Single wavelength MDM-PDM 800-Gb/s net data rate transmission over a standard multimode fiber employing a Kramers-Kronig receiver.

We propose a high-speed multimode fiber short-reach optical interconnect system based on a Kramers-Kronig (KK) field reconstruction with the mode division multiplexing (MDM) and polarization division multiplexing (PDM) technology. In this work, the LP01, LP21a, LP21b, and LP02 modes are selected as independent channels to carry information. The demonstration achieved the 800 Gb/s net data rate per wavelength with a bit-rate-distance-product (BDP) of 8 Tb/s·km. To the best of our knowledge, this is the highest experimental record of a single wavelength BDP over the SMMF with KK detection. In addition, we discuss the system performance after all multiple-input multiple-output (MIMO) and partial MIMO processing and give guidance on the trade-off between system performance and computational resource.

Joint signal-to-signal beat interference mitigation for the field recovery of symmetric carrier-assisted differential detection with low carrier-to-signal power ratio.

As a combination of direct detection and coherent detection technologies, self-coherent detection has the advantages of low cost and optical field recovery ability. However, most of the self-coherent detection techniques are limited to single sideband (SSB) signals. Recently, carrier-assisted differential detection (CADD) has been proposed to realize complex-valued double sideband (DSB) signals, but it requires a high carrier-to-signal power ratio (CSPR) to mitigate the signal-to-signal beat interference (SSBI). Later, a more cost-effective symmetric CADD (S-CADD) has been proposed while the required CSPR is still high. In order to alleviate the high requirements of CSPR, we propose a scheme based on the joint of digital pre-distortion (DPD) at transmitter and clipping at receiver to further improve the S-CADD system performance. This joint processing can not only solve the problem of non-uniform distribution of subcarrier signal-to-noise ratio (SNR) caused by non-ideal transfer function, but also the error propagation problem caused by enhanced SSBI under low CSPR. After the validation of the 64 Gbaud 16-ary quadrature amplitude modulation (16-QAM) orthogonal frequency division multiplexing (OFDM) signal transmitted over 80 km standard single mode fiber (SSMF), the CSPR required by the proposed scheme to reach the 20% soft decision-forward error correction (SD-FEC) and 7% hard decision-forward error correction (HD-FEC) can be reduced by 1.3 dB and 2.8 dB, respectively, with a comparison of the conventional S-CADD. The results show the potential of the proposed scheme in the short-reach optical transmissions.

Semaglutide alleviates early brain injury following subarachnoid hemorrhage by suppressing ferroptosis and neuroinflammation via SIRT1 pathway.

OBJECTIVES: Subarachnoid hemorrhage (SAH) is a major cause of incapacity and death, imposing a significant economic burden globally. Additionally, SAH is the third most prevalent form of stroke. Semaglutide affects oxidative stress, inflammation, and mitochondrial biogenesis. Specifically, the potential neuroprotective effect of semaglutide in SAH and its underlying mechanism is unclear. Accordingly, the present research intended to explore the neuroprotective effect of semaglutide in SAH and its potential molecular mechanisms. METHODS: We constructed a C57BL/6 mouse model of SAH. The parameters assessed were neuronal ferroptosis, neuroinflammatory cytokine levels, reactive oxygen species (ROS) levels, glutathione (GSH) and malondialdehyde (MDA) levels, brain water content, and neurological score. RESULTS: The results showed that the activation of semaglutide significantly increased neurological scores, relieved cerebral edema, decreased the levels of inflammatory cytokine nuclear factor kappa B, interleukin (IL)-1ß, IL-6, tumor necrosis factor-alpha, MDA, and ROS, and increased the levels of GSH. Suppression of SIRT1 reversed these effects, indicating that semaglutide activated SIRT1 to reduce neuroinflammation, ferroptosis, and neuronal cell death after SAH. Thus, the activation of the Nrf2/HO-1 signaling pathway contributes to the neuroprotective properties of semaglutide. CONCLUSIONS: Semaglutide can improve murine neurological outcomes and reduce neuronal damage against neuroinflammation and ferroptosis.

Blind frequency offset estimation method based on a minimum phase correction error for a full spectrum modulated NFDM system.

