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Hai-Yan Ma,1,2 Xue-Mei Wang,1,2 Xiao-Jie Huang,2 Cheng-Jia Yang,2 Dong-Fang Sheng,2 Jing-Jing Yang,2 Ming-Zhi Xu2 1The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Guangdong Mental Health Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, People’s Republic of ChinaCorrespondence: Ming-Zhi XuGuangdong Mental Health Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, No. 123 Huifu West Road, Guangzhou, 510120, Guangdong, People’s Republic of ChinaTel +86 81888553Fax +86 81862664Email mingzhixu@126.comObjective: This study aimed to evaluate the psychometric properties of the Chinese version of the Clinically Useful Depression Outcome Scale (CUDOS).Methods: One hundred ninety patients with major depressive disorder (MDD) according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria were recruited to the study. The English version of the CUDOS was translated into Chinese using a forward and backward translation method, which was according to the guidelines of adaptation and validation of instruments in cross-cultural health care research. The Chinese version of the CUDOS, the 17-item Hamilton Rating Scale for Depression (HRSD) and the improved Clinical Global Impression-Severity Scale (iCGI-S) were used to evaluate depressive symptoms in one hundred ninety patients with MDD. One week after the first evaluation, sixteen patients were selected randomly for a second assessment. Reliability and validity tests and receiver operating characteristic curves were performed.Results: The internal consistency of the CUDOS was 0.95, and the split-half reliability coefficient of the CUDOS was 0.92. The correlation coefficient of the retest in sixteen patients was 0.77 (P < 0.01). There was a significant difference in the total score of the Chinese version of the CUDOS between the different levels of depression severity groups (P < 0.01). The ability of the CUDOS to identify patients in remission was high (area under ROC curve= 0.97). A cut-off score of 14/15 yielded 90.20% sensitivity and 93.60% specificity when iCGI-S=1.Conclusion: The Chinese version of the CUDOS is valuable as a brief and reliable instrument to assess depressive symptoms and clinical outcome. The findings suggest that the optimal cut-off score to identify patients in remission was 14/15.Keywords: MDD, the Chinese version of CUDOS, validity, reliability, cut-off score

The association between lumbar bone mineral density (BMD) and triglyceride (TG) levels has been extensively studied; however, the results remain controversial. Therefore, this research aimed to elucidate the association of TG levels with lumbar BMD in patients with osteoporotic fractures (OPFs) who have undergone surgery. This cross-sectional study analyzed 3,558 OPF patients (aged 50 years and above) who were admitted to the First People's Hospital of Kunshan and assessed their TG levels, lumbar BMD, and other variables. The outcome variable of this research was bone density, whereas the baseline glycerol trihydrate levels were considered as the exposure variable. An analysis adjustment was conducted for various covariates, including age, gender, body mass index (BMI), and other baseline laboratory and clinical results. Furthermore, the potential non-linear relationships were assessed via the smooth curve fitting, and threshold effect analyses. The mean age of 3,558 included OPF patients was 68.87 ± 10.55 years. In the fully adjusted multivariate regression analysis, a positive correlation was found between TG levels and lumbar BMD (β = 0.015, 95% CI: 0.001-0.028, p = 0.033). Furthermore, the threshold effect analysis revealed a curvilinear relationship between TG levels and lumbar BMD, with a turning point at 1.26 mmol/L. Moreover, on both sides of the turning point, different patterns were observed. On the left side, TG levels were positively correlated with lumbar BMD. However, despite higher TG levels, the differences in lumbar BMD on the right side of the turning point, were not statistically significant, indicating a lack of significant association (p = 0.712). In summary, this research indicated that in OPF patients, higher TG levels were significantly positively associated with lumbar BMD. Furthermore, there was a threshold value of 1.26 mmol/L, indicating that TG levels in OPF patients with concomitant hypertriglyceridemia should be maintained within the normal range, and reducing TG levels below 1.26 mmol/L requires continuous monitoring. This approach effectively controls TG levels without adversely impacting lumbar BMD., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: We received ethical approval from the Affiliated Kunshan Hospital of Jiangsu University (approval No. 2021-06-015-K01), and was compliant with the Declaration of Helsinki. Consent to participate: Informed consent was obtained from all individual patients included in the study. Consent to publish: Patients signed informed consent regarding publishing their data., (© 2024. The Author(s).)

