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Tian-Xiang Chen,1 Bigyan Pudasaini,1 Jian Guo,2 Su-Gang Gong,1 Rong Jiang,1 Lan Wang,1 Qin-Hua Zhao,1 Wen-Hui Wu,1 Ping Yuan,1 Jin-Ming Liu1 1Department of Cardio-Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China; 2Department of Pulmonary Function Test, Shanghai Pulmonary Hospital, Tongji University, Shanghai, People’s Republic of China Background: Sex differences in chronic thromboembolic pulmonary hypertension (CTEPH) have been revealed in few studies. Although right heart catheterization (RHC) is the gold standard for clinical diagnosis and assessment of prognosis in pulmonary hypertension (PH), cardiopulmonary exercise testing (CPET) has been a more widely used assessment of functional capacity, disease severity, prognosis, and treatment response in PH. We hypothesized that the “sex-specific” CPET indices could estimate the severity of inoperable CTEPH.Methods: Data were retrieved for 33 male (age, mean ± standard deviation [SD] =62.5±13.4 years) and 40 female (age, mean ± SD =56.3±11.8 years) patients with stable CTEPH who underwent both RHC and CPET at Shanghai Pulmonary Hospital from February 2010 to February 2016. Univariate and forward/backward multiple stepwise regression analysis was performed to assess the predictive value of CPET indices to hemodynamic parameters. Event-free survival was estimated using the Kaplan–Meier method and analyzed with the log-rank test. Cox proportional hazards models were performed to determine the independent event-free survival predictors.Results: Numerous CPET parameters were different between male and female patients with CTEPH and the control group. There were no significant differences in both clinical variables and RHC parameters between male and female patients with CTEPH. O2 pulse, workload, minute ventilation (VE), and end-tidal partial pressure of O2 (PETO2) at anaerobic threshold, as well as peak O2 pulse, workload, VE, and nadir VE/CO2 were significantly higher in male patients than in female patients (P

Lan Wang,1,* Yuan-Zhe Jin,2,* Qin-Hua Zhao,1 Rong Jiang,1 Wen-hui Wu,1 Su-Gang Gong,1 Jing He,1 Jin-Ming Liu,1 Zhi-Cheng Jing1,3 1Department of Pulmonary Circulation, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; 2Department of Cardiology, The Fourth Affiliated Hospital of China Medical University, Liaoning, China; 3Thrombosis and Vascular Medicine Center, State Key Laboratory of Cardiovascular Disease, FuWai Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China *These authors contributed equally to this work Abstract: Studies have shown that vasodilators such as iloprost can be useful for treating pulmonary hypertension (PH). However, in patients with COPD, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange. The efficacy and safety of iloprost inhalation was assessed in 67 patients with PH associated with COPD (COPD-PH), diagnosed by right heart catheterization. Of these, 37 patients had severe PH (mean pulmonary arterial pressure [mPAP] >35 mmHg or mPAP 25–35 mmHg with low cardiac index [

Background and Aims: This study aimed to evaluate the hemodynamic alterations and right heart remodeling dynamics in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) undergoing treatment with balloon pulmonary angioplasty (BPA)., Methods: This retrospective cohort study involved a cohort of 31 patients with a confirmed diagnosis of CTEPH. Comprehensive clinical evaluations were systematically performed before BPA, and at 3 and 6 months following the procedure., Results: Significant clinical progress was evidenced by the uplift in the percentage of patients achieving WHO-FC II, escalating from 19.35% at baseline to 51.61% at 6 months after BPA ( p  = 0.003). NT-proBNP levels significantly dropped from a median of 614.6 to 69.9 pg/mL ( p  < 0.001). Hemodynamic assessments showed significant decreases in mean PAP from 45.53 ± 11.19 to 22.56 ± 5.81 mmHg ( p  < 0.001) and PVR from 8.33 to 2.86 WU ( p  < 0.001). Echocardiographic analysis revealed substantial reductions in the right atrial area (RAA, from 20.29 ± 7.55 to 16.79 ± 4.82 cm 2 , p  < 0.001) and right ventricular internal diameter (RVID, from 4.13 ± 0.79 to 3.68 ± 0.59 cm, p  = 0.001) at the 3-month interval post-BPA. These improvements were sustained or even enhanced by the 6-month mark, with RAA and RVID further diminishing (to 14.46 ± 3.78 cm 2 and 3.29 ± 0.54 cm, respectively; both p  < 0.01). The TAPSE/PASP ratios showed progressive improvement from baseline (0.32 ± 0.13) to 3 months (0.42 ± 0.13) and continued to improve at 6 months following BPA (0.50 ± 0.11, p  = 0.04 compared to 3 months post-BPA)., Conclusion: BPA has significantly ameliorated clinical conditions, hemodynamic profiles, and initiated a continued reversal in right heart remodeling in patients with CTEPH., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Objective: Pulmonary hypertension is a severe complication of bronchiectasis, characterized by elevated pulmonary vascular resistance (PVR) and subsequent right heart failure. The association between PVR and mortality in bronchiectasis-associated pulmonary hypertension has not been investigated previously., Methods: In the present study, a retrospective analysis was conducted on 139 consecutive patients diagnosed with bronchiectasis-associated pulmonary hypertension based on right heart catheterization, enrolled between January 2010 and June 2023. Baseline clinical characteristics and hemodynamic assessment were analyzed. The survival time for each patient was calculated in months from the date of diagnosis until the date of death or, if the patient was still alive, until their last visit., Results: Patients with bronchiectasis-associated pulmonary hypertension exhibited estimated survival rates of 89.5, 70, and 52.9 at 1-year, 3-year, and 5-year intervals respectively, with a median survival time of 67 months. Multivariable Cox regression analysis revealed that increased age [(adjusted hazard ratio per year 1.042, 95% confidence interval (CI) 1.008-1.076, P  = 0.015] and elevated PVR (adjusted HR per 1 Wood Units 1.115, 95% CI 1.015-1.224, P  = 0.023) were associated with an increased risk of all-cause mortality. In contrast, higher BMI was associated with a decreased risk of all-cause death (adjusted hazard ratio per 1 kg/m 2 0.915, 95% CI 0.856-0.979, P  = 0.009). Receiver-operating characteristic analyses identified a cutoff value for PVR at 4 Wood Units as predictive for all-cause death within 3 years [area under the curve (AUC) = 0.624; specificity= 87.5%; sensitivity= 35.8%; P  < 0.05]. Patients with a PVR greater than 4 Wood Units had a significantly higher risk of all-cause death compared with those with 4 Wood Units or less (adjusted hazard ratio 2.392; 95% CI 1.316-4.349; P  = 0.019). Notably, there were no significant differences in age, sex, BMI, WHO functional class, 6-min walk distance, and NT-proBNP levels at baseline between patients categorized as having 4 Wood Units or less or greater than 4 Wood Units for PVR., Conclusion: Based on these data, PVR could serve as a discriminative marker for distinguishing between nonsevere pulmonary hypertension (PVR ≤ 4 Wood Units) and severe pulmonary hypertension (PVR > 4 Wood Units). The utilization of a PVR cutoff value of 4.0 Wood Units provides enhanced prognostic capabilities for predicting mortality., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Sleep-disordered breathing (SDB) and nocturnal hypoxemia were known to be present in patients with chronic thromboembolic pulmonary hypertension (CTEPH), but the difference between SDB and nocturnal hypoxemia in patients who have chronic thromboembolic pulmonary disease (CTEPD) with or without pulmonary hypertension (PH) at rest remains unknown., Methods: Patients who had CTEPH (n = 80) or CTEPD without PH (n = 40) and who had undergone sleep studies from July 2020 to October 2022 at Shanghai Pulmonary Hospital were enrolled. Nocturnal mean SpO 2 (Mean SpO 2 ) <90% was defined as nocturnal hypoxemia, and the percentage of time with a saturation below 90% (T90%) exceeding 10% was used to evaluate the severity of nocturnal hypoxemia. Logistic and linear regression analyses were performed to investigate the difference and potential predictor of SDB or nocturnal hypoxemia between CTEPH and CTEPD without PH., Results: SDB was similarly prevalent in CTEPH and CTEPD without PH (P = 0.104), both characterised by obstructive sleep apnoea (OSA). Twenty-two patients with CTEPH were diagnosed with nocturnal hypoxemia, whereas only three were diagnosed with CTEPD without PH (P = 0.021). T90% was positively associated with mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance in patients with CTEPH and CTEPD without PH (P < 0.001); T90% was also negatively related to cardiac output in these patients. Single-breath carbon monoxide diffusing capacity, sex and mPAP were all correlated with nocturnal hypoxemia in CTEPH and CTEPD without PH (all P < 0.05)., Conclusion: Nocturnal hypoxemia was worse in CTEPD with PH; T90%, but not SDB, was independently correlated with the hemodynamics in CTEPD with or without PH., (© 2024 The Authors. Internal Medicine Journal published by John Wiley & Sons Australia, Ltd on behalf of Royal Australasian College of Physicians.)

