Global histone H2B degradation regulates insulin/IGF signaling-mediated nutrient stress.

Eukaryotic organisms adapt to environmental fluctuations by altering their epigenomic landscapes and transcriptional programs. Nucleosomal histones carry vital epigenetic information and regulate gene expression, yet the mechanisms underlying chromatin-bound histone exchange remain elusive. Here, we found that histone H2Bs are globally degraded in Caenorhabditis elegans during starvation. Our genetic screens identified mutations in ubiquitin and ubiquitin-related enzymes that block H2B degradation in starved animals, identifying lysine 31 as the crucial residue for chromatin-bound H2B ubiquitination and elimination. Retention of aberrant nucleosomal H2B increased the association of the FOXO transcription factor DAF-16 with chromatin, generating an ectopic gene expression profile detrimental to animal viability when insulin/IGF signaling was reduced in well-fed animals. Furthermore, we show that the ubiquitin-proteasome system regulates chromosomal histone turnover in human cells. During larval development, C. elegans epidermal cells undergo H2B turnover after fusing with the epithelial syncytium. Thus, histone degradation may be a widespread mechanism governing dynamic changes of the epigenome.

A single center retrospective study: Comparison between centrifugal separation plasma exchange with ACD-A and membrane separation plasma exchange with heparin on acute liver failure and acute on chronic liver failure.

The purpose of this retrospective study is to compare the efficacy and safety of the centrifugal separation therapeutic plasma exchange (TPE) using citrate anticoagulant (cTPEc) with membrane separation TPE using heparin anticoagulant (mTPEh) in liver failure patients. The patients treated by cTPEc were defined as cTPEc group and those treated by mTPEh were defined as mTPEh group, respectively. Clinical characteristics were compared between the two groups. Survival analyses of two groups and subgroups classified by the model for end-stage liver disease (MELD) score were performed by Kaplan-Meier method and were compared by the log-rank test. In this study, there were 51 patients in cTPEc group and 18 patients in mTPEh group, respectively. The overall 28-day survival rate was 76% (39/51) in cTPEc group and 61% (11/18) in mTPEh group (P > .05). The 90-day survival rate was 69% (35/51) in cTPEc group and 50% (9/18) in mTPEh group (P > .05). MELD score = 30 was the best cut-off value to predict the prognosis of patients with liver failure treated with TPE, in mTPEh group as well as cTPEc group. The median of total calcium/ionized calcium ratio (2.84, range from 2.20 to 3.71) after cTPEc was significantly higher than the ratio (1.97, range from 1.73 to 3.19) before cTPEc (P < .001). However, there was no significant difference between the mean concentrations of total calcium before cTPEc and at 48 h after cTPEc. Our study concludes that there was no statistically significant difference in survival rate and complications between cTPEc and mTPEh groups. The liver failure patients tolerated cTPEc treatment via peripheral vascular access with the prognosis similar to mTPEh. The prognosis in patients with MELD score < 30 was better than in patients with MELD score ≥ 30 in both groups. In this study, the patients with acute liver failure (ALF) and acute on chronic liver failure (ACLF) treated with cTPEc tolerated the TPE frequency of every other day without significant clinical adverse event of hypocalcemia with similar outcomes to the mTPEh treatment. For liver failure patients treated with cTPEc, close clinical observation and monitoring ionized calcium are necessary to ensure the patients' safety.

Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects.

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo were administered per protocol requirements. Blood samples were collected at the scheduled time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in plasma and calculated for the PK parameters. In SAD, AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25-800 mg. T1/2 was within 4.80-6.95 h. In MAD, the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect on Cmax and AUC of VV116. No serious adverse event occurred in the studies, and no subject withdrew from the studies due to adverse events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which supports the continued investigation of VV116 in patients with COVID-19.

Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection.

