Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective:To construct the targeting evaluation method of traditional Chinese medicine （TCM） preparations based on supramolecular Qi chromatography theory， and to study the liver targeting effect of Bupleuri Radix on Pien Tze Huang. Method:The molecular connectivity index （MCI） was used to analyze the characteristics of imprinted template and liver targeting tendency of TCM mainly attributed to liver meridian and components of Pien Tze Huang， and combined with target dynamics and total statistical moment principle， aimed at the independent action characteristics of multi-component imprinted template of TCM， a method for evaluating the targeting of TCM preparations was established. Hepatoma rats in Pien Tze Huang group， Bupleuri Radix group， Pien Tze Huang+Bupleuri Radix group and blank group were tested and verified. Result:After the average value of MCI of TCM mainly attributed to liver meridian was deducted， the MCI similarity between Pien Tze Huang group and Bupleuri Radix group was 0.376 8， Pien Tze Huang+Bupleuri Radix group and Bupleuri Radix group was 0.988 2， so it was predicted that Bupleuri Radix could enhance the liver targeting of Pien Tze Huang. A system for evaluating the targeting of TCM compounds was established， including relative total uptake efficiency （RUE_T）， relative total concentration （RC_T）， relative imprinted tendency （RIT_T） and relative imprinted variance （RIV_T）. The RUE_T and RC_T of liver were the highest in all tissues （RUE_T=1.88>1，RC_T=2.30>1）， and the corresponding values of other tissues were all <1， indicating that Pien Tze Huang combined with Bupleuri Radix could increase its distribution in liver and enhance liver targeting. Except for plasma， the RIT_T and RIV_T of other tissues fluctuated around 1.0， indicating that targeted modification did not change imprinted tendency of Pien Tze Huang and had no significant effect on the types of components. Conclusion:Under the guidance of supramolecular Qi chromatography theory， a targeting evaluation parameter system can be established to characterize the multi-component imprinted effect of TCM preparations by MCI and total statistical moment parameters， so as to realize the evaluation of targeting of TCM preparations. The addition of Bupleuri Radix can increase the liver targeting of Pien Tze Huang.

Objective: To explore the effect of perioperative chemotherapy on the prognosis of gastric cancer patients under real-world condition. Methods: A retrospective cohort study was carried out. Real world data of gastric cancer patients receiving perioperative chemotherapy and surgery + adjuvant chemotherapy in 33 domestic hospitals from January 1, 2014 to January 31, 2016 were collected. Inclusion criteria: (1) gastric adenocarcinoma was confirmed by histopathology, and clinical stage was cT2-4aN0-3M0 (AJCC 8th edition); (2) D2 radical gastric cancer surgery was performed; (3) at least one cycle of neoadjuvant chemotherapy (NAC) was completed; (4) at least 4 cycles of adjuvant chemotherapy (AC) [SOX (S-1+oxaliplatin) or CapeOX (capecitabine + oxaliplatin)] were completed. Exclusion criteria: (1) complicated with other malignant tumors; (2) radiotherapy received; (3) patients with incomplete data. The enrolled patients who received neoadjuvant chemotherapy and adjuvant chemotherapy were included in the perioperative chemotherapy group, and those who received only postoperative adjuvant chemotherapy were included in the surgery + adjuvant chemotherapy group. Propensity score matching (PSM) method was used to control selection bias. The primary outcome were overall survival (OS) and progression-free survival (PFS) after PSM. OS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the last effective follow-up or death. PFS was defined as the time from the first neoadjuvant chemotherapy (operation + adjuvant chemotherapy group: from the date of operation) to the first imaging diagnosis of tumor progression or death. The Kaplan-Meier method was used to estimate the survival rate, and the Cox proportional hazards model was used to evaluate the independent effect of perioperative chemo therapy on OS and PFS. Results: 2 045 cases were included, including 1 293 cases in the surgery+adjuvant chemotherapy group and 752 cases in the perioperative chemotherapy group. After PSM, 492 pairs were included in the analysis. There were no statistically significant differences in gender, age, body mass index, tumor stage before treatment, and tumor location between the two groups (all P>0.05). Compared with the surgery + adjuvant chemotherapy group, patients in the perioperative chemotherapy group had higher proportion of total gastrectomy (χ(2)=40.526, P<0.001), smaller maximum tumor diameter (t=3.969, P<0.001), less number of metastatic lymph nodes (t=1.343, P<0.001), lower ratio of vessel invasion (χ(2)=11.897, P=0.001) and nerve invasion (χ(2)=12.338, P<0.001). In the perioperative chemotherapy group and surgery + adjuvant chemotherapy group, 24 cases (4.9%) and 17 cases (3.4%) developed postoperative complications, respectively, and no significant difference was found between two groups (χ(2)=0.815, P=0.367). The median OS of the perioperative chemotherapy group was longer than that of the surgery + adjuvant chemotherapy group (65 months vs. 45 months, HR: 0.74, 95% CI: 0.62-0.89, P=0.001); the median PFS of the perioperative chemotherapy group was also longer than that of the surgery+adjuvant chemotherapy group (56 months vs. 36 months, HR=0.72, 95% CI:0.61-0.85, P<0.001). The forest plot results of subgroup analysis showed that both men and women could benefit from perioperative chemotherapy (all P<0.05); patients over 45 years of age (P<0.05) and with normal body mass (P<0.01) could benefit significantly; patients with cTNM stage II and III presented a trend of benefit or could benefit significantly (P<0.05); patients with signet ring cell carcinoma benefited little (P>0.05); tumors in the gastric body and gastric antrum benefited more significantly (P<0.05). Conclusion: Perioperative chemotherapy can improve the prognosis of gastric cancer patients.
Chemotherapy, Adjuvant ; Female ; Gastrectomy ; Humans ; Male ; Neoadjuvant Therapy ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Stomach Neoplasms/surgery*

