ObjectiveTo explore the clinical characteristics and risk factors for 30-day mortality in hospitalized patients with bloodstream infections (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP). MethodsData were obtained retrospectively from the electronic medical records of inpatients at a tertiary A-grade hospital in Shanghai from January 2016 to December 2023. The collected variables included age, gender, department, surgical treatment, empirical antibiotic therapy, Pitt Bacteremia score (PBS), Charlson comorbidity index (CCI), INCREMENT-CPE score (ICS), length of hospital stay, the time from CRKP-BSI to discharge and, etc. The follow-up period ended upon discharge, with the follow-up outcomes defined as in-hospital mortality or discharge. The endpoint was defined as death within 30 days (including day 30) caused by CRKP-BSI or infection-related complications. Patients who survived within 30 days after CRKP-BSI were classified into the survival group, while those who died within 30 days were classified into the death group. Independent risk factors for 30-day mortality in patients with CRKP-BSI were analyzed using univariate and multivariate Cox regression analysis. ResultsA total of 71 hospitalized patients with CRKP-BSI, comprising 51 males and 20 females, with an average age of (65.12±18.25) years, were included during the study period. The M (P₂₅, P₇₅) of hospital stay were 37.00 (24.00, 56.00) days, and M (P₂₅, P₇₅) of the duration from CRKP-BSI to discharge or death were 18.00 (7.00, 35.00) days. There were 20 deaths (28.17%) in the death group and 51 survivors (71.83%) in the survival group. The results of multivariate Cox regression analysis showed that the ICS as an independent risk factor for 30-day mortality in CRKP-BSI patients (HR=1.379, 95%CI: 1.137‒1.671, P=0.001). Each 1-point increase in the ICS was associated with a 37.9% increase in the risk of mortality. ConclusionThe ICS is found to be a risk factor for 30-day mortality in patients with CRKP-BSI, which may facilitate the prediction for the risk of 30-day mortality and thereby support clinical decision-making for patients with CRKP-BSI.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To compare the clinical features of severe Mycoplasma pneumoniae pneumonia (SMPP) in pediatric intensive care units (PICU) before and after the COVID-19 pandemic.Methods:A retrospective study was conducted in the PICU of Shanghai Children's Hospital. Clinical and laboratory data were collected from medical records of SMPP patients admitted to the PICU before (January to December 2019) and after (March 2023 to February 2024) the COVID-19 pandemic. Patients admitted in 2019 were categorized as the pre-COVID-19 group, while those admitted in 2023-2024 were classified as the post-COVID-19 group.Results:A total of 287 children with SMPP were included, comprising 155 males and 132 females. The pre-pandemic group consisted of 180 cases, while the post-pandemic group had 107 cases. Macrolide-resistant Mycoplasma pneumoniae (MRMP) was detected in 270 cases (94.1%), with no significant difference in MRMP prevalence between the two groups [101 cases (94.4%) vs. 169 cases (93.9%), Z= 0.031, P = 0.861]. The median age of the post-pandemic group was higher than that of the pre-pandemic group [72 (42, 108) months vs. 42 (24, 68) months, Z= 6.438, P < 0.001].Comparisons of complications between the post-pandemic and pre-pandemic groups were as follows: pleural effusion [20 cases (18.7%) vs. 81 cases (45.0%), χ2=20.365, P< 0.001], shock [4 cases (3.7%) vs. 79 cases (43.9%), χ2=52.628, P< 0.001], gastrointestinal dysfunction [2 cases (1.9%) vs. 24 cases (13.3%), χ 2=9.359, P=0.002], liver dysfunction [9 cases (8.4%) vs. 46 cases (25.6%), χ2=12.733, P< 0.001], and renal injury [0 cases vs. 10 cases (5.6%), P=0.015].There was no significant difference in the incidence of respiratory failure [102 cases (95.3%) vs. 172 cases (95.6%), χ2=0.008, P=0.928]. However, the number of cases requiring high-flow oxygen therapy and mechanical ventilation was significantly lower in the post-pandemic group compared to the pre-pandemic group [14 cases (13.3%) vs. 48 cases (26.7%), 21 cases (20.3%) vs. 122 cases (67.8%), all P<0.05].The time from symptom onset to the initiation of tetracycline/quinolone therapy was shorter in the post-pandemic group compared to the pre-pandemic group [7 (3, 10) days vs. 9 (6.3, 11) days, χ2=-3.565, P< 0.001]. The proportion of patients who had already received tetracycline/quinolone therapy before admission to the PICU was significantly higher in the post-pandemic group compared to the pre-pandemic group [25 cases (23.4%) vs. 2 cases (1.1%), χ 2=10.009, P=0.002].Both the total hospital stay and PICU stay were shorter in the post-pandemic group compared to the pre-pandemic group [10.0 (8.0, 14.0) days vs. 15.5 (12.0, 22.0) days, 5 (3.0, 8.0) days vs. 7.0 (5.0, 10.0) days, all P=0.000]. All 7 deaths occurred in the pre-pandemic group, including 5 cases with co-infections and 2 cases with underlying diseases. Conclusions:In the post-COVID-19 era, SMPP cases in the PICU were predominantly observed in children over 5 years old, with a lower incidence of shock, gastrointestinal disorders, liver injury, and kidney injury compared to the pre-pandemic period. Patients with macrolide-resistant Mycoplasma pneumoniae who received timely treatment with tetracycline/quinolones exhibited favorable outcomes.