Objective: To investigate the clinical efficacy of arthroscopic measurement of intra-articular graft length in the application of total internal reconstruction of the anterior cruciate ligament(ACL)., Methods: The 60 patients with ACL injury treated between January 2020 and January 2022 were retrospectively analyzed. There were 37 males and 23 females, aged from 22 to 44 years. According to the different surgical methods, they were divided into two groups:conventional surgery group (conventional group) and pull-line measurement group (measurement group), with 30 cases in each group. In the conventional group, there were 20 males and 10 females, with an average age of (30.00±3.95) years old;the body mass index (BMI) was (22.58±1.41) kg·m -2 ;there were 9 cases on the left side and 21 cases on the right side;the time from injury to operation was (3. 00±1.35) days. In the measurement group, there were 17 males and 13 females, with an average of(32.00±4.29) years;BMI was (23.29±1.39) kg·m -2 ;there were 12 cases on the left side and 18 cases on the right side;the time from injury to operation was (3.00±1.27) days. The clinical data of the patients before surgery, 6 months after surgery and 12 months after surgery were collected and recorded. The clinical efficacy of the two methods was compared in terms of postoperative VAS, KOOS, Lysholm score, IKDC score, knee stability (Lachman test, anterior drawer test and axial shift test), the degree of widening of bone tunnel diameter measured by CT at different stages of the postoperative period and MRI scoring system., Results: At 12 months after surgery, the VAS of the measurement group was lower than that of the conventional group( P <0.001). At 12 months after surgery, KOOS scores in the measurement group were higher than those in the conventional group, and there were statistically significant differences in all scores except symptom scores ( P <0.05). Six months after operation, Lysholm total score and IKDC total score in the measurement group were higher than those in the conventional group, and the difference was statistically significant ( P <0.05). At 12 months after surgery, knee stability tests were performed, and the differences between the Lachman test, anterior drawer test and axial shift test measurement group and the conventional group were not statistically significant ( P >0.05). However, overall knee instability analysis showed that the knee stability of the measurement group was better than that of the control group, and the difference between the groups was statistically significant ( P =0.038). The imaging assessment of patients in both groups at 6 months after surgery showed that the widening of tendon tunnel diameter in both femur and tibia was reduced in the measurement group compared with the conventional group after surgery, and the difference was statistically significant( P <0.05);MRI scores were higher in all patients in the measurement group those in the conventional group, at 6 months and 12 months agter surgery( P <0.05)., Conclusion: Arthroscopic measurement of intra-articular cavity graft length in total internal technique for ACL reconstruction, high tendon utilization, good stability, the knee joint function has recovered satisfactorily within one year, and the therapeutic effect is affirmed.

Background: This study aimed to employ plasma proteomics to investigate the molecular changes, pathway alterations, and potential novel biochemical markers associated with balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH)., Methods: Pre- and post-BPA plasma samples from five CTEPH patients in the PRACTICE study were analyzed to identify differentially expressed proteins. Proteomic and bioinformatics analyses were conducted, and the identified proteins were further validated using ELISA assays in a separate cohort of the same study. Correlation and multivariate regression analyses were performed to investigate the associations between these differentially expressed proteins and clinical parameters., Results: Significantly higher serum levels of asialoglycoprotein receptor 2 (ASGR2) were detected in 5 CTEPH patients compared to those in healthy individuals but decreased significantly after successful BPA procedures. The decrease in serum levels of ASGR2 after the completion of BPA procedures was further validated in a separate cohort of 48 patients with CTEPH [0.70 (0.51, 1.11) ng/mL vs. 0.38 (0.27, 0.59) ng/mL, P < 0.001]. Significant associations were found between the pre-BPA ASGR2 level and clinical parameters, including neutrophil percentage (R = 0.285, P < 0.05), platelet (PLT) count (R = 0.386, P < 0.05), and high-density lipoprotein cholesterol (HDL-C) before BPA (R = -0.285, P < 0.05). Significant associations were detected between post-BPA serum ASGR2 levels and lymphocyte percentage (LYM%) (R = 0.306, P < 0.05), neutrophil-to-lymphocyte ratio (R = -0.294, P < 0.05), and pulmonary vascular resistance after BPA (R = -0.35, P < 0.05). Multivariate stepwise regression analysis revealed that pre-BPA ASGR2 levels were associated with HDL-C and PLT count (both P < 0.001), while post-BPA ASGR2 levels were associated with LYM% ( P < 0.05)., Conclusion: Serum levels of ASGR2 may be a biomarker for the effectiveness of BPA treatment in CTEPH patients. The pre-BPA serum level of ASGR2 in CTEPH patients was associated with HDL-C and the PLT count. The post-BPA serum level of ASGR2 was correlated with the LYM%, which may reflect aspects of immune and inflammatory status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Wang, Zhao, Xu, Hu, Gong, He, Qiu, Luo, Xu, Li, Li, Wang, Shi, Zhao and Jiang.)

Cell therapy has been explored as a new regenerative treatment for osteoarthritis in the field of regenerative medicine. However, the efficacy of stem cell transplantation from different sources for the treatment of knee osteoarthritis (KOA) remains controversial. This study integrates and evaluates the previously published data of stem cell transplantation for KOA to explore the curative effect of different stem cells. We conducted a meta-analysis of randomized controlled trials on stem cell therapy for KOA. Measures of efficacy included Visual Analog Scale (VAS), Lequesne index, Lysholm Knee Scoring Scale (LKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Joint injury was evaluated through the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. We analyzed 16 studies involving 875 KOA patients. The stem cell treatment showed significant VAS reduction from the third month onwards. Subgroup analysis suggested the most significant pain relief at different postoperative months came from adipose-derived and umbilical cord-derived stem cells. Autologous adipose tissue resulted in better pain alleviation compared with allogenic. However, autologous bone marrow stem cells did not show increased pain relief over allogeneic ones. Combination therapy (HA and/or PRP) showed no effect. Autologous adipose-derived stem cells demonstrate the most effective recovery of knee joint function. In WORMS assessment, there was no significant difference between the stem cell group and control. Stem cell transplantation proved safe and effective for KOA treatment. Different sources stem cells have a good effect on alleviating knee joint pain, restoring knee joint function, and minimizing patient trauma., (© 2023 Orthopaedic Research Society.)

This study aimed to evaluate the effectiveness and safety of an oral sequential triple combination therapy with selexipag after dual combination therapy with endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5I)/riociguat in pulmonary arterial hypertension (PAH) patients. A total of 192 PAH patients from 10 centers had received oral sequential selexipag therapy after being on dual-combination therapy with ERA and PDE5i/riociguat for a minimum of 3 months. Clinical data were collected at baseline and after 6 months of treatment. The study analyzed the event-free survival at 6 months and all-cause death over 2 years. At baseline, the distribution of patients among the risk groups was as follows: 22 in the low-risk group, 35 in the intermediate-low-risk group, 91 in the intermediate-high-risk group, and 44 in the high-risk group. After 6 months of treatment, the oral sequential triple combination therapy resulted in reduced NT-proBNP levels (media from 1604 to 678 pg/mL), a decline in the percentage of WHO-FC III/IV (from 79.2% to 60.4%), an increased in the 6MWD (from 325 ± 147 to 378 ± 143 m) and a rise in the percentage of patients with three low-risk criteria (from 5.7% to 13.5%). Among the low-risk group, there was an improvement in the right heart remodeling, marked by a decrease in right atrium area and eccentricity index. The intermediate-low-risk group exhibited significant enhancements in WHO-FC and tricuspid annular plane systolic excursion. For those in the intermediate-high and high-risk groups, there were marked improvements in activity tolerance, as reflected by WHO-FC and 6MWD. The event-free survival rate at 6 months stood at 88%. Over the long-term follow-up, the survival rates at 1 and 2 years were 86.5% and 86.0%, respectively. In conclusion, the oral sequential triple combination therapy enhanced both exercise capacity and cardiac remodeling across PAH patients of different risk stratifications., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background: To collect data from randomized controlled trials (RCTs) to evaluate the effects of enhanced recovery after surgery on postoperative recovery of elderly patients who underwent hip or knee arthroplasty., Methods: The search was limited to studies published prior to January 1, 2023, in the electronic databases of Cochrane, Embase, Ovid Medline, Proquest, PubMed, Scopus, Web of Science, and Chinese databases, including China National Knowledge Internet (CNKI) and SinoMed. All relevant data were collected from the studies that met the inclusion criteria. The outcome variables were recovery of joint function and incidence of complications. STATA software (version 14.0) was used for the meta-analysis., Results: A total of 44 published studies met the inclusion criteria. The cumulative data included 2203 cases receiving enhanced recovery after surgery (ERAS), and 2173 cases receiving traditional recovery after surgery (non-ERAS). The meta-analysis showed that the VAS score was significantly lower in the ERAS group than in the non-ERAS group (P < .01), and there were fewer incidences of complications in the ERAS group than in the control group (P < .01)., Conclusions: ERAS significantly reduced pain and the incidence of complications in elderly patients who had undergone joint replacement surgery., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Objectives : Peripherally inserted central catheter (PICC) placement plays an important role in clinical practice. This study aimed to provide an equation for the proper estimation of catheter length in cases of PICC placement without imaging guidance in relation to patient height, weight, sex, and age. Materials and Methods : For 1137 PICC placement cases in both arm veins of 954 patients at a single center, the elbow crease to the cavoatrial junction length (ECL) was calculated as follows: ECL = (PICC length) + (distance from the elbow crease to the puncture site). We analyzed the relationship between ECL and patient characteristics and suggested a new equation for ECL based on height, weight, sex, and age. Results : The average ECL was 48.0 ± 2.4 cm in the right side and 51.0 ± 3.0 cm in the left side. ECL in the right arm was significantly correlated with patient height, sex, and age, whereas the ECL in the left arm was additionally significantly correlated with patient weight. The ECL (cm) prediction model was as follows: right ECL = 26.32 + 1.33 × (female = 1, male = 2) - 0.02 × age (years) + 0.13 × height (cm); left ECL = 22.09 + 1.28 × (female = 1, male = 2) + 0.02 × age (years) + 0.14 × height (cm) + 0.042 × weight (kg). Conclusions : The appropriate PICC length was predicted based on the patient's height, weight, sex, and age. The equations in our study can help predict the optimal catheter length and can be automatically calculated using computerized patient information for bedside procedures in PICC.