BACKGROUNDThe radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma (GBM). However, its median overall survival (OS) is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen.

METHODSA randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide (early TMZ group) or standard concomitant radiochemotherapy regimen (control group). Overall response was assessed based on objective tumor assessments, administration of corticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event (AE), and neurological condition were measured for 24 months of follow-up. The primary efficacy endpoint of this study was overall survival (OS). The secondary endpoint was progression free survival (PFS).

RESULTSThe median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group (log-rank test P = 0.021). In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively (P < 0.05). The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group (log-rank test P = 0.695). AEs occurred in 29 (55.8%) and 31(73.8%) patients respectively in early and control groups, including nausea (15.4% vs. 33.3%), vomiting (7.7% vs. 28.6%), fever (7.7% vs. 11.9%), and headache (3.8% vs. 23.8%). Only 30.8% and 33.3% were drug-related, respectively.

CONCLUSIONSAddition of TMZ chemotherapy in the early break of the standard concomitant radiochemotherapy regimen was well tolerated and significantly improved the OS of the GBM patients, compared with standard concomitant radiochemotherapy regimen. However, a larger randomized trial is warranted to verify these results.

Adult ; Aged ; Antineoplastic Agents, Alkylating ; therapeutic use ; Chemoradiotherapy ; methods ; Dacarbazine ; analogs & derivatives ; therapeutic use ; Glioblastoma ; drug therapy ; radiotherapy ; Humans ; Middle Aged ; Treatment Outcome ; Young Adult

