Nine months of bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine chemotherapy for rifampicin/multidrug-resistant tuberculosis: a multicenter, randomized, open-label non-inferiority trial in China.

BACKGROUND: We concurrently developed a prospective study to assess clinical outcomes among patients receiving 9-month bedaquiline (BDQ)-containing regimens, aiming to provide valuable data on the use of this short-course regimen in China. METHODS: This open-label, randomized, controlled, multicenter, non-inferiority trial was conducted at sixteen hospitals, and enrolled participants aged 18 years and older with pulmonary rifampicin/multidrug tuberculosis. Participants were randomly assigned, in a 1:1 ratio. Individuals within the standard-regimen group received 6 months of BDQ, linezolid, levofloxacin, clofazimine, and cycloserine plus 12 months of levofloxacin, and any three potentially effective drugs from clofazimine, cycloserine pyrazinamide, ethambutol and protionamide, whereas individuals within shorter-regimen group received 9 months of BDQ, linezolid, levofloxacin, clofazimine and cycloserine. The primary outcome was the percentage of participants with a composite unfavorable outcome (treatment failure, death, treatment discontinuation, or loss to follow-up) by the end of the treatment course after randomization in the modified intention-to-treat population. The noninferiority margin was 10%. This trial was registered with www.chictr.org.cn , ChiCTR2000029012. RESULTS: Between Jan 1, 2020, and Dec 31, 2023, 264 were screened and randomly assigned, 132 of 264 participants were assigned to the standard-regimen group and 132 were assigned to the shorter-regimen. Thirty-three (12.55%) of 264 participants were excluded from the modified intention-to-treat analysis. As a result, 231 participants were included in the modified intention-to-treat analysis (116 in the standard-regimen group and 115 in the shorter-regimen group).In the modified intention-to-treat population, unfavorable outcomes were reported in 19 (16.5%) of 115 participants for whom the outcome was assessable in the shorter-regimen group and 26 (22.4%) of 116 participants in the standard care group (risk difference 5.9 percentage points (97.5% CI - 5.8 to 17.5)). One death was reported in the standard-regimen group. The incidence of QTcF prolongation in the shorter-regimen group (22.6%, 26/115) was similar to the standard-regimen group (24.1%, 28/116). CONCLUSIONS: The 9-month, all-oral regimen is safe and efficacious for the treatment of pulmonary rifampicin/multidrug-resistant tuberculosis. The high incidence of QTc prolongation associated with the use of BDQ highlights the urgent need of routine electrocardiogram monitoring under treatment with BDQ-containing regimens in the Chinese population.

Epidemiology and Association Rules Analysis for Pulmonary Tuberculosis Cases with Extrapulmonary Tuberculosis from Age and Gender Perspective: A Large-Scale Retrospective Multicenter Observational Study in China.

Background: Tuberculosis (TB), a multisystemic disease with protean presentation, remains a major global health problem. Although concurrent pulmonary tuberculosis (PTB) and extrapulmonary tuberculosis (EPTB) cases are commonly observed clinically, knowledge regarding concurrent PTB-EPTB is limited. Here, a large-scale multicenter observational study conducted in China aimed to study the epidemiology of concurrent PTB-EPTB cases by diagnostically defining TB types and then implementing association rules analysis. Methods: The retrospective study was conducted at 21 hospitals in 15 provinces in China and included all inpatients with confirmed TB diagnoses admitted from Jan 2011 to Dec 2017. Association rules analysis was conducted for cases with concurrent PTB and various types of EPTB using the Apriori algorithm. Results: Evaluation of 438,979TB inpatients indicated PTB was the most commonly diagnosed (82.05%) followed by tuberculous pleurisy (23.62%). Concurrent PTB-EPTB was found in 129,422 cases (29.48%) of which tuberculous pleurisy was the most common concurrent EPTB type observed. The multivariable logistic regression models demonstrated that odds ratios of concurrent PTB-EPTB cases varied by gender and age group. For PTB cases with concurrent EPTB, the strongest association was found between PTB and concurrent bronchial tuberculosis (lift = 1.09). For EPTB cases with concurrent PTB, the strongest association was found between pharyngeal/laryngeal tuberculosis and concurrent PTB (lift = 1.11). Confidence and lift values of concurrent PTB-EPTB cases varied with gender and age. Conclusions: Numerous concurrent PTB-EPTB case types were observed, with confidence and lift values varying with gender and age. Clinicians should screen for concurrent PTB-EPTB in order to improve treatment outcomes.