BACKGROUND: Accurate etiology diagnosis is crucial for central nervous system infections (CNS infections). The diagnostic value of metagenomic next-generation sequencing (mNGS), an emerging powerful platform, remains to be studied in CNS infections. METHODS: We conducted a single-center prospective cohort study to compare mNGS with conventional methods including culture, smear and etc. 248 suspected CNS infectious patients were enrolled and clinical data were recorded. RESULTS: mNGS reported a 90.00% (9/10) sensitivity in culture-positive patients without empirical treatment and 66.67% (6/9) in empirically-treated patients. Detected an extra of 48 bacteria and fungi in culture-negative patients, mNGS provided a higher detection rate compared to culture in patients with (34.45% vs. 7.56%, McNemar test, p < 0.0083) or without empirical therapy (50.00% vs. 25.00%, McNemar test, p > 0.0083). Compared to conventional methods, positive percent agreement and negative percent agreement was 75.00% and 69.11% separately. mNGS detection rate was significantly higher in patients with cerebrospinal fluid (CSF) WBC > 300 * 106/L, CSF protein > 500 mg/L or glucose ratio ≤ 0.3. mNGS sequencing read is correlated with CSF WBC, glucose ratio levels and clinical disease progression. CONCLUSION: mNGS showed a satisfying diagnostic performance in CNS infections and had an overall superior detection rate to culture. mNGS may held diagnostic advantages especially in empirically treated patients. CSF laboratory results were statistically relevant to mNGS detection rate, and mNGS could dynamically monitor disease progression.

Mitoflash frequency in early adulthood predicts lifespan in Caenorhabditis elegans.

It has been theorized for decades that mitochondria act as the biological clock of ageing, but the evidence is incomplete. Here we show a strong coupling between mitochondrial function and ageing by in vivo visualization of the mitochondrial flash (mitoflash), a frequency-coded optical readout reflecting free-radical production and energy metabolism at the single-mitochondrion level. Mitoflash activity in Caenorhabditis elegans pharyngeal muscles peaked on adult day 3 during active reproduction and on day 9 when animals started to die off. A plethora of genetic mutations and environmental factors inversely modified the lifespan and the day-3 mitoflash frequency. Even within an isogenic population, the day-3 mitoflash frequency was negatively correlated with the lifespan of individual animals. Furthermore, enhanced activity of the glyoxylate cycle contributed to the decreased day-3 mitoflash frequency and the longevity of daf-2 mutant animals. These results demonstrate that the day-3 mitoflash frequency is a powerful predictor of C. elegans lifespan across genetic, environmental and stochastic factors. They also support the notion that the rate of ageing, although adjustable in later life, has been set to a considerable degree before reproduction ceases.

Infection within 2 weeks before liver transplantation closely related to prognosis of posttransplant infection: A single-center retrospective observational study in China.

BACKGROUND: Infections still represent the main factors influencing morbidity and mortality following liver transplantation. This study aimed to evaluate the incidence and risk factors for infection and survival after liver transplantation. METHODS: We retrospectively examined medical records in 210 liver recipients who underwent liver transplantation between April 2015 and October 2017 in our hospital. Clinical manifestations and results of pathogen detection test were used to define infection. We analyzed the prevalence, risk factors and prognosis of patients with infection. RESULTS: The median follow-up was 214 days; the incidence of infection after liver transplantation was 46.7% (n = 98) which included pneumonia (43.4%), biliary tract infection (21.9%), peritonitis (21.4%) and bloodstream infection (7.6%). Among the pathogens in pneumonia, the most frequently isolated was Acinetobacter baumanii (23.5%) and Klebsiella pneumoniae (21.2%). Model for end-stage liver disease (MELD) score (OR = 1.083, 95% CI: 1.045-1.123; P < 0.001), biliary complication (OR = 4.725, 95% CI: 1.119-19.947; P = 0.035) and duration of drainage tube (OR = 1.040, 95% CI: 1.007-1.074; P = 0.017) were independent risk factors for posttransplant infection. All-cause mortality was 11.0% (n = 23). The prognostic factors for postoperative infection in liver recipients were prior-transplant infection, especially pneumonia within 2 weeks before transplantation. Kaplan-Meier curves of survival showed that recipients within 2 weeks prior infection had a significantly lower cumulative survival rate compared with those without infection (65.2% vs. 90.0%; hazard ratio: 4.480; P < 0.001). CONCLUSIONS: Infection, especially pneumonia within 2 weeks before transplantation, complication with impaired renal function and MELD score after 7 days of transplantation was an independent prognostic factor for postoperative infection in liver transplant recipients.

