 patients healed at the primary stage. Their operation duration was (268.4±26.5) min, intraoperative blood loss (994.9±180.4) mL, shortening rate of the osteotomy area 3.94%±7.58%, and follow-up duration (24.1±13.5) months. At 2 weeks after surgery and the last follow-up, the VAS pain scores [(3.08±0.79) points and (1.17±0.58) points] and ODIs (27.59%±6.10% and 16.67%±2.22%) were significantly lower than those before surgery [(8.08±0.79) points and 73.14%±5.64%], and the values at the last follow-up were further significantly lower than those at 2 weeks after surgery (all P<0.05). There was no statistically significant difference in the Cobb angle at the last follow-up (5.29°±1.30°) compared with 2 weeks after surgery (4.74°±1.31°) ( P>0.05), but there was a statistically significant difference compared with the preoperative value (49.41°±4.40°) ( P<0.05). At the last follow-up, the ASIA grading in all the 12 patients recovered to grade E, with good bone healing at the fixation segment. No screw loosening or fracture was found. Two patients had a biomimetic bone column sinking of 3.5 and 4.0 mm, respectively, but their Marchi's grading was still 0. During the follow-up period, one patient developed proximal junctional kyphosis, and one patient developed an osteoporotic fracture of the proximal vertebral body at the fixed level. Conclusions:In the treatment of stage Ⅲ Kümmell's disease plus kyphosis, PVCR combined with double row nanomimetic bone column implantation and internal fixation can significantly correct the kyphosis and improve clinical symptoms, leading to good clinical efficacy.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective:To observe the clinical efficacy of posterior vertebral column resection (PVCR) combined with double row nanomimetic bone column implantation and internal fixation in the treatment of stage Ⅲ Kümmell's disease plus kyphosis.Methods:A retrospective study was conducted to analyze the clinical data of the 12 patients with stage Ⅲ Kümmell's disease plus kyphosis who had been admitted to Department of Spine Surgery, Zhengzhou Orthopedic Hospital from March 2017 to September 2023. There were 2 males and 10 females, with an age of (63.4±6.4) years and a disease duration of (8.6±5.1) months. The injured segment was T 11 in 1 patient, T 12 in 5 ones, and L 1 in 6 ones. The preoperative spinal nerve injury was graded according to American Spinal Injury Association (ASIA): grade D in 5 cases and grade E in 7 cases. All the patients were treated with PVCR combined with double row nanomimetic bone column implantation and internal fixation. The operation time, intraoperative blood loss, shortening rate of the osteotomy area, complications during follow-up, and spinal nerve recovery at the last follow-up were recorded. The visual analogue scale (VAS) pain scores, Oswestry Disability Indexes (ODIs), and local kyphosis Cobb angles were compared between pre-surgery, 2 weeks after surgery, and the last follow-up. Results:Incisions in all the 12 patients healed at the primary stage. Their operation duration was (268.4±26.5) min, intraoperative blood loss (994.9±180.4) mL, shortening rate of the osteotomy area 3.94%±7.58%, and follow-up duration (24.1±13.5) months. At 2 weeks after surgery and the last follow-up, the VAS pain scores [(3.08±0.79) points and (1.17±0.58) points] and ODIs (27.59%±6.10% and 16.67%±2.22%) were significantly lower than those before surgery [(8.08±0.79) points and 73.14%±5.64%], and the values at the last follow-up were further significantly lower than those at 2 weeks after surgery (all P<0.05). There was no statistically significant difference in the Cobb angle at the last follow-up (5.29°±1.30°) compared with 2 weeks after surgery (4.74°±1.31°) ( P>0.05), but there was a statistically significant difference compared with the preoperative value (49.41°±4.40°) ( P<0.05). At the last follow-up, the ASIA grading in all the 12 patients recovered to grade E, with good bone healing at the fixation segment. No screw loosening or fracture was found. Two patients had a biomimetic bone column sinking of 3.5 and 4.0 mm, respectively, but their Marchi's grading was still 0. During the follow-up period, one patient developed proximal junctional kyphosis, and one patient developed an osteoporotic fracture of the proximal vertebral body at the fixed level. Conclusions:In the treatment of stage Ⅲ Kümmell's disease plus kyphosis, PVCR combined with double row nanomimetic bone column implantation and internal fixation can significantly correct the kyphosis and improve clinical symptoms, leading to good clinical efficacy.