Hepatic alveolar echinococcosis is a zoonotic disease with a high incidence in western China, particularly affecting plateau areas such as Qinghai, Tibet, and Xinjiang. Research has indicated the presence of neovascularization in the peripheral infiltration area of hepatic alveolar echinococcosis, with a strong correlation between angiogenesis and vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor 1-alpha (HIF-1α) overexpression. Given the similarities between hepatic alveolar echinococcosis and liver cancer, current research is focused on treating the disease by targeting related signaling pathways using molecular drugs used for liver cancer. This article aims to summarize the biological regulation of HIF-1α and VEGFA overexpression in angiogenesis related to hepatic alveolar echinococcosis, as well as the impact of the BMP9-ID1 signaling pathway on the expression levels of HIF-1α and VEGFA, providing new insights for potential treatment strategies., 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 Ke, Xu, Ma, Chen, He and A.)

The association between inflammatory markers (IMs) and bone turnover markers (BTMs) in osteoporotic fracture patients has not been comprehensively studied. Therefore, this study examined the correlation between the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), or Monocyte-to-lymphocyte ratio (MLR) and BTMs in osteoporosis (OP) fracture patients. This retrospective cross-sectional study analyzed 740 OP fracture patients admitted to the hospital from January 2017 to July 2022. MLR, NLR, and PLR were calculated based on each patient's complete blood count. The relationship between IMs and BTMs was assessed using three models by adjusting variables. Furthermore, the potential curve relationship between IMs and BTMs was also determined via the threshold effect analysis and curve fittings. In addition, stratified analysis was performed on each adjusted variable to confirm the stability of the results. After adjusting the variables, the results showed that NLR was negatively correlated with procollagen type 1 N-terminal propeptide (P1NP) (β = -1.1788, 95% CI: -1.7230 to -0.6345, P-value < 0.0001) and β-C-terminal telopeptide of type I collagen (β-CTX) (β = -0.0104, 95% CI: -0.0145 to -0.0062, P-value < 0.0001), Furthermore, MLR was negatively correlated with P1NP (β = -17.4523, 95% CI: -27.7335 to -7.1710, P-value = 0.0009) and β-CTX (β = -0.1327, 95% CI: -0.2211 to -0.0443, P-value = 0.0034). However, PLR indicated a positive correlation with P1NP (β = 0.0326, 95% CI: 0.0007 to 0.0645, P-value = 0.0458) and β-CTX (β = 0.0003, 95% CI: 0.0001 to 0.0006, P-value = 0.0204). The threshold effect analysis and curve fittings revealed the presence of a turning point between NLR, MLR, and P1NP, β-CTX. In addition, the stratified analysis validated the result's stability. In conclusion, this study indicates a negative correlation between NLR and MLR with P1NP, while PLR shows a positive correlation with P1NP. Additionally, NLR and MLR exhibit a negative correlation with β-CTX, whereas PLR demonstrates a positive correlation with β-CTX. Further research is required to assess the intricate mechanisms linking IM with bone metabolism., (© 2024. The Author(s).)

This study aimed to investigate the effects of Shuanglongjiegu pill (SLJGP) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explore its mechanism based on miR-217/RUNX2 axis. Results found that drug-containing serum of SLJGP promoted BMSCs viability with a dose-dependent effect. Under osteogenic differentiation conditions, SLJGP promoted the expression of ALP, OPN, BMP2, RUNX2, and the osteogenic differentiation ability of BMSCs. In addition, SLJGP significantly reduced miR-217 expression, and miR-217 directly targeted RUNX2. After treatment with miR-217 mimic, the promoting effects of SLJGP on proliferation and osteogenic differentiation of BMSCs were significantly inhibited. MiR-217 mimic co-treated with pcDNA-RUNX2 further confirmed that the miR-217/RUNX2 axis was involved in SLJGP to promote osteogenic differentiation of BMSCs. In addition, analysis of Wnt/β-catenin pathway protein expression showed that SLJGP activated the Wnt/β-catenin pathway through miR-217/RUNX2. In conclusion, SLJGP promoted osteogenic differentiation of BMSCs by regulating miR-217/RUNX2 axis and activating Wnt/β-catenin pathway., (© 2024. The Author(s).)