Objective To investigate the effects of glutamine on intestinal functions of dogs following abdominal open injury coupled with seawater immersion.Methods Following open abdominal injury,30 adult dogs were randomly divided into 3 groups:the seawater immersion group(the control group),the routine treatment group(the conventional group)and the glutamine treatment group(the observation group),each consisting of 10 animals.Blood pressure,heart rate,respiration,abdominal circumference,bowel sound were monitored both before and after injury.Blood samples were collected for the detection of endotoxin,D-lactate,diamine oxidase(DAO),tumor necrosis factor alpha(TNF-a),interleukin-1(IL-1 and lactulose/mannitol(L/M)ratio.After 24 hours,small intestine tissues were taken for pathological detection and measurement of intestinal mucosal thickness and villous height.Results When compared with the conventional group,no statistically significant differences could be seen in mean artery pressure(MAP),heart rate,respiration,bowel sound and abdominal circumference for the observation group(P＞0.05).When compared with the conventional group and the observation group,significant differences could be noted in MAP and bowel sound for the control group(P＜0.05).And statistical significance could also be noted for heart rate,respiration and abdominal circumference at hours 12 and 24 respectively following injury(P＞0.05).Endotoxin:when compared with the conventional and observation groups,statistical significance could also be noted in endotoxin for the control group at hours 12 and 24 following injury(P＞0.05),and statistical significance could also be noticed for the observation group at hour 24,when compared with the control and conventional groups(P＞0.05).D-lactate:there were statistically significant differences for the conventional group,when comparisons were made between the 3 groups at hour 12 following injury(P＜0.05),however,no statistical significance could be noted between the observation group and the control group(P＞0.05).Statistical significance was observed for the conventional group,when compared with the control and observation groups(P＜0.05).And no statistical significance was noted,when a comparison was made between the observation and control groups(P＜0.05).DAO:when compared with the control and conventional groups,statistical significance could be noted for the observation group at hours 8 and 24 respectively following injury(P＜0.05).TNF-α:when compared with observation and conventional groups,there was statistical significance for the observation group at hours 12 and 24 respectively following injury(P＜0.05).IL-1:when compared with the control[(7.40±2.71)ng/L]and the conventional groups[(8.71±3.13)ng/L],statistical significance could be observed for the observation group at hour 12 following injury(P＜0.05),however no statistical significance could be noted,when a comparison was made between the observation and control groups.At hour 24 following injury,when compared with the control[(9.91±3.18)ng/L]and conventional groups[(10.12±2.25)ng/L],statistical significance could be noticed for the observation group(P＜0.05).Urine L/M ratio:statistical significance would be noticed for the observation group,when compared with the control and conventional groups(P＜0.05).Pathological results:only mild edema could be seen in the intestinal mucosal cells of the animals in the observation group under optical microscope,which was obviously lighter,when compared with the observation and control groups.And there were statistical differences in intestinal mucosal thickness and villous height,when compared with the conventional group(P＜0.05),however,no statistical differences could be noted,when a comparison was made between the control and conventional groups(P＞0.05).Conclusions Glutamine seems to have definitive therapeutic effects on intestinal dysfunction induced by abdominal injury coupled with seawater immersion.

Objective To investigate the effects of glutamine on intestinal functions of dogs following abdominal open injury coupled with seawater immersion.Methods Following open abdominal injury,30 adult dogs were randomly divided into 3 groups:the seawater immersion group(the control group),the routine treatment group(the conventional group)and the glutamine treatment group(the observation group),each consisting of 10 animals.Blood pressure,heart rate,respiration,abdominal circumference,bowel sound were monitored both before and after injury.Blood samples were collected for the detection of endotoxin,D-lactate,diamine oxidase(DAO),tumor necrosis factor alpha(TNF-a),interleukin-1(IL-1 and lactulose/mannitol(L/M)ratio.After 24 hours,small intestine tissues were taken for pathological detection and measurement of intestinal mucosal thickness and villous height.Results When compared with the conventional group,no statistically significant differences could be seen in mean artery pressure(MAP),heart rate,respiration,bowel sound and abdominal circumference for the observation group(P＞0.05).When compared with the conventional group and the observation group,significant differences could be noted in MAP and bowel sound for the control group(P＜0.05).And statistical significance could also be noted for heart rate,respiration and abdominal circumference at hours 12 and 24 respectively following injury(P＞0.05).Endotoxin:when compared with the conventional and observation groups,statistical significance could also be noted in endotoxin for the control group at hours 12 and 24 following injury(P＞0.05),and statistical significance could also be noticed for the observation group at hour 24,when compared with the control and conventional groups(P＞0.05).D-lactate:there were statistically significant differences for the conventional group,when comparisons were made between the 3 groups at hour 12 following injury(P＜0.05),however,no statistical significance could be noted between the observation group and the control group(P＞0.05).Statistical significance was observed for the conventional group,when compared with the control and observation groups(P＜0.05).And no statistical significance was noted,when a comparison was made between the observation and control groups(P＜0.05).DAO:when compared with the control and conventional groups,statistical significance could be noted for the observation group at hours 8 and 24 respectively following injury(P＜0.05).TNF-α:when compared with observation and conventional groups,there was statistical significance for the observation group at hours 12 and 24 respectively following injury(P＜0.05).IL-1:when compared with the control[(7.40±2.71)ng/L]and the conventional groups[(8.71±3.13)ng/L],statistical significance could be observed for the observation group at hour 12 following injury(P＜0.05),however no statistical significance could be noted,when a comparison was made between the observation and control groups.At hour 24 following injury,when compared with the control[(9.91±3.18)ng/L]and conventional groups[(10.12±2.25)ng/L],statistical significance could be noticed for the observation group(P＜0.05).Urine L/M ratio:statistical significance would be noticed for the observation group,when compared with the control and conventional groups(P＜0.05).Pathological results:only mild edema could be seen in the intestinal mucosal cells of the animals in the observation group under optical microscope,which was obviously lighter,when compared with the observation and control groups.And there were statistical differences in intestinal mucosal thickness and villous height,when compared with the conventional group(P＜0.05),however,no statistical differences could be noted,when a comparison was made between the control and conventional groups(P＞0.05).Conclusions Glutamine seems to have definitive therapeutic effects on intestinal dysfunction induced by abdominal injury coupled with seawater immersion.

