Surgical outcomes of transvaginal natural orifice transluminal endoscopy in treating ovarian cysts and risk factors for surgical conversions.

Objective: This study aimed to assess the surgical outcomes and identify the conversion risk factors of Transvaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) in treating ovarian cyst. Methods: This was a retrospective study of 505 patients who underwent vNO TES for treating ovarian cyst from March 2019 to February 2022 wherein the patients were classified into "converted" or "nonconverted" groups. T-tests, χ2 tests, and logistic regression were used for statistical analyses. Results: There were 16 (3.17 %) surgical conversions and 12 (2.38 %) other surgical complications in our study cohort. Teratomas accounted for 56.8 % of complications in nonconverted cases and 18.8 % in converted cases. Adenocystomas were found in 12.3 % of nonconverted cases and 18.8 % of converted cases. Other types included paraovarian cysts (3.3 % and 0 %), fibroma, granulosa cell tumor, Brenner tumor (1.2 % and 0 %), corpus luteum cysts, follicular cysts (7.6 % and 6.3 %), old abscess (0.2 % and 0 %), and simple cysts (17.6 % and 12.5 %) in the nonconverted and converted groups, respectively. The converted group included more cases of endometriotic cysts (43.8 % vs 12.3 %, p = 0.023), bilateral cysts (37.5 % vs 8.2 %, p < 0.001), severe pelvic adhesion (68.8 % vs 3.3 %, p < 0.001), deep endometriosis (12.5 % vs 0.4 %, p < 0.001), and at least two cysts (37.5 % vs 8.81 %; p < 0.001). Severe pelvic adhesion (adjusted odds ratio [OR], 86.96; range, 18.33-431.77; p < 0.001), bilateral cysts (adjusted OR, 4.75; range, 1.05-21.57, p = 0.043) and endometriotic cysts (adjusted OR, 7.69; range, 3.11-17.08; p < 0.001) were also predictors of surgical conversion. Conclusion: vNOTES demonstrates low complication and conversion rates in treating ovarian cyst compared with TU-LESS. Surgical conversion is associated with severe pelvic adhesions, bilateral cysts, and endometriotic cysts.

Screening and diagnosis of cardiovascular disease using artificial intelligence-enabled cardiac magnetic resonance imaging.

Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis. The screening and diagnostic models achieved high performance (area under the curve of 0.988 ± 0.3% and 0.991 ± 0.0%, respectively) in both internal and external datasets. Furthermore, the diagnostic model outperformed cardiologists in diagnosing pulmonary arterial hypertension, demonstrating the ability of artificial intelligence-enabled CMR to detect previously unidentified CMR features. This proof-of-concept study holds the potential to substantially advance the efficiency and scalability of CMR interpretation, thereby improving CVD screening and diagnosis.

Antitumor Activity and Mechanistic Insights of a Mitochondria-Targeting Cu(I) Complex.

Using copper-ionophores to translocate extracellular copper into mitochondria is a clinically validated anticancer strategy that has been identified as a new type of regulated cell death termed "cuproptosis." This study reports a mitochondria-targeting Cu(I) complex, Cu(I)Br(PPh3)3 (CBP), consisting of a cuprous ion coordinated by three triphenylphosphine moieties and a Br atom. CBP exhibited antitumor and antimetastatic efficacy in vitro and in vivo by specifically targeting mitochondria instigating mitochondrial dysfunction. The cytotoxicity of CBP could only be reversed by a copper chelator rather than inhibitors of the known cell death, indicating copper-dependent cytotoxicity. Furthermore, CBP induced the oligomerization of lipoylated proteins and the loss of Fe-S cluster proteins, consistent with characteristic features of cuproptosis. Additionally, CBP induced remarkable intracellular generation of reactive oxygen species (ROS) through a Fenton-like reaction, indicating a complex antitumor mechanism. This is a proof-of-concept study exploiting the antitumor activity and mechanism of the Cu(I)-based mitochondria-targeting therapy.

Effects of concurrent chemoradiotherapy with or without Endostar on the regression of retropharyngeal lymph node and prognosis of patients with locally advanced nasopharyngeal carcinoma: a retrospective study.