Roadmap to functional cure of chronic hepatitis B: An expert consensus.

Hepatitis B virus (HBV) infection continues to be a major public health issue worldwide. HBsAg loss is associated with functional remission and improved long-term outcome, and is considered to be a 'functional cure' (also referred to as clinical or immunologic cure) for chronic hepatitis B. This ideal goal of therapy can be achieved using optimized combination regimens with direct-acting antivirals [eg nucleos(t)ide analogues (NAs)] and immunomodulators [eg pegylated interferon alpha2a (Peg-IFN)] in selected patients with chronic hepatitis B. Among different combination therapies currently available, those with NA lead-in followed by Peg-IFN in virally suppressed patients has been demonstrated to be effective. This review provides an updated overview of the evidence supporting the use of combination therapies and summarizes expert consensus on the roadmap to attain functional cure for chronic hepatitis B patients.

Serum hepatitis B virus RNA levels as a predictor of HBeAg seroconversion during treatment with peginterferon alfa-2a.

BACKGROUND: Hepatitis B e antigen (HBeAg) seroconversion represents an endpoint of treatment of chronic hepatitis B virus (HBV) infections. METHODS: We have studied whether levels of serum hepatitis B virus ribonucleic acid (HBV RNA) during pegylated interferon alfa-2a treatment might be helpful for predicting HBeAg seroconversion. 61 HBeAg-positive chronic hepatitis B (CHB) patients treated with pegylated interferon alfa-2a alone or in combination with adefovir (10 mg/day) for 48 weeks were included in this retrospective analysis. Response was defined as HBeAg seroconversion at 24 weeks posttreatment. Receiver operating characteristic analyses were used to identify baseline and on-treatment HBV RNA levels associated with response. RESULTS: Twenty-two of 61 (36.1%) patients achieved a response. Baseline HBV RNA levels were lower in responders than in nonresponders (4.55 ± 1.19 and 5.90 ± 1.13 copies/mL, respectively, P = 0.001). Baseline HBV RNA cut off level (200,000 copies/mL) provided a positive predictive value (PPV) of 56.0% and a negative predictive value (NPV) of 77.8%. HBV RNA level (3000 copies/mL) at week 12 provide a PPV of 75.0% and a NPV of 82.8%. Moreover, HBeAg seroconversion rates at 24 weeks posttreatment were significantly higher in patients with HBV RNA ≤ 200,000 copies/mL at baseline and HBV RNA ≤ 3000 copies/mL at week 12 (92.9%) versus others (12.5%) (All P < 0.05). CONCLUSIONS: In Conclusions, serum HBV RNA levels may serve as a novel tool for prediction of HBeAg seroconversion during therapy with pegylated interferon alfa-2a in HBeAg-positive CHB patients.

Human Endophthalmitis Caused By Pseudorabies Virus Infection, China, 2017.

We report human endophthalmitis caused by pseudorabies virus infection after exposure to sewage on a hog farm in China. High-throughput sequencing and real-time PCR of vitreous humor showed pseudorabies virus sequences. This case showed that pseudorabies virus might infect humans after direct contact with contaminants.

Case report: lactic acidosis and rhabdomyolysis during telbivudine and tenofovir treatment for chronic hepatitis B.

BACKGROUND: Current treatment options for chronic hepatitis B (CHB) are pegylated interferon alpha and nucleoside analogues (NAs). NAs have relatively fewer side effects than interferon alpha, and generally well tolerated. Previously 12.9% of patients on telbivudine treatment were reported to develop severe elevation of serum creatine phosphokinase (CPK) levels, but related clinical disease, like lactic acidosis (LA) and rhabdomyolysis (RM) were rare. The pathophysiology may be mitochondrial toxicity, for the NAs inhibit not only hepatitis B virus (HBV) polymerase, but also the host mitochondrial DNA polymerase γ. As mitochondria are the main sites of oxidative phosphorylation, there will be an increase of pyruvate reduction to lactic acid and insufficient adenosine triphosphate. The accumulation of lactic acid causes LA, while lack of energy leads to cell dysfunction and mitochondria-associated disease, including RM. All five NAs, except tenofovir, have been reported causing LA and RM. Here we report the first case of CHB patients developing fatal LA and RM during telbivudine and tenofovir treatment. CASE PRESENTATION: The patient is a 51-year-old man who was hospitalized in November 2015. He had taken telbivudine regularly because of CHB. Later, tenofovir was added to antiviral treatment because of HBV resistance. Then he had myalgia, chest tightness and anorexia. The blood lactate was 12.7 mmol/L. The arterial blood gas analysis showed pH 7.25, base excess 21.1 mmol/L. CPK was 991 U/L, myoglobin was 1745 ng/ml and creatine was 83 µmol/L. Abdomen magnetic resonance revealed cirrhosis. Muscle biopsy revealed myogenic lesion with abnormality of mitochondria and fat metabolism. The patient was diagnosed with Hepatitis B envelope Antigen positive CHB, cirrhosis, LA and RM characterized by myalgia and elevated myoglobin. He was given tenofovir alone as antiviral treatment instead. After hemodialysis and 4 weeks` treatment of corticosteroids, his symptoms recovered, and blood lactate gradually returned to a normal range. CONCLUSIONS: This case shows that tenofovir may trigger muscle damage and fatal RM in combination with telbivudine treatment in CHB patients. Thus, patients receiving tenofovir and telbivudine should be closely monitored for muscular abnormalities, blood lactate level and other mitochondrial toxicity associated side effects.

Rapid and precise diagnosis of disseminated T.marneffei infection assisted by high-throughput sequencing of multifarious specimens in a HIV-negative patient: a case report.

BACKGROUND: Talaromyces marneffei, is an opportunistic pathogenic fungus that is most commonly reported in Southeast Asia and disseminated T.marneffei infection predominantly occurs in patients with immunodeficiency. With a potential to invade multiple organs, it can be fatal for patients if diagnosis and treatment are delayed. In current clinical practice, the diagnosis of T.marneffei infection relies heavily on tissue culture and histologic analysis, which may suffer from limited positive rate and is sometimes time consuming. The rapid and accurate diagnosis of disseminated T.marneffei infection remains challenging. CASE PRESENTATION: A 22-year-old man gradually developed fever, cough, lower extremities weakness, jaundice and rash, for which a 3-month extensive investigation failed to reach a diagnosis. After admitted into our hospital, laboratory and radiological tests revealed multiple lesions in the patient's brain, spinal cord, and lungs. We performed next generation sequencing on the patient's skin tissue, bone marrow, blood and cerebrospinal fluid, which all identified numerous Talaromyces marneffei nucleotide sequences and leaded to the rapid diagnosis and treatment of disseminated T.marneffei infection. CONCLUSIONS: This case underline the clinical significance of T.marneffei as a possible pathogen in immune-competent patients. This successful application of the next generation sequencing assisting the rapid diagnosis of disseminated T.marneffei infection provides a new perspective in the clinical approach to the systematic fungi infections and highlights the potential of this technique in rapid etiological diagnosis.

Clinical findings in 111 cases of influenza A (H7N9) virus infection.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

Molecular mechanisms of bacterial persistence and phenotypic antibiotic resistance.

Bacterial persistence refers to a state of reduced metabolic activity that endows a subpopulation of isogenic bacteria with multidrug tolerance. Persisters are phenotypic variants but not mutants. Since its discovery in 1944, bacterial persistence has not received enough attention until recently when its implications in persistent infections and biofilm infections become apparent. Much research has been done in recent years to investigate the mechanisms underlying bacterial persistence and phenotypic antibiotic resistance. The mechanisms of bacterial persistence are complex and the following pathways are involved in persister formation: toxin-antitoxin systems, reduced metabolism, energy production, protein and nucleic acid synthesis, DNA repair and protection, protein degradation, transporters/efflux systems, and transcriptional regulators etc. Although persistence mechanisms are conserved in terms of the gene function and pathways involved among different bacterial species, they may vary in gene homology and relative importance of a given pathway. For example, Escherichia coli toxin-antitoxin systems play an important role in persister formation, while Staphylococcus aureus persister formation does not appear to use toxin-antitoxin systems. Here we provide an update on recent progress in persistence mechanisms using E. coli and S. aureus as models, as well as discuss approaches in the treatment of persistent bacterial infections.

Sequential combination therapy with pegylated interferon leads to loss of hepatitis B surface antigen and hepatitis B e antigen (HBeAg) seroconversion in HBeAg-positive chronic hepatitis B patients receiving long-term entecavir treatment.

Nucleos(t)ide analogues rarely result in a durable off-treatment response in chronic hepatitis B infection, whereas pegylated interferon (Peg-IFN) induces a long-lasting response only in a subset of patients. We assessed the effect of sequential combination therapy with Peg-IFN-α2a and entecavir in hepatitis B e antigen (HBeAg)-positive patients with prior long-term entecavir therapy and investigated the predictors of response to treatment. HBeAg-positive individuals who did not achieve HBeAg seroconversion during previous long-term entecavir therapy, receiving Peg-IFN-α2a added to ongoing entecavir therapy (sequential combination [S-C] therapy; n = 81) for 48 weeks or remaining on entecavir monotherapy (n = 116), were retrospectively included. A matched pair was created at a 1:1 ratio from each treatment group. The primary endpoint was HBeAg seroconversion at week 48. Subgroup analysis of response prediction was conducted for 81 patients with S-C therapy. More patients in the S-C therapy group achieved HBeAg seroconversion than those in the entecavir group (44% versus 6%; P < 0.0001). An HBeAg level of <200 signal-to-cutoff ratio (S/CO) at baseline was a strong predictor for higher HBeAg seroconversion than that achieved when HBeAg was ≥200 S/CO (64.2% versus 17.9%; P < 0.0001). Hepatitis B surface antigen (HBsAg) levels at baseline and the decrease in HBsAg levels predicted HBsAg loss in the S-C therapy group. The combination of baseline HBeAg of <200 S/CO and HBsAg of <1,000 IU/ml and an HBsAg decline at week 12 of ≥0.5 log10 IU/ml provided the highest rate of HBeAg seroconversion (92.31%) and HBsAg loss (83.3%) at week 48. Patients receiving sequential combination therapy have a higher rate of HBeAg seroconversion and are more likely to experience HBsAg clearance than do those continuing entecavir monotherapy. Sequential combination therapy can be guided by baseline HBsAg/HBeAg levels and on-treatment HBsAg dynamics.

Docosahexaenoic Acid Supplementation for Neonatal Hyperbilirubinemia: A Double-Blind, Randomized Clinical Trial.

Docosahexaenoic acid (DHA) is an essential component for brain development during fetal and early postnatal life. Hyperbilirubinemia is characterized by abnormally high levels of bilirubin in the bloodstream, frequently leading to jaundice in newborns. In severe instances, this condition can progress to neurological damage or kernicterus, a form of brain damage. Initial cell-based experiments conducted by our research team revealed that DHA significantly enhances the survival rate of nerve cells treated with bilirubin and diminishes the oxidative stress indicated by reduced peroxide activity caused by unconjugated bilirubin (UCB). Further investigations through animal studies demonstrated that DHA effectively mitigates bilirubin-induced brain injury in neonatal rats. However, the potential of DHA to decrease the incidence of bilirubin-induced brain damage in clinical settings has not been previously explored or reported. Infants with neonatal hyperbilirubinemia (n = 30 per group) participated in a double-blind, randomized, placebo-controlled parallel study. They received either 100 mg/d DHA or placebo syrup immediately when they were diagnosed. The study found that the bilirubin level at 48 hours of treatment, serum neuron-specific enolase (NSE) levels, mean phototherapy duration, and abnormal rate of cranial magnetic resonance imaging (MRI) were lower in the DHA group than those in the control group (P < .05). These results suggested that DHA is effective as an adjuvant treatment for hyperbilirubinemia in children. It can reduce the incidence of neonatal hyperbilirubinemia brain injury and plays a certain protective role. Clinical study on protective effect of DHA on neonatal bilirubin injury is registered at Chinese Clinical Trial Registry as ChiCTR2300070250.

Anti-GM-CSF autoantibodies predict outcome of cryptococcal meningitis in patients not infected with HIV: A cohort study.

OBJECTIVES: To explore the seroprevalence of anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibodies in non-HIV cryptococcal meningitis (CM) and assess its predictive value for survival. METHODS: This is a retrospective study of 12 years of non-HIV CM. We detected serum anti-GM-CSF autoantibodies, and evaluated the clinical features and outcomes, together with the exploration of prognostic factors for 2-week and 1-year survival. RESULTS: A total of 584 non-HIV CM cases were included. 301 of 584 patients (51.5%) were phenotypically healthy. 264 Cryptococcus isolates were obtained from cerebrospinal fluid (CSF) culture, of which 251 were identified as C. neoformans species complex and 13 as C. gattii species complex. Thirty-seven of 455 patients (8.1%) tested positive for serum anti-GM-CSF autoantibodies. Patients with anti-GM-CSF autoantibodies were more susceptible to C. gattii species complex infection (66.7% vs. 6.3%; p < 0.001) and more likely to develop pulmonary mass lesions with a diameter >3 centimetres (42.9% vs. 6.5%; p 0.001). Of 584 patients 16 (2.7%) died within 2 weeks, 77 of 563 patients (13.7%) died at 1 year, and 93 of 486 patients (19.1%) lived with disabilities at 1 year. Univariant Cox regression analysis found that anti-GM-CSF autoantibodies were associated with lower 1-year survival (HR, 2.66; 95% CI, 1.34-5.27; p 0.005). Multivariable Cox proportional hazards modelling revealed that CSF cryptococcal antigen titres ≥1:1280 were associated with both, reduced 2-week and 1-year survival rates (HR, 5.44; 95% CI, 1.23-24.10; p 0.026 and HR, 5.09; 95% CI, 1.95-13.26; p 0.001). DISCUSSION: Presence of serum anti-GM-CSF autoantibodies is predictive of poor outcomes, regardless of host immune status and the causative Cryptococcus species complex.

[The trend of changes in spine-pelvic sagittal parameters before and after surgery in patients with double-segment lumbar spondylolisthesis and their evaluating for surgery efficacy].