BACKGROUND:Overactive osteoclasts disrupt bone homeostasis and play a bad role in the pathological mechanisms of related skeletal diseases,such as osteoporosis,fragility fractures,and osteoarthritis.Studies have confirmed that ellagic acid and ellagtannin have the potential to inhibit osteoclast differentiation.As their natural metabolites,urolithin A has antioxidant,anti-inflammatory,anti-proliferative and anti-cancer effects,but its effect on osteoclast differentiation and its underlying molecular mechanisms remain unclear. OBJECTIVE:To explore the effect of urolithin A on osteoclast differentiation induced by receptor activator for nuclear factor-κB ligand and its mechanism. METHODS:Mouse mononuclear macrophage leukemia cells(RAW264.7)that grew stably were cultured in vitro.Toxicity of urolithin A(0,0.1,0.5,1.5,2.5 μmol/L)to RAW264.7 cells were detected by cytotoxic MTS assay to screen out the safe concentration.Different concentrations of urolithin A were used again to intervene with receptor activator for nuclear factor-κB ligand-induced differentiation of RAW264.7 cells in vitro.Then,tartrate-resistant acid phosphatase staining and F-actin ring and nucleus staining were performed to observe its effect on the formation and function of osteoclasts.Finally,the expressions of urolithin A on upstream and downstream genes and proteins in the MAPK signaling pathway were observed by western blot and RT-qPCR assays. RESULTS AND CONCLUSION:Urolithin A inhibited osteoclast differentiation and F-actin ring formation in a concentration-dependent manner and 2.5 μmol/L had the strongest inhibitory effect.Urolithin A inhibited the mRNA expression of Nfatc1,Ctsk,Mmp9 and Atp6v0d2 and the protein synthesis of Nfatc1 and Ctsk,related to osteoclast formation and bone resorption.Urolithin A inhibited the activity of osteoclasts by downregulating the phosphorylation of p38 protein to inhibit the mitogen-activated protein kinase signaling pathway.

COVID-19 is caused by a novel coronavirus-severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), which has being spreading around the world, posing a serious threat to human health and lives. Neutralizing antibodies and small molecule inhibitors for virus replication cycle are the main antiviral treatment for novel coronavirus recommended in China. To further promote the rational use of antiviral therapy in clinical practice, the National Center for Infectious Diseases (Beijing Ditan Hospital Capital Medical University and the First Affiliated Hospital, Zhejiang University School of Medicine) invited experts in fields of infectious diseases, respiratory and intensive care to develop an Expert Consensus on Antiviral Therapy of COVID-19 based on the Diagnosis and Treatment Guideline for COVID-19 ( trial version 10) and experiences in the diagnosis and treatment of COVID-19 in China. The consensus is concise, practical and highly operable, hopefully it would improve the understanding of antiviral therapy for clinicians and provide suggestions for standardized medication in treatment of COVID-19.

With the dramatically increasing detection rate of ground-glass nodules (GGN), exact understanding and treatment strategy of them has become the hottest issue currently. More and more studies have begun to explore the underlying mechanisms of their indolent characteristics and favorable prognosis from the perspectives of molecular evolution and immune microenvironment. GGN has different dominating gene mutations at different evolutional stages. The pure GGN has a lower tumor mutation burden and genomic instability, while a gradually evolutionary feature of genomic mutation along with the pathological progression can be observed. GGN has less infiltration of immune cells, and they are under the pressure of immune surveillance with weakened immune escape. With the increase of solid components, an inhibitory immune microenvironment is gradually established and immune escape is gradually enhanced, leading to rapid tumor growth. Further exploration of the molecular characteristics of GGN will help to more precisely distinguish these highly heterogeneous lesions, which could be helpful to make personalized treatment plans.

With the dramatically increasing detection rate of ground-glass nodules (GGN), exact understanding and treatment strategy of them has become the hottest issue currently. More and more studies have begun to explore the underlying mechanisms of their indolent characteristics and favorable prognosis from the perspectives of molecular evolution and immune microenvironment. GGN has different dominating gene mutations at different evolutional stages. The pure GGN has a lower tumor mutation burden and genomic instability, while a gradually evolutionary feature of genomic mutation along with the pathological progression can be observed. GGN has less infiltration of immune cells, and they are under the pressure of immune surveillance with weakened immune escape. With the increase of solid components, an inhibitory immune microenvironment is gradually established and immune escape is gradually enhanced, leading to rapid tumor growth. Further exploration of the molecular characteristics of GGN will help to more precisely distinguish these highly heterogeneous lesions, which could be helpful to make personalized treatment plans.

