Diagnostic performance analysis of Xpert MTB/RIF in lymph node tuberculosis: A retrospective study.

AIMS: To retrospectively analyze the diagnostic efficacy of Xpert MTB/RIF (Xpert) in lymph node tuberculosis (LNTB). METHODS: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the curve (AUC) of Xpert, pathological examination and culture for LNTB were calculated. RESULTS: 421 suspected LNTB cases were categorized into the LNTB group (377 cases) and non-LNTB group (44 cases). The sensitivities of Xpert, pathological examination, and culture were 72.15%, 20.69%, 30.24%, respectively, with NPVs of 29.53%, 12.83%, 14.33%. The AUC values were 0.861, 0.603, 0.651, respectively. The sensitivity of Xpert varied across sample types: tissue (64.73%), puncture fluid (74.42%), and pus (96.05%). For specific lymph node locations, the sensitivity was head-and-neck (72.51%), mediastinal (84.21%), and axillary (45.83%). CONCLUSIONS: Xpert demonstrates high diagnostic value for LNTB, particularly in pus samples. It also performs better in mediastinal and head-and-neck lymph node samples compared to axillary lymph node samples.

Factors influencing false-positive results of rifampicin resistance detected by Xpert MTB/RIF: A retrospective study in Zhejiang, China.

Objective: This study aimed to explore the factors influencing false-positive results for rifampicin resistance (RIF-R) detected using Xpert MTB/RIF (Xpert). Methods: This retrospective analysis included the clinical data of patients from September 2019 to February 2023. The chi-square and rank sum tests were used to compare differences in patient characteristics between the true-positive and false-positive groups. Logistic regression was used to analyze the factors influencing false positives in the detection of RIF-R by Xpert. Results: A total of 384 patients were included. Logistic regression analysis revealed that, with mutation of probe E as the reference, mutations on probe A or C (OR = 72.68, P < 0.001), probe D (OR = 6.44, P < 0.001), and multiple probes (OR = 5.94, P = 0.002) were associated with false-positive results in Xpert detection of RIF-R. Taking probe delay ΔCt <4 as the reference, ΔCt (4-5.9) (OR = 13.54, P < 0.001), ΔCt (6-7.9) (OR = 48.08, P < 0.001) probe delays were associated with false positives in Xpert detection of RIF-R. When very low quantification is accompanied by a probe delay, the probability of false-positive RIF-R detection can reach 80 %. Conclusions: Clinicians should consider factors such as probe mutation type, probe delay, and very low quantification accompanied by probe delay when interpreting Xpert results, which can reduce the misdiagnosis of tuberculosis drug resistance.

Effect of an organic acid blend as an antibiotic alternative on growth performance, antioxidant capacity, intestinal barrier function, and fecal microbiota in weaned piglets.

This study was conducted to evaluate the effects of dietary organic acid blend on growth performance, antioxidant capacity, intestinal barrier function, and fecal microbiota in weaned piglets compared to antibiotic growth promoters (AGP). A total of 90 weaned crossbred barrows (24 ± 1 days of age) with an initial body weight of 7.40 kg were allocated into 3 experimental treatments. Each treatment consisted of 6 replicate pens, with 5 piglets housed in each pen. The dietary treatments included the basal diet (NC), the basal diet supplemented with antibiotics (PC), and the basal diet supplemented with organic acid blend (OA). On day 42, one piglet per pen was randomly selected for plasma and small intestinal sample collection. The results showed that dietary AGP significantly improved growth performance and reduced diarrhea incidence compared to the NC group (P < 0.05). Dietary OA tended to increase body weight on day 42 (P = 0.07) and average daily gain from day 0 to 42 (P = 0.06) and reduce diarrhea incidence (P = 0.05). Dietary OA significantly increased plasma catalase (CAT) activity and decreased the plasma concentration of malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-8, and IL-6, which were accompanied by upregulated the relative mRNA abundance of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1) and nuclear factor erythroid 2-related factor 2 (NRF2) in comparison to that in the NC group (P < 0.05). Moreover, pigs fed the OA diet significantly increased the ratio of villus height to crypt depth and upregulated the relative expression of zonula occludens-1 (ZO-1) and Claudin1 gene in the jejunum compared to the NC group (P < 0.05). Interestingly, dietary AGP or OA did not affect the fecal microbiota structure or volatile fatty acid content (P > 0.05). In conclusion, our results suggested that dietary OA supplementation could improve growth performance and antioxidant capacity and protect the intestinal barrier of weaned piglets, therefore it has the potential to be consideredas an alternative to AGP in the pig industry.

