CD38 deficiency prevents diabetic nephropathy by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Diabetic nephropathy (DN) is one of the most common complications of diabetes. Our previous study showed that CD38 knockout (CD38KO) mice had protective effects on many diseases. However, the roles and mechanisms of CD38 in DN remain unknown. Here, DN mice were generated by HFD feeding plus streptozotocin (STZ) injection in male CD38KO and CD38flox mice. Mesangial cells (SV40 MES 13 cells) were used to mimic the injury of DN with palmitic acid (PA) treatment in vitro. Our results showed that CD38 expression was significantly increased in kidney of diabetic CD38flox mice and SV40 MES 13 cells treated with PA. CD38KO mice were significantly resistant to diabetes-induced renal injury. Moreover, CD38 deficiency markedly decreased HFD/STZ-induced lipid accumulation, fibrosis and oxidative stress in kidney tissue. In contrast, overexpression of CD38 aggravated PA-induced lipid accumulation and oxidative stress. CD38 deficiency increased expression of SIRT3, while overexpression of CD38 decreased its expression. More importantly, 3-TYP, an inhibitor of SIRT3, significantly enhanced PA-induced lipid accumulation and oxidative stress in CD38 overexpressing cell lines. In conclusion, our results demonstrated that CD38 deficiency prevented DN by inhibiting lipid accumulation and oxidative stress through activation of the SIRT3 pathway.

Quantum ghost imaging of a vector field.

Quantum ghost image technique utilizing position or momentum correlations between entangled photons can realize nonlocal reconstruction of the image of an object. In this work, based on polarization entanglement, we experimentally demonstrate quantum ghost imaging of vector images by using a geometric phase object. We also provide a corresponding theoretical analysis. Additionally, we offer a geometrical optics path explanation of ghost imaging for vector fields. The proposed strategy offers new insights into the fundamental development of ghost imaging and also holds great promise for developing complex structured ghost imaging techniques. Our work expanding the principle of ghost imaging to spatially varying vector beams will lead to interesting developments of this field.

Tetracycline Three Times Daily Versus Four Times Daily in Bismuth-Containing Quadruple Therapy as the First-Line Treatment of Helicobacter pylori Infection: A Multicenter, Noninferiority, Randomized Controlled Trial.

BACKGROUND: Current guidelines recommend bismuth-containing quadruple therapy for patients newly diagnosed with Helicobacter pylori (H. pylori) infection. We aimed to compare the efficacy and safety of tetracycline administered three times daily versus four times daily in bismuth-containing quadruple therapy for first-line treatment of H. pylori infection. METHODS: This multicenter, noninferiority, randomized controlled study, conducted in China, recruited treatment-naïve adults with H. pylori infection, randomized 1:1 into two treatment groups to receive either of the following bismuth-containing quadruple therapies: esomeprazole 20 mg twice-daily; bismuth 220 mg twice-daily; amoxicillin 1000 mg twice-daily; and tetracycline 500 mg three times daily (TET-T) versus 500 mg four times daily (TET-F). At least 6 weeks post-treatment, a 13C-urea breath test was performed to evaluate H. pylori eradication. RESULTS: In total, 406 patients were randomly assigned to the two treatment groups. Intention-to-treat eradication rates were 91.63% (186/203; 95% confidence interval [CI] 87.82%-95.44%) versus 90.15% (183/203; 95% CI 86.05%-94.25%) (p = 0.0005) and per-protocol eradication rates were 95.34% (184/193; 95% CI 92.36%-98.31%) versus 95.72% (179/187; 95% CI 92.82%-98.62%) (p = 0.0002) for the TET-T and TET-F group, respectively. TET-T-treated patients had a lower incidence of adverse effects than TET-F-treated patients (21.61% vs. 31.63%, p = 0.024), with no significant differences in compliance to treatment between the groups. CONCLUSION: As a first-line therapy for H. pylori infection, the eradication rate of the TET-T therapy was noninferior to that of the TET-F therapy while significantly reducing the incidence of adverse reactions. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05431075.

Small-molecule caspase-1 inhibitor CZL80 terminates refractory status epilepticus via inhibition of glutamatergic transmission.