We conducted a retrospective cohort analysis to examine the association between hemoglobin (Hb) levels and refracture risk in elderly patients with osteoporotic fractures (OPFs). Our findings suggest a nonlinear relationship exists in females, and females with Hb levels below 10.7 g/dL may be at a higher risk of refracture., Introduction: Hematopoiesis and bone health have a reciprocal influence on each other. Nevertheless, there is a scarcity of in-depth research on the association between Hb levels and the occurrence of fractures. The present research aimed to investigate the correlation between Hb levels and the rate of refracture within 5 years among individuals with OPFs., Methods: A retrospective cohort analysis was undertaken between 2017 and 2022. The study included 1906 individuals who were inhabitants of Kunshan and were over 60 years old. These individuals had experienced an OPF between January 1, 2017, and July 27, 2022, resulting in their hospitalization. Cox proportional hazard regression models were used to evaluate the risk of refracture within 5 years based on the Hb levels acquired during the admission examination, with consideration for sex differences. A nonlinear relationship was identified using smoothed curve fitting and threshold analysis. Kaplan-Meier curves were used to compare refracture rates between patients with low and high Hb levels., Results: Elderly female patients with OPFs and lower Hb levels exhibited a significantly higher risk of a 5-year refracture. Conversely, no significant associations were observed between the two variables in male patients. A nonlinear correlation was found between Hb levels and the probability of refracture in females, with a turning point identified at 10.7 g/dL of Hb levels. A strong negative association was observed with the five-year refracture rate when Hb levels fell below 10.7 g/dL (hazard ratio (HR) = 0.63; 95% confidence interval (CI) 0.48 to 0.83; P-value = 0.0008). This finding suggests that for every 1 g/dL increase in Hb below 10.7 g/dL, the risk of refracture reduced by 37%. However, no statistically significant association was observed when Hb levels were above 10.7 g/dL., Conclusions: The findings demonstrated a significant negative correlation between Hb levels and the likelihood of refracture in elderly female patients with OPFs and suggested that elderly females with recent OPFs and Hb levels below 10.7 g/dL may be at a higher risk of refracture. Additionally, the Hb levels can serve as an indicator of bone fragility in elderly female patients with OPFs. These findings highlight the importance of monitoring Hb levels as a part of comprehensive management strategies to both assess skeletal health and prevent refractures in this population., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Objective: To evaluate the correlation between the triglyceride-glucose (TyG) index and bone turnover markers (BTMs) in osteoporotic fractures (OPFs) patients hospitalized for surgical intervention., Methods: A retrospective cross-sectional study was conducted on 3558 OPFs patients hospitalized for surgical intervention between January 2017 and July 2022. The study obtained baseline values for various biomarkers and covariates, including fasting blood glucose, β-C-terminal telopeptide of type I collagen (β-CTX), procollagen type 1 N-terminal propeptide (P1NP), triglycerides, age, sex, body mass index, smoking, drinking, low-density lipoprotein, high-density lipoprotein, aspartate aminotransferase, uric acid, the score of American society of anesthesiologists, homocysteine, parathyroid hormone, apolipoprotein B, apolipoprotein A, magnesium, phosphorus and calcium. Multiple linear regression, curve fitting, threshold effects, and subgroup analyses were also applied., Results: After adjusting for covariates in the regression analysis, the results revealed a negative correlation between β-CTX and P1NP levels and the baseline TyG index. Specifically, a one-unit increase in the TyG index was associated with a reduction in β-CTX levels of -0.06 (95% CI: -0.10, -0.01; P-value = 0.012) and a reduction in P1NP levels of -4.70 (95% CI: -9.30, -0.09; P-value = 0.046). Additionally, the inflection points for the nonlinear correlation between the TyG index and β-CTX and P1NP were found to be K = 6.31 and K = 6.63, respectively., Conclusion: The study demonstrated a negative, non-linear relationship among the TyG index, β-CTX and P1NP in OPFs patients hospitalized for surgical intervention. These findings suggest that elevated TyG index levels may adversely affect bone turnover, potentially contributing to the progression of OP., 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, Guo, Xu, Li, Gong and Lu.)

Megaloptera larvae are important bioindicator species and potential resource insects. To further cultivate their economic role, their living environment must be examined in more detail. In this study, we analyzed the physiological and biochemical effects of a sublethal dose of imidacloprid, a widely used neonicotinoid insecticide, on the larvae of Protohermes xanthodes. After treatment with imidacloprid, P. xanthodes larvae exhibited clear symptoms of poisoning, including the head curling up toward the ventral surface. Additionally, the activity of acetylcholinesterase was significantly inhibited following exposure. The activities of glutathione S-transferases initially continuously increased but showed a slight decrease after 8 days. Catalase activity initially increased and then decreased following imidacloprid treatment; superoxide dismutase activity fluctuated over time, and peroxidase activity continuously increased. The expression levels of HSP70s genes were evaluated using qRT-PCR. These results indicate that P. xanthodes larvae exhibit a toxic response to imidacloprid exposure, manifested as oxidative stress, as observed through behavioral and physiological indicators., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The relationship between the levels of high-density lipoprotein (HDL) and bone mineral density (BMD) is controversial. Furthermore, the specific role of apolipoprotein A1 (APOA1), a primary HDL component, in regulating BMD remains unclear. This study aimed to elucidate the correlation between APOA1 levels and lumbar BMD in patients with osteoporotic fracture (OPF) for novel insights into potential therapeutic strategies against osteoporosis., Methods: This study included 587 OPF patients enrolled at the Kunshan Hospital, Affiliated with Jiangsu University between January 2017 and July 2022. The patient's serum APOA1 levels were determined, followed by the assessment of lumbar BMD and C-terminal telopeptide of type I collagen (β-CTX) as outcome variables. The association of APOA1 levels with lumbar BMD and β-CTX was assessed via Generalized Estimating Equations (GEE) and spline smoothing plot analyses. A generalized additive model (GAM) helped ascertain non-linear correlations. Moreover, a subgroup analysis was also conducted to validate the result's stability., Results: It was observed that APOA1 levels were positively correlated with lumbar BMD (β = 0.07, 95% CI: 0.02 to 0.11, p = 0.0045), indicating that increased APOA1 levels were linked with enhanced lumbar BMD. Furthermore, APOA1 levels were negatively related to β-CTX (β = -0.19, 95% CI: -0.29 to -0.09, p = 0.0003), suggesting APOA1 might reduce osteolysis. In addition, these findings were robustly supported by subgroup and threshold effect analyses., Conclusion: This study indicated that increased APOA1 levels were correlated with enhanced lumbar BMD and decreased osteolysis in OPF patients. Therefore, APOA1 may inhibit osteoclast activity to prevent further deterioration in osteoporotic patients. However, further research I warranted to validate these conclusions and elucidate the underlying physiologies., 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 Feng, Lu, Li, Xu, Ye, Yin and Shan.)