BACKGROUND AND PURPOSE: To investigate the effect of combining Endostar with concurrent chemoradiotherapy (ECCRT) compared to concurrent chemoradiotherapy (CCRT) on the regression rate of retropharyngeal lymph nodes (RLNs) and the relationship between regression rate of RLNs and prognosis of patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A total of 122 LANPC patients with RLNs metastasis were included. Metastatic RLNs were delineated both before and after treatment slice by slice on the magnetic resonance images cross-section. The regression rate of RLNs, adverse effects (AE) were evaluated. The median regression rate of RLNs was taken as the cut-off value, and the patients were furtherly divided into high regression rate (HRR) group and low regression rate (LRR) group, then survival times were evaluated. RESULTS: The median regression rates of RLNs in the ECCRT and CCRT groups were 81% and 50%, respectively (P < 0.001). There was no statistically significant difference in the incidence of grade 3/4 AEs between the two groups, except for oral mucositis (ECCRT 26.23% vs. CCRT 44.26%, P = 0.037). The 3-year overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS) and locoregional failure-free survival (LRFFS) rates in the HRR and LRR groups were 85.48% and 86.67% (P = 0.983), 80.65% and 68.33% (P = 0.037), 83.87% and 85% (P = 0.704), 93.55% and 81.67% (P = 0.033), respectively. CONCLUSIONS: Patients in the ECCRT group had higher regression rates of RLNs and lower incidence of severe oral mucositis. Furthermore, patients in the HRR group had a better 3-year PFS and LRFFS rate than those in the LRR group.

Multi-targeted nanoarrays for early broad-spectrum detection of lung cancer based on blood biopsy of tumor exosomes.

Liquid biopsies utilizing tumor exosomes offer a noninvasive approach for cancer diagnosis. However, validation studies consistently report that in the early stages of cancer, the secretion of exosomes by cancer cells is relatively low, while bodily fluids exhibit a high abundance of other interfering biomolecules. Additionally, target mutations or differences in biomarker expression among various lung cancer subtypes may contribute to detection failures. In this study, we propose a targeted nanoarray-based early cancer diagnostic approach for multiple subtypes of lung cancer. The targeted nanoarray was constructed by modifying five targeting aptamers onto mesoporous silica nanoparticles through the conjugation between amino and carboxyl groups. The flow cytometry experiments demonstrated the specific recognition ability of the targeted nanoarray to tumor exosomes in PBS, even at biomarker expression levels as low as 1.5 %. Moreover, the TEM results indicated that the targeted nanoarray could isolate tumor exosomes in the blood of tumor-bearing mice. Furthermore, the targeted nanoarray could detect tumor exosomes in the blood of various lung cancer bearing mice, including at the early stages of cancer, which has just been established for 7 days. Overall, the targeted nanoarray represents a promising tool for the early detection of various subtypes of lung cancer.

First report of Colletotrichum karstii causing anthracnose on soybean in China.