Craniosynostosis is a common yet complex birth defect, characterized by premature fusion of the cranial sutures that can be syndromic or nonsyndromic. With over 180 syndromic associations, reaching genetic diagnoses and understanding variations in underlying cellular mechanisms remains a challenge. Variants of FGFR2 are highly associated with craniosynostosis and warrant further investigation. Using the missense mutation FGFR2 W290R , an effective mouse model of Crouzon syndrome, craniofacial features were analyzed using geometric morphometrics across developmental time (E10.5-adulthood, n = 665 total). Given the interrelationship between the cranial vault and basicranium in craniosynostosis patients, the basicranium and synchondroses were analyzed in perinates. Embryonic time points showed minimal significant shape differences. However, hetero- and homozygous mutant perinates and adults showed significant differences in shape and size of the cranial vault, face, and basicranium, which were associated with cranial doming and shortening of the basicranium and skull. Although there were also significant shape and size differences associated with the basicranial bones and clear reductions in basicranial ossification in cleared whole-mount samples, there were no significant alterations in chondrocyte cell shape, size, or orientation along the spheno-occipital synchondrosis. Finally, shape differences in the cranial vault and basicranium were interrelated at perinatal stages. These results point toward the possibility that facial shape phenotypes in craniosynostosis may result in part from pleiotropic effects of the causative mutations rather than only from the secondary consequences of the sutural defects, indicating a novel direction of research that may shed light on the etiology of the broad changes in craniofacial morphology observed in craniosynostosis syndromes., (© 2024 The Authors. The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

The transportation of dissolved sulfate (SO 4 2- ) to the ocean via river systems plays a critical role in the global sulfur cycle. However, the increasing anthropogenic input has made it challenging to quantify the various pristine contributions accurately. The riverine sulfur and oxygen isotopes of sulfates (δ 34 S SO4 and δ 18 O SO4 ) and the advantages of the Markov-Chain Monte Carlo model were used to distinguish the anthropogenic input in Fenhe River, a tributary of the Yellow River. The SO 4 2- concentrations and δ 34 S SO4 and δ 18 O SO4 values of the mainstream river were normally distributed with minor seasonal variations (P > 0.05). However, the upstream riverine SO 4 2- concentrations were significantly altered by the water diversion from the Yellow River. The midstream and downstream sections exhibited a continuous increase in the riverine SO 4 2- concentration and δ 34 S SO4 and δ 18 O SO4 values during both seasons. The coal mining drainage significantly impacted the tributaries near coal mining activities, and chemical fertilizers and sewage contributed more sulfate in the midstream and downstream sections. The yearly sulfate flux of the Fenhe River accounted for 4.2% of that of Yellow River, among which over 60% was from anthropogenic sources. The average δ 34 S SO4 and δ 18 O SO4 values had elevated to 11.0‰ and 6.0‰, respectively, due to the extensive input of anthropogenic sulfate. Our findings confirm the utility of δ 34 S SO4 and δ 18 O SO4 for tracing anthropogenic input and underscore its impacts on river systems and the global sulfur cycle., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To investigate the antimicrobial activity of a novel commensal strain of Streptococcus salivarius, LAB813, against Streptococcus mutans biofilms., Methods: The inhibitory activity of LAB813 towards S. mutans was tested using mono-, dual-, and multi-species cariogenic biofilms formed on three types of orthodontic appliances (metal, ceramic, aligner). The activity of the commercially available probiotic, BLIS M18™ was used as control., Results: LAB813 significantly inhibited S. mutans biofilms with cell killing approximating 99% for all materials. LAB813 showed effectiveness at inhibiting S. mutans in more complex multi-species biofilms with cell killing approximating 90% for all three materials. When comparing the killing kinetics of the probiotics, LAB813 had a faster rate of killing biofilms than M18. Experiments conducted with cell-free culture supernatant confirmed the presence of an inhibitory substance of proteinaceous nature. The addition of xylitol, a common sugar substitute used for human consumption, potentiated the inhibitory effects of LAB813 against S. mutans embedded in a more complex fungal-bacterial biofilm., Conclusions: LAB813 possesses strong antimicrobial activity, potent anti-biofilm properties, and enhanced antimicrobial activity in the presence of xylitol. The identification and characterization of strain LAB813 exhibiting antimicrobial activity towards S. mutans hold exciting promise for this novel strain to be developed as an oral probiotic for use in the prevention of dental caries., Competing Interests: Declaration of Competing Interest The authors declare that they have no financial or non-financial interests to disclose., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Persisters are a small fraction of growth-arrested phenotypic variants that can survive lethal concentrations of antibiotics but are able to resume growth once antibiotics are stopped. Their formation can be a stochastic process or one triggered by environmental cues. In the human pathogen Streptococcus mutans , the canonical peptide-based quorum-sensing system is an inducible DNA repair system that is pivotal for bacterial survival. Previous work has shown that the CSP-signaling peptide is a stress-signaling alarmone that promotes the formation of stress-induced persisters. In this study, we exposed S. mutans to the CSP pheromone to mimic DNA damage conditions and isolated the antibiotic persisters by treating the cultures with ofloxacin. A transcriptome analysis was then performed to evaluate the differential gene expression between the normal stationary-phase cells and the persisters. RNA sequencing revealed that triggered persistence was associated with the upregulation of genes related to several stress defense mechanisms, notably, multidrug efflux pumps, the arginine deaminase pathway, and the Opu/Opc system. In addition, we showed that inactivation of the VicK kinase of the YycFG essential two-component regulatory system abolished the formation of triggered persisters via the CSP pheromone. These data contribute to the understanding of the triggered persistence phenotype and may suggest new therapeutic strategies for treating persistent streptococcal infections.

Pulmonary fibrosis (PF) and pulmonary hypertension (PH) have common pathophysiological features, such as the significant remodeling of pulmonary parenchyma and vascular wall. There is no effective specific drug in clinical treatment for these two diseases, resulting in a worse prognosis and higher mortality. This study aimed to screen the common key genes and immune characteristics of PF and PH by means of bioinformatics to find new common therapeutic targets. Expression profiles are downloaded from the Gene Expression Database. Weighted gene co-expression network analysis is used to identify the co-expression modules related to PF and PH. We used the ClueGO software to enrich and analyze the common genes in PF and PH and obtained the protein-protein interaction (PPI) network. Then, the differential genes were screened out in another cohort of PF and PH, and the shared genes were crossed. Finally, RT-PCR verification and immune infiltration analysis were performed on the intersection genes. In the result, the positive correlation module with the highest correlation between PF and PH was determined, and it was found that lymphocyte activation is a common feature of the pathophysiology of PF and PH. Eight common characteristic genes ( ACTR2, COL5A2, COL6A3, CYSLTR1, IGF1, RSPO3, SCARNA17 and SEL1L ) were gained. Immune infiltration showed that compared with the control group, resting CD4 memory T cells were upregulated in PF and PH. Combining the results of crossing characteristic genes in ImmPort database and RT-PCR, the important gene IGF1 was obtained. Knocking down IGF1 could significantly reduce the proliferation and apoptosis resistance in pulmonary microvascular endothelial cells, pulmonary smooth muscle cells, and fibroblasts induced by hypoxia, platelet-derived growth factor-BB (PDGF-BB), and transforming growth factor-β1 (TGF-β1), respectively. Our work identified the common biomarkers of PF and PH and provided a new candidate gene for the potential therapeutic targets of PF and PH in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhao, Wang, Yan, Zhao, He, Jiang, Luo, Qiu, Miao, Gong, Yuan and Wu.)