To improve the spectral efficiency of a full spectrum modulated nonlinear frequency division multiplexing (FS-NFDM) system, a blind frequency offset estimation (FOE) method has been proposed. The approach based on the minimum phase correction error can achieve high estimation accuracy of sub-MHz without need of any training symbols. Furthermore, in order to reduce the computational complexity, an eigenvalue-shift method is used to get a coarse search interval of FO, and then the one-dimensional optimization algorithm based on golden section search and parabolic interpolation is used to get the optimal FOE for the coarse search interval. The feasibility and reliability of the proposed blind FOE approach have been demonstrated in both BTB and fiber transmission scenarios. Compared with the grid search method, the proposed solving scheme can save hundreds of times of the searches. The experimental results reveal that the proposed method is robust to the amplified spontaneous emission noise and phase noise and has the capabilities of a wide FOE range and a high FOE accuracy.

Experimental demonstration of optical waveform transmission with multiple-eigenvalue 16-APSK modulation.

The multi-eigenvalue multiplexing-based discrete spectrum-modulated nonlinear frequency-division multiplexing (DS-NFDM) system with higher-order modulation format has been demonstrated experimentally. After designing the coefficients of the eigenvalue set and the constellation point distribution of 16-amplitude phase shift keying (16-APSK), the realizations of 14-, 30-, and 46-eigenvalue multiplexed DS-NFDM signals have been implemented. The results show that 46-eigenvalue and 30-eigenvalue multiplexed DS-NFDM signals can transmit 50 km and 400 km over a nonzero dispersion-shifted fiber (NZDSF) under soft-decision forward error correction (SD-FEC) threshold of 2.4E-2, respectively. This demonstration shows for the first time, to the best of our knowledge, the record for multiplexed eigenvalue number and data rate of the multiple-eigenvalue-based DS-NFDM system.

Non-sweep DC component estimation method for a virtual-carrier assisted Kramers-Kronig receiver.

The Kramers-Kronig (KK) receiver has attracted much attention in short-range optical interconnection because of its ability to recover the phase of the signal from the intensity information through KK algorithm. In high-speed KK systems, such as virtual-carrier (VC) assisted ones, an alternating current (AC) coupled photo-detector (PD) is preferred due to relaxing the requirements of analog-to-digital converter (ADC) and electronic amplifier by filtering direct current (DC) component. However, the loss of the DC component will cause the KK algorithm to break down, so it is necessary to accurately recover DC value in the digital domain with multiple-sweep. In this paper, we propose what we believe is a novel non-sweep DC component estimation scheme based on optimized digital carrier-to-signal power ratio (OD-CSPR) method, which can accurately estimate the DC component with only 3-4 iterations in the scenario of VC-assisted KK receiver optical transmission. The scheme utilizes the one-dimensional search optimization algorithm based on golden section search and parabolic interpolation without sweeping. The simulation and experimental results of the proposed non-sweep OD-CSPR method show that the DC component can be estimated accurately in a large CSPR range, and the system performance is close to that of the conventional DC-sweep method. Compared with the typical defined digital CSPR (DD-CSPR) based optimization method, the proposed one can realize optical signal-to-noise ratio (OSNR) gains of 0.9 dB in the back-to-back (B2B) and 0.7 dB under 80 km fiber transmission scenarios respectively with a total bit rate of 160Gb/s.

Host factors associated with false negative results in an interferon-γ release assay in adults with active tuberculosis.

Objective: To identify host factors associated with false-negative results of interferon-γ release tests in adults with active tuberculosis. Methods: The clinical data of 943 patients with active tuberculosis diagnosed by acid-fast smear staining, Mycobacterium tuberculosis culture, Mycobacterium tuberculosis PCR and pathological examination at West China Hospital of Sichuan University were retrospectively analysed. According to the results of the interferon γ release test (IGRA), the patients were divided into the IGRA- group and IGRA+ group. Logistic regression was used to analyze the sociodemographic data and clinical characteristics of participants in the IGRA- group and IGRA+ group. Results: Among 943 patients with active tuberculosis, 174 (18.5 %) were IGRA negative (false negative), and 769 (81.5 %) were IGRA positive. Multivariate logistic regression analysis identified the following characteristics independently associated with IGRA negativity: age (OR: 1.02; 95 % CI: 1.01 1.03; p = 0.006), anti-tuberculosis treatment >1 month (OR: 1.68; 95 % CI: 1.12 2.52; p = 0.013), HIV infection (OR: 9.48; 95 % CI: 3.23 27.85; p = 0.000), combined with connective tissue diseases (OR: 2.78; 95 % CI: 1.30 5.94; p = 0.008) and low hemoglobin (OR: 0.99; 95 % CI: 0.98 1.00; p = 0.044) was associated with an increased false-negative probability of IGRA. Conclusion: Age, anti-tuberculosis therapy >1 month, coinfection with HIV, coassociated connective tissue disease and decreased hemoglobin were identified as risk factors for false-negative results of IGRA. Our results suggest a careful interpretation of IGRA in adults with these characteristics.