Soybean (Glycine max) is a significant grain and oil crop. Among the various challenges faced by soybean cultivation, anthracnose stands out as one of the most prevalent diseases. In June 2023, anthracnose symptoms on leaves characterized by irregular disease spots featuring gray-white centers and brown edges, along with many small black dots on their surface, were observed in a 20-hectare soybean (variety "Liu Yuehuang") field located in Luodian County (25°40'20″ N, 106°53'50″ E, 575 m), Guizhou Province, China. Around 30% of the 300 soybean plants examined were symptomatic, and a total of ten leaves were collected. Fragments (5×5 mm) from the edge of disease spots were sheared and surface-sterilized with 3% sodium hypochlorite and 75% ethanol for 60 s and 30 s, respectively. They were then flushed twice with sterile water, dried using sterile filter papers, finally placed on potato dextrose agar (PDA) and incubated at 28°C for two days. In total, 11 isolates with identical morphological characteristics were obtained. The colonies grown with white aerial mycelia on their surface; conidia were cylindrical, both ends are rounded, aseptate, hyaline, 11.0-14.0 (12.5) × 4.5-6.0 (5.0) µm (n = 30); appressoria were nearly ovoid, brown to black, 8.5-10.5 (9.5) × 5.5-7.5 (6.0) µm (n = 30). The morphological characteristics closely resembled the description of C. karstii (Damm et al., 2012). To further identify the isolates, chitin synthase (CHS-1), actin (ACT), beta-tubulin (TUB2), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and the internal transcribed spacer (ITS) loci were amplified by using CHS-79F/CHS-345R, ACT-512F/ACT-783R (Carbone and Kohn, 1999), Bt2F/Bt2R (Woudenberg et al., 2009), GDF/GDR (Guerber et al., 2003) and ITS1/ITS4 (White et al., 1990) PCR primers, respectively. The BLAST results showed that the sequences of two representative strains, LD 2023048-1 and LD 2023048-2, were highly similar to those of strain C. karstii CGMCC3.14194 (ITS: OR342620 (99%) and OR342621 (99%) with HM585409, ACT: OR412337 (97%) and OR423341 (100%) with HM581995, CHS-1: OR423344 (99%,) and OR423345 (100%) with HM582023, GAPDH: OR423348 (98%) and OR423349 (98%) with HM585391, and TUB: OR423352 (99%) and OR423353 (99%) with HM585428). The phylogenetic tree combined five sequences showed that the two strains clustered into a branch of C. karstii CGMCC3.14194 with high support values. Thirty-day-old soybean plants (n = 10) (variety Liu Yuehuang) were separately sprayed with 1 × 105 spore suspensions/mL of the two strains by spray method, and plants sprayed with sterile distilled water were used as the negative control (n = 5). All the plants were then covered with plastic bags and cultured in the greenhouse (28℃, 80% humidity, 12 h light dark cycle). After ten days of inoculation, plants inoculated with C. karstii began to produce typical anthracnose symptoms, while the control remained asymptomatic. The confirmation of the reisolated pathogen as C. karstii was established through a comprehensive analysis of morphology and five sequencing loci. Pathogenicity tests were repeated three times. Anthracnose on soybean is caused by Colletotrichum spp. reported in China including C. truncatum (Hu et al., 2015), C. brevisporum (Shi et al., 2021) and C. fructicola (Xu et al., 2023). As far as we know, this study is the initial report of C. karstii inducing anthracnose on soybean to date, which establishes a fundamental reference for preventing and controlling this disease.

Calculation and measurement of trapping stiffness in femtosecond optical tweezers.

Due to the characteristics of ultra-short pulse width and ultra-high peak power, femtosecond pulse laser can effectively induce nonlinear optical effects in trapped objects. As a result, it holds great value in the fields of micro and nano manipulation, microfluidics, and cell biology. However, the nonlinear optical effects on the stiffness of femtosecond optical traps remain unclear. Calibration of trap stiffness is crucial for accurately measuring forces and manipulating small particles. In this paper, we compare the stiffness between femtosecond optical traps and continuous wave optical traps. Experimental results demonstrate that the stiffness of the femtosecond optical trap in the splitting direction is greater than that in other directions and the stiffness of the continuous wave optical trap under the same laser power condition. Additionally, as the laser power increases, the stiffnesses of both the femtosecond optical trap and the continuous wave optical trap gradually increases. In contrast to a linear increase of the continuous wave optical trap, the stiffness of the femtosecond optical trap exhibits an exponential rise with increasing laser power. This research provides guidance and reference for improving the force measurement accuracy of femtosecond optical tweezer system.

Association of serum uric acid with right cardiac chamber remodeling assessed by cardiovascular magnetic resonance feature tracking in patients with connective tissue disease.