Background: Idiopathic pulmonary hypertension (IPAH) is a rare and devastating disease often accompanied by persistent inflammation and immune responses. We aim to provide a reference atlas of neutrophils to facilitate a better understanding of cellular phenotypes and discovery of candidate genes., Methods: Peripheral neutrophils from naive patients with IPAH and matched controls were profiled. Whole-exon sequencing was performed to exclude known genetic mutations before establishing single-cell RNA sequencing. Marker genes were validated by flow cytometry and histology in a separate validation cohort., Results: Seurat clustering analysis revealed that the landscape of neutrophils encompassed 5 clusters, including 1 progenitor, 1 transition, and 3 functional clusters. The intercorrelated genes in patients with IPAH were mainly enriched in antigen processing presentation and natural killer cell mediated cytotoxicity. We identified and validated differentially upregulated genes, including MMP9 (matrix metallopeptidase 9), ISG15 (ISG15 ubiquitin-like modifier), and CXCL8 (C-X-C motif ligand 8). The positive proportions and fluorescence quantification of these genes were significantly increased in CD16 + neutrophils in patients with IPAH. The higher proportion of positive MMP9 neutrophils increased mortality risk after adjustment for age and sex. Patients with higher proportions of positive MMP9 neutrophils had worse survival, while the fraction of ISG15- or CXCL8-positive expression neutrophils failed to predict outcome., Conclusions: Our study yields a comprehensive dataset of the landscape of neutrophils in patients with IPAH. The predictive values of a neutrophil cluster characterized by higher MMP9 expression indicate a functional role for neutrophil-specific matrix metalloproteinases in the pathogenesis of pulmonary arterial hypertension., Competing Interests: Disclosures None of authors has any conflict of interest to declare regarding the content of this article.

Probiotics are living microorganisms that confer a health benefit on the host when administered in adequate amounts. Streptococcus salivarius , a commensal bacterium found in the oral cavity, has been shown to secrete antimicrobial peptides and can be used as probiotics. This study aimed to develop a delivery system for the probiotic LAB813, a novel S. salivarius strain first identified in the laboratory. Probiotics can be delivered and protected through the encapsulation of biomaterials such as polysaccharides. Their biocompatibility, biodegradability, user-friendliness, and ease of access make polysaccharides useful for encapsulating probiotics. Alginate (Alg) and chitosan (Ch) are naturally obtained polysaccharides and, hence, tested for LAB813 encapsulation. An extrusion method of encapsulation was performed to form Alg microcapsules (Alg-LAB813), some of which were coated with Ch (Alg-LAB813-Ch) to provide dual-layered protection. Inhibitory assays of the Alg-LAB813 and Alg-LAB813-Ch microcapsules were assayed against an indicator strain. Alg-LAB813-Ch microcapsules showed superior antibacterial properties compared to Alg-LAB813 microcapsules over 24 h and when subject to temperatures ranging from 4 to 68 °C. In addition, Alg-LAB813-Ch microcapsules retained antibacterial activity for up to 28 days of storage at 4 °C. The strong and sustained inhibitory activities of Ch-coated Alg encapsulated LAB813 signify the potential for their use to improve oral health., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Chilodonella uncinata is an aerobic ciliate capable of switching between being free-living and parasitic on fish fins and gills, causing tissue damage and host mortality. It is widely used as a model organism for genetic studies, but its mitochondrial metabolism has never been studied. Therefore, we aimed to describe the morphological features and metabolic characteristics of its mitochondria., Methods: Fluorescence staining and transmission electron microscopy (TEM) were used to observe the morphology of mitochondria. Single-cell transcriptome data of C. uncinata were annotated by the Clusters of Orthologous Genes (COG) database. Meanwhile, the metabolic pathways were constructed based on the transcriptomes. The phylogenetic analysis was also made based on the sequenced cytochrome c oxidase subunit 1 (COX1) gene., Results: Mitochondria were stained red using Mito-tracker Red staining and were stained slightly blue by DAPI dye. The cristae and double membrane structures of the mitochondria were observed by TEM. Besides, many lipid droplets were evenly distributed around the macronucleus. A total of 2594 unigenes were assigned to 23 functional classifications of COG. Mitochondrial metabolic pathways were depicted. The mitochondria contained enzymes for the complete tricarboxylic acid (TCA) cycle, fatty acid metabolism, amino acid metabolism, and cytochrome-based electron transport chain (ETC), but only partial enzymes involved in the iron-sulfur clusters (ISCs)., Conclusions: Our results showed that C. uncinata possess typical mitochondria. Stored lipid droplets inside mitochondria may be the energy storage of C. uncinata that helps its transmission from a free-living to a parasitic lifestyle. These findings also have improved our knowledge of the mitochondrial metabolism of C. uncinata and increased the volume of molecular data for future studies of this facultative parasite., (© 2023. The Author(s).)

It remains a great challenge to design and manufacture battery-type supercapacitors with satisfactory flexibility, appropriate mechanical property, and high energy density under high power density. Herein, a concept of porous engineering is proposed to simply prepare two-layered bimetallic heterojunction with porous structures. This concept is successfully applied in fabrication of flexible electrode based on CuO-Co(OH) 2 lamella on Cu-plated carbon cloth (named as CPCC@CuO@Co(OH) 2 ). The unique structure brings the electrode a high specific capacity of 3620 mF cm -2 at 2 mA cm -2 and appropriate mechanical properties with Young's modulus of 302.0 MPa. Density functional theory calculations show that porous heterojunction provides a higher intensity of electron state density near the Fermi level (E-E f  = 0 eV), leading to a highly conductive CPCC@CuO@Co(OH) 2 electrode with both efficient charge transport and rapid ion diffusion. Notably, the supercapacitor assembled from CPCC@CuO@Co(OH) 2 //CC@AC shows high energy density of 127.7 W h kg -1 at 750.0 W kg -1 , remarkable cycling performance (95.53% capacity maintaining after 10 000 cycles), and desired mechanical flexibility. The methodology and results in this work will accelerate the transformative developments of flexible energy storage devices in practical applications., (© 2023 Wiley-VCH GmbH.)

Objective: The aims of this study were to develop a novel rodent model of masticatory muscle ischaemia via unilateral ligation of the external carotid artery (ECA), and to undertake a preliminary investigation to characterize its downstream effects on mechanosensitivity and cellular features of the masseter and temporalis muscles., Design: The right ECA of 18 male Sprague-Dawley rats was ligated under general anaesthesia. Mechanical detection thresholds (MDTs) at the masseter and temporalis bilaterally were measured immediately before ECA ligation and after euthanasia at 10-, 20-, and 35-days (n = 6 rats/timepoint). Tissue samples from both muscles and sides were harvested for histological analyses and for assessing changes in the expression of markers of hypoxia and muscle degeneration (Hif-1α, VegfA, and Fbxo32) via real time PCR. Data were analyzed using mixed effect models and non-parametric tests. Statistical significance was set at p < 0.05., Results: MDTs were higher in the right than left hemiface (p = 0.009) after 20 days. Histological changes indicative of muscle degeneration and fibrosis were observed in the right muscles. Hif-1α, VegfA, and Fbxo32 were more highly expressed in the masseter than temporalis muscles (all p < 0.05). Hif-1α and, VegfA did not change significantly with time in all muscles (all p > 0.05). Fbxo32 expression gradually increased in the right masseter (p = 0.024) and left temporalis (p = 0.05)., Conclusions: ECA ligation in rats induced hyposensitivity in the homolateral hemiface after 20 days accompanied by tissue degenerative changes. Our findings support the use of this model to study pathophysiologic mechanisms of masticatory muscle ischaemia in larger investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Rationale: Chronic pancreatitis is an ongoing fibroinflammatory disease of the pancreas characterized by irreversible damage to the pancreatic parenchyma and ductal system. Besides, chronic pancreatitis can present with a variety of life-threatening complications., Patient Concerns: The patients visited our hospital due to abdominal pain and anemia, and had chronic pancreatitis as an underlying disease., Diagnoses: Computed tomography showed a large gastroduodenal artery pseudoaneurysm, arterioportal vein fistula, and portal vein stenosis., Interventions: We would like to report the successful use of the coils, and N-butyl cyanoacrylate glue for the therapeutic embolization of the pseudoaneurysm and fistula between the gastroduodenal artery and the portal vein, and stenting for portal vein stenosis., Outcomes: On the day following the endovascular management, the patient reported remission of abdominal pain, and hemoglobin level returned to normal after transfusion. It was confirmed that it was still well maintained in the follow-up examination after 1 month., Lessons: Although chronic pancreatitis causes many vascular complications, simultaneous occurrence of these lesions is extremely rare. Herein, we share our experience with a unique case of an extrahepatic arterioportal fistula induced by the rupture of gastroduodenal artery pseudoaneurysm with concomitant portal vein stenosis. In these complex cases, combined transarterial embolization and transportal stenting can be helpful., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Whether exercise-induced venous-to-systemic shunt (EIS) during cardiopulmonary exercise testing (CPET) has different manifestations or characteristics in idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) patients remains unknown. We explored the differences in hemodynamics, echocardiography, and prognosis between IPAH and CTEPH patients with and without EIS., Methods: We conducted a retrospective cross-sectional cohort study and included 161 PH patients at Shanghai Pulmonary Hospital. Demographic, echocardiography, pulmonary hemodynamic, and CPET variables were compared between patients with and without EIS stratified by IPAH and CTEPH. EIS was determined by CPET. Binary logistic regression analyses were performed to explore independent influencing factors of EIS. Cox survival analysis was used to quantify the impact of EIS on the prognosis of patients., Results: Exercise-induced venous-to-systemic shunt was found in approximately 17.4% of 86 IPAH patients and 20% of 75 CTEPH patients. All-cause mortality occurred in 43 (26.7%) patients during a median follow-up of 6.5 years. Compared with those without EIS, patients with EIS had higher peak end-tidal O 2 and lower VO 2 /VE and tricuspid annular plane systolic excursion (TAPSE). Among the IPAH patients, EIS was associated with lower cardiac output, cardiac index, mixed venous oxygen saturation, VO 2 /VE, and TAPSE and higher VE/VCO 2 and right ventricular end-diastolic transverse diameter. Logistic regression analysis indicated that VO 2 /VE was an independent factor influencing whether IPAH patients developed EIS during CPET. Cox logistic regression indicated that female IPAH patients or IPAH patients with higher VO 2 /VE and EIS had a better prognosis. Female IPAH patients had better 10-year survival. In IPAH patients without EIS, patients with higher VO 2 /VE had better 10-year survival. However, compared with CTEPH patients without EIS, those with EIS had similar echocardiographic, hemodynamic, CPET parameter results and 10-year survival., Conclusion: Exercise-induced venous-to-systemic shunt exhibits different profiles among IPAH and CTEPH patients. Among IPAH patients, those with EIS had worse peak end-tidal O 2 , VO 2 /VE, and TAPSE than those without EIS. VO 2 /VE was an independent factor of EIS among IPAH patients. IPAH patients with EIS, female sex or higher VO 2 /VE had better survival. However, the association between EIS and PAH severity or prognosis in CTEPH patients needs to be further explored., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Guo, Sun, Yuan, Zhao, Wu, Qiu, Luo, Gong, Li, Zhang, He, Wang, Liu, Guo and Jiang.)

Background: Significantly improved survival in patients with pulmonary hypertension (PH) has raised interest in maintaining a good quality of long-term survivorship. In this study, health-related quality of life (HRQOL) measurement was used to assess the long-term changes of physical and mental outcomes., Methods: A total of 559 consecutive inpatients with PH completed generic HRQOL (Short Form-36) who were diagnosed with PH by right heart catheterization. Assessments were carried out at short-term (1 year), midterm (3 years), and long-term (5 years) follow-ups., Results: Patients with PH suffered more severe impairments in both physical and emotional domains than the U.S. population normative values. Patients with PH due to chronic lung disease had the worst physical component summary (PCS) score, but there was no difference in mental component summary (MCS) score among different PH types. A reduced PCS score was correlated with WHO FC severity and pulmonary vascular resistance (PVR). The Z score showed that the changing trend of mental conditions continuously declined from baseline to midterm and long-term follow-ups, but the PCS score seemed to be stable or improved. Cox regression analysis indicated increased baseline PVR and WHO FC III and IV, and decreased physical subscale of role physical, mental subscale of social functioning, and the MCS score have increased risk of mortality in the long-term follow-up., Conclusion: Patients with PH have poor HRQOL. The long-term change of physical status seemed to be stable, but the mental state was continuously worse. These suggested identifying and intervening mental health progresses is a noteworthy issue in PH chronic management., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Xiao, Liu, Li, Zhao, Sun, Zhu, Yan, Wang, Luo, Gong, Jiang, Liu, Zhang and Wang.)

Percutaneous transhepatic biliary drainage (PTBD) has been an effective treatment to access the biliary tree, especially in case of endoscopically inaccessible biliary tree. In general, PTBD techniques are divided into two methods: fluoroscopy-guided PTBD and ultrasound (US)-guided PTBD. This study aimed to evaluate the effectiveness of US-guided PTBD, focusing on radiation exposure according to intrahepatic duct (IHD) dilatation degree, differences between right- and left-sided approaches and differences between benign and malignant biliary stenosis/obstruction. We evaluated technical success, clinical success, procedural data (the number of liver capsule punctures, procedural time, fluoroscopy time and radiation dose), and procedure-related complications. During the study period, a total of 123 patients with biliary stenosis/obstruction or bile leakage were initially eligible. We excluded 76 patients treated with only ERCP or initially treated with ERCP followed underwent PTBD insertion. Finally, a total of 50 procedures were performed in 47 patients. Of the 47 patients, 8 patients had anatomical alteration due to previous surgery, 6 patients refused ERCP, and 3 patients failed ERCP. For the remaining 30 patients, PTBD was performed on weekend or at night, 11 of whom had poor general condition, 10 patients underwent ERCP 3 to 4 days later after PTBD insertion, 6 patients improved after PTBD insertion without ERCP, 1 patient died, and 1 patient was referred to other hospital. Remaining 1 patient underwent surgery due to Mirizzi syndrome. All procedures were performed by two interventional radiologists. Technical success rate was 100%, clinical success was 94%, and the complication rate was 10%. Fluoroscopy time and the reported radiation dose were significantly lower in patients with dilated bile ducts than in those with non-dilated bile ducts, when biliary puncture under US guidance was performed initially. However, even in patients with non-dilated bile ducts undergoing initial trials of biliary puncture under US guidance, the fluoroscopy time and the reported radiation dose were low, based on current studies. No statistical significant differences were observed in terms of technical and dosimetry results according to right-sided and left-sided procedures and benign and malignant biliary stenosis/obstruction. Thus, US-guided PTBD was found to be a safe and effective technique that significantly reduced fluoroscopy time and radiation doses., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Park et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Although chronic thromboembolic pulmonary hypertension (CTEPH) and chronic thromboembolic pulmonary disease (CTEPD) are known to be accompanied by symptoms associated with sleep-disordered breathing (SDB) and nocturnal hypoxemia, the sex-specific differences of SDB and nocturnal hypoxemia in patients with CTEPH and CTEPD remain unknown., Methods: Between July 2020 and August 2022, data were retrieved from 57 males and 63 female patients with CTEPH and CTEPD who underwent sleep study at Shanghai Pulmonary Hospital. Nocturnal mean SpO 2 (mean SpO 2 ) < 90% was defined as nocturnal hypoxemia. Logistic and linear regression analysis was performed to assess the predictive value of sleep study indices to hemodynamic parameters. Receiver operating characteristic (ROC) curve was applied to analyze the specific parameters to predict the risk of CTEPH., Results: SDB was similarly present in males and females, and both sexes predominantly had obstructive sleep apnea (OSA); more women were diagnosed with nocturnal hypoxemia (32 vs. 7%, p = 0.002). SaO 2 was negatively associated with mean pulmonary arterial pressure (mPAP) in men ( p < 0.001), whereas the ratio of nocturnal SpO 2 < 90% of the total monitoring time (T90%) was positively correlated with mPAP. Mean SpO 2 was an independent predictor for pulmonary vascular resistance and cardiac output in women ( p = 0.001, p < 0.001, p = 0.001, respectively). T90%, SaO 2 , and minimal SpO 2 were combined to develop a new composite parameter: hypoxemia scoring index (HSI). ROC curve analysis indicated that HSI levels of 0.55 could discriminate CTEPH from CTEPD with a sensitivity of 92.3% and specificity of 87.5% in female patients (an area under the curve, 0.937; 95% CI: 0.879-0.995, p < 0.001)., Conclusion: Sex-specific nocturnal hypoxemia was present in patients with CTEPH or CTEPD. In female patients, the HSI showed high capacity for predicting the risk of CTEPH., Clinical Trials Registration: Registry: chictr.org.cn; Identifier: ChiCTR-DDD-16009406., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Li, Yuan, Zhao, Gong, Jiang, Li, Liu, Qiu, Wu, Luo, He, Wang and Liu.)

Monascus pigments (MPs) are natural edible pigments with high safety and strong function, which have been widely used in food and health products. In this study, different types of tea extracts (rich in polyphenols) were used to regulate the biosynthesis of MPs. The results showed that 15% ethanol extract of pu-erh tea (T11) could significantly increase MPs production in liquid fermentation of Monaco's purpureus M3. Comparative transcriptomic and metabolomic analyses combined with reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to further explore the regulatory mechanism of T11 on the biosynthesis of MPs. Comparative transcriptomic analysis showed that there were 1503 differentially expressed genes (DEGs) between the Con group and the T11 group, which were mainly distributed in carbohydrate metabolism, amino acid metabolism, energy metabolism, lipid metabolism, metabolism of terpenoids and polyketides, etc. A total of 115 differential metabolites (DMs) identified by metabolomics between the Con and T11 groups were mainly enriched in glutathione metabolism, starch and sucrose metabolism, alanine, aspartic acid and glutamate metabolism and glycine, serine and threonine metabolism, etc. The results of metabolomics were basically consistent with those of gene transcriptomics, indicating that the regulatory effect of T11 on the biosynthesis of MPs is mainly achieved through affecting the primary metabolic pathway, providing sufficient energy and more biosynthetic precursors for secondary metabolism. In this study, tea extracts with low economic value and easy access were used as promoters of MPs biosynthesis, which may be conducive to the application of MPs in large-scale industrial production. At the same time, a more systematic understanding of the molecular regulatory mechanism of Monascus metabolism was obtained through multi-omics analysis.

In this study, we investigated the dynamics of microbial community and flavor metabolites during the traditional fermentation of Hongqu aromatic vinegar (HAV) and subsequently explored the potential relationship between microbiota and flavor metabolites. The microbiome analysis based on high-throughput sequencing (HTS) of amplicons demonstrated that Lactobacillus , Acetobacter and Clostridium were the dominant bacterial genera, while Alternaria , Candida , Aspergillus and Issatchenkia were the dominant fungal genera during the acetic acid fermentation (AAF) of HAV. A total of 101 volatile flavor compounds were identified through gas chromatography-mass spectrometry (GC-MS) during HAV fermentation, including esters (35), alcohols (17), aldehydes (11), acids (11), ketones (7), phenols (10), and others (10). Redundancy analysis (RDA) was used to reveal the correlation between microbiota and volatile flavor compounds. Lactobacillus and Acetobacter were the two bacterial genera that have the great influence on the production of volatile flavor components in HAV. Among them, Lactobacillus was positively correlated with a variety of ethyl esters, while Acetobacter positively contributed to the formation of several organic acids. Furthermore, the non-volatile metabolites were detected by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). A total of 41 dipeptides were identified during HAV fermentation, and most of them may have sensory characteristics and biological activities. RDA showed that Aspergillus , Epicoccum , Issatchenkia , Candida and Malassezia were the most influential fungal genera on non-volatile metabolites. In particular, Epicoccum was first reported in Hongqu vinegar and showed a positive correlation with the production of various organic acids. In conclusion, this study provides a scientific basis for understanding the flavor generation mechanism of HAV, and may be valuable for developing effective techniques to select suitable strains to improve the flavor quality of HAV., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

As a typical representative of Chinese rice wine ( Huangjiu ), Hongqu rice wine is famous for its red color, mellow taste and strong fragrance. However, due to the open brewing environment and traditional fermentation technology, there are some safety risks in traditional brewed Hongqu rice wine, such as a certain amount of biogenic amines. In this study, the dynamic changes and the differences of microbial communities and volatile flavor components between two types of Hongqu rice wine with high and low biogenic amine contents (LBAW and HBAW) during the traditional brewing were systematically investigated. The results showed that the total biogenic amine contents in LBAW and HBAW were 20.91 and 69.06 mg/L, respectively. The contents of putrescine, cadaverine, spermine and spermidine in HBAW were significantly higher than those in LBAW, and it was noteworthy that spermine content in HBAW was 17.62 mg/L, which was not detected in LBAW. In addition, the volatile flavor characteristics of the two kinds of Hongqu rice wine were obviously different. The contents of acetophenone, n-butyl butanoate and benzothiazole were obviously higher in HBAW, while the contents of isoamyl acetate, ethyl lactate, ethyl caprate and phenylethyl alcohol were significantly higher in LBAW. High-throughput sequencing of 16S/ITS amplicon revealed that Weissella , Kosakonia , Pantoea , Monascus , Saccharomyces and Millerozyma were the predominant microbial genera during the traditional brewing of HBAW, while Weissella , Kosakonia , Monascus , Saccharomyces and Issatchenkia were the predominant microbial genera during the traditional brewing of LBAW. Correlation analysis revealed that biogenic amines were significantly negatively correlated with unclassified&#95;o&#95; Saccharomycetales , Cyberlindnera , Zygoascus , Aspergillus and Acinetobacter , but positively correlated with Lactobacillus , Pediococcus , Millerozyma and Apiotrichum . In addition, we also found that Lactobacillus , Pediococcus and Saccharomyces were significantly positively correlated with most of the volatile flavor components, while Candida , Trichosporon and Monascus were significantly negatively correlated with most of the volatile flavor components. In addition, bioinformatical analysis based on PICRUSt demonstrated that the key enzymes for biogenic amine biosynthesis were more abundant in the microbial community of HBAW than LBAW. These findings demonstrate that the formations of volatile flavor and biogenic amines in Hongqu rice wine are influenced by microbial community during the fermentation. This work facilitates scientific understanding of the formation mechanism of biogenic amines, and may be useful to develop effective strategies to improve the quality of Hongqu rice wine., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Bacteria use quorum sensing (QS) to communicate with each other via secreted small autoinducers produced by individuals. QS allows bacteria to display a unified response that benefits the species during adaptation to environment, colonization, and defense against competitors. In oral streptococci, the CSP-ComDE QS is an inducible DNA damage repair system that is pivotal for bacterial survival. In the oral pathogen Streptococcus mutans, the QS system positively influences the formation of antibiotic persisters, cells that can survive antibiotic attack by entering a non-proliferative state. We recently identified a novel gene, pep299, that is activated in the persister cell fraction induced by QS. In this study, we focused our investigation on the role of pep299, a gene encoding a bacteriocin-like peptide, in the formation of antibiotic persisters. Mutant Δ299, unable to produce Pep299, showed a dramatic reduction in the number of stress-induced persisters. Using a co-culture assay, we showed that cells overproducing pep299 induced the formation of persisters in the mutant, suggesting that Pep299 was actively secreted and detected by neighboring cells. Cells exposed to DNA damage conditions activated the gene expression of pep299. Interestingly, our results suggested that the pep299 gene was also involved in the regulation of a QS-inducible toxin−antitoxin system. Our study suggests that the pep299 gene is at the core of the triggered persistence phenotype in S. mutans, allowing cells to transition into a state of reduced metabolic activity and antibiotic tolerance.

Here, through single-molecule real-time sequencing, we present a high-quality genome sequence of the Japanese larch (Larix kaempferi), a conifer species with great value for wood production and ecological afforestation. The assembled genome is 10.97 Gb in size, harboring 45,828 protein-coding genes. Of the genome, 66.8% consists of repeat sequences, of which long terminal repeat retrotransposons are dominant and make up 69.86%. We find that tandem duplications have been responsible for the expansion of genes involved in transcriptional regulation and stress responses, unveiling their crucial roles in adaptive evolution. Population transcriptome analysis reveals that lignin content in L. kaempferi is mainly determined by the process of monolignol polymerization. The expression values of six genes (LkCOMT7, LkCOMT8, LkLAC23, LkLAC102, LkPRX148, and LkPRX166) have significantly positive correlations with lignin content. These results indicated that the increased expression of these six genes might be responsible for the high lignin content of the larches' wood. Overall, this study provides new genome resources for investigating the evolution and biological function of conifer trees, and also offers new insights into wood properties of larches., (© 2022 The Authors. Journal of Integrative Plant Biology published by John Wiley & Sons Australia, Ltd on behalf of Institute of Botany, Chinese Academy of Sciences.)

Background and Aims: In Mainland China and Hong Kong, health authorities utilize Agkistrodon halys antivenom in the treatment of patients who sustained bites from green pit vipers. However, the treatment benefit of Agkistrodon halys antivenom among such patients is still controversial. The purpose of this study is to evaluate the coagulation parameters normalization time of Agkistrodon halys antivenom in patients who sustained green pit viper bites and explore independent risk factors of patient prognosis., Methods: Data were extracted from the Donghua Hospital Information System. Comparison of the two groups of patients - who used antivenom (GPUA) and who did not use antivenom (GPNUA) were performed using stratified analysis, univariate and multivariate ordered logistic regression models to evaluate the coagulation parameters normalization time. Univariate and multivariate ordered logistic regression models were used to explore independent risk factors of patient prognosis., Results: Between the GPUA and GPNUA groups, there is no significant difference in the coagulation parameters normalization time with the treatment of Agkistrodon halys antivenom. GPNUA consumed more cryoprecipitate and platelets and had a lower cost. The patient's severity of the bite, first coagulation profile, and dosages of fresh frozen plasma, platelet, and red cell suspension was found to be risk factors for the normalization time of coagulation parameters., Conclusions: The therapeutic effect of Agkistrodon halys antivenom in green pit vipers bite patients is not quite satisfying. In addition, more attention should be paid to the first coagulation profile, blood clotting factors indices, platelet count (PLT), and hemoglobin when treating such patients.