Status epilepticus (SE), a serious and often life-threatening medical emergency, is characterized by abnormally prolonged seizures. It is not effectively managed by present first-line anti-seizure medications and could readily develop into drug resistance without timely treatment. In this study, we highlight the therapeutic potential of CZL80, a small molecule that inhibits caspase-1, in SE termination and its related mechanisms. We found that delayed treatment of diazepam (0.5 h) easily induces resistance in kainic acid (KA)-induced SE. CZL80 dose-dependently terminated diazepam-resistant SE, extending the therapeutic time window to 3 h following SE, and also protected against neuronal damage. Interestingly, the effect of CZL80 on SE termination was model-dependent, as evidenced by ineffectiveness in the pilocarpine-induced SE. Further, we found that CZL80 did not terminate KA-induced SE in Caspase-1-/- mice but partially terminated SE in IL1R1-/- mice, suggesting the SE termination effect of CZL80 was dependent on the caspase-1, but not entirely through the downstream IL-1ß pathway. Furthermore, in vivo calcium fiber photometry revealed that CZL80 completely reversed the neuroinflammation-augmented glutamatergic transmission in SE. Together, our results demonstrate that caspase-1 inhibitor CZL80 terminates diazepam-resistant SE by blocking glutamatergic transmission. This may be of great therapeutic significance for the clinical treatment of refractory SE.

Prediction of gastrointestinal symptoms trajectories using omega-3 and inflammatory biomarkers in early-stage breast cancer patients receiving chemotherapy.

PURPOSE: Gastrointestinal (GI) symptoms are common among breast cancer patients undergoing chemotherapy, negatively impacting treatment outcomes and quality of life. Evidence points to inflammatory processes as the underlying cause of chemotherapy-associated GI symptoms. Relatedly, omega-3 (n-3) has been linked to anti-inflammatory processes. The primary objective of this study was to examine the associations between baseline n-3, baseline inflammatory markers and GI symptom progression in early-stage breast cancer patients receiving chemotherapy. METHODS: In this secondary analysis of a prospective cohort study, we analyzed baseline levels of inflammatory biomarkers (measured using a Luminex bead-immunoassay) and plasma levels of DHA, EPA, and FFA (measured using enzyme-linked immunosorbent assay). GI symptoms were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire in Cancer Patients (EORTC QLQ-C30) symptom scale scores at baseline (T1) and at least 6 weeks after, during chemotherapy (T2). Inferential statistics were used to analyze associations between the variables of interest. RESULTS: The analysis included 31 female breast cancer patients (mean age ± SD = 50.5 ± 8.8; 89.6% receiving anthracycline-based chemotherapy). Higher levels of docosahexaenoic acid (DHA) and interleukin-8 (IL-8) predicted increases in appetite loss. Similarly, higher IL-8 predicted worsened nausea and vomiting. CONCLUSION: Baseline IL-8 and DHA predicted GI symptom progression in early-stage breast cancer patients undergoing chemotherapy. Future studies are required to evaluate how therapeutic intervention targeting these biomarkers may mitigate gastrointestinal symptoms in cancer patients.

Equity, diversity, and inclusion in the Multinational Association for Supportive Care in Cancer: a global membership survey.

Equity, diversity, and inclusion (EDI) are essential for healthcare organizations since they allow for the development of programs and initiatives that bring together diverse perspectives and knowledge. Global multidisciplinary organizations, such as the Multinational Association for Supportive Care in Cancer (MASCC), need to understand the perspective of their members regarding EDI to identify opportunities to enhance diversity and inclusiveness and to better meet the needs of members from different backgrounds and resources. The MASCC Health Disparities Committee designed a survey to identify issues related to disparities faced by MASCC members when providing supportive care to patients with cancer and to examine the EDI landscape within the organization. Here, we report results related to EDI initiatives within the organization. Two-hundred and eighteen MASCC members responded to the survey (response rate 10.2%). The results indicated that respondents were generally satisfied with how MASCC manages leadership, membership, and organization-related EDI issues. Opportunities for improvement noted by respondents included developing strategies to foster a more diverse membership, improving communication regarding diversity in the organization, and increasing EDI content in educational sessions and publications. The results of this survey represent the first attempt at understanding how to improve EDI within MASCC and will be utilized to guide further initiatives and programs.

The characterization and comorbidities of heterozygous Bardet-Biedl syndrome carriers.

Introduction: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical features of retinal dystrophy, obesity, postaxial polydactyly, renal anomalies, learning disabilities, hypogonadism, and genitourinary abnormalities. Nevertheless, previous studies on the phenotypic traits of BBS heterozygous carriers have generated inconclusive results. The aim of our study was to investigate the impact of BBS heterozygosity on carriers when compared to non-carriers within the Taiwanese population. Materials and Methods: This study follows a hospital-based case-control design. We employed the Taiwan Biobank version 2 (TWBv2) array to identify three specific loci associated with BBS (rs773862084, rs567573386, and rs199910690). In total, 716 patients were included in the case group, and they were compared to a control group of 2,864 patients who lacked BBS alleles. The control group was selected through gender and age matching at a ratio of 1:4. The association between BBS-related loci and comorbidity was assessed using logistic regression models. Results: We found that BBS heterozygous carriers exhibited a significant association with elevated BMI levels, especially the variant rs199910690 in MKS1 (p=0.0037). The prevalence of comorbidities in the carriers' group was not higher than that in the non-carriers' group. Besides, the average values of the biochemistry data showed no significant differences, except for creatinine level. Furthermore, we conducted a BMI-based analysis to identify specific risk factors for chronic kidney disease (CKD). Our findings revealed that individuals carrying the CA/AA genotype of the BBS2 rs773862084 variant or the CT/TT genotype of the MKS1 rs199910690 variant showed a reduced risk of developing CKD, irrespective of their BMI levels. When stratified by BMI level, obese males with the MKS1 rs199910690 variant and obese females with the BBS2 rs773862084 variant exhibited a negative association with CKD development. Conclusion: We found that aside from the association with overweight and obesity, heterozygous BBS mutations did not appear to increase the predisposition of individuals to comorbidities and metabolic diseases. To gain a more comprehensive understanding of the genetic susceptibility associated with Bardet-Biedl Syndrome (BBS), further research is warranted.