Background: Right cardiac chamber remodeling is widespread in patients with connective tissue disease (CTD). Serum uric acid (SUA) is considered a potential independent risk factor for cardiovascular disease, and elevated SUA levels are often observed in patients with CTD. The correlation between SUA levels and right cardiac chamber remodeling remains unclear. This study investigated the association of SUA with right cardiac chamber remodeling as assessed by cardiac magnetic resonance feature-tracking (CMR-FT) in CTD patients. Methods and results: In this cross-sectional study, a total of 104 CTD patients and 52 age- and sex-matched controls were consecutively recruited. All individuals underwent CMR imaging, and their SUA levels were recorded. The patients were divided into three subgroups based on the tertiles of SUA level in the present study. CMR-FT was used to evaluate the right atrial (RA) longitudinal strain and strain rate parameters as well as right ventricular (RV) global systolic peak strain and strain rate in longitudinal and circumferential directions for each subject. Univariable and multivariable linear regression analyses were used to explore the association of SUA with RV and RA strain parameters. Compared with the controls, the CTD patients showed significantly higher SUA levels but a lower RV global circumferential strain (GCS) and RA phasic strain parameters (all p < 0.05), except the RA booster strain rate. RV GCS remained impaired even in CTD patients with preserved RV ejection fraction. Among subgroups, the patients in the third tertile had significantly impaired RV longitudinal strain (GLS), RV GCS, and RA reservoir and conduit strain compared with those in the first tertile (all p < 0.05). The SUA levels were negatively correlated with RV GLS and RV GCS as well as with RA reservoir and conduit strain and strain rates (the absolute values of ß were 0.250 to 0.293, all P < 0.05). In the multivariable linear regression analysis, the SUA level was still an independent determinant of RA conduit strain (ß = -0.212, P = 0.035) and RV GCS (ß = 0.207, P = 0.019). Conclusion: SUA may be a potential risk factor of right cardiac chamber remodeling and is independently associated with impaired RA conduit strain and RV GCS in CTD patients.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy: A case report and review of literature.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of death due to its complexity, heterogeneity, rapid metastasis and easy recurrence after surgical resection. We demonstrated that combination therapy with transcatheter arterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), Epclusa, Lenvatinib and Sintilimab is useful for patients with advanced HCC. CASE SUMMARY: A 69-year-old man who was infected with hepatitis C virus (HCV) 30 years previously was admitted to the hospital with abdominal pain. Enhanced computed tomography (CT) revealed a low-density mass in the right lobe of the liver, with a volume of 12.9 cm × 9.4 cm × 15 cm, and the mass exhibited a "fast-in/fast-out" pattern, with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL. Therefore, he was judged to have advanced HCC. During treatment, the patient received three months of Epclusa, three TACE treatments, two HAIC treatments, three courses of sintilimab, and twenty-one months of lenvatinib. In the third month of treatment, the patient developed severe side effects and had to stop immunotherapy, and the Lenvatinib dose had to be halved. Postoperative pathological diagnosis indicated a complete response. The patient recovered well after the operation, and no tumor recurrence was found. CONCLUSION: Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect. Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

Recent Progress on Targeted Gel Media for the Application of Bioanalysis.

Targeted gels have been attractive and regarded as a kind of promising adsorptive media for bioanalysis due to their advantages of high specific surface area, enough stability, and adjustable porous structure. Recently, targeted gel media have been applied for separation and enrichment of various biomolecules from different biological samples. Moreover, targeted gel media have been introduced into surface-enhanced Raman scattering (SERS) technology to eliminate matrix effect for rapid and accurate analysis of biological samples. In this article, we introduced the preparation methods of targeted gel media including in-situ polymerization method, self-assembly method and one-pot method. Then, the functions of targeted gel media in bioanalysis including separation-enrichment media, SERS substrates, and target-responsive units were also reviewed in detail. Additionally, the applications of targeted gel media for biomarker analysis, bioimaging analysis and cell engineering were further discussed. Finally, we tried to elucidate the trend and perspective into the future landscape of targeted gel media for bioanalysis.

[Resources and utilization of medicinal plants in countries and regions involved in "the Belt and Road" Initiative].

The protection, development, and utilization of medicinal plant resources are important cornerstones of maintaining human health. However, due to factors such as the reduction of high-quality land resources, deterioration of ecological environments, and excessive and disorderly resource development, medicinal plant resources are becoming scarce, and some of them are insufficiently supplied. With the proposal of "the Belt and Road" Initiative, the cooperation between China and "the Belt and Road" partners(the countries and regions involved in "the Belt and Road" Initiative)is increasingly close, which provides a new opportunity for carrying out trade of medicinal plant resources and alleviating the problem of imbalance and relative inadequacy of medicinal plant resources in countries. This study first determined the distribution and species information of plant resources in countries and regions involved in "the Belt and Road" Initiative by investigating the database of plant distribution and that of medicinal plant resources. Then, according to the published data from the International Union for Conservation of Nature(IUCN) and the Convention on International Trade in Endangered Species of Wild Fauna and Flora(CITES), this study identified the rare and endangered medicinal plants and the medicinal plants under trade control in countries and regions involved in "the Belt and Road" Initiative and finally sorted out the list of potential medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative that can be used by China. This data resource can not only be used for the overall protection of important endangered species but also scientifically guide the development and utilization of medicinal resources, providing guidance and a theoretical basis for the sustainable development of medicinal plant resources in countries and regions involved in "the Belt and Road" Initiative.

A tough and bioadhesive injectable hydrogel formed with maleimidyl alginate and pristine gelatin.