Introduction: Systemic sclerosis (SSc) is associated with interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). This study aimed to explore the prevalence, clinical features, hemodynamic characteristics and prognosis of different severity of ILD in a cohort of patients with SSc-associated precapillary pulmonary hypertension (SSc-PH) and investigate the differences between SSc-PAH and idiopathic pulmonary arterial hypertension (IPAH) patients., Method: SSc-PH patients and IPAH patients, admitted to Shanghai Pulmonary Hospital (August 1, 2008-January 31, 2020) and diagnosed by right-sided heart catheterization (RHC) or echocardiography, were retrospectively included. SSc-PH patients had a baseline chest high-resolution computed tomography (HRCT), and PH classification was based on the extent of ILD. Clinical, pulmonary function, hemodynamic characteristics and survival data were extracted., Results: The study included 45 SSc-PH patients (60% had coexisting ILD and 77.8% were SSc-Group 1 PH/SSc-PAH [without ILD or with mild ILD], 22.2% were SSc-Group 3 PH/SSc-PH with severe ILD) and 52 IPAH patients. SSc-PH with ILD had lower arterial oxygen partial pressure (PaO 2 ) than those without ILD. Hemodynamic characteristics and survival rates were comparable between SSc-PAH with mild ILD and those without ILD. SSc-Group 3 PH had lower pulmonary vascular resistance (PVR) and more severe restrictive ventilatory dysfunction than SSc-Group 1 PH, but the survival rate was equally poor. SSc-PAH had a poorer prognosis than IPAH patients despite the better hemodynamic characteristics., Conclusions: ILD was common in SSc-PH patients. Careful phenotyping of PH in SSc-PH patients is very important as it is imperative to recognize its impact on clinical course, treatment and survival., Key Points: • ILD was common in Chinese SSc-PH patients. • SSc-PH patients with ILD had lower PaO 2 than those without ILD. • Hemodynamic characteristics and survival rates were similar in SSc-PAH patients with mild ILD and those without ILD. • Patients in SSc-Group 3 PH had lower pulmonary vascular resistance (PVR) and more severe restrictive ventilatory dysfunction than those in SSc-Group 1 PH, but the survival rate was equally poor. SSc-PAH patients had a poorer prognosis than IPAH patients despite their better hemodynamic characteristics., (© 2022. International League of Associations for Rheumatology (ILAR).)

Background: Patients with pulmonary arterial hypertension (PAH) have reduced exercise capacity and poor quality of life. Exercise-based rehabilitation in PAH results in clinically relevant improvements in exercise capacity and hemodynamics. To clarify the mechanism, we will evaluate the effect of aerobic exercise training rehabilitation on right ventricular (RV) remodeling and function as determined measured by cardiac magnetic resonance imaging (CMR)., Methods: We will conduct a 26-week multicenter randomized controlled trial. Patients on stable and unchanged PAH-targeted medication are randomly assigned (1:1) to the control and training groups. The primary endpoint is the RV stroke volume (RVSV) change from baseline to Week 26, determined by CMR. Comprehensive RV function is also performed using CMR. Other characteristics of the RV and left ventricle, World Health Organization functional class, 6-min walk distance, and N-terminal pro-B-type natriuretic peptide are included in secondary endpoints. We also investigate the proteomic, metabolomic, and transcriptomic changes after exercise training as exploratory endpoints., Ethics and Dissemination: The study and protocol were approved by the Ethics Committee of Shanghai Pulmonary Hospital (Approved No. of ethics committee: L20-17). The results will be disseminated at medical conferences and in journal publications. All participants will sign written informed consent., Trial Registration Number: ChiCTR2000031650., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Wang, Yuan, Zhao, Gong, He, Qiu, Luo, Zhang, Shen, Zhan, Jiang, Chen, Liu and Shen.)

Background: Pulmonary hypertension in left heart disease (PH-LHD), which includes combined post- and precapillary PH (Cpc-PH) and isolated postcapillary PH (Ipc-PH), differs significantly in prognosis. We aimed to assess whether cardiopulmonary exercise testing (CPET) predicts the long-term survival of patients with PH-LHD., Methods: A single-center observational cohort enrolled 89 patients with PH-LHD who had undergone right heart catherization and CPET (mean pulmonary arterial pressure > 20 mm Hg and pulmonary artery wedge pressure ≥ 15 mm Hg) between 2013 and 2021. A receiver operating characteristic curve was plotted to determine the cutoff value of all-cause death. Survival was estimated using the Kaplan-Meier method and analyzed using the log-rank test. The Cox proportional hazards model was performed to determine the association between CPET and all-cause death., Results: Seventeen patients died within a mean of 2.2 ± 1.3 years. Compared with survivors, nonsurvivors displayed a significantly worse 6-min walk distance, workload, exercise time and peak oxygen consumption (VO 2 )/kg with a trend of a lower oxygen uptake efficiency slope (OUES) adjusted by Bonferroni's correction. Multivariate Cox regression revealed that the peak VO 2 /kg was significantly associated with all-cause death after adjusting for Cpc-PH/Ipc-PH. Compared with Cpc-PH patients with a peak VO 2 /kg ≥ 10.7 ml kg -1  min -1 , Ipc-PH patients with a peak VO 2 /kg < 10.7 ml kg -1  min -1 had a worse survival (P < 0.001)., Conclusions: The peak VO 2 /kg is independently associated with all-cause death in patients with PH-LHD. The peak VO 2 /kg can also be analyzed together with Cpc-PH/Ipc-PH to better indicate the prognosis of patients with PH-LHD., (© 2022. The Author(s).)

Severe pulmonary hypertension in chronic lung diseases (severe CLD-PH) differs significantly from other types of PH in physiology and prognosis. We aimed to assess whether echocardiography helps predict long-term survival in patients with severe CLD-PH. This single-centre, observational cohort study enrolled 100 patients with severe CLD-PH (mean pulmonary arterial pressure ≥35 mm Hg or ≥25 mm Hg with cardiac index <2.0 L/min/m2 or pulmonary vascular resistance ≥6 Wood units) between 2009 and 2014. The population was randomly divided into a derivation and validation cohort in a 2:1 ratio. To construct a nomogram, a multivariable logistic regression model was applied, and scores were assigned based on the hazard ratio of independent echocardiographic predictors. Multivariate Cox hazards analysis identified the strongest predictors of mortality as pulmonary arterial systolic pressure (PASP), tricuspid annular plane systolic excursion, and right ventricular end-diastolic transverse dimension. The three independent predictors were entered into the nomogram. Compared with PASP alone, the nomogram resulted in an integrated discrimination improvement of 15.5% (95% confidence interval, 5.52−25.5%, p = 0.002) with a net improvement in model discrimination (C-statistic from 0.591 to 0.746). Using echocardiographic parameters, we established and validated a novel nomogram to predict all-cause death for patients with severe CLD-PH.

Pulmonary hypertension (PH) refers to a clinical and pathophysiological syndrome in which pulmonary vascular resistance and pulmonary arterial pressure are increased due to structural or functional changes in pulmonary vasculature caused by a variety of etiologies and different pathogenic mechanisms. It is followed by the development of right heart failure and even death. In recent years, most studies have found that PH and cancer shared a complex common pathological metabolic disturbance, such as the shift from oxidative phosphorylation to glycolysis. During the shifting process, there is an upregulation of glutamine decomposition driven by glutaminase. However, the relationship between PH and glutamine hydrolysis, especially by glutaminase is yet unclear. This review aims to explore the special linking among glutamine hydrolysis, glutaminase and PH, so as to provide theoretical basis for clinical precision treatment in PH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Yan, Xu, Gong, Zhong, An, Zhao, Liu, Wang, Yuan and Jiang.)