The current clinical landscape of neonatal respiratory failure in Jiangsu Province of China: patient demographics, NICU treatment interventions, and patient outcomes.

INTRODUCTION: Neonatal respiratory failure (NRF) is a serious condition that often has high mortality and morbidity, effective interventions can be delivered in the future by identifying the risk factors associated with morbidity and mortality. However, recent advances in respiratory support have improved neonatal intensive care units (NICUs) care in China. We aimed to provide an updated review of the clinical profile and outcomes of NRF in the Jiangsu province. METHODS: Infants treated for NRF in the NICUs of 28 hospitals between March 2019 and March 2022 were retrospectively reviewed. Data collected included baseline perinatal and neonatal parameters, NICU admission- and treatment-related data, and patient outcomes in terms of mortality, major morbidity, and survival without major morbidities. RESULTS: A total of 5548 infants with NRF were included in the study. The most common primary respiratory disorder was respiratory distress syndrome (78.5%). NRF was managed with non-invasive and invasive respiratory support in 59.8% and 14.5% of patients, respectively. The application rate of surfactant therapy was 38.5%, while that of neonatal extracorporeal membrane oxygenation therapy was 0.2%. Mortality and major morbidity rates of 8.5% and 23.2% were observed, respectively. Congenital anomalies, hypoxic-ischemic encephalopathy, invasive respiratory support only and inhaled nitric oxide therapy were found to be significantly associated with the risk of death. Among surviving infants born at < 32 weeks of gestation or with a birth weight < 1500 g, caffeine therapy and repeat mechanical ventilation were demonstrated to significantly associate with increased major morbidity risk. CONCLUSION: Our study demonstrates the current clinical landscape of infants with NRF treated in the NICU, and, by proxy, highlights the ongoing advancements in the field of perinatal and neonatal intensive care in China.

ENABLE-SG (Educate, Nurture, Advise, Before Life Ends for Singapore) as a proactive palliative care model: protocol for a hybrid type 1 effectiveness-implementation randomized wait-list controlled trial.

BACKGROUND: Specialist palliative care is often provided late in the patient's disease trajectory in response to uncontrolled symptoms. Shifting from this reactionary illness-stress paradigm to a proactive health-wellness approach, the ENABLE (Educate, Nurture, Advise, Before Life Ends) telehealth model aims to enhance the coping, stress and symptom management, self-care, and advance care planning skills of patients with advanced cancers and their caregivers. The ENABLE model has been culturally adapted to Singapore (ENABLE-SG) and pilot-tested. A hybrid type 1 effectiveness-implementation design will be used to evaluate the effectiveness of ENABLE-SG while collecting real-world implementation data. METHODS: This single-centre, assessor-blind, wait-list (immediately vs. 6 months) randomized controlled trial will recruit 300 adult patients within 60 days of an advanced cancer diagnosis and their family caregivers from the National Cancer Centre of Singapore. ENABLE-SG comprises structured psychoeducational sessions with a telehealth coach, covering essential topics of early palliative care. Participants will be assessed at baseline and every 3 months until patient's death, 12 months (caregivers), or end of study (patients). The primary outcome is patient quality of life 6 months after baseline. Secondary patient-reported outcomes include mood, coping, palliative care concerns, and health status. Secondary caregiver-reported outcomes include caregiver quality of life, mood, coping, and care satisfaction. Mixed-effects regression modelling for repeated measurements will be used. To assess the effectiveness of ENABLE-SG versus usual care, patient and caregiver outcomes at 6 months will be compared. To compare earlier versus delayed ENABLE-SG, patient and caregiver outcomes at 12 months will be compared. Within the hybrid type 1 effectiveness-implementation design, implementation outcomes will be evaluated in both the early and delayed groups. Acceptability, adoption, appropriateness, and feasibility will be assessed using a feedback survey and semi-structured interviews with a purposive sample of patients, caregivers, and healthcare providers. Transcribed interviews will be analysed thematically. Other implementation outcomes of penetration, fidelity, and cost will be assessed using records of study-related processes and summarized using descriptive statistics. A cost-effectiveness analysis will also be conducted. DISCUSSION: This study will assess both effectiveness and implementation of ENABLE-SG. Insights into implementation processes can facilitate model expansion and upscaling. TRIAL REGISTRATION: Registered prospectively on ClinicalTrials.gov, NCT06044441. Registered on 21/09/2023.

