Microdialysis probes were implanted into the rabbit cerebral cortex and caudate nucleus followed by perfusion with Ringer solution at a flow rate of 3.0?l/min. Cerebral ischemia was induced by electrical stimulation of the unilateral superior cervical ganglion for 1h. Dialysate samples were analyzed by high performance liquid chromatography (HPLC). Following ischemia, extracelluar (EC) contents of adenosine (Ado) and its metabolites were significantly increased upto 6 ～ lOfold(Ado), 5 ～ 6fold(Inosine, Ino) and 2 ～ 3fold(Hypoxanthine, Hyp) in both the cerebral cortex and caudate nucleus(P

AIM: To observe the effects of repeated hypoxia on the neuropeptide Y(NPY)-like immunoreactivity in the mouse brain. METHODS: Forty male kunming mice were divided into 5 groups: Control, H 1(after the 1 st hypoxic run), H 2(the 2 nd hypoxic run), H 3(the 3 rd hypoxic run)and H 4(the 4 th hypoxic run). The hypoxic groups were subjected to different runs of hypoxia exposure. The NPY-like immunoreactivity in the moue brain was measured by using radioimmunoassary method.RESULTS: The standard tolerance time of the mouse exposed to hypoxia significantly increased following each increase in runs of hypoxia exposure. After the 1 st and 2 nd hypoxic run the NPY-like immunoreactivities in the mice brain significantly increased by 145.5%?3.2% and 147.3%?2.5% compared with the control(P

Objective To measure the level of interleukin-15(IL-15) in serum and its expression in lung tissues,and analyze the correlations between IL-15 and IL-4,IFN-?,eosinophil(Eos),and explore the effect of IL-15 on bronchial asthma.Methods Thirty femal BALB/C mice were randomly divided into three group(n=10),group A(asthma model),group B(corticosteroid treatment) and group C(normal control).All mice were killed 24 h after final OVA challenge.Blood were obtained for measurement of serum IgE,IL-4,IFN-? and IL-15 levels by enzyme-linked immunoabsorbent assay(ELISA).Bronchoalveolar lavage fluid(BLAF) was collected for Eos count.The left lungs were isolated for pathological examination.The lung sections were stained with hematoxylin and eosin(HE).The expressions of IL-15 in lung tissues were measured by immunohistochemical SP method.Results ①The mouse asthma model appeared ethological changes specific to asthma,the Eos count in BALF was increased,and IgE and IL-4 levels in serum were also increased compared with control group(P

Objective To compare the safety and effectiveness between treatments with autologous platelet gel (APG) versus standard care for treating refractory diabetic dermal ulcers.Methods The 46 patients with proved nonhealing diabetic dermal ulcers were enrolled. Eligible for the study were patients with grade II/III ulcers according to Wagner, lasting for at least 2 weeks and with no signs of infection at recruitment.Patients were given their informed consent document and randomly assigned to two groups: standard care (ST, n=23) or standard care plus topic application of APG (APG, n=23) for twelve weeks.The treatment of blood glucose, blood pressure and lipids was optimized and the empiric antibiotic treatment was further adjusted according to the results of culture and sensitivity testing in all patients. APG treatment consisted of wound dressing with APG, followed by topical washing and cleaning. The APG was then covered with vaseline gauze for 72 hours, after which the ulcers were treated by standard care. Participants were seen thrice a week, twice a week, or at weekly intervals. Twelve weeks observation was set as the end point.Results The would of APG group were improved in 22 patients with ulcers healed completely and 1 case with would area reduced. In the ST group, 13 ulcers were healed, 6 worsened and 4 with would area reduced. The cumulative rate of ulcer healing was 95.7% in the APG group versus 56.5% in the ST group (P=0.002). The total effective rate in APG vs ST group was 100.0% vs 73.9% (P=0.009). By Kaplan-Meier analysis,the time-to-healing of ulcer and time-to-lutation of sinus were significantly different between two groups (log-rank, P=0.006, 0.000, respectively). No treatment-related adverse events were observed. Conclusions Treatment with APG in addition to standard care results in a significantly faster and better healing for a refractory diabetic dermal ulcer and does not raise any safety concerns. So APG treatment can be a valuable and effective aid in the management of diabetic foot ulcers.

Objective To analyze the clinical characteristics and the antimicrobial resistance of respiratory tract infection in children in Baoshan City,guide clinicians to rationally apply antibiotics,and improve the success rate of treatment.Methods Retrospective analysis of the distribution characteristics and drug sensitivity results of 1039 strains of pathogens detected in pediatric inpatients of hospitals from 2019 to 2022 was conducted.Results The main pathogens causing the respiratory infections in children in Baoshan area were Streptococcus pneumoniae,Escherichia coli,Staphylococcus aureus,Haemophilus influenzae,Klebsiella pneumoniae and Pseudomonas aeruginosa.Analysis of the drug sensitivity results of pathogenic bacteria with a detected quantity greater than 80 revealed that Streptococcus pneumoniae had a high resistance rate to erythromycin,clindamycin,and compound sulfamethoxazole.The resistance rates of penicillin,ceftriaxone,cefotaxime,and meropenem were P<0.05,and the difference was statistically significan.Methicillin-resistant Staphylococcus aureus(MRSA)was11.1%;CTX/CRO-R-ECO,CTX/CRO-R-KPN,CR-ECO and CR-KPN were lower than the 2021 ISPED level;The P.aeruginosa drug resistance rate and H.influenzae's ampicillin and ampicillin/sulbactam were higher than the 2021 ISPED level.Conclusion The treatment of respiratory tract infections in pediatric patients faces great challenges.The non-standard use of empirical medication has led to the emergence of multidrug-resistant bacteria,and the selection of anti infection treatment drugs is limited.Therefore,it is imperative to grasp the epidemic characteristics and drug resistance of pathogenic bacteria in the local area.

Background: Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. Despite the effectiveness of anticonvulsants, antidepressants, and lidocaine patches in reducing PHN, many patients still face intractable pain disorders.In this randomized controlled study, we evaluated whether hydromorphone through intravenous patient-controlled analgesia (IV PCA) was effective in relieving PHN. Methods: Patients with PHN were randomly divided into two groups, one group received oral pregabalin with IV normal saline, another group received oral pregabalin with additional IV PCA hydromorphone for two weeks. Efficacy was evaluated at 1, 4, and 12 weeks after the end of the treatments. Results: Two hundred and one patients were followed up for 12 weeks. After treatment, numerical rating scale (NRS) score of patients in the hydromorphone group was significantly lower than that of the control group, and the difference of NRS scores between the two groups was statistically significant at 4 and 12 weeks after treatment. The frequency of breakthrough pain in the hydromorphone group was significantly lower than that in the control group 1 and 4 weeks after treatment.After treatment, the quality of sleep in the hydromorphone group was significantly improved compared with the control group. The most common adverse reactions in the hydromorphone group were dizziness and nausea, with no significant respiratory depression. Conclusions IV PCA hydromorphone combined with oral pregabalin provides superior pain relief in patients with PHN, which is worthy of clinical application and promotion.

Background: Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. Despite the effectiveness of anticonvulsants, antidepressants, and lidocaine patches in reducing PHN, many patients still face intractable pain disorders.In this randomized controlled study, we evaluated whether hydromorphone through intravenous patient-controlled analgesia (IV PCA) was effective in relieving PHN. Methods: Patients with PHN were randomly divided into two groups, one group received oral pregabalin with IV normal saline, another group received oral pregabalin with additional IV PCA hydromorphone for two weeks. Efficacy was evaluated at 1, 4, and 12 weeks after the end of the treatments. Results: Two hundred and one patients were followed up for 12 weeks. After treatment, numerical rating scale (NRS) score of patients in the hydromorphone group was significantly lower than that of the control group, and the difference of NRS scores between the two groups was statistically significant at 4 and 12 weeks after treatment. The frequency of breakthrough pain in the hydromorphone group was significantly lower than that in the control group 1 and 4 weeks after treatment.After treatment, the quality of sleep in the hydromorphone group was significantly improved compared with the control group. The most common adverse reactions in the hydromorphone group were dizziness and nausea, with no significant respiratory depression. Conclusions IV PCA hydromorphone combined with oral pregabalin provides superior pain relief in patients with PHN, which is worthy of clinical application and promotion.

Biliary malignant tumors have an insidious onset and rapid development, and most patients have lost the opportunity for radical surgery at initial diagnosis and often have poor prognosis. Gemcitabine-based chemotherapy is the first-line treatment for biliary malignant tumors, but with a limited clinical effect. The improvement in next-generation sequencing technology provides the possibility for the precise treatment of biliary malignant tumors, but the application and development of the precise treatment of biliary malignant tumors are limited by the low positive rate of targets and the poor accessibility of therapeutic drugs. The advent of the era of immunotherapy represented by the immune checkpoint inhibitor PD1/PD-L1 monoclonal antibody brings a promising future for the treatment of malignant tumors, including biliary malignant tumors. Combined chemotherapy and/or targeted therapy based on immune checkpoint inhibitors has shown a good effect in the treatment of biliary malignant tumors, which is the direction of the treatment of advanced biliary malignant tumors in the future.

To prepare a lipid nanoparticle (LNP)-based subunit vaccine of Mycobacterium tuberculosis (Mtb) antigen EsxV and study its immunological characteristics, the LNP containing EsxV and c-di-AMP (EsxV: C: L) was prepared by thin film dispersion method, and its encapsulation rate, LNP morphology, particle size, surface charge and polyphase dispersion index were measured. BALB/c mice were immunized with EsxV: C: L by nasal drops. The levels of serum and mucosal antibodies, transcription and secretion of cytokines in lung and spleen, and the proportion of T cell subsets were detected after immunization. EsxV: C: L LNPs were obtained with uniform size and they were spherical and negatively charged. Compared with EsxV: C immunization, EsxV: C: L mucosal inoculation induced increased sIgA level in respiratory tract mucosa. Levels of IL-2 secreted from spleen and ratios of memory T cells and tissue-resident T cells in mice were also elevated. In conclusion, EsxV: C: L could induce stronger mucosal immunity and memory T cell immune responses, which may provide better protection against Mtb infection.
Animals ; Mice ; Mycobacterium tuberculosis ; Antigens, Bacterial ; Immunization ; Nanoparticles ; Vaccines, Subunit ; Mice, Inbred BALB C

OBJECTIVETo investigate the relationship of the mutational status of the ND4 gene and the clinical features of acute myelogenous leukemia (AML) patients with ND4 mutations.

METHODSUsing PCR combined with directly sequencing, we identified somatic mutations of ND4 in 121 primary AML patients to couple with their clinical features.

RESULTSThere were 58 male patients and 63 female patients (median age 49 years, 10-86 years). Eight of 121 patients (6.6%) with de novo AML were found harboring missense mutation of ND4 gene, including 3 patients with A131V (3/8, 37.5%), 2 patients with A404T (2/8, 25%), 1 patient with F149L (1/8, 12.5%), 1 patient with G242D (1/8, 12.5%) and 1 patient with Y409H (1/8, 12.5%), respectively. Patients with ND4 mutations were associated with good karyotype (P=0.049), regardless of gender, age, white blood cell, hemoglobin, platelet, blast cells of bone marrow or immunophenotype (P>0.05). There were no statistical significance in mutations of FLT3-ITD, NPM1, CEBPA, c-KIT and DNMT3A between patients with ND4 mutation and wild-type (wt) ND4 (P>0.05). The median overall survival of patients with ND4 mutations and wt ND4 were all not reached. The median relapse-free survival were not reached and 29(2-53) months, respectively (P>0.05). There was no significance in the ratio of CR and RR patients between wt ND4 and ND4 mutated groups (P>0.05).

CONCLUSIONIt was concluded that novel ND4 mutations could be found in de novo AML patients, especially in patients with good karyotype. Thus, ND4 mutations might play an important role in AML prognosis. However, whether the mitochondria dysfunction contribute to leukemogenesis needs to be further investigated.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; Male ; Middle Aged ; Mutation ; NADH Dehydrogenase ; genetics ; Prognosis ; Young Adult