Rapid Selection of Patients Suitable for Deep Inspiration Breath-Hold Using an Automatic Delineating System and RapidPlan Model in Left Breast Cancer Patients undergoing Adjuvant Radiotherapy with IMRT.

PURPOSE: This study aimed to determine whether radiotherapy plans created using an automatic delineating system and a RapidPlan (RP) module could rapidly and accurately predict heart doses and benefit from deep inspiratory breath-hold (DIBH)in left breast cancer patients. METHODS AND MATERIALS: One hundred thirty-six clinically approved free breathing (FB) plans for patients with left breast cancer were included, defined as manual delineation-manual plan (MD-MP). A total of 104/136 plans were selected for RP model training. A total of 32/136 patients were automatically delineated by software, after which the RP generated plans, defined as automatic delineation-RapidPlan (AD-RP). In addition, 40 patients who used DIBH were included to analyze differences in heart benefits from DIBH. RESULTS: Two RP models were established for post breast-conserving surgery (BCS) and post modified radical mastectomy (MRM). There were no significant differences in most of the dosimetric parameters between the MD-MP and AD-RP. The heart doses of the two plans were strongly correlated in patients after BCS (0.80 ≤ r ≤ 0.88, P < 0.05) and moderately correlated in patients after MRM (0.46 ≤ r ≤ 0.58, P < 0.05). The RP model predicted the mean heart dose (MHD) within ± 59.67 cGy and ± 63.32 cGy for patients who underwent the two surgeries described above. The heart benefits from DIBH were significantly greater in patients with FB-MHD ≥ 4 Gy than in those with FB-MHD < 4 Gy. CONCLUSIONS: The combined automatic delineation RP model allows for the rapid and accurate prediction of heart dose under FB in patients with left breast cancer. FB-MHD ≥ 4 Gy can be used as a dose threshold to select patients suitable for DIBH.

Genistein Alleviates Intestinal Oxidative Stress by Activating the Nrf2 Signaling Pathway in IPEC-J2 Cells.

In the weaning period, piglets often face oxidative stress, which will cause increased diarrhea and mortality. Genistein, a flavonoid, which is extracted from leguminous plants, possesses anti-inflammatory and antioxidative bioactivities. However, little is known about whether genistein could attenuate the oxidative stress that occurs in porcine intestinal epithelial cells (IPEC-J2). Herein, this experiment was carried out to investigate the protective effects of genistein in the IPEC-J2 cells oxidative stress model. Our results disclosed that H2O2 stimulation brought about a significant diminution in catalase (CAT) activity and cell viability, as well as an increase in the levels of reactive oxygen species (ROS) in IPEC-J2 cells (p < 0.05), whereas pretreating cells with genistein before H2O2 exposure helped to alleviate the reduction in CAT activity and cell viability (p < 0.05) and the raise in the levels of ROS (p = 0.061) caused by H2O2. Furthermore, H2O2 stimulation of IPEC-J2 cells remarkably suppressed gene level Nrf2 and CAT expression, in addition to protein level Nrf2 expression, but pretreating cells with genistein reversed this change (p < 0.05). Moreover, genistein pretreatment prevented the downregulation of occludin expression at the gene and protein level, and ZO-1 expression at gene level (p < 0.05). In summary, our findings indicate that genistein possesses an antioxidant capacity in IPEC-J2 cells which is effective against oxidative stress; the potential mechanism may involve the Nrf2 signaling pathway. Our findings could offer a novel nutritional intervention strategy to enhance the intestinal health of piglets during the weaning process.