Neoscytalidium dimidiatum causing stem canker on Hylocereus megalanthus in China.

Hylocereus megalanthus (syn. Selenecereus megalanthus), commonly known as Yanwo fruit (bird's nest fruit), is an important tropical fruit, which is popular and widely planted due to its high nutritional and economic value in southern China. In September 2022, a serious stem and fruit canker was observed on Ecuadorian variety of Yanwo fruit plant in a 0.2 ha orchard in Guangdong (N21°19'1.24" E110°7'28.49"). Almost all plants were infected and disease incidence of fruits and stems was about 80% and 90% respectively. Symptoms on the stem and fruits were small, circular or irregular, sunken, orangish brown spots that developed into cankers (Fig 1 A, B and C). Black pycnidia were embedded under the surface of the cankers at the initial stage, subsequently they became erumpent from the surface, and the infected parts rotted. Five symptomatic stems from five plants were collected, 0.2 cm2 tissues adjacent to cankers were surface sterilized and placed on potato dextrose agar (PDA) to incubate at 25 to 28 ℃. Fungal isolates each with similar morphology grew from 100% of the tissues. Colonies covered with aerial mycelium were grayish white, and then gradually turned to grayish black. Septate hyphae were hyaline to brown and constricted into arthroconidial chains. The arthroconidia were variously shaped and colored, orbicular to rectangular, hyaline to dark brown, thick-walled, and zero- to one- septate, averaging 7.7 × 3.6 µm (n>50) (Fig 1 D, E, F and G). To identify the fungus, the internal transcribed spacer region (ITS), translation elongation factor 1-alpha (tef1), beta-tubulin (tub2), histone H3 (his3) and chitin synthase (chs) gene of isolate ACCC 35488 and ACCC 35489 (Agricultural Culture Collection of China) were amplified and sequenced with primer pairs: ITS1/ITS4 (White et al. 1990), EF1-728F/EF2-rd (Carbone & Kohn 1999; O'Donnell et al.1998), TUB2Fd/ TUB4Rd（Aveskamp et al 2009）, CYLH3F/H3-1b (Crous et al. 2004) and CHS-79F/CHS-345R (Carbone & Kohn 1999) (ITS: OQ381102 and PP488350; tef1: OQ408545 and PP510454; tub2: OQ408546 and PP510455; his3: OQ408544 and PP510453; chs: OQ408543 and PP510452). Sequence Blastn results showed above 99% identical with those of Neoscytalidium dimidiatum ex-type strain CPC38666. Phylogenetic tree inferred from Maximum Likelihood analysis of the combined ITS, tub2 and tef1 sequences revealed two isolates clustered with N. dimidiatum (Fig 2). Pathogenicity was tested on healthy one-year-old cuttings and fruits of Ecuadorian variety at room temperature. Six sites were pin-pricked on each stem and fruit. Both wounded stems and fruits were inoculated with spore suspensions (106 spore/ml) and 6-mm fungal plugs respectively. Sterile water and agar were used as control. The test was repeated twice. Stems and fruits were enclosed in plastic boxes with 80% relative humidity. Symptoms described above were observed on inoculated stems and fruits at five days post inoculation (Fig 1 H and I). No symptoms developed on the controls. Neoscytaliudium dimidiatum was reisolated from the cankers with a frequency of 100% via morphological and molecular analysis. This is first report of stem and fruit canker caused by N. dimidiatum on H. megalanthus in China and this disease represents a serious risk of Yanwo fruit yield losses. This fungus is widespread occurring throughout the world causing diseases on a wide variety of plants. The finding will be helpful for its prevention and control.

Occurrence of Cassava (Manihot esculenta) Leaf Spot Disease Caused by Diaporthe ueckeri in China.