Objective To analyze the resistance proifle of bacterial strains isolated from geriatric patients in 17 hospitals across China from 2005 to 2014.Methods A total of 17 representative general hospitals were involved in this program. Bacterial susceptibility testing was carried out by means of a uniifed protocol using Kirby-Bauer method and MIC determination. The results were analyzed according to CLSI 2014 breakpoints.Results The proportion of the strains isolated from geriatric patients among all the clinical isolates increased with time from 30.0% in 2005 to 32.7% in 2014. A total of 159 888 clinical isolates were collected from geriatric patient during the period from 2005 to 2014, about 33.1% of the whole patient population. Gram negative organisms and gram positive cocci accounted for 77.1% (123 229/159 888) and 22.9% (36 659/159 888), respectively. Majority (92.8%, 148 376/159 888) of the isolates were from inpatients and more than half (55.2%, 88 201/159 888) of the isolates were from sputum or other respiratory tract specimens. Methicillin-resistant strains inS. aureus (MRSA) and coagulase negativeStaphylococcus (MRCNS) accounted for an average of 67.1% and 75.9%, respectively. The resistance rates of methicillin-resistant strains to β-lactams and other antimicrobial agents were much higher than those of methicillin-susceptible strains. No staphylococcal strains were found resistant to vancomycin, teicoplanin or linezolid. Some strains ofE. faecalis (0.4%) andE. faecium (4.6%) were resistant to vancomycin, which was higher than average national level (0.3%, 3.2%). Vancomycin-resistant strains ofE. faecalisandE. faecium were mainly VanA type and VanB type based on their phenotype. The prevalence of penicillin-susceptibleS. pneumoniae strains was 78.2%, slightly lower than the 95.0% in Chinese adults in year 2014. The prevalence of ESBLs-producing strains was 67.5% inE. coli, 40.4% inKlebsiella (K. pneumoniae andK. oxytoca) and 34.3% inProteus mirabilis isolates on average. The strains ofEnterobacteriaceae were still highly susceptible to carbapenems (<10% resistant), followed by amikacin and the beta-lactam and beta-lactamase inhibitor combinations. Overall, 35.9% and 33.0% of theP. aeruginosa strains were resistant to imipenem and meropenem. More than 50% of theA. baumannii strains were resistant to imipenem and meropenem. The prevalence of extensively drug-resistant (XDR)P. aeruginosa (4.0%-1.8%) was higher than the average national level (2.1%-1.6%). The prevalence of XDR A. baumannii (19.2%-15.5%) and XDREnterobacteriaceae (0.1%-1.0%) was lower than the average national level (21.4%-19.7% and 0.3%-3.2%).Conclusions The proportion of clinical isolates from geriatric patients is different from average national level at the same period. The isolates from geriatric patients are more likely from inpatients, respiratory tract specimens and more likely non-fermentative gram-negative bacilli compared to average national level. The proportion of fastidious bacteria andEnterobacteriaceae species is generally lower than average national level. MRSA, VRE, ESBLs-producing strains and XDRP. aeruginosa are more prevalent in geriatric patients than in general Chinese patient population. This study suggests that surveillance of antimicrobial resistance for the clinical isolates from geriatric patients is very important for rational antimicrobial therapy.

Objective To investigate the distribution and changing resistance proifle ofSalmonella isolates in hospitals across China during the period from January 2005 to December 2014.Methods Seventeen general hospitals and two children’s hospitals were involved in this program. Antimicrobial susceptibility testing was carried out by means of a unified protocol using Kirby-Bauer method or MIC determination. The results were analyzed according to CLSI 2014 breakpoints.Results The proportion ofSalmonella isolates increased with time from 0.2% in 2005 to 0.7% in 2014. A total of 3 478Salmonella strains were collected from 19 hospitals. The proportion ofSalmonella typhimurium andSalmonella enteritidis was 27.4% and 24.4%, respectively. During the 10-year period, theSalmonella strains showed highest resistance rate to ampicillin (33.3%-64.8%), but low resistance to cefoperazone-sulbactam (0-5.3%) and ciprofloxacin (2.4%-14.3%).S. typhimurium showed higher resistance rate thanS. typhi,S. paratyphi andS. enteritidis. About 76.8% and 50.5% ofS. typhimurium were resistant to ampicillin and trimethoprim-sulfamethoxazole. The average prevalence of multi-drug resistantSalmonellawas 3.9% in the ten-year period, the highest (7.5%) was in 2005, the lowest (1.5%) in 2013.Conclusions During the period from 2004 to 2015, majority of theSalmonella isolates in hospitals across China wasS. typhimurium andS. enteritidis. Ampicillin and trimethoprim-sulfamethoxazole are no longer appropriate for empirical treatment ofS. typhimurium infection due to high resistance rate.Salmonella isolates are relatively more susceptible to third-generation cephalosporins and quinolones. Ongoing monitoring is necessary to identify multi-drug resistant strains ofSalmonella.