Balloon compression, neuroendoscopy and electrophysiological monitoring-assisted retrosigmoid approach for resection of cholesteatoma in the cerebellopontine angle-Meckel's cave: a technical description.

We report a case of cholesteatoma that caused left facial pain with facial numbness. The tumour was located in the left cerebellopontine angle (CPA) and Meckel's cave. A balloon was first placed into Meckel's cave, and then, under electrophysiological monitoring, the tumour within the CPA cistern was resected via the retrosigmoid approach. The balloon was inflated in Meckel's cave to push the tumour out of Meckel's cave, and then, the tumour was completely removed under endoscopy. The symptoms, including pain and numbness, subsided after surgery.

JKAP serves as a potential biomarker for the evaluation of inflammatory condition, disease activity, and treatment response to TNF inhibitor in ankylosing spondylitis patients.

OBJECTIVE: This study aimed to evaluate the value of JKAP as a biomarker in estimating treatment response to TNF inhibitor in AS patients. METHODS: Totally, 63 AS patents who planned to receive adalimumab (TNF inhibitor) treatment were enrolled. Baseline JKAP level was determined in serum samples. All patients received 40 mg adalimumab every two weeks for 12 weeks. At W2, W4, W8, and W12, ASAS40 response rates were evaluated. RESULTS: JKAP was negatively correlated with CRP (P = 0.032), BASDAI score (P = 0.021), BASFI score (P = 0.045), ASDASCRP score (P = 0.038), TNF-α (P = 0.031), IL-6 (P = 0.025) and IL-17A (P = 0.022). The ASAS40 response rates were 17.5%, 31.7%, 44.4% and 55.5% at W2, W4, W8 and W12, respectively. Baseline JKAP level was lower in patients with ASAS40 response than those without ASAS40 response (25.8 (13.2-42.7) pg/mL vs. 47.3 (26.7-71.2) pg/mL, P = 0.003). Multivariate logistic regression disclosed that JKAP level (P = 0.049) and CRP level (P = 0.014) independently correlated with ASAS40 response; further analyses disclosed that they exhibited acceptable to good ability in distinguishing patients with ASAS40 response from those without ASAS40 response. CONCLUSION: JKAP serves as a potential biomarker for evaluation of inflammatory condition, disease activity, especially for assessing treatment response to TNF inhibitor in AS patients.

The prevalence and risks of major comorbidities among inpatients with pulmonary tuberculosis in China from a gender and age perspective: a large-scale multicenter observational study.

In clinical practice, PTB patients have concurrent many types of comorbidities such as pneumonia, liver disorder, diabetes mellitus, hematological disorder, and malnutrition. Detecting and treating specific comorbidities and preventing their development are important for PTB patients. However, the prevalence of most comorbid conditions in patients with PTB is not well described. We conducted a large-scale, multicenter, observational study to elucidate and illustrate the prevalence rates of major comorbidities in inpatients at 21 hospitals in China. The 19 specific comorbidities were selected for analysis in this patient cohort, and stratified the inpatient cohort according to age and gender. A total of 355,929 PTB inpatients were included, with a male:female ratio of 1.98 and the proportion of ≥ 65 years PTB inpatients was the most. Approximately 70% of PTB inpatients had at least one defined type of comorbidity. The prevalence of 19 specific comorbidities in inpatients with PTB was analyzed, with pneumonia being the most common comorbidity. The prevalence of most comorbidities was higher in males with PTB except thyroid disorders, mental health disorders, etc. The prevalence of defined most comorbidities in patients with PTB tended to increase with increasing age, although some specific comorbidities tended to increase initially then decrease with increasing age. Our study describes multiple clinically important comorbidities among PTB inpatients, and their prevalence between different gender and age groups. The results will enhance the clinical aptitude of physicians who treat patients with PTB to recognize, diagnose, and treat PTB comorbidities early.

Efficacy of and risk factors for percutaneous balloon compression for trigeminal neuralgia in elderly patients.