Cassava (Manihot esculenta) is a perennial crop of the family Euphorbiaceae, widely cultivated due to its phytopharmacological and economic values in China. In November 2022, a leaf spot disease on cassava was observed in Zhanjiang, Guangdong, China (21.17° N, 110.18° E), with 100% disease incidence. About 80 % of leaves were covered with spots on the infected plants. Typical symptoms initially appeared as irregular water-soaked lesions that became brown and whitish with the progress of the disease, lesions gradually expanded and coalesced, causing leaf withering, drying and final fall. Tissues (4 to 5 mm) were excised from the margin of lesions, sterilized in 3% H2O2 solution for 3 min, rinsed three times with sterile water, placed on potato dextrose agar (PDA) medium (containing 50mg/L penicillin), and incubated at 25-28 °C. Ten single hypha isolates with similar morphology were obtained and further purified as single conidium subcultures. The colony was grey whitish with sparse aerial mycelium and colony diameter reached 70.4 mm after four days incubation at 25-28℃ in the dark. Black pycnidia occurring as clusters were spherical or irregular, erumpent at maturity, often with a creamy whitish, conidial cirrus extruding from ostiole after 30-days incubation. Conidiophores were hyaline, smooth, unbranched. Alpha conidia were bi-guttulate, hyaline, ellipsoidal, aseptate, with dimensions of 5.1~7.5×1.9~3.4µm (mean 6.2×2.8 µm, n>50). Beta conidia were abundant, filiform, hyaline, smooth, curved in a hooked shape, with a truncate base and dimensions of 18.5-26.4 × 0.6-1.2µm (mean 23.4 × 1.0 µm, n= 40) . Gamma conidia were not observed. The morphological characteristics were similar to those of Diaporthe ueckeri (Udayanga et al. 2015). The internal transcribed spacer (ITS) region, large subunit (LSU) rRNA sequence, actin (ACT), calmodulin (CAL), histone H3 (HIS), translation elongation factor 1-alpha (TEF1-α), and ß-tubulin (TUB) genes of a representative isolate CCAS-MS-6 (ACCC 35497) were amplified and sequenced using primer pairs: ITS5/ITS4, LR0R/LR5, ACT-512F/ACT-783R, CAL228F/CAL737R, CYLH3F/ H3-1b, EF1-728F/ EF1-986R and Bt2a/Bt2b (Gao et al 2017；Udayanga et al 2014). All sequences were deposited in GenBank (OR361671, OR361672, and OR365605-9). BLAST search showed high similarities with sequences of Diaporthe ueckeri (Tab 1). Maximum likelihood analyses of the concatenated data of CAL, HIS, ITS, TEF and TUB using Mega 11 placed CCAS-MS-6 in the D. ueckeri clade. Thus, the fungus was identified as D. ueckeri. Three one-year old healthy plants were used for pathogenicity tests in pots. Two 15-day old leaves of each plant were cleaned with 75% alcohol, three sites on each leaf were wounded, and sites on one of the leaf were covered with fungal plugs from 15-day-old cultures on PDA, and sites on the other leaf with PDA plugs as a control. All plants were kept at ambient temperature (about 28℃) and covered with plastic bags containing sterile wet cotton to maintain the humidity. Seven days after inoculation, all inoculated sites showed symptoms of necrosis, while control sites showed no symptoms. The same fungus identified on the basis of morphological and molecular criteria was reisolated from symptomatic inoculated leaves. In China, D. ueckeri had been reported to cause diseases on Eucalyptus citriodora, Camellia sinensis, and Michelia shiluensis (Gao et al 2016; Liao et al 2023; Yi et al 2018), this is the first report on M. esculenta. The definition of the disease etiology is a prerequisite to develop effective management strategies.

Smooth-Muscle-Cell-Specific Deletion of CD38 Protects Mice from AngII-Induced Abdominal Aortic Aneurysm through Inhibiting Vascular Remodeling.

Abdominal aortic aneurysm (AAA) is a serious vascular disease which is associated with vascular remodeling. CD38 is a main NAD+-consuming enzyme in mammals, and our previous results showed that CD38 plays the important roles in many cardiovascular diseases. However, the role of CD38 in AAA has not been explored. Here, we report that smooth-muscle-cell-specific deletion of CD38 (CD38SKO) significantly reduced the morbidity of AngII-induced AAA in CD38SKOApoe-/- mice, which was accompanied with a increases in the aortic diameter, medial thickness, collagen deposition, and elastin degradation of aortas. In addition, CD38SKO significantly suppressed the AngII-induced decreases in α-SMA, SM22α, and MYH11 expression; the increase in Vimentin expression in VSMCs; and the increase in VCAM-1 expression in smooth muscle cells and macrophage infiltration. Furthermore, we demonstrated that the role of CD38SKO in attenuating AAA was associated with the activation of sirtuin signaling pathways. Therefore, we concluded that CD38 plays a pivotal role in AngII-induced AAA through promoting vascular remodeling, suggesting that CD38 may serve as a potential therapeutic target for the prevention of AAA.

[Comparison of the efficacy of LARS ligament and autogenous hamstring tendon plus high-strength suture in posterior cruciate ligament reconstruction].

