Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.

Objective:To investigate the role of serotonin reuptake transporter(SERT)and P2X3 receptor of dorsal root ganglion(DRG)in regulating visceral hypersensitivity of rats with irritable bowel syndrome(IBS)by electroacupuncture(EA). Methods:Male Sprague-Dawley and SERT-/-rats were subjected to preparing IBS visceral hypersensitivity models with 2,4,6-trinitrobenzene sulfonic acid(TNBS)enema.Three weeks post-modeling,interventions including EA,intrathecal injection,and EA plus intrathecal injection were applied,respectively.Hematoxylin-eosin staining and abdominal withdrawal reflex(AWR)score were used to confirm the successful establishment of the IBS model.AWR score,whole-cell patch clamp technique,and Western blotting assay were used to evaluate the changes in visceral pain sensitivity,electrophysiological properties of DRG neurons,and the expression of DRG P2X3 receptor and SERT in IBS rats. Results:Compared to the model group,the AWR score in the EA group decreased significantly(P<0.05),the resting membrane potential(P<0.05)and the number of action potentials(P<0.05)of DRG neurons reduced,and the baseline intensity increased(P<0.05);additionally,the expression of P2X3 receptor in DRG decreased(P<0.01),and the SERT expression increased(P<0.05).Compared to the P2X3 receptor agonist group,the SERT protein expression in DRG was higher in the EA group.In SERT-/-rats,the P2X3 receptor expression in DRG increased in the EA group compared to the model group(P<0.01). Conclusion:EA modulates the electrophysiological characteristics of intestinal primary sensory neurons by regulating the expression of SERT and P2X3 receptor in DRG of IBS rats.This modulation may contribute to the mechanism by which EA alleviates peripheral sensitization of visceral pain in IBS rats.

Periarticular fracture of the shoulder is a common type of fractures in the elderly. Postoperative adverse events such as internal fixation failure, humeral head ischemic necrosis and upper limb dysfunction occur frequently, which seriously endangers the exercise and health of the elderly. Compared with the fracture with normal bone mass, the osteoporotic periarticular fracture of the shoulder is complicated with slow healing and poor rehabilitation, so the clinical management becomes more difficult. At present, there is no targeted guideline or consensus for this type of fracture in China. In such context, experts from Youth Osteoporosis Group of Chinese Orthopedic Association, Orthopedic Expert Committee of Geriatrics Branch of Chinese Association of Gerontology and Geriatrics, Osteoporosis Group of Youth Committee of Chinese Association of Orthopedic Surgeons and Osteoporosis Committee of Shanghai Association of Chinese Integrative Medicine developed the Chinese expert consensus on the diagnosis and treatment of osteoporotic periarticular fracture of the shoulder in the elderly ( version 2023). Nine recommendations were put forward from the aspects of diagnosis, treatment strategies and rehabilitation of osteoporotic periarticular fracture of the shoulder, hoping to promote the standardized, systematic and personalized diagnosis and treatment concept and improve functional outcomes and quality of life in elderly patients with osteoporotic periarticular fracture of the shoulder.

Objective To preliminarily verify the effectiveness and safety of bloodletting combined with drug bamboo cups in intervention of degenerative lumbar spinal stenosis,and to explore the prognostic factors that affect the efficacy of TCM regimens in the treatment of DLSS.Methods 64 consecutive patients with degenerative lumbar spinal stenosis were enrolled.Bloodletting combined with drug bamboo cup intervention was used.Acupoints were selected and treated with the same length of the governor channel of the lumbar spine,the first and second side lines of the bladder meridian and Ashi point,weekly 2 times,8 times per course,2 consecutive courses of treatment.Before treatment,after treatment,and 1 month follow-up,the changes of the patient's lumbar spinal stenosis specific scale(SSM),modified Oswestry dysfunction index(ODI),and 12 health survey summary scores(SF-12)were observed.Using SSM symptom or function score≥0.5,the criteria for grouping were first single-factor analysis,and then logistic regression was used to analyze the prognostic factors of the treatment.Results After 2 courses of treatment,the patient's SSM symptom score(2.25±0.56),SSM function score(2.06±0.67),ODI index(15.49±8.72),and SF-12 physiological score(36.31±7.35)were more significant than before treatment Improved,the difference was statistically significant(P<0.05),the SF-12 psychological score(49.70±9.47),the difference was not statistically significant compared with before treatment(P>0.05);the patient's SSM symptom score(2.22±0.54)was followed up for one month,SSM function score(2.09±0.66),ODI index(15.53±8.23),SF-12 physiological score(36.55±7.25),SF-12 psychological score(50.62±9.17),which are significantly better than before treatment,and the difference is statistically significant(P<0.05),the difference was not statistically significant(P>0.05)after 2 courses of treatment.The univariate logistic regression analysis of each influencing factor showed that:BMI,baseline symptom dimension,baseline functional dimension,foraminal stenosis,lateral recess stenosis,and two-stage stenosis had statistically significant differences between the effective and ineffective groups(P<0.05).Conclusion Bloodletting combined with drug bamboo cups has a certain clinical effect on degenerative lumbar spinal stenosis.