OBJECTIVE: To investigate the efficacy and safety of percutaneous balloon compression (PBC) for the treatment of trigeminal neuralgia in elderly patients. Methods: We retrospectively analysed data of 105 elderly patients with primary trigeminal neuralgia who were over 70 years and underwent percutaneous balloon compression using anatomic positioning and imaging guidance from January 2019 to November 2019. Results: The immediate cure rate of pain in this group of patients was 97.1% (Barrow Neurological Institute (BNI) pain scores: class I and II; numbness score: class II). Postoperative keratitis was reported in 1 patient, masticatory muscle weakness and muscle atrophy in 1 patient, herpes labialis in 8 patients and lacunar infarction in 2 patients. Facial numbness and decreased sensation occurred in patients with significant pain relief. No serious complications were reported. There was no statistically significant difference in efficacy between the short compression and long compression time groups. Conclusion: PBC is a safe and effective approach to treat trigeminal neuralgia.

Long noncoding RNA intersectin 1-2 gradually declines during adalimumab treatment, and its reduction correlates with treatment efficacy in patients with ankylosing spondylitis.

Previous studies show that long noncoding RNA intersectin 1-2 (lnc-ITSN1-2) promotes the inflammation process and serves as a potential biomarker in autoimmune diseases, except for ankylosing spondylitis (AS). Therefore, this study aimed to explore the correlation of baseline lnc-ITSN1-2 expression with disease risk and activity of AS, and to investigate its longitudinal change with treatment response to a tumour necrosis factor alpha (TNFα) inhibitor in patients with AS. In total, 63 patients with AS receiving 12-week adalimumab treatment were included and their baseline clinical features were collected. Lnc-ITSN1-2 expression in peripheral blood mononuclear cells (PBMC) of patients with AS was detected by reverse transcription quantitative polymerase chain reaction. Meanwhile, Assessment in Spondyloarthritis International Society (ASAS) 40 response was evaluated at week 2 (W2), W4, W8, and W12. According to the ASAS40 response status at W12, patients with AS were classified into responders and non-responders. PBMC lnc-ITSN1-2 expression was also determined in healthy controls (N = 60). Lnc-ITSN1-2 expression was elevated in patients with AS compared to controls (P < 0.001). Baseline lnc-ITSN1-2 expression was positively associated with C-reaction protein (CRP) (P = 0.021), interleukin (IL)-1ß (P = 0.020), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score (P = 0.040), and Ankylosing Spondylitis Disease Activity score with C-reactive protein (ASDASCRP) (P = 0.045) in patients with AS. Furthermore, lnc-ITSN1-2 expression declined during the treatment with adalimumab (P < 0.001). Notably, this reduction was more obvious in responders than non-responders. In conclusion, declined lnc-ITSN1-2 expression during the TNFα inhibitor treatment correlates with good treatment efficacy in patients with AS, suggesting its clinical value for AS management.

Sclerenchyma cell thickening through enhanced lignification induced by OsMYB30 prevents fungal penetration of rice leaves.

Broad-spectrum resistance is highly preferred in crop breeding programmes. Previously, we have reported the identification of the broad-spectrum resistance-Digu 1 (bsr-d1) allele from rice Digu. The bsr-d1 allele prevents activation of Bsr-d1 expression by Magnaporthe oryzae infection and degradation of H2 O2 by peroxidases, leading to resistance to M. oryzae. However, it remains unknown whether defence pathways other than H2 O2 burst and peroxidases contribute to the bsr-d1-mediated immunity. Blast resistance was determined in rice leaves by spray and punch inoculations. Target genes of OsMYB30 were identified by one-hybrid assays in yeast and electrophoretic mobility shift assay. Lignin content was measured by phloroglucinol-HCl staining, and acetyl bromide and thioacidolysis methods. Here, we report the involvement of the OsMYB30 gene in bsr-d1-mediated blast resistance. Expression of OsMYB30 was induced during M. oryzae infection or when Bsr-d1 was knocked out or downregulated, as occurs in bsr-d1 plants upon infection. We further found that OsMYB30 bound to and activated the promoters of 4-coumarate:coenzyme A ligase genes (Os4CL3 and Os4CL5) resulting in accumulation of lignin subunits G and S. This action led to obvious thickening of sclerenchyma cells near the epidermis, inhibiting M. oryzae penetration at the early stage of infection. Our study revealed novel components required for bsr-d1-mediated resistance and penetration-dependent immunity, and advanced our understanding of broad-spectrum disease resistance.