OBJECTIVE: To compare the clinical efficacy of ligament advanced reinforcement system (LARS) and autogenous hamstring tendon plus high-strength suture in arthroscopic reconstruction of posterior cruciate ligament(PCL). METHODS: A total of 96 patients with simple PCL injury treated with arthroscopic posterior cruciate ligament reconstructive surgery admitted to our hospital between August 2019 and December 2021 were selected for complete follow-up. There were 78 males and 18 females, 40 cases of left leg and 56 cases of right leg, the aged from 20 to 56 years old with an average of (32.50±8.68 ) years old. The transplants were divided into two groups:LARS group (52 cases) and autogenous hamstring tendon plus high-strength suture group (44 cases). In the LARS group, there were 42 males and 10 females;with an average age of (31.84±8.62) years old;body mass index (BMI) was (24.73±2.29) kg﹒m-2;7 mm LARS was used to reconstruct PCL. In the autologous tendon group, there were 36 males and 8 females, with an average age of (33.06±8.99) years old, BMI was (23.52±2.16) kg·m-2, and the PCL was reconstructed with four strands of hamstring tendons and three pieces of Ethibond suture. All patients underwent functional rehabilitation guided exercise and were followed up regularly after surgery to objectively evaluate the stability of the knee joint by KT-1000 measurement of knee relaxation, and subjective evaluation of knee function by Lysholm score, Tegner score, and International Knee Documentation Council (IKDC) score. Data from preoperative, 3, 6, and 12 month follow-up were collected and analyzed by SPSS software to compare postoperative recovery and ligament relaxation between the two groups of patients. RESULTS: Ninety-six patients were followed up for 12 months. KT-1000 measurement of knee joint in autogenous tendon group and LARS group before operation [(10.73±1.46) points vs (10.55±1.53) points], 6 months after operation[(3.02±0.75) points vs (2.35±0.60) points], 12 months after operation[(3.77±1.76) points vs (2.44±0.60) points]. There was significant difference between the two groups at 6 and 12 months after operation (P<0.05), but there was no significant difference between the two groups at 3 months after operation (P>0.05). In the autogenous tendon group and LARS group, before operation and 12 months after operation, total Lysholm score [(40.6±16.8), (91.25±6.35) points vs (51.92±18.52), (92.35±5.30) points], Tegner score[(1.8±0.7), (5.8±0.6) points vs(1.7±0.8)、(5.7±0.7) points] and total IKDC score[(54.50±6.33), (83.90±3.93) points vs (54.40±4.24), (83.62±3.64) points], the differences were statistically significant (P<0.05), indicating that the knee function of the two groups was improved after surgery. At 3 and 6 months after operation in the autogenous tendon group and LARS group, the total Lysholm score[(65.86±11.54), (74.60±6.46) points vs (73.46±6.42), (86.73±4.62) points], Tegner score[(2.5±0.6), (3.5±0.5) points vs (4.3±0.7), (5.0±1.4) points], the total scores of IKDC [(55.78±2.68), (70.62±4.74) points vs (65.31±4.60), (79.71±2.93) points]. The difference between two groups was statistically significant (P<0.05). The results showed that the function of the knee joint in the LARS group was better than that the autologous tendon group. However, at 12 months after the operation, there was no significant difference in the score of knee joint function between the two groups (P>0.05). The results showed that the stability of LARS group was better than that of autologous tendon group. CONCLUSION: Both the autogenous hamstring tendon plus high-strength suture and LARS reconstruction can significantly improve the knee function and stability, with satisfactory postoperative results. Howervr the LARS provides superior postoperative stability.

Differentiation of Acute Leukemia Cells Including Cells with MLL-AF4 Rearrangements Induced by Jiyuan Oridonin A.

BACKGROUND: Chromosomal rearrangements involving the Mixed lineage leukemia (MLL) gene are observed in acute leukemia (AL) patients, which have poor prognosis, especially in infants. Hence, there is still a challenge to develop other effective agents to treat AL with MLL rearrangements (MLLr). MLL has been shown to rearrange with partner genes, of which the most frequently observed are AF4 and AF9. Moreover, AL is characterized by a differentiation blockage resulting in the accumulation of immature cells. An ent-kaurene diterpenoid compound, Jiyuan Oridonin A (JOA), has been shown to reduce the viability of AML cells by differentiation. METHODS: We aimed to evaluate the effect of JOA on the growth and differentiation of AL cells (SEM, JURKAT and MV4-11) including cells with MLLr-AF4 by cell proliferation assay, colony formation assay, cell cycle analysis, cell apoptosis analysis, measurement of cell surface antigens, cell morphology, mRNA-sequencing analysis, quantitative Real-time PCR and Western blotting analysis. RESULTS: Our findings demonstrated that the proliferation of AL cells including cells with MLLr-AF4 was significantly suppressed by JOA, which induced cell differentiation followed by G0/G1 cell cycle withdrawal. Moreover, JOA-mediated cell differentiation was likely due to activation of G-CSFR in MV4-11 cells. CONCLUSION: Our results suggest that JOA may be considered a promising anti-leukemia compound to develop to surmount the differentiation block in AL patients.