Objective : To investigate the effect of sinomenine on proliferation and migration of multiple myeloma (MM) cells by regulating STAT3 and NF-κB signaling pathway． Methods : The cultured U266 cells were treated with different concentrations of sinomenine (0，0．5，1，2 mmol / L) ．The control group was added DMSO with 0．5% concentration．CCK-8 assay was used to detect the proliferation of U266 cells．Flow cytometry was used to detect the apoptosis of U266 cells．Western blot assay was used to detect the expression levels of apoptosis-related proteins， STAT3 and NF-κB signaling pathway proteins in the each group. Results : Compared with CON group，the apopto- sis of U266 cells increased after Sinomenine treatment，the proliferation was inhibited ; B lymphoma-2 (Bcl-2) mye- loid and cell leukemia-1 (Mcl-1) expression level decreased ; activated Caspase-3 (cleaved Caspase-3) and PARP (Cleaved Caspase-3) expression levels increased ; the activity of STAT3 and NF-κB signaling pathway decreased. Conclusion Sinomenine can down-regulate the activity of STAT3 and NF-κB signaling pathway，promote the apop- tosis of U266 cells and inhibit the proliferation of U266 cells.

We conducted a randomized, open-label, parallel-controlled, multicenter trial on the use of Shuanghuanglian (SHL), a traditional Chinese patent medicine, in treating cases of COVID-19. A total of 176 patients received SHL by three doses (56 in low dose, 61 in middle dose, and 59 in high dose) in addition to standard care. The control group was composed of 59 patients who received standard therapy alone. Treatment with SHL was not associated with a difference from standard care in the time to disease recovery. Patients with 14-day SHL treatment had significantly higher rate in negative conversion of SARS-CoV-2 in nucleic acid swab tests than the patients from the control group (93.4% vs. 73.9%, P = 0.006). Analysis of chest computed tomography images showed that treatment with high-dose SHL significantly promoted absorption of inflammatory focus of pneumonia, which was evaluated by density reduction of inflammatory focus from baseline, at day 7 (mean difference (95% CI), -46.39 (-86.83 to -5.94) HU; P = 0.025) and day 14 (mean difference (95% CI), -74.21 (-133.35 to -15.08) HU; P = 0.014). No serious adverse events occurred in the SHL groups. This study illustrated that SHL in combination with standard care was safe and partially effective for the treatment of COVID-19.
COVID-19 ; Humans ; Medicine, Chinese Traditional ; Research ; SARS-CoV-2 ; Treatment Outcome

BACKGROUND: Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown. METHODS: Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 μL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 μL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed. RESULTS: Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 down-regulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 down-regulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin β1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9). CONCLUSIONS Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.