Inflammatory risk of albumin combined with C-reactive protein predicts long-term cardiovascular risk in patients with diabetes.

AIMS: The purpose of this study was to evaluate the predictive value of inflammatory risk as defined by the Glasgow Prognostic Score (GPS) for cardiovascular death in patients with diabetes. METHODS: This study included 4956 patients (≥18 years old) with diabetes in the National Health and Nutrition Survey from 1999 to 2010. The mortality rate was determined by the correlation with the national death index on December 31, 2019. The GPS was composed of the serum C-reactive protein and the albumin. The primary outcome was cardiovascular death and the secondary outcome was all-cause death. The Cox proportional risk model adjusted for demographic factors and traditional cardiovascular risk factors was used to analyze the cumulative risk of outcomes. RESULTS: Among 4956 diabetes patients with a median follow-up of 10.9 years, 601 cardiovascular deaths and 2187 all-cause deaths were recorded. After adequate model adjustment, compared with the low GPS group, the high GPS group (HR, 1.257 (1.007-1.570), P = 0.043) had a higher cardiovascular mortality. Compared with the low GPS group, the all-cause mortality of the high GPS group (HR, 1.394 (1.245-1.560), P < 0.001) was higher. The results of subgroup analyses were similar with that of the overall cohort. CONCLUSIONS: The inflammatory risk as defined by the GPS was closely related to the increased risk of cardiovascular and all-cause death in patients with diabetes. It may be a convenient and efficient clinical practical risk assessment tool for patients with diabetes.

Silybin Alleviated Hepatic Injury by Regulating Redox Balance, Inflammatory Response, and Mitochondrial Function in Weaned Piglets under Paraquat-Induced Oxidative Stress.

Silybin (Si) is the main element of silymarin isolated from the seeds of Silybum marianum L. Gaernt., which has superior antioxidant properties. However, the protective role of Si in maintaining liver health under oxidative stress remains ambiguous. This study aimed to investigate the underlying mechanism of the beneficial effect of dietary Si against hepatic oxidative injury induced by paraquat (PQ) in weaned piglets. A total of 24 piglets were randomly allocated to four treatments with six replicates per treatment and 1 piglet per replicate: the control group; Si group; PQ group; and Si + PQ group. Piglets in the control group and PQ group were given a basal diet, while piglets in the Si and Si + PQ groups were given a Si-supplemented diet. On the 18th day, the pigs in the PQ treatment group received an intraperitoneal injection of PQ, and the others were intraperitoneally injected with the same volume of saline. All piglets were sacrificed on day 21 for plasma and liver sample collection. The results showed that dietary Si supplementation mitigated PQ-induced liver damage, as proven by the reduction in liver pathological changes and plasma activity of alanine transaminase and aspartate transaminase. Si also improved superoxide dismutase and glutathione peroxidase activities and total antioxidant capacity, as well as decreased malondialdehyde and hydrogen peroxide concentration in the liver, which were closely related to the activation of the nuclear factor-erythroid 2-related factor 2 signaling pathway. Meanwhile, Si reduced tumor necrosis factor-α and interleukin-8 production and their transcript levels as well as abrogated the overactivation of nuclear factor-κB induced by PQ. Importantly, Si improved mitochondrial function by maintaining mitochondrial energetics and mitochondrial dynamics, which was indicated by the elevated activity of mitochondrial complexes I and V and adenosine triphosphate content, decreased expression of dynamin 1 protein, and increased expression of mitofusin 2 protein. Moreover, Si inhibited excessive hepatic apoptosis by regulating the B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated-X-protein signaling pathway. Taken together, these results indicated that Si potentially mitigated PQ-induced hepatic oxidative insults by improving antioxidant capacity and mitochondrial function and inhibiting inflammation and cell apoptosis in weaned piglets.