OBJECTIVE: To explore the trend of changes in the parameters of the spine-pelvic sagittal plane before and after surgery in patients with double-segment lumbar spondylolisthesis (LSL) and to evaluate the value of the surgical effect. METHODS: A retrospective analysis of 95 double-segment lumbar spondylolisthesis patients treated with posterior lumbar interbody fusion from October 2019 to October 2020 were analyzed, including 31 males and 64 females;age ranging from 41 to 63 years old, with an average of (52.10±4.35) years old;degree of lesion, 47 patients with gradeⅠand 48 patients with gradeⅡ. The surgical efficacy was evaluated according to the Oswestry dysfunction index(ODI) improvement rate at 3 months after operation. ODI improvement rate ≥50% was considered good, and <50% was considered bad. Ninety-five patients were divided into good curative effect group (74 cases) and poor curative effect group (21 cases) according to surgical curative effect. The clinical data, such as gender, age, body mass index, course of disease, degree of disease, operation time, intraoperative blood loss, and comorbidities were compared between two groups were compared. The parameters of spine pelvis sagittal plane were observed before and 3 months after operation, including spine sacral angle (SSA), T1 pelvic angle (TPA), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS). Clinical symptoms were evaluated using visual analogue scale (VAS) and ODI. The correlation between the changes of spine pelvis sagittal plane parameters and the changes of VAS and ODI before and after surgery were analyzed, and the value of spine pelvis sagittal plane parameters in evaluating the surgical efficacy of patients with double level lumbar spondylolisthesis at 3 months after surgery was evaluated. RESULTS: The courses of disease and surgical time in the group with poor efficacy were longer than those in the group with good efficacy, and the degree of lesion was higher in the group with poor efficacy (P<0.05). The SSA, TPA, LL, and SS of the group with good efficacy were higher than those of the group with poor efficacy before and 3 months after surgery, while the PT was lower than that of the group with poor efficacy (P<0.05). The changes in SSA, TPA, LL, PT, and SS before and after surgery in the group with good efficacy were greater than those in the group with poor efficacy (P<0.05). The VAS and ODI of both groups were lower at 3 months after surgery than before, and the group with good efficacy was lower(P<0.05). The changes in VAS and ODI before and after surgery in the group with good efficacy were greater than those in the group with poor efficacy (P<0.05). The changes in SSA, TPA, LL, PT, SS before and after surgery were positively correlated with the changes in VAS and ODI (P<0.05). Three months after surgery, SSA, TPA, LL, PT, and SS were used to evaluate the surgical efficacy of patients with dual level lumbar spondylolisthesis. The area under the curve (AUC) was 0.868, 0.797, 0.875, 0.822, and 0.853, respectively. The combined evaluation of all indicators resulted in the highest AUC, 0.927, and the best sensitivity and specificity were 90.50% and 91.89%, respectively. CONCLUSION: The spine pelvis sagittal plane parameters SSA, TPA, LL, and SS of patients with double level lumbar spondylolisthesis before and after surgery show an upward trend;PT shows a downward trend;PI do not change significantly. And the changes of SSA, TPA, LL, SS, and PT are closely related to the patient's pain level and the improvement of lumbar function, which can be used as parameters to evaluate the surgical efficacy.

Clinical application and drug-use-guidance value of metagenomic next-generation sequencing in central nervous system infection.

OBJECTIVE: Timely and precise etiology diagnosis is crucial for optimized medication regimens and better prognosis in central nervous system infections (CNS infections). We aimed to analyze the impact of mNGS tests on the management of patients with CNS infections. METHODS: We conducted a single-center retrospective cohort study to analyze the value of mNGS in clinical applications. Three hundred sixty-nine patients with a CNS infection diagnosis were enrolled, and their clinical data were collected. CDI and DDI were defined in our study to describe the intensity of drug use in different groups. We used LOH and mRS to evaluate if the application of mNGS can benefit CNS infected patients. RESULTS: mNGS reported a 91.67% sensitivity in culture-positive patients and an 88.24% specificity compared with the final diagnoses. Patients who participated with the mNGS test had less drug use, both total (58.77 vs. 81.18) and daily (22.6 vs. 28.12, P < 0.1, McNemar) intensity of drug use, and length of hospitalization (23.14 vs. 24.29). Patients with a consciousness grading 1 and 3 had a decrease in CDI (Grade 1, 86.49 vs. 173.37; Grade 3, 48.18 vs. 68.21), DDI (Grade 1, 1.52 vs. 2.72; Grade 3, 2.3 vs. 2.45), and LOH (Grade 1, 32 vs. 40; Grade 3, 21 vs. 23) with the application of mNGS. Patients infected with bacteria in the CNS had a reduced CDI, DDI, and LOH in the mNGS group. This was compared with the TraE group that had 49% of patients altered medication plans, and 24.7% of patients reduced drug intensity four days after mNGS reports. This was because of the reduction of drug types. CONCLUSION: mNGS showed its high sensitivity and specificity characteristics. mNGS may assist clinicians with more rational medication regimens and reduce the drug intensity for patients. The primary way of achieving this is to reduce the variety of drugs, especially for severe patients and bacterial infections. mNGS has the ability of improving the prognosis of CNS infected patients.