OBJECTIVETo investigate the role of methylation on E-cadherin inactivation in nasopharyngeal carcinoma (NPC) cell line HNE1 and CNE2, as well as evaluate the inhibitory effect of 5-aza-2'-deoxycytidine (5-Aza-dC) on cell abilities of proliferation and invasion.

METHODSThe expression level of E-cadherin was measured by RT-PCR, Western blot and immunohistochemistry (polymer method), the methyaltion status was analyzed by methylation-specific PCR (MSP), and cell proliferation and invasion were examined by MTT and invasion assay, separately before and after treatment with demethylating agent 5-Aza-dC.

RESULTSThe expression level of E-cadherin was down-regulated compared with the normal tissue, simultaneously partially methylated in gene promoter. Treatment with 20 µmol/L 5-Aza-dC increased the expression of E-cadherin and reduced the methylation degree. Moreover, it also significantly suppressed cell growth (27.6% for HNE1 cells and 34.3% for CNE2 cells, P < 0.05) and invasiveness (37.2% for HNE1 cells and 29.7% for CNE2 cells, P < 0.05).

CONCLUSIONSAberrant methylation around gene promoter region may play an important part in down regulation of E-cadherin in NPC, suggesting a potential therapeutic strategy for demethylating agents such as 5-Aza-dC.

Antimetabolites, Antineoplastic ; pharmacology ; Azacitidine ; analogs & derivatives ; pharmacology ; Cadherins ; genetics ; metabolism ; Cell Line, Tumor ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; DNA Methylation ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Humans ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Invasiveness ; Promoter Regions, Genetic

Objective To explore the mechanism of intestinal lesion induced by seawater immersion following open chest injury in dogs. Methods Twenty adult mongrel dogs were randomly divided into the control group (n = 10) and the seawater immersion group (n = 10). The control group was put under observation soon after abdominal injury. The seawater immersion group was immersed in manually prepared seawater immediately after abdominal injury. Arterial blood pressure and intestinal mucosa pH were monitored before injury (0 hour) and at hour4, 8, 12, and 24 after injury. Intestinal tissue samples were collected after 24 hours for the detection of MDA, NO/NOS and SOD. Results Arterial blood pressure for the animals of group B dropped significantly with statistical difference (P < 0.05), when it was compared with that of the control group. Intestinal mucosa pH of group B decreased at hour 4 with a marked difference, when it was compared with that of the control group (P < 0. 05). However, an increase was noted at hour 12 after immersion, with no significant difference, when a comparison was made between the 2 groups (P > 0. 05). Detection showed that levels of MDA, NO and NOS for the seawater immersion group increased obviously, when it was compared with that of the control (P < 0.05). Monitoring of intestinal SOD indicated that there was a clear reduction in the level of SOD for the seawater immersion group (P < 0. 05). Conclusions Trauma -induced ischemia and ischemia-reperfusion might be involved in lesion to the intestine of experimental dogs following seawater immersion.