Frequency offset estimation for nonlinear frequency division multiplexing with continuous spectrum modulation.

Carrier frequency offset (CFO) estimation is very important for the optical fiber communications and has been studied widely in linear coherent systems, while only a few works have been reported for nonlinear Fourier transform (NFT) based systems. In continuous spectrum (CS) modulation nonlinear frequency division multiplexing (CS-NFDM) systems, frequency offset (FO) has a great influence on its performance, requiring an improved frequency offset estimation (FOE) method. We found that the oversampling rate R0 adopted in NFDM to ensure the accuracy of the NFT and inverse NFT (INFT) calculations, would cause the estimation accuracy of the traditional FFT-FOE method to decrease by R0 times. Moreover, CS-NFDM signals with higher baud rate require more subcarriers and then result in an oversampling factor greater than 16. This makes the traditional FFT-FOE method be ineffective to use the common training sequence (TS) overhead to meet the FOE error requirement of CS-NFDM system. Therefore, a modified FOE method based on FFT assisted by TS and autocorrelation has been proposed. The theoretical analysis and simulation results show that the proposed method is applicable to CS-NFDM system, no matter what modulation format is used. For 512 subcarriers, with a high rate of 70GBaud and the TS length of 8192, the proposed method can obtain a minimum FO estimation error about 0.1 MHz, which is better than the other two typical FFT-FOE and Schmidl & Cox methods. In addition, the proposed method can save at least 87.5% and 50% overhead. Thus, the proposed method has obvious improvement for CS-NFDM system with requiring high oversampling rate.

The Causal Impact of the Gut Microbiota on Respiratory Tuberculosis Susceptibility.

INTRODUCTION: Recent cross-sectional research has demonstrated a substantial link between tuberculosis (TB) and gut microbiota. Nevertheless, the causal impact of the gut microbiota on TB susceptibility in humans remains unknown. METHODS: The Mendelian randomization (MR) method was utilized for investigating the causality between them. The main method used for MR analysis was the inverse variance weighted (IVW) test, with the MR-Egger, weighted median, weighted mode, and simple median methods serving as supplements. And several sensitivity tests were carried out to validate the MR findings. RESULTS: The IVW outcomes suggested that three bacterial traits exhibited associations with susceptibility to respiratory TB after Bonferroni correction, namely Lachnospiraceae UCG010 (odds ratio [OR] 1.73, 95% confidence interval [CI] 1.17-2.55, P = 0.005), Eubacterium (brachy group) (OR 1.33, 95% CI 1.07-1.65, P = 0.009), and Ruminococcaceae UCG005 (OR 0.71, 95% CI 0.52-0.98, P = 0.034). Sensitivity analyses demonstrated that horizontal pleiotropy and heterogeneity were absent, thereby guaranteeing the reliability of the results. CONCLUSION: This research sheds light on the causal impact of gut microbiota on respiratory tuberculosis susceptibility, improving our knowledge of therapeutic strategies for managing TB.

The incidence and risk factors of unplanned reoperation in endoscopic endonasal surgeries: a single center study.