Background: A national standardized emergency medicine (EM) curriculum for medical students, including specific competencies in procedural skills, are absent in many countries. The development of an intensive simulating training program in EM, based on a tight schedule, is anticipated to enhance the competency of medical students., Methods: A 3-day intensive EM training program, consisting of four procedural skills and 8-hour case-based learning (CBL), was developed by experienced physicians from the EM department in Peking Union Medical College Hospital (PUMCH). Medical students from Peking Union Medical College (PUMC) and Tsinghua University (THU) participated in the training. Three written tests were cautiously designed to examine the short-term (immediately after the program) and long-term (6 months after the program) efficacy of the training. After completion of the training program, an online personal appraisal questionnaire was distributed to the students on WeChat (a mobile messaging App commonly used in China) to achieve anonymous self-evaluation., Results: Ninety-seven out of 101 students completed the intensive training and took all required tests. There was a significant increase in the average score after the intensive simulating training program (pre-training 13.84 vs. 15.57 post-training, P <0.001). Compared with the pre-training test, 63 (64.9%) students made progress. There was no significant difference in scores between the tests taken immediately after the program and 6 months later (15.57±2.22 vs. 15.38±2.37, P =0.157). Students rated a higher score in all diseases and procedural skills, and felt that their learning was fruitful., Conclusions: The introduction of a standardized intensive training program in EM focusing on key competencies can improve clinical confidence, knowledge, and skills of medical students toward the specialty. In addition, having such a program can also enhance student's interest in EM as a career choice which may enhance recruitment into the specialty and workplace planning., Competing Interests: Conflicts of interests: There are no financial or other conflicts of interest related to the submitted article., (Copyright: © World Journal of Emergency Medicine.)

Background: Management of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remains a clinical challenge. Currently, riociguat, a soluble guanylate-cyclase stimulator is recommended by international guidelines. More recently, balloon pulmonary angioplasty (BPA) develops as an alternative treatment for inoperable CTEPH., Method: This study is a single-center randomized controlled trial. Subjects with inoperable CTEPH are randomized into either a BPA combined with riociguat or riociguat monotherapy group (2:1) and observed for 12 months after initiation of treatment. The primary endpoint is the change in pulmonary vascular resistance from baseline to 12 months after initiation of treatment. The secondary endpoints include 6-min walk distance (6MWD), WHO-FC, NT-proBNP, SF-36, and other hemodynamic parameters. Safety endpoints are analyzed too., Discussion: This study aims to compare the efficacy and safety of BPA combined with riociguat and riociguat monotherapy for inoperable CTEPH., Trial Registration: Chinese Clinical Trial Registry ChiCTR2000032403 . Registered on 27 April 2020., (© 2021. The Author(s).)

Ten new triterpenoids, including nine 9,10- seco -cycloartanes ( 1 - 9 ) and one 9,19-cyclolanostane ( 10 ), as well as one sesquiterpenoid ( 11 ) and four known compounds ( 12 - 15 ), were extracted and purified from the whole plant of the Chinese liverwort Lepidozia reptans . Multiple techniques (NMR, HRESIMS, IR, and X-ray crystallographic analysis) were applied to determine the structures of the isolated compounds. Bioassay determinations showed that compound 7 , which contains an α,β-unsaturated carbonyl moiety in its structure, inhibited the growth of a panel of cancer cell lines with IC 50 values ranging from 4.2 ± 0.2 to 5.7 ± 0.5 μM. Further investigation revealed that compound 7 induces PC-3 cell death via mitochondrial-related apoptosis.

Cardiopulmonary exercise testing and pulmonary function test are important methods for detecting human cardio-pulmonary function. Whether they could screen vasoresponsiveness in idiopathic pulmonary artery hypertension (IPAH) patients remains undefined. One hundred thirty-two IPAH patients with complete data were retrospectively enrolled. Patients were classified as vasodilator-responsive (VR) group and vasodilator-nonresponsive (VNR) group on the basis of the acute vasodilator test. Pulmonary function test and cardiopulmonary exercise testing were assessed subsequently and all patients were confirmed by right heart catheterization. We analyzed cardiopulmonary exercise testing and pulmonary function test data and derived a prediction rule to screen vasodilator-responsive patients in IPAH. Nineteen of VR-IPAH and 113 of VNR-IPAH patients were retrospectively enrolled. Compared with VNR-IPAH patients, VR-IPAH patients had less severe hemodynamic effects (lower RAP, m PAP, PAWP, and PVR). And VR-IPAH patients had higher anaerobic threshold (AT), peak partial pressure of end-tidal carbon dioxide (P ET CO 2 ), oxygen uptake efficiency (OUEP), and FEV 1 /FVC (P all <0.05), while lower peak partial pressure of end-tidal oxygen (P ET O 2 ) and minute ventilation (VE)/carbon dioxide output (VCO 2 ) slope (P all <0.05). FEV 1 /FVC (Odds Ratio [OR]: 1.14, 95% confidence interval [CI]: 1.02-1.26, P = 0.02) and PeakP ET CO 2 (OR: 1.13, 95% CI: 1.01-1.26, P = 0.04) were independent predictors of VR adjusted for age, sex, and body mass index. A novel formula (=-16.17 + 0.123 × PeakP ET CO 2  + 0.127×FEV 1 /FVC) reached a high area under the curve value of 0.8 (P = 0.003). Combined with these parameters, the optimal cutoff value of this model for detection of VR is -1.06, with a specificity of 91% and sensitivity of 67%. Compared with VNR-IPAH patients, VR-IPAH patients had less severe hemodynamic effects. Higher FEV 1 /FVC and higher peak P ET CO 2 were associated with increased odds for vasoresponsiveness. A novel score combining PeakP ET CO 2 and FEV 1 /FVC provides high specificity to predict VR patients among IPAH., (© The Author(s) 2021.)

Background: The 2015 European pulmonary hypertension (PH) guidelines recommend a risk stratification strategy for pulmonary arterial hypertension (PAH). We aimed to investigate the validation and potential prognostic information in Chinese patients. Methods: The risk assessment variables proposed by the PH guidelines were performed by using the WHO function class, 6-min walking distance, brain natriuretic peptide or its N-terminal fragment, right arterial pressure, cardiac index, mixed venous saturation, right atrium area, pericardial effusion, peak oxygen consumption, and ventilatory equivalents for carbon dioxide. An abbreviated version also was applied. Results: A total of 392 patients with idiopathic PAH (IPAH) were enrolled between 2009 and 2018. After a median interval of 13 months, re-evaluation assessments were available for 386 subjects. The PAH guidelines risk tool may effectively discriminate three risk groups and mortality ( p < 0.001) both at the baseline and re-evaluation. Meanwhile, its simplified risk version was valid for baseline and accurately predicted the risk of death in all the risk groups ( p < 0.001). At the time of re-evaluation, the percentage of low-risk group has an increase, but a greater proportion achieved the high-risk group and a lesser proportion maintained in the intermediate-risk group. Conclusion: The 2015 European PH guidelines and its simplified version risk stratification assessment present an effective discrimination of different risk groups and accurate mortality estimates in Chinese patients with IPAH. Changes of risk proportion at re-evaluation implicated that natural treatment decisions may not be consistently with goal-oriented treatment strategy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gong, Wu, Li, Zhao, Jiang, Luo, Qiu, Liu, Wang and Zhang.)

To explore the influence characteristics of the interaction effects between meteorological factors on ozone(O 3 ) concentration in Chengdu, daily air pollutants and meteorological data from 2014 to 2019 were collected. Generalized additive models(GAMs) were adopted to explore the effects of different factors on O 3 concentration. The results showed that the relationship between O 3 and maximum temperature, sunshine hours, relative humidity, wind speed, precipitation, maximum mixed depth(MMD), and ventilation coefficient(VC) was non-linear. Specifically, the maximum temperature, sunshine hours, MMD, and relative humidity had a significant influence on O 3 concentration throughout the year. It is worth noting that the influence of relative humidity and precipitation on O 3 concentration during summer was more significant than that for the whole year. In the multi-meteorological factors GAMs of O 3 concentration, the meteorological factors mentioned above, except average wind, had significant impacts on O 3 concentration change. For the whole year, the judgment coefficient( R 2 ) was 0.849 and the variance explanation rate was 85.1%. The maximum temperature was the most important influencing factor on O 3 concentration throughout the year. During summer, corresponding R 2 was 0.811 and the explanation rate of variance was 81.3%; however, maximum temperature and MMD were the dominant meteorological factors. In the interaction GAMs, for the whole year, the interaction between maximum temperature and sunshine hours, relative humidity, and precipitation, and the interaction between sunshine hours and MMD had a significant impact on O 3 concentrations. The interaction between maximum temperature and sunshine hours played a leading role in changes of O 3 concentration. The high temperature+strong radiation+MMD(about 2000 m) +no precipitation were conducive to the formation of O 3 concentration, but in summer, only the maximum temperature, sunshine hours, and VC had the most significant effect on the O 3 concentration, and strong high temperatures+strong radiation+the little horizontal wind in summer were conducive to the formation of O 3 concentration near the surface. In summary, GAMs model can not only be used to identify the dominant influencing factors of O 3 pollution, but also quantitatively analyze the influence of single effects and interaction of influencing factors on O 3 concentration, which has great significance for the prevention and control of O 3 pollution.