Injectable hydrogels have wide applications in clinical practice. However, the development of tough and bioadhesive ones based on biopolymers, along with biofriendly and robust crosslinking strategies, still represents a great challenge. Herein, we report an injectable hydrogel composed of maleimidyl alginate and pristine gelatin, for which the precursor solutions could self-crosslink via mild Michael-type addition without any catalyst or external energy upon mixing. This hydrogel is tough and bioadhesive, which can maintain intactness as well as adherence to the defect of porcine skin under fierce bending and twisting, warm water bath, and boiling water shower. Besides, it is biocompatible, bioactive and biodegradable, which could support the growth and remodeling of cells by affording an extracellular matrix-like environment. As a proof of application, we demonstrate that this hydrogel could significantly accelerate diabetic skin wound healing, thereby holding great potential in healthcare.

Values in Action: Unveiling the Impact of Self-Transcendence and Self-Enhancement on Domestic Consumption Choices.

Against the backdrop of a global emphasis on supporting local businesses and fostering domestic consumption, this study aims to shed light on the influence of personal values on the intentions behind domestic-product consumption. Drawing from the Schwartz value theory, we explore how values of self-transcendence, which embody benevolence and universalism, versus self-enhancement, characterized by a focus on power and achievement, influence consumer behavior. Utilizing data from the Chinese Social Survey (CSS2021) and a survey of 316 participants, structural equation modeling and Dematel analysis are employed to reveal causal relationships between values and consumption intentions. We reveal a dichotomous impact of these value orientations. Self-transcendence values are found to positively affect domestic consumption intentions by enhancing awareness of consequence and ascription of responsibility, thereby strengthening personal norms. In contrast, self-enhancement values tend to impede these intentions. By integrating the Norm-Activation Model (NAM), this study comprehensively uncovers the unique mechanism through which values activate personal norms and subsequently encourage the consumption of domestic products. It enriches the body of research related to values and domestic consumption and offers pertinent recommendations for promoting local enterprises' products.

From "resistance genes expression" to "horizontal migration" as well as over secretion of Extracellular Polymeric Substances: Sludge microorganism's response to the increasing of long-term disinfectant stress.

Glutaraldehyde-Didecyldimethylammonium bromides (GDs) has been frequently and widely employed in livestock and poultry breeding farms to avoid epidemics such as African swine fever, but its long-term effect on the active sludge microorganisms of the receiving wastewater treatment plant was keep unclear. Four simulation systems were built here to explore the performance of aerobic activated sludge with the long-term exposure of GDs and its mechanism by analyzing water qualities, resistance genes, extracellular polymeric substances and microbial community structure. The results showed that the removal rates of CODCr and ammonia nitrogen decreased with the exposure concentration of GDs increasing. It is worth noting that long-term exposure to GDs can induce the horizontal transfer and coordinated expression of a large number of resistance genes, such as qacE, sul1, tetx, and int1, in drug-resistant microorganisms. Additionally, it promotes the secretion of more extracellular proteins, including arginine, forming a "barrier-like" protection. Therefore, long-term exposure to disinfectants can alter the treatment capacity of activated sludge receiving systems, and the abundance of resistance genes generated through horizontal transfer and coordinated expression by drug-resistant microorganisms does pose a significant threat to ecosystems and health. It is recommended to develop effective pretreatment methods to eliminate disinfectants.

SARS-CoV-2 Infection Causes Heightened Disease Severity and Mortality in a Mouse Model of Down Syndrome.

Recent epidemiological studies suggest that individuals with Down syndrome are more susceptible to SARS-CoV-2 infection and have higher rates of hospitalization and mortality than the general population. However, the main drivers behind these disparate health outcomes remain unknown. Herein, we performed experimental infections with SARS-CoV-2 in a well-established mouse model of Down syndrome. We observed similar SARS-CoV-2 replication kinetics and dissemination in the primary and secondary organs between mice with and without Down syndrome, suggesting that both groups have similar susceptibilities to SARS-CoV-2 infection. However, Down syndrome mice exhibited more severe disease as defined by clinical features including symptoms, weight loss, pulmonary function, and survival of mice. We found that increased disease severity in Down syndrome mice could not be attributed solely to increased infectivity or a more dramatic pro-inflammatory response to infection. Rather, results from RNA sequencing suggested that differences in the expression of genes from other physiological pathways, such as deficient oxidative phosphorylation, cardiopulmonary dysfunction, and deficient mucociliary clearance in the lungs may also contribute to heightened disease severity and mortality in Down syndrome mice following SARS-CoV-2 infection.