The incidence of unplanned reoperation after surgery during the same hospitalization is considered one of most important evaluation indicators for health care quality. The purpose of this study was to determine the incidence and risk factors related to unplanned reoperation after an endoscopic endonasal approach (EEA). All patients who underwent elective endoscopic endonasal surgery from January 2016 to December 2021 in the Department of Neurosurgery, Tangdu Hospital, Air Force Military Medical University, were included. We identified the patients who underwent an unplanned reoperation and those who did not and divided them into two groups. The demographic data and risk factors were compared between the groups by univariate and multivariate logistic regression analyses. Of the 1783 patients undergoing EEA for various lesions of the skull base, the incidence of unplanned reoperation was 2.3%. The most common unplanned reoperations were repair of cerebrospinal fluid (CSF) leakage (39%), sellar hematoma evacuation (34.1%), hemostasis of epistaxis (14.6%) and external ventricular drainage for obstructive hydrocephalus (9.8%). The maximum diameter of tumor ≥ 3 cm (OR 2.654, CI 1.236-5.698; p = 0.012), meningioma (OR 4.198, CI 1.169-15.072; p = 0.028), craniopharyngioma (OR 5.020, CI 2.020-12.476; p = 0.001) and other sellar lesions (OR 4.336, CI 1.390-13.527; p = 0.012) and an operation time ≥ 240 min (OR 2.299, CI 1.170-4.518; p = 0.016) were the independent risk factors for unplanned reoperations in multivariate regression analysis. Of the 41 patients undergoing unplanned reoperation, 16 patients died, twenty-one patients had panhypopituitarism, 13 patients had transient and 6 had permanent diabetes insipidus, and 11 patients presented with intracranial infection and 6 of these patients were cured. By reviewing our department's data, we stated the incidence and risk factors for unplanned reoperation. It is important for the hospital administration and neurosurgeons to place more emphasis on these indicators. Furthermore, we suggest some effective quality improvement initiatives to reduce the incidence of unplanned reoperation.

Association between a single nucleotide polymorphism of the ALOX5 gene and susceptibility to multisystem tuberculosis in a Chinese Han population.

BACKGROUND: Host genetic single nucleotide polymorphisms can exert an influence susceptibility to tuberculosis infection. Previous investigations have demonstrated an association between the polymorphism in the ALOX5 gene and a range of diseases, encompassing not only noninfectious conditions like asthma, acute myocardial infarction, and cerebral infarction but also infections caused by various pathogens. However, the relationship between ALOX5 gene polymorphism and susceptibility to tuberculosis has received limited research attention. The ALOX5 gene encodes arachidonic acid 5-lipoxygenase(5-LO), which serves as the initiating catalyst in the generation of the inflammatory mediator leukotriene. Leukotrienes, products derived from the 5-LO pathway, are potent proinflammatory lipid mediators that assume a pivotal role in tuberculosis infections.Consequently, ALOX5 gene variants may be intricately associated with the pathogenesis of tuberculosis. In instances where the host exhibits immunocompromisation, infection with Mycobacterium tuberculosis can impact multiple systems. The involvement of multiple systems significantly augments the complexity of treatment and escalates patient mortality rates. Regrettably, the underlying mechanisms driving multisystem tuberculosis pathogenesis remain enigmatic, with clinicians paying scant attention to this aspect. Although the protein encoded by the ALOX5 gene represents a pivotal enzyme that catalyzes the metabolism of arachidonic acid into LXA4, and thereby plays a significant role in the inflammatory response during tuberculosis infection, studies investigating ALOX5 gene polymorphism and its association with susceptibility to multisystem tuberculosis in the Chinese Han population are exceptionally scarce. Therefore, the primary objective of this study is to comprehensively examine the correlation between ALOX5 gene polymorphisms and susceptibility to tuberculosis within the Chinese Han population, with particular emphasis on multisystemic tuberculosis. METHODS: A case‒control study design was employed, encompassing 382 individuals with pulmonary tuberculosis and 367 individuals with multisystemic tuberculosis as the case groups, along with 577 healthy controls.Whole blood DNA was extracted from all patients and healthy controls. Subsequently, three tag polymorphisms (rs2029253, rs7896431, rs2115819) within the ALOX5 gene were selectively identified and genotyped. RESULTS: After adjusting for age and sex, the presence of allele A at rs2029253 exhibited a pronounced association with an elevated risk of TB susceptibility when compared to the tuberculosis group and healthy control group. (ORa: 2.174, 95% CI: 1.827-2.587; Pa<0.001, respectively). Notably, the rs2029253 AG genotype and AA genotype displayed a significantly increased susceptibility to tuberculosis (ORa: 2.236, 95% CI: 1.769-2.825; Pa <0.001 and ORa: 4.577, 95% CI: 2.950-7.100; Pa <0.001, respectively) compared to the GG genotype. Moreover, in the analysis utilizing genetic models, rs2029253 also exhibited a markedly heightened susceptibility to tuberculosis in additive models, dominant models, and recessive models (Pa <0.001). Conversely, no significant association was observed between rs7896431, rs2115819, and tuberculosis. In the subgroup analysis, when comparing the pulmonary tuberculosis group with the healthy control group, we observed no significant disparities in the distribution frequencies of alleles, genotypes, and gene models (additive model, dominant model, and recessive model) for the three tag SNPs, with P-values were >0.05 after adjusting for age and sex. Additionally, we noted that the presence of allele A at rs2029253 was linked to an increased susceptibility to tuberculosis in the multisystemic tuberculosis group relative to the healthy control group (ORa: 2.292, 95% CI: 1.870-2.810; Pa<0.001). Similarly, the rs2029253 AG genotype, AA genotype, and gene models, including the additive model, dominant model, and recessive model, demonstrated a significantly elevated risk of tuberculosis susceptibility. CONCLUSIONS: The polymorphism in the ALOX5 gene is associated with susceptibility to multisystemic tuberculosis in the Chinese Han population.