OBJECTIVE: To investigate the efficacy of bone marrow mesenchymal stem cells (BMMSC) on children with refractory graft-versus-host disease (GVHD) and to judge the efficacy of BMMSC by dynamically monitoring the changes of cytokines in children with GVHD before and after infusion of BMMSC, so as to provide a theoretical basis for clarifying the mechanism of BMMSC. METHODS: 17 children with refractory aGVHD including 7 of grade II, 6 cases of grade III and 4 cases of grade IV after allo-HSCT were enrolled. All the children with aGVHD, who received routine immunosuppressive therapy, but the state of disease not improved, were treated with immunosuppressive drugs combined with BMMSC infusion. Study endpoints included safety of BMMSC infusion, response to BMMSC, and overall response of aGVHD. The serum levels of IL-2α, IL-6, IL-10, IL-8 and TNF-α in aGVHD patients were measured by chemiluminescence before infusion of BMMSCs and Day 7, Day 14 after infusion of BMMSCs. RESULTS: The cumulative median dose of BMMSCs was 5.5 (3.4-11.1) × 10/kg for average of 3.7 times, and the median time of 16.5 (4-95) days for the first infusion of MSCs. In 17 cases of refractory GVHD, 14 responded to treatment, whereas 3 patients failed. The total effective rate was 82.4% and no adverse reactions occurred. Of the 14 survived cases (82.4%), the median follow-up time was 944 (559-1245) days from the first infusion of MSCs. The levels of TNF-α in children with grade II, III and IV GVHD before treatment were 9.5±4.3 pg/ml, 16.3±10.9 pg/ml and 35.8±21.2 pg/ml respectively. The difference between grade II and IV, III and IV was statistically significant (P<0.05). Compared with the ineffective group of BMMSC infusion, the serum TNF-αlevel in the BMMSCs treatment effective group was 10.8±5.6 pg/ml vs 40.6±14.8 pg/ml (t=-3.901, P<0.05) before treatment. In the effective group of BMMSCs infusion, IL-10 20±17.4 pg/ml of day 14 was significantly higher than that 7.3±3.1 pg/ml before the treatment (t=-2.850, P<0.05), while , the serum levels of IL-2α, IL-6, IL-8, TNF-α were not statistically significantly different (P＞0.05). CONCLUSION The infusion of BMMSC is safe and effective in the treatment of refractory GVHD in children. TNF-αlevel relates with the severity of GVHD. BMMSC may play an anti-GVHD role by up regulating the level of cytokine IL-10 in vivo.

In the original publication, the label of Fig. 2C should be read as "GFAP/lectin/DAPI" not "DMP1/GFAP/lectin/DAPI".

The blood-brain barrier (BBB) is a tight boundary formed between endothelial cells and astrocytes, which separates and protects brain from most pathogens as well as neural toxins in circulation. However, detailed molecular players involved in formation of BBB are not completely known. Dentin matrix protein 1 (DMP1)-proteoglycan (PG), which is known to be involved in mineralization of bones and dentin, is also expressed in soft tissues including brain with unknown functions. In the present study, we reported that DMP1-PG was expressed in brain astrocytes and enriched in BBB units. The only glycosylation site of DMP1 is serine89 (S89) in the N-terminal domain of the protein in mouse. Mutant mice with DMP1 point mutations changing S89 to glycine (S89G), which completely eradicated glycosylation of the protein, demonstrated severe BBB disruption. Another breed of DMP1 mutant mice, which lacked the C-terminal domain of DMP1, manifested normal BBB function. The polarity of S89G-DMP1 astrocytes was disrupted and cell-cell adhesion was loosened. Through a battery of analyses, we found that DMP1 glycosylation was critically required for astrocyte maturation both in vitro and in vivo. S89G-DMP1 mutant astrocytes failed to express aquaporin 4 and had reduced laminin and ZO1 expression, which resulted in disruption of BBB. Interestingly, overexpression of wild-type DMP1-PG in mouse brain driven by the nestin promoter elevated laminin and ZO1 expression beyond wild type levels and could effectively resisted intravenous mannitol-induced BBB reversible opening. Taken together, our study not only revealed a novel element, i.e., DMP1-PG, that regulated BBB formation, but also assigned a new function to DMP1-PG.
Animals ; Astrocytes ; cytology ; metabolism ; Blood-Brain Barrier ; cytology ; metabolism ; Cells, Cultured ; Extracellular Matrix Proteins ; genetics ; metabolism ; Female ; Glycosylation ; Male ; Mice ; Proteoglycans ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction