[Multivariate correlation analysis of T1S and C7S].

OBJECTIVE: To determine whether C7 angles (C7 slope, C7S) could replace T1 angles (T1 slope, T1S) by correlation analysis of T1S and C7S. METHODS: A total of 442 patients from July 2015 to July 2020 in outpatient and inpatient department were enrolled retrospectively, and 259 patients who could identify the upper endplate of T1 were screened out . Of them, there were 145 males and 114 females, aged from 20 to 83 years old with an average of (58.6±11.2) years, including 163 patients with cervical spine surgery and 96 non-surgical patients. Patients were stratified by sex, age, cervical kyphosis, cervical alignment imbalance, and cervical spine surgery. These 259 patients included 145 cases in the male group, 114 cases in the female group;76 cases in the youth group (<40 years old), 109 cases in the middle-aged group (40 to 60 years old), and 74 cases in the elderly group(>60 years old); 92 cases in the cervical kyphosis group, 167 cases in the non-kyphosis group;51 cases in the cervical sequence imbalance group, 208 cases in the non-imbalance group;163 cases in the cervical surgery group, 96 cases in the non-operation group. The correlations of C7S and T1S in various modalities groups were analyzed. RESULTS: Of 442 patients, the recognition rate of upper endplate of T1 was 58.6%(259/442), and that of C7 was 90.7%. The mean T1S and C7S of the 259 patients were (24.5±8.0)° [(25.9±7.7)° in the male group and (23.7±6.9)° in the female group] and (20.8±7.3)° [(22.5±7.5)° in the male group and(19.7±5.8)° in the female group], respectively. The total correlation coefficient between C7S and T1S was r=0.89, R2=0.79, and the linear regression equation was T1S=0.91×C7S+4.35. In the above general information and the grouping of deformity factors, T1S was highly correlated with C7S(r value 0.85 to 0.92, P<0.05). CONCLUSION: There is a high correlation between T1S and C7S in different factor groups. For cases where T1S cannot be measured, C7S can be used to provide guidance and reference for evaluating the sagittal balance of the spine, analyzing the condition, and formulating surgical plans.

[Research progress on activities and mechanisms of anti-hepatitis B virus drugs].

Hepatitis B virus(HBV) is the pathogen causing hepatitis B, which is characterized by strong infectivity, high incidence, and widespread prevalence and has seriously threatened human health and affected their quality of life. Anti-HBV drugs in western medicine mainly include nucleosides(nucleic acids) and interferons, among which nucleosides(nucleic acids) are used more often. Due to the easy development of drug resistance, their therapeutic effects are not remarkable. Interferons can easily cause serious adverse reactions such as liver injury. Anti-HBV drugs in traditional Chinese medicine mainly include single Chinese herbs(Artemisiae Scopariae Herba, Artemisiae Annuae Herba, Salviae Miltiorrhizae Radix et Rhizoma, etc.) and Chinese herbal compounds(Yinchenhao Decoction, Xiaochaihu Decoction, Tiaogan Huaxian Pills, etc.), whose chemical compositions and action targets have not been fully identified. The combined medication is better than single medication, in that the former can improve drug resistance, make up each other's deficiencies, reduce adverse reactions, and prolong the action time. This study reviewed the anti-HBV activities and mechanisms of western drugs, Chinese herbs, and combined medications, in order to provide reference for the development and research of new anti-HBV drugs.

Memantine Displays Antimicrobial Activity by Enhancing Escherichia coli Pathogen-Induced Formation of Neutrophil Extracellular Traps.

Bacterial infection remains one of the leading causes of death worldwide due to the continuous rise of multiple antibiotic-resistant bacteria. Focusing solely on bacteria as the drug targets is a major limitation inherent in the conventional antibiotic therapy. Recently, host-directed therapies have become such an innovative approach to modulate the host defense system and the interplay of innate and adaptive immunity. Our previous studies showed that memantine (MEM), an α7 nAChR antagonist, could efficiently block multi-drug resistant Escherichia coli-caused bacteremia and meningitis in a mouse model. However, the underlying mechanisms that govern the antibacterial effects of MEM are still unknown. In this study, we demonstrated that MEM is able to significantly suppress E. coli infection by enhancing E. coli-induced formation and release of NETs in vitro and in vivo. MEM could promote the trapping and bactericidal activities of the polymorphonuclear neutrophils (PMNs) in a manner dependent on α7 nAChR, since knockdown of this receptor noticeably reduces the survival ability of bacteria in PMNs while MEM no longer affects the survival of bacteria in PMNs. Our results also showed that when the expression of S100A9, an antiseptic protein, is inhibited, pathogen survival rates in PMNs increase significantly. MEM reverses this effect in a concentration-dependent manner. MEM stimulates the production of MPO, S100A9, and DNA in PMNs and accelerates the release of depolymerized chromatin fibers into the extracellular space, suggesting the formation of NETs. Taken together, our data suggest that MEM effectively blocks bacterial infection through the promotion of the antibacterial function of NETs induced by E. coli.

[Efficacy Comparison of Different Salvage Treatment Regimens for Patients with Refractory/Relapsed Acute Myeloid Leukemia].

OBJECTIVE: To compare the efficacy and safety of 3 different regimens, namely MAC, FLAG and CAG, as the re-induction chemotherapy for acute myeloid leukemia(AML) patients with primary induction failure and relapse. METHODS: The clinical data of 156 AML patients with primary induction failure and relapse, except patients with acute promyelocytic leukemia(APL), treated with any of the above 3 regimens in our center from January 2008 to April 2016 were analyzed retrospectively. According to the treatment regimens, 156 patients were divided into MAC group (n=60), FLAG group (n=45) and CAG group (n=51). The complete remission(CR), partial remissison(PR), overall survival(OS), disease-free survival(DFS) and adverse events during the treatment were analyzed, so as to compare and evaluate the efficacy and safety of the 3 different regimens. RESULTS: After 1 course of re-induction chemotherapy, CR in MAC group was significantly higher than that in FLAG and CAG group (55.4% vs 34.1% vs 34.0%)(P<0.05). The OS was not statistically significantly different among 3 groups (P>0.05) with a median OS of 11 months, 5.46 months and 10.2 months, respectively. The myelosuppression was the main adverse event with no significant difference among the groups(P>0.05). More patients treated with MAC regimen underwent febrile neutropenia (93.3% vs 86.7% vs 64.7%)(P<0.001). However, the incidence of fatal infections was not signicantly different among 3 groups(5% vs 8.9% vs 5.9%)(P>0.05). CONCLUSION: Compared with FLAG and CAG regimen, the MAC regimen can enable more AML patients with primary induction failure and refractory to achieve CR without increasing severe adverse events,therefore,this regimen may provide a opportunity for patients to recieve hematopoietic stem cell transplantation.

[Preliminary Clinical Efficiency of Autologous Peripheral Blood Mononuclear Cells for Treating Critical Limb Ischemia of Thromboangiitis Obliterans].

OBJECTIVE: To evaluate the long-term clinical effect of autologous peripheral blood mononuclear cells (PB-MNC) on critical limb ischemia (CLI) in patients with thromboangiitis obliterans (TAO) patients. METHODS: The clinical data of 22 patients with CLI caused by TAO from July 2004 to May 2013 were analyzed retrospectively, 22 patients were divided into 2 groups; out of them 12 cases in one group were treated with granulocyte colony-stimulating factor (G-CSF)-mobilized autologous peripheral blood mononuclear cells (auto-PBMNC group), 10 cases in another group received conservative treatment (CT group). The log-rank test was used to compare the long-term outcomes in auto-PBMNC group and CT group. RESULTS: The wound healing rate (P=0.016) and CLI-free rate (P=0.013) were significantly higher in PB-MNC group compared with that in CT group. No difference was found in amputation rates between the 2 groups (major amputation: P=0.361, minor and major amputation: P=0.867). No patients died or no serious adverse events occurred during the follow-up period. CONCLUSION: The auto-PBMNC therapy can significantly promote the wound healing, and protect against CLI in TAO patients, but the risk of amputation is not low in comparison with conservative treatment.

Involvement of polyphosphate kinase in virulence and stress tolerance of uropathogenic Proteus mirabilis.

Proteus mirabilis (P. mirabilis), a gram-negative enteric bacterium, frequently causes urinary tract infections. Many virulence factors of uropathogenic P. mirabilis have been identified, including urease, flagella, hemolysin and fimbriae. However, the functions of polyphosphate kinase (PPK), which are related to the pathogenicity of many bacteria, remain entirely unknown in P. mirabilis. In this study, a ppk gene encoding the PPK insertional mutant in P. mirabilis strain HI4320 was constructed, and its biological functions were examined. The results of survival studies demonstrated that the ppk mutant was deficient in resistance to oxidative, hyperosmotic and heat stress. The swarming and biofilm formation abilities of P. mirabilis were also attenuated after the ppk interruption. In vitro and in vivo experiments suggested that ppk was required for P. mirabilis to invade the bladder. The negative phenotypes of the ppk mutant could be restored by ppk gene complementation. Furthermore, two-dimensional gel electrophoresis and liquid chromatography-mass spectrometry were used to analyze the proteomes of the wild-type strain and the ppk mutant. Compared with the wild-type strain, seven proteins including TonB-dependent receptor, universal stress protein G, major mannose-resistant/Proteus-like fimbrial protein (MR/P fimbriae), heat shock protein, flagellar capping protein, putative membrane protein and multidrug efflux protein were down-regulated, and four proteins including exported peptidase, repressor protein for FtsI, FKBP-type peptidyl-prolyl cis-trans isomerase and phosphotransferase were up-regulated in the ppk mutant. As a whole, these results indicate that PPK is an important regulator and plays a crucial role in stress tolerance and virulence in uropathogenic P. mirabilis.

Alpha7 nicotinic acetylcholine receptor is required for blood-brain barrier injury-related CNS disorders caused by Cryptococcus neoformans and HIV-1 associated comorbidity factors.

BACKGROUND: Cryptococcal meningitis is the most common fungal infection of the central nervous system (CNS) in HIV/AIDS. HIV-1 virotoxins (e.g., gp41) are able to induce disorders of the blood-brain barrier (BBB), which mainly consists of BMEC. Our recent study suggests that α7 nAChR is an essential regulator of inflammation, which contributes to regulation of NF-κB signaling, neuroinflammation and BBB disorders caused by microbial (e.g., HIV-1 gp120) and non-microbial [e.g., methamphetamine (METH)] factors. However, the underlying mechanisms for multiple comorbidities are unclear. METHODS: In this report, an aggravating role of α7 nAChR in host defense against CNS disorders caused by these comorbidities was demonstrated by chemical [inhibitor: methyllycaconitine (MLA)] and genetic (α7(-/-) mice) blockages of α7 nAChR. RESULTS: As shown in our in vivo studies, BBB injury was significantly reduced in α7(-/-) mice infected with C. neoformans. Stimulation by the gp41 ectodomain peptide (gp41-I90) and METH was abolished in the α7(-/-) animals. C. neoformans and gp41-I90 could activate NF-κB. Gp41-I90- and METH-induced monocyte transmigration and senescence were significantly inhibited by MLA and CAPE (caffeic acid phenethyl ester, an NF-κB inhibitor). CONCLUSIONS: Collectively, our data suggest that α7 nAChR plays a detrimental role in the host defense against C. neoformans- and HIV-1 associated comorbidity factors-induced BBB injury and CNS disorders.

Mucin2 is Required for Probiotic Agents-Mediated Blocking Effects on Meningitic E. coli-Induced Pathogenicities.

Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl- L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5- Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.

Repositioning of Memantine as a Potential Novel Therapeutic Agent against Meningitic E. coli-Induced Pathogenicities through Disease-Associated Alpha7 Cholinergic Pathway and RNA Sequencing-Based Transcriptome Analysis of Host Inflammatory Responses.

Neonatal sepsis and meningitis (NSM) remains a leading cause worldwide of mortality and morbidity in newborn infants despite the availability of antibiotics over the last several decades. E. coli is the most common gram-negative pathogen causing NSM. Our previous studies show that α7 nicotinic receptor (α7 nAChR), an essential regulator of inflammation, plays a detrimental role in the host defense against NSM. Despite notable successes, there still exists an unmet need for new effective therapeutic approaches to treat this disease. Using the in vitro/in vivo models of the blood-brain barrier (BBB) and RNA-seq, we undertook a drug repositioning study to identify unknown antimicrobial activities for known drugs. We have demonstrated for the first time that memantine (MEM), a FDA-approved drug for treatment of Alzheimer's disease, could very efficiently block E. coli-caused bacteremia and meningitis in a mouse model of NSM in a manner dependent on α7 nAChR. MEM was able to synergistically enhance the antibacterial activity of ampicillin in HBMEC infected with E. coli K1 (E44) and in neonatal mice with E44-caused bacteremia and meningitis. Differential gene expression analysis of RNA-Seq data from mouse BMEC infected with E. coli K1 showed that several E44-increased inflammatory factors, including IL33, IL18rap, MMP10 and Irs1, were significantly reduced by MEM compared to the infected cells without drug treatment. MEM could also significantly up-regulate anti-inflammatory factors, including Tnfaip3, CISH, Ptgds and Zfp36. Most interestingly, these factors may positively and negatively contribute to regulation of NF-κB, which is a hallmark feature of bacterial meningitis. Furthermore, we have demonstrated that circulating BMEC (cBMEC) are the potential novel biomarkers for NSM. MEM could significantly reduce E44-increased blood level of cBMEC in mice. Taken together, our data suggest that memantine can efficiently block host inflammatory responses to bacterial infection through modulation of both inflammatory and anti-inflammatory pathways.

Loss of signal in recurrent nerve neuromonitoring: causes and management.

During recurrent laryngeal nerve (RLN) neuromonitoring in thyroid surgery, laryngeal electromyography (EMG) amplitude may be correlated with the number of muscle fibers participating in the polarization and these might be correlated with the function of RLN. If RLN is severely injured during the operation, most nerve fibers do not transmit nerve impulse and substantial decrease of EMG amplitude or loss of signal (LOS) will occur. True LOS at the end of an operation often indicates a postoperative fixed vocal cord, and the surgeon should consider the optimal contralateral surgery timing in patients with planned bilateral thyroid operation to avoid the disaster of bilateral vocal cord palsy. However, LOS recovery and false LOS may occur and may lead to an unnecessary 2(nd) operation. Therefore, a reliable modality for intraoperative LOS evaluation and management would afford the surgeon real-time information that could help guide surgical procedure and planning. The updated causes, algorithm, and management of LOS during RLN neuromonitoring are reviewed and summarized.