Association between a single nucleotide polymorphism of the IL23R gene and tuberculosis in a Chinese Han population: a case‒control study.

BACKGROUND: Severe tuberculosis constitutes a significant menace to human safety and well-being, with a considerable mortality rate. The severity of tuberculosis can be impacted by genetic variations in host genes, particularly single nucleotide polymorphisms (SNPs). METHODS: A case‒control study was undertaken, encompassing a cohort of 1137 tuberculosis patients (558 with severe tuberculosis and 579 with mild tuberculosis), alongside 581 healthy controls within the age range of fifteen to forty-five years. Whole blood DNA was extracted from all participants, and three tag polymorphisms (rs1884444, rs7518660, rs7539625) of the IL23R gene were selectively identified and genotyped. RESULTS: No significant correlation was observed between the IL23R gene polymorphisms (rs1884444, rs7518660, and rs7539625) and tuberculosis. Upon comparing the tuberculosis group with the healthy control group, the mild tuberculosis group with the healthy control group, and the severe tuberculosis group with the healthy control group, the obtained P-values were> 0.05. However, in the comparison between severe tuberculosis and mild tuberculosis, the presence of rs1884444 G alleles exhibited a significantly increased risk of severe tuberculosis after adjusting for age and sex (ORa: 1.199, 95% CI: 1.009-1.424; Pa=0.039, respectively). In subgroup analysis, after accounting for confounding factors, including age and sex, rs1884444 G alleles continued to demonstrate a significantly heightened risk of severe tuberculosis. Nonetheless, the comparison between the multisystemic tuberculosis group and the mild tuberculosis group was no significant difference. Notably, rs1884444 of the IL23R gene exhibited a noteworthy association with the risk of severe tuberculosis in the comparison between severe tuberculosis and mild tuberculosis before and after adjusting for age and sex (ORa: 1.301, 95% CI: 1.030-1.643; Pa=0.027, respectively). Furthermore, the presence of the rs1884444 G allele exhibited a significantly increased risk of severe tuberculosis after adjusting for age and sex in the comparison between tuberculous meningitis and mild tuberculosis (ORa: 1.646, 95% CI: 1.100-2.461; Pa=0.015, respectively). CONCLUSIONS: The present study suggests that there is no significant association between IL23R gene polymorphism and tuberculosis susceptibility in the Chinese Han population. However, it does indicate a potential link between IL23R polymorphism and an increased risk of developing severe tuberculosis.

2.4-Tb/s/λ*km fundamental mode transmission over OM2 fiber employing Kramers-Kronig receiver.

We propose a digital-carrier Kramers-Kronig (DC-KK) scheme based high-speed multimode fiber short-reach optical interconnect system with fundamental mode transmission. After optimization of the parameters, including the roll-off factor of the root-raised-cosine (RRC) filter, and the guard interval (GI) between signal and carrier tone, as well as the carrier signal power ratio (CSPR), 200-Gb/s 32-quadrature amplitude modulation (32QAM) signal transmission over 12-km OM2 fiber has been experimentally demonstrated with a bit error ratio (BER) below the soft-decision forward error correction (SD-FEC) threshold of 4 × 10-2. To the best of our knowledge, this is the highest experimental record of single lambda bitrate-distance-product (SLBDP) achieved by direct-detection (DD)-based transmission over a standard multimode fiber (MMF). The proposed scheme has potential to improve the system performance without replacing massive deployed legacy MMFs for future large-capacity data center interconnects (DCIs).

Drug transdermal delivery by electrophonophoresis can increase the concentration of rifampicin in the pleural effusion of patients with tuberculous pleurisy but has no effect on the concentration of rifampicin in plasma.

BACKGROUND: Electrophonophoresis (EP) has been widely used in various clinical fields. The purpose of this study was to evaluate the dermal permeability of rifampicin (RIF) in patients with tuberculous pleurisy assisted by EP and to verify the clinical application of this percutaneous drug delivery system in the treatment of tuberculous pleurisy, verify the system's influencing factors, and determine whether plasma drug concentration was increased. METHOD: Patients were given oral isoniazid 0.3-0.4 g, rifampicin 0.45-0.60 g, pyrazinamide 1.0-1.5 g and ethambutol 0.75 g according to their body weight once a day. After 5 days of anti-tuberculosis treatment, 3 ml of rifampicin was delivered transdermally with EP. Pleural effusion and peripheral blood samples in patients were collected at and after dosing. The drug concentration in the samples was determined by high-performance liquid chromatography. RESULT: The median plasma concentration (interquartile ranges) of RIF in 32 patients was 8.80 (6.65, 13.14) µg/ml before RIF transdermal injection plus EP and decreased to 8.09 (5.58, 11.82) µg/ml after 30 min of RIF transdermal injection plus EP. The RIF concentration in pleural effusion was higher than that before RIF-transdermal plus EP. In patients who received RIF via EP transdermal administration, the concentration of the drug at the local site was statistically higher than the concentration at the local site prior to penetration. However, no such enhancement was observed in plasma after transdermal administration of RIF. CONCLUSION: EP can effectively increase the concentration of rifampicin in the pleural effusion of tuberculous pleurisy and has no effect on the circulating plasma concentration. The increased concentration of the drug in the lesion helps to destroy the bacteria.

Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

PURPOSE: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. METHODS: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nick-end labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. RESULTS: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. CONCLUSIONS: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Efficacy of BCG Vaccination against COVID-19: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Beneficial off-target effects of the Bacillus Calmette-Guérin (BCG) vaccination might offer general protection from respiratory tract infections. We conducted a systematic review and meta-analysis of published randomized controlled trials (RCTs) to ascertain BCG vaccination effectiveness against COVID-19. We looked up English RCTs from 1 January 2019 to 15 November 2022 in Embase, the Cochrane Library, and the Web of Science in this systematic review and meta-analysis. Nine RCTs, including 7963 participants, were included. The infection rate of COVID-19 was not decreased in people who were vaccinated with BCG (OR, 0.96; 95% CI, 0.82-1.13; I2 = 4%), and the BCG vaccination group did not have decreased COVID-19 related-hospitalization (OR, 0.66; 95% CI, 0.37-1.18; I2 = 42%), admission to the ICU (OR, 0.25; 95% CI, 0.05-1.18; I2 = 0%), and mortality (OR, 0.64; 95% CI, 0.17-2.44; I2 = 0%) compared with the control group. There is not sufficient evidence to support the use of BCG vaccination in the prevention of COVID-19 infection and severe COVID-19 and avoid overstating the role of BCG vaccination leading to its misuse.

Impacts of clofazimine on the treatment outcomes of drug-resistant tuberculosis.

BACKGROUND: The purpose of this research was to evaluate the effect of clofazimine on drug-resistant tuberculosis treatment outcomes. METHODS: A systematic search was conducted in the PubMed, Web of Science and EMBASE databases to identify eligible studies published up to July 10, 2021. The search terms were as follows: "clofazimine," "tuberculosis," "multidrug resistant tuberculosis" or "extensively drug resistant tuberculosis" and their synonyms or similar words. Two researchers independently screened the titles, abstracts, and full texts for inclusion. Meta-analysis was performed with Stata version 16.0 (Stata Corp., College Station, Texas, USA). Risk ratios (RRs) with 95% CIs were calculated to evaluate the treatment outcome. RESULTS: Eight studies including 3219 participants were included in the meta-analysis. The meta-analysis found that the rates of treatment completion was higher in patients receiving clofazimine-containing regimens than in those not receiving clofazimine-containing regimens (RR: 1.185 (1.060-1.325), P = 0.003). Significant reduction in treatment failure (RR: 0.598 (0.473-0.756), P < 0.001) was found in the clofazimine treatment group. The subgroup analyses of randomized controlled trials (RCTs) found a higher rates of favorable outcomes, treatment completion and cure in the clofazimine group than in the control group (RR: 1.203 (1.029-1.407), P = 0.020; RR: 3.167 (2.043-4.908), P < 0.001; and RR: 1.251 (1.031-1.518), P = 0.023, respectively). Patients receiving clofazimine had a lower risk of treatment failure than those not receiving clofazimine (RR: 0.529 (0.454-0.616), P < 0.001). However, clofazimine treatment did not have a statistically significant effect on all-cause mortality in RCTs. CONCLUSIONS: This study demonstrated that compared with patients who do not receive clofazimine, this drug has the potential to achieve a higher favorable outcome, treatment completion and cure rates, and a lower treatment failure risk among drug-resistant tuberculosis cases.

Combination therapy with long-acting bronchodilators and the risk of major adverse cardiovascular events in patients with COPD: a systematic review and meta-analysis.

INTRODUCTION: Accumulated high-quality data from randomised controlled trials (RCTs) indicate that long-acting muscarinic antagonist (LAMA)/long-acting ß2 agonist (LABA) combination therapy significantly improves clinical symptoms and health status in patients with chronic obstructive pulmonary disease (COPD) and reduces exacerbation risk. However, there is a growing concern that LAMA/LABA therapy may increase the risk of cardiovascular disease in patients with COPD. The aim of this paper is to determine whether the use of LAMA/LABA combination therapy modifies the risk of cardiovascular disease in patients with COPD. METHODS: Two reviewers independently searched Embase, PubMed and Cochrane Library to identify relevant RCTs of LAMA/LABA or LABA/LAMA/inhaled corticosteroids (ICS) for the management of patients with COPD that reported on cardiovascular end-points. The primary outcome was major adverse cardiovascular events (MACE), which was a composite of cardiovascular death, myocardial infarction or stroke. RESULTS: A total of 51 RCTs enrolling 91 021 subjects were analysed. Both dual LAMA/LABA (1.6% versus 1.3%; relative risk 1.42, 95% CI 1.11-1.81) and triple therapy (1.6% versus 1.4%; relative risk 1.29, 95% CI 1.03-1.61) significantly increased the risk of MACE compared with ICS/LABA. The excess risk was most evident in RCTs in which the average underlying baseline risk for MACE was >1% per year. Compared with LAMA only, LABA only or placebo, dual LAMA/LABA therapy did not significantly increase the risk of MACE, though these comparisons may have lacked sufficient statistical power. CONCLUSION: Compared with ICS/LABA, dual LAMA/LABA or triple therapy increases cardiovascular risk in patients with COPD. This should be considered in the context of the incremental benefits of these therapies for symptoms and exacerbation rates in patients with COPD, especially in those with a MACE risk of >1% per year.

A Predictive Model for Chronic Hydrocephalus After Clipping Aneurysmal Subarachnoid Hemorrhage.

Chronic hydrocephalus after clipping aneurysmal subarachnoid hemorrhage (aSAH) often results in poor outcomes. This study was to establish and validate model to predict chronic hydrocephalus after aSAH by least absolute shrinkage and selection operator logistic regression. The model was constructed from a retrospectively analyzed. Two hundred forty-eight patients of aSAH were analyzed retrospectively in our hospital from January 2019 to December 2021, and the patients were divided into chronic hydrocephalus (CH) group (n=55) and non-CH group (n=193) according to whether occurred CH within 3 months. In summary, 16 candidate risk factors related to chronic hydrocephalus after aSAH were analyzed. Univariate analysis was performed to judging the risk factors for CH. The least absolute shrinkage and selection operator regression was used to filter risk factors. Subsequently, the nomogram was designed by the above variables. And area under the curve and calibration chart were used to detect the discrimination and goodness of fit of the nomogram, respectively. Finally, decision curve analysis was constructed to assess the practicability of the risk of chronic hydrocephalus by calculating the net benefits. Univariate analysis showed that age (60 y or older), aneurysm location, modified Fisher grade, Hunt-Hess grade, and the method for cerebrospinal fluid drainage, intracranial infections, and decompressive craniectomy were significantly related to CH ( P <0.05). Whereas 5 variables [age (60 y or older), posterior aneurysm, modified Fisher grade, Hunt-Hess grade, decompression craniectomy] from 16 candidate factors were filtered by LASSO logistic regression for further research. Area under the curve of this model was 0.892 (95% confidence interval: 0.799-0.981), indicating a good discrimination ability. Meanwhile, the result of calibration indicated a good fitting between the prediction probability and the actual probability. Finally, decision curve analysis showed a good clinical efficacy. In summary, this model could conveniently predict the occurrence of chronic hydrocephalus after aSAH. Meanwhile, it could help physicians to develop personalized treatment and close follow-up for these patients.