Home-based vs center-based exercise on patient-reported and performance-based outcomes for knee osteoarthritis: a systematic review with meta-analysis.

Background: Home-based exercise (HBE) represents an alternative to increase the accessibility of rehabilitation programs and relieve the burden on the health care system for people with knee osteoarthritis. Objectives: To summarize for the first time the effectiveness of HBE as compared to center-based exercise (CBE), both with and without HBE, on patient-reported and performance-based outcomes in people with KOA. Methods: Searches were conducted on PubMed, Cochrane, Embase, Web of Science, and Scopus until March 10, 2023, without date or language restrictions. Randomized controlled trials investigating HBE versus CBE or HBE combined with CBE for people with KOA were eligible. The primary outcomes were patient-reported: pain, physical disability, and quality of life. The secondary outcomes were performance-based: walking ability, lower limb muscle strength, and balance function. Risk of bias was assessed with the Cochrane Risk of Bias tool and quality of evidence according to the GRADE. Results: Eleven trials involving 956 participants were included. There was no difference in short-term pain (SMD, 0.22 [95% CI, -0.04 to 0.47], p = 0.09; I2 = 0%), physical disability (SMD, 0.17 [95% CI, -0.19 to 0.54], p = 0.35; I2 = 0%), walking ability (SMD, -0.21 [95% CI, -0.64 to 0.22], p = 0.33; I2 = 35%) and lower limb muscle strength (SMD, -0.24 [95% CI, -0.88 to 0.41], p = 0.47; I2 = 69%) between HBE and CBE. HBE combined with CBE has better benefits compared with HBE alone in short-term pain (SMD, 0.89 [95% CI, 0.60 to 1.17], p < 0.001; I2 = 11%) and physical disability (SMD, 0.25 [95% CI, 0.00 to 0.50], p = 0.05; I2 = 0%). Conclusion: Based on limited evidence, HBE is as effective as CBE on short-term pain, physical disability, walking ability, and lower limb muscle strength in people with knee osteoarthritis. Furthermore, combining HBE with CBE may enhance the overall efficacy of the intervention. Systematic review registration: PROSPERO, CRD42023416548.

The Effectiveness of Exercise-based Rehabilitation in People with Hand Osteoarthritis: A Systematic Review with Meta-analysis.

OBJECTIVE: To investigate the effectiveness of exercise-based rehabilitation programs compared with non-exercise intervention or no intervention for people with hand osteoarthritis (OA). DESIGN: Intervention systematic review with meta-analysis. LITERATURE SEARCH: We searched five databases on 23/07/2023. STUDY SELECTION CRITERIA: We included randomized controlled trials that compared the effectiveness of rehabilitation programs that included an exercise component, with non-exercise intervention or no intervention for people with hand OA. DATA SYNTHESIS: Standardized mean differences (SMD) were pooled using a random effects model. The risk of bias was assessed using the Cochrane Risk of Bias 2.0 tool. The certainty of the evidence was evaluated using the GRADE approach. RESULTS: Fourteen trials were included in the meta-analysis (n = 1341 participants). In the immediate-term (<24 weeks) there was low-certainty evidence of an effect of exercise-based rehabilitation on improving pain (13 trials; SMD -0.65, 95%CI: -1.06, -0.25), function (11 trials; SMD -0.35, 95%CI: -0.54, -0.15), and grip strength (14 trials; SMD 0.21, 95%CI: 0.03, 0.38). There was moderate-certainty evidence of an effect on reducing stiffness (7 trials; SMD -0.33, 95%CI: -0.51, -0.16). There was low-certainty evidence of no effect on improving pinch strength and quality of life. For the long-term ⩾24 weeks), there was low-certainty evidence that exercise-based rehabilitation had no additional effect on improving pain, function, and stiffness. CONCLUSION: Exercise-based rehabilitation improved pain, function, stiffness, and grip strength in people with hand OA in the immediate-term; the benefits were not maintained in the long-term.

Elevated dorsal medial prefrontal cortex to lateral habenula pathway activity mediates chronic stress-induced depressive and anxiety-like behaviors.