Birth Outcomes of Pregnant Women Infected with COVID-19 in Highland Areas of China from 2020 to 2022: A Retrospective Analysis.

Purpose: To explore the effect of coronavirus disease 2019 (COVID-19) infection on neonates in plateau regions. Methods: Cases of newborns born to pregnant women infected with COVID-19 who received prenatal care or treatment at the Women and Children's Hospital of the Tibet Autonomous Region and the Lhasa People's Hospital between January 2020 and December 2022 (infected group) and newborns born to healthy pregnant women (non-infected group) who were included by age, underlying disease and length of hospital stay were retrospectively collected. According to the inclusion and exclusion criteria, 381 patients in the infected group and 314 patients in the non-infected group were included in the study. Results: The results of multivariate analysis showed that admission to the neonatal intensive care unit (OR = 3.342, 95% CI = 1.564-6.764), shortness of breath (OR = 2.853, 95% CI = 1.789-3.154), irregular breathing (OR = 2.465, 95% CI = 1.879-4.112) and neonatal jaundice (OR = 2.324, 95% CI = 1.989-2.445) were the factors influencing the low Apgar scores of neonates in the infected group (all P < 0.05). Conclusion: Neonates born to pregnant women infected with COVID-19 had lower Apgar scores and higher incidences of complications, such as shortness of breath, groaning, irregular breathing and neonatal jaundice, than newborns born to pregnant women not infected with COVID-19.

Evaluation of the Prognostic Role of Neutrophil-Lymphocyte Ratio, C-Reactive Protein-Albumin Ratio, and Platelet-Lymphocyte Ratio in Patients with the Co-Presentation of Coronary Artery Disease and COVID-19.

Aim: The purpose of this study was to investigate the role of neutrophil-lymphocyte ratio (NLR), C-reactive protein-albumin ratio (CAR), and platelet-lymphocyte ratio (PLR) in the prognosis of patients with coronary artery disease (CAD) complicated with coronavirus disease 2019 (COVID-19). Methods: This study included 265 patients. A receiver operating characteristic (ROC) curve analysis was performed to preliminarily evaluate the predictive ability of NLR, CAR, and PLR for all-cause death. The primary outcome was all-cause death during hospitalization, while the secondary outcomes were cardiovascular death and respiratory failure death. The Cox proportional hazard model with adjusted covariates was used to analyze the cumulative risk of outcomes. We also conducted subgroup analyses based on the acute and chronic characteristics of CAD. Propensity score matching (PSM) was used to further evaluate the robustness of the primary outcome. Results: The ROC curve analysis results showed that the area under curve (AUC) values were 0.686 (95% CI 0.592-0.781, P<0.001) for NLR, 0.749 (95% CI 0.667-0.832, P<0.001) for CAR, and 0.571 (95% CI 0.455-0.687, P=0.232) for PLR. The Cox proportional hazard model showed that trends in NLR and PLR did not affect the risk of all-cause death (P=0.096 and P=0.544 for trend, respectively), but a higher CAR level corresponded to a higher risk of all-cause death (P<0.001 for trend). Similarly, The trends of NLR and PLR did not affect the risk of cardiovascular death and respiratory failure death, while a higher CAR level corresponded to a higher risk of cardiovascular death and respiratory failure death. The results of subgroup analyses and PSM were consistent with the total cohort. Conclusion: In patients with CAD complicated with COVID-19, a higher CAR level corresponded to a higher risk of all-cause death, cardiovascular death, and respiratory failure death, while trends in NLR and PLR did not.

The impact of urinary albumin-creatinine ratio and glomerular filtration rate on long-term mortality in patients with heart failure: The National Health and Nutrition Examination Survey 1999-2018.