A New Perspective on Dry Eye Classification: Proposal by the Asia Dry Eye Society.

The 2017 consensus report of the Asia Dry Eye Society (ADES) on the definition and diagnosis of dry eyes described dry eye disease as "Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage." The report emphasized the instability of tear film and the importance of visual dysfunction in association with dry eyes, highlighting the importance of the evaluation of tear film stability. This report also discussed the concept of tear film-oriented therapy, which stemmed from the definition, and which is centered on provision of insufficient components in each tear film layer and ocular surface epithelium. The current ADES report proposes a simple classification of dry eyes based on the concept of tear film-oriented diagnosis and suggests that there are three types of dry eye: aqueous-deficient, decreased wettability, and increased evaporation. It is suggested that these three types respectively coincide with the problems of each layer: aqueous, membrane-associated mucins, and lipid/secretory mucin. Although each component cannot be quantitatively evaluated with the current technology, a practical diagnosis based on the patterns of fluorescein breakup is recommended. The Asia Dry Eye Society classification report suggests that for a practical use of the definition, diagnostic criteria and classification system should be integrated and be simple to use. The classification system proposed by ADES is a straightforward tool and simple to use, only through use of fluorescein, which is available even to non-dry eye specialists, and which is believed to contribute to an effective diagnosis and treatment of dry eyes.

Percutaneous Transhepatic Biliary Stent Implantation for Obstructive Jaundice of Perihilar Cholangiocarcinoma: A Prospective Study on Predictors of Stent Patency and Survival in 92 Patients.

PURPOSE: To evaluate prognostic factors for stent patency and survival in patients with perihilar cholangiocarcinoma (pCCA) who underwent percutaneous biliary stent placement. MATERIALS AND METHODS: This prospective study followed 92 consecutive patients with pCCA who underwent metal stent placement between January 2013 and July 2014. Of the total number of patients, 11 had ascites, and 36 had biliary obstruction for > 1 month at the time of stent placement. Cumulative patency and survival rates were assessed with Kaplan-Meier curves, and independent predictors were calculated with Cox regression. A new formula was developed to predict patient survival. RESULTS: Tumor size was significantly associated with stent patency (hazard ratio = 2.425; 95% confidence interval, 1.134-5.168). Independent predictors of survival included lymph node metastasis, intrahepatic mass lesion, cancer antigen 19-9 (CA19-9), ascites, and duration of jaundice. A new equation was developed to assess risk: R = 7 × (duration of biliary obstruction-0 if < 30 d, 1 if > 30 d) + 7 × (CA19-9-0 if < 500, 1 if > 500) + 7 × (ascites-0 if none present, 1 if ascites present) + 10 × (lymph node metastasis-0 if no metastasis, 1 if metastasis present) + 9 (intrahepatic mass lesion-0 if absent, 1 if present). Among patients who developed stent occlusion, patients who underwent recanalization of the occluded stent had longer survival compared with patients who did not undergo recanalization (109 d vs 29 d, P = .001). CONCLUSIONS: Prognostic factors for survival after percutaneous stent placement in patients with pCCA were tumor stage, duration of jaundice, CA19-9, and ascites. Tumor size affected stent patency. Prognosis for patients with reintervention after occlusion of the stent improved.

Clofazimine for the treatment of multidrug-resistant tuberculosis: prospective, multicenter, randomized controlled study in China.

BACKGROUND: Clofazimine (Cfz) has shown activity against Mycobacterium tuberculosis, including multidrug-resistant (MDR) strains in vitro and in animal studies. Here we evaluate the clinical efficacy and tolerability of using Cfz to treat MDR tuberculosis in China. METHODS: We enrolled 105 patients who had sputum culture-positive MDR tuberculosis in 6 major tuberculosis specialty hospitals in China. Patients were randomly assigned to either the Cfz therapy group (n = 53) or control group (n = 52). Patients in the 2 groups were given 21 months of individual-based chemotherapy regimens based on medication history and drug susceptibility test results. The Cfz therapy group regimens incorporated 100 mg of Cfz once daily for 21 months. RESULTS: Three patients in each group discontinued therapy because of side effects or other reasons. Sputum culture conversion to negative was earlier in patients who received Cfz compared with controls (P = .042 by log-rank test). Chest computed tomography showed cavitary changes in 46 patients in the Cfz therapy group and 45 in the control group. Cavity closure was earlier in patient who received Cfz compared with controls (P = .047 by log-rank test). The treatment success rate in the Cfz group was 73.6%, higher than that in control group (53.8%; P = .035). Side effects in skin only occurred in the Cfz group. The rates of skin discoloration and ichthyosis were 94.3% and 47.2%, respectively. CONCLUSIONS: Using Cfz to treat MDR tuberculosis promotes cavity closure, accelerates sputum culture conversion, and improves treatment success rates.