The medial prefrontal cortex (mPFC) sends projections to numerous brain regions and is believed to play a significant role in depression and anxiety. One of the key downstream targets of the mPFC, the lateral habenula (LHb), is essential for chronic stress (CS)-induced depressive and anxiety-like behaviors. Nevertheless, whether the mPFC-LHb pathway mediates the co-occurrence of depression and anxiety and the underlying mechanism remain incompletely understood. Here, using chemogenetics, we first determined that activation of LHb-projecting mPFC neurons is essential for the development of depressive and anxiety-like behaviors induced by CS. Subsequently, we identify the extent and distribution of LHb-projecting neurons originating from the mPFC subregion. Through circuit-specific in vivo fiber photometry, we found that Ca2+ activity in dorsal mPFC (dmPFC) axon terminals within the LHb was increased during exposure to stressful and anxiety-related stimuli, highlighting the potential role of LHb-projecting dmPFC neurons in conveying stressful and anxiety-related information to the LHb. Finally, we observed that activation of both LHb-projecting dmPFC neurons and their postsynaptic counterparts in the LHb was necessary for CS-induced depressive and anxiety-like behaviors. Overall, this study provides multiple lines of evidence demonstrating that activation of the dmPFC-LHb pathway is a crucial neural circuitry for CS-induced depressive and anxiety-like behaviors.

Anti-allergic effect of vitamin C through inhibiting degranulation and regulating TH 1/TH 2 cell polarization.

BACKGROUND: Food allergy has become a global public health problem. This study aimed to explore the possible anti-allergic effect of vitamin C (VC). A rat basophilic leukemia (RBL)-2H3 cell degranulation model was used to assess the effect of VC on degranulation in vitro, and an ovalbumin (OVA)-induced BALB/c mouse allergy model was used to assess the anti-allergy effect of VC in vivo. RESULTS: In vitro, VC significantly attenuated the release of ß-hexosaminidase, tryptase and histamine, and also reduced cytokine production (interleukins 4 and 6, tumor necrosis factor α) significantly (P < 0.05), with the inhibitory effect demonstrating a positive correlation with VC dose. In vivo, compared with the OVA group, the levels of serum immunoglobulins E and G1 of the VC low-dose (VCL) group (50 mg kg-1 ) and high-dose (VCH) group (200 mg·kg-1 ) were significantly reduced (P < 0.05). Furthermore, the plasma histamine level was also significantly decreased (P < 0.05). Moreover, TH 2 cell polarization in mice of the VCL and VCH groups was significantly inhibited (P < 0.05), promoting the TH 1/TH 2 cell polarization balance. Additionally, VC treatment enhanced the expression of CD80 (P < 0.05) in spleen and small intestine tissues, while significantly inhibiting the expression of CD86 (P < 0.05); notably, high-dose VC treatment was more effective. CONCLUSION: VC exerted an anti-allergic effect through inhibiting degranulation and regulating TH 1/TH 2 cell polarization balance. © 2024 Society of Chemical Industry.

[Cloning and functional analysis of 3ß-hydroxysteroid dehydrogenase gene involved in biosynthesis of digitoxin].

Digitoxin, an important secondary metabolite of Digitalis purpurea, is a commonly used cardiotonic in clinical practice. 3ß-Hydroxysteroid dehydrogenase(3ßHSD) is a key enzyme involved in the biosynthesis of digitoxin. It belongs to the short-chain dehydrogenase/reductase(SDR) family, playing a role in the biosynthesis of cardiac glycosides by oxidizing and isomerizing the precursor sterol. In this study, two 3ßHSD genes were cloned from D. purpurea. The results showed that the open reading frame(ORF) of Dp3ßHSD1 was 780 bp, encoding 259 amino acid residues. The ORF of Dp3ßHSD2 was 774 bp and encoded 257 residues. Dp3ßHSD1/2 had the cofactor binding site TGxxxA/GxG and the catalytic site YxxxK. In vitro experiments confirmed that Dp3ßHSD1/2 catalyzed the generation of progesterone from pregnenolone, and Dp3ßHSD1 had stronger catalytic capacity than Dp3ßHSD2. The expression level of Dp3ßHSD1 was much higher than that of Dp3ßHSD2 in leaves, and digitoxin was only accumulated in leaves. The results implied that Dp3ßHSD1 played a role in the dehydrogenation of pregnenolone to produce progesterone in the biosynthesis of digitoxin. This study provides a reference for further exploring the biosynthetic pathway of cardiac glycosides in D. purpurea.