BACKGROUND AND AIMS: The urinary albumin‒creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are important markers of renal dysfunction, but few studies have simultaneously examined their impact on long-term mortality in patients with heart failure (HF). METHODS AND RESULTS: This study included patients with HF from the National Health and Nutrition Survey from 1999 to 2018. The fully adjusted Cox proportional risk model was adopted, and propensity score matching (PSM) was also used for risk adjustment. Among 988 patients, a median follow-up of 7.75 years was recorded. A higher UACR corresponded to a higher risk of cardiovascular death (P < 0.001 for trend). No statistically significant difference was found in the trend of eGFR risk stratification on the risk of cardiovascular death (P = 0.09 for trend). After PSM, the results showed that when grouped by UACR, the high-risk group had a higher risk of cardiovascular death regardless of a cutoff value of 30 or 300 mg/g (all P < 0.05). When grouped by eGFR, regardless of a cutoff value of 45 or 30 mL/min/1.73 m2, compared to the low-risk group, the high-risk group did not have a statistically significant increase in cardiovascular death (P = 0.086 and P = 0.093, respectively). The subgroup analysis of the main outcome showed an interaction between the UACR and eGFR (P = 0.044). CONCLUSIONS: Both the UACR and eGFR are markers for predicting the progression of HF, but the UACR may be a more important indicator than the eGFR, and they synergistically and complementarily reflect the long-term cardiovascular risk of HF patients.

Prevalence of Pelvic Floor Disorders in Parous Women from the Tibet Autonomous Region: A Cross-Sectional Study.

Purpose: Pelvic floor disorder (PFD) seriously affects the everyday life of women. This cross-sectional study aimed to evaluate the prevalence and risk factors for postpartum PFD in women living in the Tibet Autonomous Region (TAR). Methods: Parous women who attended the outpatient gynaecology clinic at our hospital between June 2022 and August 2022 were screened in this study. The demographic and clinical data of these women were collected. Their pelvic floor functions were evaluated via a pelvic organ prolapse (POP) quantification examination, the Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) and the Overactive Bladder Symptom Score (OABSS). Results: A total of 201 women were included in this study, of whom 81.09% (163/201) were Tibetan. Twenty-seven women (13.43%) were diagnosed with POP stage ≥2 and 27 women (13.43%) with an OABSS score ≥3. The median PFDI-20 total score was 4.17 (range 0-43.75). Han women (n = 38) in the TAR had much lower PFDI-20 total scores, compared with Tibetan women (n = 163) (p < 0.05). The results of the multiple linear regression models showed that the PFDI-20 scores obtained from women living in the TAR were closely related to parity, history of heavy weight lifting, age, history of instrumental deliveries, ethnicity and number of caesarean sections. Conclusion: Pelvic floor disorder is common among parous women living in the TAR. Ethnicity, parity, history of heavy weight lifting, age, history of instrumental deliveries and number of caesarean sections are the factors closely related to the PFDI-20 scores.

Rapid detection of Mycobacterium tuberculosis in sputum using CRISPR-Cas12b combined with cross-priming amplification in a single reaction.

IMPORTANCE: In this study, we successfully established a new One-Pot method, named TB One-Pot, for detecting Mtb in sputum by combining CRISPR-cas12b-mediated trans-cleavage with cross-priming amplification (CPA). Our study evaluated the diagnostic performance of TB One-Pot in clinical sputum samples for tuberculosis. The findings provide evidence for the potential of TB One-Pot as a diagnostic tool for tuberculosis.

Spatial transcriptomics defines injury-specific microenvironments in the adult mouse kidney and novel cellular interactions in regeneration and disease.

Kidney injury disrupts the intricate renal architecture and triggers limited regeneration, and injury-invoked inflammation and fibrosis. Deciphering molecular pathways and cellular interactions driving these processes is challenging due to the complex renal architecture. Here, we applied single cell spatial transcriptomics to examine ischemia-reperfusion injury in the mouse kidney. Spatial transcriptomics revealed injury-specific and spatially-dependent gene expression patterns in distinct cellular microenvironments within the kidney and predicted Clcf1-Crfl1 in a molecular interplay between persistently injured proximal tubule cells and neighboring fibroblasts. Immune cell types play a critical role in organ repair. Spatial analysis revealed cellular microenvironments resembling early tertiary lymphoid structures and identified associated molecular pathways. Collectively, this study supports a focus on molecular interactions in cellular microenvironments to enhance understanding of injury, repair and disease.

The Effects of Dietary Silybin Supplementation on the Growth Performance and Regulation of Intestinal Oxidative Injury and Microflora Dysbiosis in Weaned Piglets.

Oxidative stress is the major incentive for intestinal dysfunction in weaned piglets, which usually leads to growth retardation or even death. Silybin has caught extensive attention due to its antioxidant properties. Herein, we investigated the effect of dietary silybin supplementation on growth performance and determined its protective effect on paraquat (PQ)-induced intestinal oxidative damage and microflora dysbiosis in weaned piglets. In trial 1, a total of one hundred twenty healthy weaned piglets were randomly assigned into five treatments with six replicate pens per treatment and four piglets per pen, where they were fed basal diets supplemented with silybin at 0, 50, 100, 200, or 400 mg/kg for 42 days. In trial 2, a total of 24 piglets were randomly allocated to two dietary treatments with 12 replicates per treatment and 1 piglet per pen: a basal diet or adding 400 mg/kg silybin to a basal diet. One-half piglets in each treatment were given an intraperitoneal injection of paraquat (4 mg/kg of body weight) or sterile saline on day 18. All piglets were euthanized on day 21 for sample collection. The results showed that dietary supplementation with 400 mg/kg silybin resulted in a lower feed conversion ratio, diarrhea incidence, and greater antioxidant capacity in weaned piglets. Dietary silybin enhanced intestinal antioxidant capacity and mitochondrial function in oxidative stress piglets induced by PQ. Silybin inhibited mitochondria-associated endogenous apoptotic procedures and then improved the intestinal barrier function and morphology of PQ-challenged piglets. Moreover, silybin improved intestinal microbiota dysbiosis induced by the PQ challenge by enriching short-chain fatty-acid-producing bacteria, which augmented the production of acetate and propionate. Collectively, these findings indicated that dietary silybin supplementation linearly decreased feed conversion ratio and reduced diarrhea incidence in normal conditions, and effectively alleviated oxidative stress-induced mitochondrial dysfunction, intestinal damage, and microflora dysbiosis in weaned piglets.

Potentiation and Mechanism of Berberine as an Antibiotic Adjuvant Against Multidrug-Resistant Bacteria.

The growing global apprehension towards multi-drug resistant (MDR) bacteria necessitates the development of innovative strategies to combat these infections. Berberine (BER), an isoquinoline quaternary alkaloid derived from various medicinal plants, has surfaced as a promising antibiotic adjuvant due to its ability to enhance the effectiveness of conventional antibiotics against drug-resistant bacterial strains. Here, we overview the augmenting properties and mechanisms of BER as an adjunctive antibiotic against MDR bacteria. BER has been observed to exhibit synergistic effects when co-administered with a range of antibiotics, including ß-lactams, quinolones, aminoglycosides, tetracyclines, macrolides, lincosamides and fusidic acid. The adjunctive properties of BER led to an increase in antimicrobial effectiveness for these antibiotics against the corresponding bacteria, a decrease in minimal inhibitory concentrations, and even the reversal from resistance to susceptibility sometimes. The potential mechanisms responsible for these effects included the inhibition of antibiotic efflux, the disruption of biofilm formation, the modulation of host immune responses, and the restoration of gut microbiota homeostasis. In brief, BER demonstrated significant potential as an antibiotic adjuvant against MDR bacteria and is a promising candidate for combination therapy. Further research is necessary to fully elucidate its mechanism of action and address the challenges associated with its clinical application.

Analysis of genetic and chemical variability of five Curcuma species based on DNA barcoding and HPLC fingerprints.