A systematic literature review of the epidemiology and burden of herpes zoster in selected locales in Asia Pacific.

Herpes zoster (HZ) is a painful rash which typically affects older adults. This is of concern in Asia-Pacific given its aging population. As HZ epidemiology and burden are evolving, this systematic literature review aimed to update the current understanding of HZ burden and associated costs for selected Asia-Pacific locales. MEDLINE and Embase were searched for English articles of HZ studies conducted in Australia, China, Hong Kong, Japan, Korea, New Zealand, Singapore, and Taiwan. Eligible outcomes included HZ incidence and prevalence, occurrence of HZ-related complications, healthcare resource utilization, costs, and HZ-associated quality of life outcomes. This paper focused on HZ data in the general adult population (N = 90 articles). Substantial HZ-related disease and economic burden were observed in these locales, consistent with global trends. These findings reinforce the increasing burden of HZ and need for preventive strategies, which may include raising awareness and encouraging timely vaccination.

Herpes zoster, also known as shingles, is a painful rash that usually resolves after a few weeks, although some people experience serious or long-lasting complications. Shingles is common, affecting around one in every three individuals in their lifetime, and older persons are more likely to have shingles. Given the aging population in the Asia-Pacific region, shingles represents an increasingly important health issue as the proportion of older people increases. Vaccination can help prevent shingles and avoid its complications. New data on the trends and burden of shingles in this region are regularly generated. Therefore, in this study, we looked at studies from selected countries published over the past twenty years to summarize the latest available information on: how many people experience shingles in selected Asia-Pacific areas, how these individuals and societies are affected, and the related costs. Consistent with previous research, this study observed an increasing trend in the number of persons with shingles and costs of managing it, especially in older adults. In populations that are aging, there is a need for ways to reduce the risk of shingles and to lessen its burden on the healthcare system and society. Our findings can help to inform current development of strategies to reduce the risk of shingles, including education (on the burden and risk of shingles) and encouraging uptake of preventive measures.

Feasibility of Weekly Integrated Palliative Care Outcome Scale (IPOS) Within a Stepped Care Model.

CONTEXT: Patients with advanced cancer may experience symptoms and concerns that are inadequately identified by the healthcare team, leading to calls for patient-reported symptom monitoring. OBJECTIVES: Assess the feasibility of administering weekly patient-reported online Integrated Palliative care Outcome Scale (IPOS) questionnaires within the context of a stepped care model in the outpatient care setting. METHODS: Analysis of intervention group data in a randomized controlled trial to assess the effectiveness of a stepped care model of palliative care for patients with advanced cancer. Patients in the intervention group were invited to complete the IPOS weekly for 16 weeks through a remotely-administered online questionnaire. At the end of the 16-week period, patients were invited to complete a feedback survey. Multivariable logistic regression was used to assess factors associated with more versus less than 70% completion of weekly questionnaires. RESULTS: Among 111 patients who survived more than 16 weeks, the mean number of questionnaires completed was 9.2/16 (58%). A total of 53 out of the 111 patients (48%) completed more than 70% of the questionnaires. Higher education level was found to be associated with higher completion of the questionnaires. A total of 79 out of 111 (71%) patients responded to the feedback survey, of which 67 (85%) felt comfortable with completing the online questionnaire and 11 (14%) felt it was troublesome to complete it on a weekly basis. CONCLUSION: In our study, there was suboptimal completion of patient-reported IPOS questionnaire. Further research is needed to improve the uptake of patient-reported outcomes in real-world clinical settings.

Exploring usage pattern variation of free-floating bike-sharing from a night travel perspective.

Free-floating bike sharing (FFBS) attracts increasing research focusing on usage patterns, determining factors, and integrated transportation. However, existing researchers tend to overlook the variation in usage characteristics over various time ranges, particularly the usage pattern at night. This paper is conducted to fill the gap through a series of analysis approaches on FFSB in Beijing. The characteristics of the usage pattern, including time-varying usage and traveling distance distributions, are initially illustrated. Subsequently, the spatial patterns of FFBS are visualized and thoroughly analyzed in different time ranges and origin-destination (O-D) flows. A statistical model evaluating the environmental effects of FFBS trips revealed the source of FFBS usage. In addition to focusing on the nighttime, the usage patterns varying day and night are compared through the analysis. The findings explain the usage pattern variation and the unique pattern at night, providing valuable insight for improving the management of the FFBS system.

Pituitary metastasis from lung adenocarcinoma: A case report.