[Unilateral versus bilateral biliary drainage for malignant hilar obstruction: a systematic review and meta-analysis].

OBJECTIVE: To assess the efficacy and safety of bilateral versus unilateral biliary drainage in malignant hilar obstruction. METHODS: Topically relevant studies,regardless of randomized or observational design, were searched for in PubMed, EmBase and the Cochrane Library database. Risk ratios (RRs) with 95% confidence intervals (CIs) were calculated to compare the effect of the two treatments. RESULTS: Three randomized trials and 7 observational studies were included, involving 894 patients with malignant hilar obstruction. The meta-analysis assessment of primary outcomes showed that the stent patency rate was better in bilateral drainage than in unilateral drainage (Rr=2.03,95% CI [1.16-3.56], P=0.01), but there were no significant differences in successful drainage rate (Rr=1.07,95% CI [0.97-1.18], P=0.20) and patient survival rate (Rr=-0.16,95% CI [-0.40-0.08], P=0.20). In the analysis of secondary outcomes,there were also no significant differences in the technical success rate (Rr=1.05,95% CI [0.98-1.17], P=0.34),the early complication rate (Rr=1.15, 95% CI [0.75-1.76], P=0.52), late complication rate (Rr=1.09,95% CI [0.75-1.60], P=0.60) and 30-day mortality rate (Rr=0.68,95% CI [0.38-1.23], P=0.20). CONCLUSION: Although the cumulative stent patency was better for the bilateral than the unilateral drainage approach, based on the available data, there is not enough data to support bilateral drainage for malignant hilar obstruction. Well-designed randomized controlled trials are necessary to confirm it.

rs4711751 and rs1999930 are not associated with neovascular age-related macular degeneration or polypoidal choroidal vasculopathy in the Chinese population.

PURPOSE: rs1999930 and rs4711751 have recently been identified as novel variants associated with advanced age-related macular degeneration (AMD) in populations of European ancestry. We aimed to investigate whether these two single nucleotide polymorphisms (SNPs) were associated with neovascular AMD (nAMD) or with polypoidal choroidal vasculopathy (PCV), a variant of AMD in Asians, using a Chinese case-control study. METHODS: A total of 900 subjects, including 300 controls, 300 cases with nAMD and 300 cases with PCV, were included in the present study. Genomic DNA was extracted from venous blood leukocytes. The allelic variants of rs1999930 and rs4711751 were determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The differences in allele distribution between cases and controls were tested by a χ(2) test, with additional adjustments for age and gender using logistic regression. The statistical power was also calculated. Values of p < 0.05 were considered statistically significant. RESULTS: No statistically significant association was observed between the two polymorphisms of nAMD or PCV phenotype (p > 0.05 for all comparisons). The difference remained insignificant after correction for age and gender (p > 0.05 for all comparisons). The statistical powers to detect the association between these two SNPs and nAMD or PCV range from 0.05 to 0.36, assuming conventional levels of statistical significance. CONCLUSIONS: In the present study, we could not replicate the reported association of these two SNPs and either nAMD or PCV in a Chinese population, suggesting that they are unlikely to be a major AMD and PCV susceptibility gene locus in the Chinese population. Considering the low power value, a large sample size is required to draw more reliable conclusions.

ABCA1 rs1883025 polymorphism shows no association with neovascular age-related macular degeneration or polypoidal choroidal vasculopathy in a Northern Chinese population.

PURPOSE: To analyze the association between ABCA1 rs1883025 variants with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) in a northern Chinese population. METHODS: The study enrolled 900 subjects, including 300 controls, 300 cases with nAMD and 300 cases with PCV. Genomic DNA was extracted from venous blood leukocytes. Single-nucleotide polymorphisms in the ABCA1 (rs1883025) gene were genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. RESULTS: The ABCA1 rs1883025 polymorphism was not significantly associated with nAMD (22.5%; p > 0.05) or PCV (20.8%; p > 0.05) in a northern Chinese population. The association remained insignificant after adjustment for age and gender differences (p > 0.05). CONCLUSIONS: This study suggests that ABCA1 rs1883025 variants are not associated with nAMD or PCV in a Chinese population, which is likely due to an ethnic difference.

Hemifacial Spasm Associated With the Specific Offending Vein.

BACKGROUND AND OBJECTIVES: Hemifacial spasm (HFS) caused by venous compression is a rare occurrence. Currently, there is no relevant research on the venous characteristics and potential pathogenic mechanisms causing venous HFS. Exploring the venous characteristics in venous-type HFS may reduce the likelihood of repeated surgery. METHODS: The authors presented 4 cases of HFS caused by veins of middle cerebellar peduncle (V. of Mid.Cer.Ped) successfully treated with microvascular decompression. RESULTS: Based on intraoperative observations and abnormal muscle response (AMR) monitoring, it was determined that V. of Mid.Cer.Ped were offending vessels in these patients. Moreover, veins crossed between the facial and vestibulocochlear nerves, and then surrounded the ventral aspect of the facial nerve root. Microvascular decompression for the offending vessel was successfully performed, and AMR disappeared for each patient. These patients were discharged without any complications and involuntary contractions or twitching of facial muscles. CONCLUSION: The study demonstrated that veins can indeed induce HFS. The characteristic of the V. of Mid.Cer.Ped that leads to HFS is that these veins traverse between the facial nerve and the vestibulocochlear nerve, and then surround the ventral aspect of the facial nerve root. The dynamic influence of cerebrospinal fluid leads to pulsatile impingement of the facial nerve on the vein, resulting in facial nerve bending and deformation at the location of the vein. Significantly, in the context of surgery, if it is noticed that the V. of Mid.Cer.Ped surrounds the ventral aspect of the facial nerve root and the facial nerve is compressed and deformed, when AMR disappears after decompression of the artery, it may be necessary to perform vein decompression.

Clinical Diagnostic Challenge in a Case of Disseminated Talaromyces marneffei Infection Misdiagnosed Initially as Pulmonary Tuberculosis: A Case Report and Literature Review.

This case reports a middle-aged male patient who was HIV-negative and initially misdiagnosed as pulmonary tuberculosis but was eventually diagnosed with disseminated Talaromyces marneffei (T. marneffei) infection by next-generation sequencing. The patient presented with respiratory symptoms, recurrent bone pain, and subcutaneous masses as the main symptoms. After one year of antifungal treatment, the symptoms improved obviously, but the symptoms recurred after two weeks of drug withdrawal, and the symptoms were relieved after re-administration of antifungal drugs again. This report highlights the need for the rapid evaluation of fungal infections with metagenomic next-generation sequencing (mNGS) in patients with an inadequate diagnostic basis for tuberculosis infection or a poor response to antituberculosis drugs. In addition, long-term follow-up is needed to observe disease recurrence in patients with disseminated T. marneffei infection.

A causal relationship between sarcopenia and cognitive impairment: A Mendelian randomization study.

OBJECTIVE: Sarcopenia and cognitive impairment often coexist in the elderly. In this study, we investigated the causal relationship between sarcopenia-related muscle characteristics and cognitive performance. METHODS: We used linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR) analyses to estimate genetic correlations and causal relationships between genetically predicted sarcopenia-related muscle traits and cognitive function, as well as cognitive function-based discovery samples and replicated samples. Estimated effect sizes were derived from a fixed-effects meta-analysis. RESULTS: Our univariate genome-wide association study (GWAS) meta-analysis indicated a causal relationship between appendicular lean mass (ALM) (ß = 0.049; 95% confidence interval (CI): 0.032-0.066, P < 0.001) and walking pace (ß = 0.349; 95% CI: 0.210-0.487, P < 0.001) with cognitive function, where a causal relationship existed between ALM in both male and female (ßALM-Male(M) = 0.060; 95% CI: 0.031-0.089, PALM-M < 0.001; ßALM-Female(F) = 0.045; 95% CI: 0.020-0.069, PALM-F < 0.001) with cognitive function. Low grip strength was not causally associated with cognitive function (ß = -0.045; 95% CI: -0.092 - -0.002, P = 0.062). A reverse causality GWAS meta-analysis showed a causal relationship between cognitive function and ALM (ß = 0.033; 95% CI: 0.018-0.048, P < 0.001) and walking pace (ß = 0.039; 95% CI: 0.033-0.051, P < 0.001), where ALM in both male and female showed a causality (ßALM-M = 0.041; 95% CI: 0.019-0.063, PALM-M < 0.001; ßALM-F = 0.034; 95% CI: 0.010-0.058, PALM-F = 0.005). Cognitive function was not causally related to low grip strength (ß = -0.024; 95% CI: -0.073-0.025, P = 0.344). Multivariable MR1 (MVMR1) analyses showed a significant causal relationship for ALM (ß = 0.077; 95% CI: 0.044-0.109, P = 0.000) and walking pace (ß = 0.579; 95% CI: 0.383-0.775, P = 0.000) and cognitive function. Multivariable MR2 (MVMR2) multivariate analysis showed that ALM causality remained (ß = 0.069; 95% CI: 0.033-0.106, P = 0.000), and walking pace (ß = 0.589; 95% CI: 0.372-0.806, P = 0.000). CONCLUSIONS: Bidirectional two-sample MR demonstrated that sarcopenia-related muscle characteristics and cognitive performance were positive causal genetic risk factors for each other, while a multivariable MR study demonstrated that low ALM and a slow walking pace were causally involved in reduced cognitive performance. This study suggests a causal relationship between sarcopenia and cognitive impairment in older adults and provide new ideas for prevention and treatment.

Trigeminal neuralgia secondary to osteoma and vascular compression: illustrative case.

BACKGROUND: Trigeminal neuralgia (TN) is a common neurosurgical issue that has a detrimental impact on patients' quality of life. Osteoma at the petrous apex is a rare etiology of TN. Here, the authors present a case involving the co-occurrence of petrous osteoma and a vascular loop around the trigeminal nerve. Both exerted pressure or compression on the exit of the trigeminal nerve. OBSERVATIONS: A 46-year-old male presented with a 3-year history of persistent severe pain in the right side of his face. Magnetic resonance tomographic angiography of the trigeminal nerve revealed an abnormal signal in the right prepontine cistern, along with a vascular loop accompanying the right trigeminal nerve. A computed tomography scan of the skull indicated a nodular calcified density. The combined anterior transpetrosal approach for petrous osteoma and microvascular decompression (MVD) for the offending vessel were successfully performed. The patient was discharged without any complications or facial pain. LESSONS: Although extremely rare, TN simultaneously secondary to petrous osteoma and offending vessels should be considered in the diagnosis. In this case, the combined surgical removal of petrous osteoma and MVD for the offending vessels proved to be an effective treatment for TN secondary to osteoma and vascular compression.

Circ_0000253 promotes the progression of osteosarcoma via the miR-1236-3p/SP1 axis.

OBJECTIVE: Circular RNAs (circRNAs) play important roles in modulating tumour progression. This study investigated the role of circ_0000253 in osteosarcoma (OS). METHODS: We downloaded the chip dataset GSE140256 from the Gene Expression Omnibus database and the circRNAs differentially expressed in OS tissue and normal tissue samples were analysed. Quantitative real-time PCR (qRT-PCR) was carried out to examine circ_0000253 expression in OS tissues and cells. Cell counting kit-8, BrdU and flow cytometry assays were performed to verify the effects of circ_0000253 on OS cell growth and apoptosis. Bioinformatics analysis was conducted to predict, and RNA immunoprecipitation assay and dual-luciferase reporter gene assay were performed to verify the targeted relationships of miR-1236-3p with circ_0000253 and Sp1 transcription factor (SP1) mRNA 3'UTR. The effects of miR-1236-3p and circ_0000253 on SP1 expression in OS cells were detected through Western blot. KEY FINDINGS: Circ_0000253 was upregulated in OS tissues and cell lines. Circ_0000253 overexpression facilitated OS cell growth and suppressed apoptosis, whereas knocking down circ_0000253 inhibited OS cell growth and facilitated apoptosis. Circ_0000253 targeted miR-1236-3p directly and negatively modulated its expression. SP1 was miR-1236-3p's target gene and positively regulated by circ_0000253. CONCLUSION: Circ_0000253 promotes OS cell proliferation and suppresses cell apoptosis via regulating the miR-1236-3p/SP1 molecular axis.