The rhizomes of Curcuma species have a long medicinal history in Asia. In China, Curcuma species mainly be utilized to make pharmaceutical products, including C. phaecocaulis, C. aromatica, C. wenyujin, C. kwangsiensis and C. longa. In this study, twenty-four samples were selected to study the genetic and chemical variability among five Curcuma species. The ITS2 and trnK intron gene fragment were used to identify the five Curcuma species, the differences in chemical composition were computed using the Euclidean distance based on the data of HPLC characteristic peak areas and the content of six key components, and agronomic characteristics were analyzed including morphological and volatile oil characteristics. The ITS2 and trnK intron gene fragment could distinguish the five Curcuma species clearly. The genetic distance between Curcuma species ranged from 0.0085 to 0.0767 based on the data of ITS2 gene sequences with 32 variation sites, and the genetic distance between Curcuma species ranged from 0.0003 to 0.0194 based on the data of trnK intron gene sequences with 39 variation sites. Five Curcuma species showed otherness chemical composition characteristics, with the Euclidean distance ranging from 3.373 to 6.998. The C. longa showed the biggest variation compared with other species, with the Euclidean distance above 6.239. Among the samples of the original plants of Ezhu, the volatile oil yield of W1 was the highest, reached to 105.75 mL per single plant. Among all the samples, J6 showed the highest yield of volatile oil, reached to 149.42 mL per single plant. The results showed that chemical composition similarity of the medicinal plants was the primary proof for the selection of the original plants of the Curcuma medicinal materials. The genetic distance and chemical variability were important references for discovering new medicinal plant resources.

Developing a method to detect lipoarabinomannan in pleural fluid and assessing its diagnostic efficacy for tuberculous pleural effusion.

Objectives: The diagnosis of tuberculosis pleural effusion (TPE) remains challenging, traditional diagnostic tests have limited diagnostic efficacy. This study aimed to assess the diagnostic performance of pleural fluid (PF) lipoarabinomannan (LAM) in TPE. Methods: A diagnostic method for PF LAM (LAM-PF) was established using LEDBIO's AIMLAM kit. The diagnostic performance of LAM-PF was evaluated in 162 HIV-negative patients with suspected TPE. Results: The LAM-PF method established in this study exhibited good linearity and recovery rate, with a limit of detection (LOD) of 2.90 pg/mL. Using a cut-off value of 5.33 pg/mL, the sensitivity and specificity of LAM-PF in diagnosing TPE (n = 128) were 47.7% and 100.0%, respectively. The sensitivity in patients with probable TPE (n = 29) and definite TPE (n = 99) were 41.4% and 49.5%, respectively. LAM-PF displayed a significantly higher sensitivity in probable TPE compared to other tuberculosis detection methods. Combined testing of adenosine deaminase (ADA)and LAM increased the detection sensitivity of TPE to 68.0%, and the area under the curve was 0.84 (0.77-0.89). Conclusion: This study successfully established a method for detecting LAM in PF, which exhibited favorable diagnostic performance for TPE, particularly in challenging cases of probable TPE. Combined detection of LAM and ADA in PF significantly improves TPE diagnostic efficiency.

SMYD3 induces sorafenib resistance by activating SMAD2/3-mediated epithelial-mesenchymal transition in hepatocellular carcinoma.

Drug resistance prominently hampers the effects of systemic therapy of sorafenib to hepatocellular carcinoma (HCC). Epigenetics have critical regulatory roles in drug resistance. However, the contributions of histone methylatransferase SET and MYND domain containing 3 (SMYD3) to sorafenib resistance in HCC remain largely unknown. Here, using our established sorafenib-resistant HCC cell and xenograft models, we found SMYD3 was markedly elevated in sorafenib-resistant tumors and cells. Functionally, loss- and gain-of-function studies showed that SMYD3 promoted the migration, invasion, metastasis and stemness of sorafenib-resistant HCC cells. Mechanistically, SMYD3 is required for SMAD2/3-mediated epithelial-mesenchymal transition (EMT) in sorafenib-resistant HCC cells by interacting with SMAD2/3 and epigenetically promoting the expression of SOX4, ZEB1, SNAIL1 and MMP9 genes. In summary, our data demonstrate that targeting SMYD3 is an effective approach to overcome sorafenib resistance in HCC.