ObjectiveTo investigate the risk factors for liver cancer in patients with chronic hepatitis B （CHB） in the Qidong Chronic Hepatitis B cohort， and to construct a nomogram model for predicting the risk of liver cancer in CHB patients. MethodsA structured questionnaire survey was conducted among the CHB patients， aged ≥18 years， who attended the outpatient service of Qidong Third People’s Hospital from January 1 to December 31， 2016. The onset of liver cancer was defined as the primary outcome， and the outcomes of the cohort were obtained from Qidong Cancer Registry. Baseline clinical features were compared ；between the liver cancer group and the non-liver cancer group. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The Cox regression model was used to analyze the risk factors for liver cancer in CHB patients and calculate their hazard ratio （HR） and 95% confidence interval （CI）； the variables with statistical significance in the univariate Cox regression analysis were included in the LASSO regression analysis， and then the variables obtained were included in the multivariate Cox regression analysis to establish a predictive model. The nomogram was used to visualize the complex model. The receiver operating characteristic （ROC） curve， index of concordance （C-index）， and the calibration curve were used to assess the predictive efficacy of the model， and the decision curve was used to evaluate the clinical practicability of the nomogram. ResultsA total of 1 479 CHB patients were selected， among whom 58 patients with a confirmed diagnosis of liver cancer， 15 with missing data on testing indicators， and 164 with missing data on important information in the questionnaire were excluded， and finally 1 242 subjects were included in the study. Up to December 31， 2023， there were 67 new cases of liver cancer after a median follow-up time of 7.71 years， and the incidence density of liver cancer was 729.78/100，000 person-years. There were significant differences between the liver cancer group and the non-liver cancer group in age， sex， educational level， liver cirrhosis， duration of liver cirrhosis， history of diabetes mellitus， albumin， total bilirubin （TBil）， direct bilirubin， aspartate aminotransferase， aspartate aminotransferase， gamma-glutamyl transpeptidase （GGT）， and alkaline phosphatase （all P<0.05）. The multivariate Cox regression analysis showed that the increase in age （HR=1.07， 95%CI： 1.05‍ ‍—‍ ‍1.10， P<0.001）， a relatively high level of TBil （HR=1.98， 95%CI： 1.15‍ ‍—‍ ‍3.42， P=0.014）， a relatively high level of GGT （HR=2.41， 95%CI： 1.43‍ ‍—‍ ‍4.08， P=0.001）， and a long duration of liver cirrhosis （HR=1.09， 95%CI： 1.02‍ ‍—‍ ‍1.15， P=0.009） were independent risk factors for liver cancer in CHB patients. A nomogram prediction model was constructed based on the above four indicators， with an area under the ROC curve of 0.790， 0.845， and 0.829， respectively， in predicting the risk of liver cancer in CHB patients at 1， 3， and 5 years， and the bootstrap resampling method was used for internal validation and showed a C-index of 0. 778. The calibration curve showed that the prediction model had good stability， and the decision curve showed that it had certain clinical practicability. ConclusionThe increase in age， relatively high levels of TBil and GGT， and a long duration of liver cirrhosis are independent risk factors for liver cancer in CHB patients， and the nomogram model constructed based on these factors has a good predictive value and can be used in clinical practice to help develop strategies for the long-term monitoring of liver cancer.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

To develop a blue cap anticoagulant tube blood volume measuring card of to solve the problem of insufficient or excessive blood collection in clinical coagulation specimens.The device was composed of a measuring card,a transparent housing with a base and a tube holder.The measuring card was divided into qualified and unqualified areas,the housing was used to insert the card,the tube holder was used to place blood collection tubes.The device was used by clinical nurses to judge the adequacy of blood collection volume in blue cap anticoagulant tube.After the use of the device,the failure rate of clinical blue cap anticoagulation tube specimens submission was reduced from 6.71‰ to 2.73‰,shortened the time limit for specimen submission.At the same time,the device made the rejection judgment of department specimens more standardized and avoided the acceptance of unqualified specimens caused by subjective judgment errors.The device has simple structure,convenient operation and strong practicability,and has promotion value.

AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.

Objective:To establish an antibody expression system to reduce the antibody-dependent enhancement (ADE) effect of target antibody.Methods:Site-directed mutagenesis was used to mutate the 234 and 235 sites of the Fc region of the mammalian cell antibody expression vector-L234A and L235A to establish the antibody expression vector pFRT-IgG1κ-FcM. An antibody Wt-WNV with significant ADE effect obtained in previous work was selected and expressed by the pFRT-IgG1κ-FcM system to obtain mutant antibody FcM-WNV. The binding ability of FcM-WNV to target antigen West Nile virus envelope protein-DⅢ (WNV E-DⅢ) was detected by ELISA, and the its binding ability to human high-affinity IgG Fc receptor hFcγRⅠ (hCD64 ) was analyzed by flow cytometry. The neutralizing activity of FcM-WNV in vitro was detected by pseudovirus infection of host cells (BHK21 and K562). Results:The expression levels of FcM-WNV and Wt-WNV were comparable, and FcM-WNV could recognize and bind to WNVE-DIII in a concentration-dependent manner. Compared with Wt-WNV, the binding ability of FcM-WNV to hCD64 was significantly weakened, showing a significant decrease in fluorescence intensity. Consistent with the previous experimental results, Wt-WNV at a concentration of 5 μg/ml significantly enhanced the infection of K562 by WNV pseudovirus, while FcM-WNV at a concentration of 5 μg/ml could effectively block pseudovirus infection in both K562 and BHK21 cells.Conclusions:The established antibody expression system can effectively reduce the ADE effect of the target antibody.

ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease （DKD） in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose （FBG）. Mice with FBG ≥ 16.7 mmol·L^-1， increased urine output， and persistent albuminuria were considered successful in model establishment. After successful modeling， they were randomly divided into a model group， a dapagliflozin group （1.5 mg·kg^-1·d^-1）， and high， medium， and low dose groups of Dahuang Tangluo pills （3.6， 1.8， 0.9 g·kg^-1·d^-1， respectively）， with eight mice in each group. All medication groups were administered orally， while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks， the survival status of the mice was observed， and their body weight， FBG， and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products （AGEs） and receptors for advanced glycation end products （RAGE） proteins. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were utilized to detect the gene and protein expression levels of AGEs， RAGE， inhibitor of nuclear factor-κB （NF-κB） kinase （IKK）， and NF-κB in the renal tissues of mice in each group. ResultCompared with control group， the model group showed a significant increase in body weight， FBG， serum creatinine （SCr）， urinary microalbumin/urine creatinine ratio （ACR）， total cholesterol （TC）， and triglycerides （TG） （P<0.05）. The levels of intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） in renal tissues were significantly elevated （P<0.05）. Renal histopathological staining and electron microscopy revealed loose arrangement， gaps， structural disarray， mesangial proliferation， and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE， IKK， and NF-κB genes in renal tissues （P<0.05）. Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues （P<0.05）. Western blot results showed a significant increase in the expression of AGEs， RAGE， IKK， and NF-κB proteins in renal tissues （P<0.05）. After drug intervention， compared with model group， the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight， FBG， SCr， and ACR （P<0.05）， and a significant decrease in TC in mouse serum （P<0.05）， while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum （P<0.05）. All treatment groups showed a significant reduction in ICAM-1， IL-6， and TNF-α in renal tissues （P<0.05）. Renal histopathological staining and electron microscopy showed improved kidney injury， decreased collagen fiber deposition， and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE， IKK， and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Western blot results showed a significant decrease in the expression of AGEs， RAGE， IKK， and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice， possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

Japan is one of the main trading partners for the import and export of experimental animals in China,and its quarantine and supervision policies for the import and export of experimental animals are very detailed and strict.This article takes experimental dogs,cats,and monkeys as examples to provide an in-depth analysis of the quarantine and supervision policies for the main experimental animals exported to Japan.At the same time,it reflects on the current laws and regulations,import and export management method,standards,biosafety,breeding and management status,as well as the import and export business status of experimental animals in China.Suggestions are provided in improving the laws and regulations,import and export management method,ensuring national biosafety,improving the management level of experimental animal breeding,and promoting the import and export trade of experimental animals,in order to provide reference for comprehensively improving the production,use,and breeding management level of experimental animals in China and strengthening the trade between China and Japan.