BACKGROUND: Pituitary gland metastasis is an unusual event, and pituitary metastasis from lung adenocarcinoma is extremely rare and associated with poor prognosis. To date, approximately 15 cases have been reported. CASE SUMMARY: Here, we present the case of a 64-year-old woman with pituitary metastasis derived from lung adenocarcinoma, which was difficult to distinguish from other sellar tumors. The patient presented to the neurosurgery clinic with blurred vision and intermittent headache. During hospitalization, brain computed tomography (CT) and magnetic resonance imaging revealed a pituitary macroadenoma. Chest CT revealed irregular nodules in the basal segment of the lower lobe of the left lung, which were likely lung cancer. Positron emission tomography-CT revealed a carbohydrate metabolism tumor in the lungs and sellar region, which was considered malignant. Postoperative pathological examination of the sellar tumor revealed lung adenocarcinoma. CONCLUSION: Excision of pituitary metastases combined with radiotherapy and chemotherapy should be a priority treatment for patients with pituitary metastasis.

Efficacy and safety of eszopiclone combined with drug therapy in the treatment of insomnia after stroke: A network meta-analysis and systematic review.

OBJECTIVE: To evaluate the efficacy and safety of multi-drug therapy based on eszopiclone in the treatment of insomnia after stroke using a network meta-analysis method and to provide evidence for clinical practice. METHOD: Computer searches of PubMed, Excerpt Medica Database (Embase), Cochrane Library Central Register of Controlled Trials, APA PsycInfo, CNKI, WanFang, Sinomed and other databases were performed to search for clinical randomized controlled studies (RCTs) on multi-drug therapy based on eszopiclone in the treatment of insomnia patients after stroke. The search time was from the establishment of each database until July 2023. The bias risk assessment tool recommended by Cochrane was used to evaluate the quality of the included RCTs. Stata 14.0 was applied to perform network meta-analysis using Review Manager 5.3 software for traditional meta-analysis. RESULT: Eighteen RCTs and 1646 patients were ultimately included, involving 11 treatment options. The results of the network meta-analysis showed that the ranking of Pittsburgh Sleep Quality Index (PSQI) decline was eszopiclone combined with sweet dream oral liquid (ESZ+SDOL)>eszopiclone combined with a shugan jieyu capsule (ESZ+SGJYC)>eszopiclone combined with agomelatine (ESZ+AGO)>eszopiclone combined with flupentixol and melitracen tablets (ESZ+FMT)>eszopiclone combined with yangxue qingnao granules (ESZ+YXQNG)>eszopiclone combined with mirtazapine (ESZ+MIR)>ESZ>FMT; the modified Edinburgh Scandinavia Stroke Scale (MESSS) decline ranking was ESZ+SDOL>ESZ+AGO>ESZ; and the clinical total effective rate ranking was eszopiclone combined with a xuefu zhuyu capsule (ESZ+XFZYC)>ESZ+MIR>ESZ+SGJYC>ESZ+SDOL> ESZ+FMT>ESZ+YXQNG>ESZ>FMT. In terms of clinical adverse reactions, in addition to ESZ therapy, ESZ+ESC had the highest number of adverse reactions, with abdominal pain being the most common. ESZ+YXQNG had the most types of adverse reactions, with 8 types. CONCLUSION: Multi-drug therapy based on eszopiclone can effectively improve the sleep quality of patients with insomnia after stroke, and ESZ+SDOL has significant efficacy and safety. However, due to the limitations of this study, efficacy ranking cannot fully explain the superiority or inferiority of clinical efficacy. In the future, more multicentre, large sample, double-blind randomized controlled trials are needed to supplement and demonstrate the results of this study.

New Insights into the Umami and Sweet Taste of Oolong Tea: Formation of Enhancer N-(1-carboxyethyl)-6-(hydroxymethyl) pyridinium-3-ol (Alapyridaine) in Roasting Via Maillard Reaction.

Roasting is pivotal for enhancing the flavor of Wuyi rock tea (WRT). A study investigated a novel compound that enhances the umami taste of WRT. Metabolomics of Shuixian tea (SXT) and Rougui tea (RGT) under light roasting (LR), medium roasting (MR), and heavy roasting (HR) revealed significant differences in nonvolatiles compounds. Compared LR reducing sugars and amino acids notably decreased in MR and HR, with l-alanine declining by 69%. Taste-guided fractionation identified fraction II-B as having high umami and sweet intensities. A surprising taste enhancer, N-(1-carboxyethyl)-6-(hydroxymethyl) pyridinium-3-ol (alapyridaine), was discovered and identified. It formed via the Maillard reaction, positively correlated with roasting in SXT and RGT. Alapyridaine levels were highest in SXT among the five oolong teas. Roasting tea with glucose increased alapyridaine levels, while EGCG inhibited its formation. HR-WRT exhibited enhanced umami and sweet taste, highlighting alapyridaine's impact on WRT's flavor profile. The formation of alapyridaine during the roasting process provides new insights into the umami and sweet perception of oolong tea.