Background: The systemic inflammatory response index (SIRI) is a novel composite biomarker of inflammation. However, there is limited information on its use in the context of osteoporotic fractures. Hence, this study aimed to investigate the association between baseline SIRI values and bone turnover markers (BTMs) in Chinese patients diagnosed with osteoporotic fractures (OPFs), to offer a more precise method for assessing bone health and inflammation in clinical settings., Methods: A retrospective cross-sectional study was conducted on 3,558 hospitalized patients with OPFs who required surgery or hospitalization at the First People's Hospital of Kunshan City from January 2017 to July 2022. Baseline measurements of SIRI, β-CTX (beta-C-terminal telopeptide of type I collagen), and P1NP (procollagen type I N-terminal propeptide) were obtained. The analyses were adjusted for variables, including age, sex, body mass index (BMI), and other initial laboratory and clinical findings. Furthermore, multivariable logistic regression, smooth curve fitting, and threshold analysis were also performed., Results: The results revealed a negative correlation between baseline SIRI values and both β-CTX and P1NP levels. After adjusting for covariates in the regression analysis, each unit increase in SIRI was found to be inked to a reduction of 0.04 ( β  = -0.04; 95% confidence interval [CI], -0.05 to -0.03; with p -value <0.001) in β-CTX levels and a decrease of 3.77 ( β  = 3.77; 95% CI, 5.07 to 2.47; with p -value <0.001) in P1NP levels. Furthermore, a curvilinear relationship and threshold effect were also identified. Turning points were identified at SIRI values of 1.41 and 1.63 on the adjusted smooth curve., Conclusion: The results showed a negative correlation between the baseline SIRI value and β-CTX level, as well as the level of P1NP. This suggests a possible link between the systemic inflammatory response and reduced bone metabolism. If these findings are verified, SIRI has the potential to function as a predictive indicator for BTMs. Nevertheless, additional research is necessary to verify these findings., 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 Zhou, Lu, Li, Xu, Ye, Shan and Yin.)

The relationship between the Systemic Inflammatory Response Index (SIRI) and the Fibrinogen-to-albumin ratio (FAR) has not been extensively investigated. The objective of this study was to determine the independent relationship between FAR and SIRI in people with osteoporotic fractures (OPF). A cross-sectional study was conducted using retrospective data from 3431 hospitalized OPF patients. The exposure variable in this study was the baseline FAR, while the outcome variable was the SIRI. Covariates, including age, gender, BMI, and other clinical and laboratory factors, were adjusted. Cross-correlation analysis and linear regression models were applied. The generalized additive model (GAM) investigated non-linear relationships. Adjusted analysis revealed an independent negative association between FAR and SIRI in OPF patients (β = - 0.114, p = 0.00064, 95% CI - 0.180, - 0.049). A substantial U-shaped association between FAR and SIRI was shown using GAM analysis (p < 0.001). FAR and SIRI indicated a negative association for FAR below 6.344% and a positive correlation for FAR over 6.344%. The results of our study revealed a U-shaped relationship between SIRI and FAR. The lowest conceivable FAR for a bone-loose inflammatory disease might be 6.344%, suggesting that this has particular significance for the medical diagnosis and therapy of persons with OPF. Consequently, the term "inflammatory trough" is proposed. These results offer fresh perspectives on controlling inflammation in individuals with OPF and preventing inflammatory osteoporosis., (© 2024. The Author(s).)

Background: To examine the factor structure and psychometric properties of the Patient Health Questionnaire for Adolescents (PHQ-A) in Chinese children and adolescents with major depressive disorder (MDD)., Methods: A total of 248 MDD patients aged between 12 and 18 years were recruited and evaluated by the Patient Health Questionnaire for Adolescents (PHQ-A), the Center for Epidemiological Survey Depression Scale (CES-D), the Mood and Feelings Questionnaire (MFQ), and the improved Clinical Global Impression Scale, Severity item (iCGI-S). Thirty-one patients were selected randomly to complete the PHQ-A again one week later. Confirmatory factor analysis (CFA) was used to test the construct validity of the scale. Reliability was evaluated by Macdonald Omega coefficient. Pearson correlation coefficient was used to assess the item-total correlation and the correlation of PHQ-A with CES-D and MFQ respectively. Spearman correlation coefficient was used to assess test-retest reliability. The optimal cut-off value, sensitivity, and specificity of the PHQ-A were achieved by estimating the Receiver Operating Characteristics (ROC) curve., Results: CFA reported adequate loadings for all items, except for item 3. Macdonald Omega coefficient of the PHQ-A was 0.87. The Spearman correlation coefficient of the test-retest reliability was 0.70. The Pearson correlation coefficients of the PHQ-A with CES-D and MFQ were 0.87 and 0.85, respectively (p < 0.01). By taking the iCGI-S as the remission criteria for MDD, the optimal cut-off value, sensitivity and specificity of the PHQ-A were 7, 98.7%, 94.7% respectively., Conclusion: The PHQ-A presented as a unidimensional construct and demonstrated satisfactory reliability and validity among the Chinese children and adolescents with MDD. A cut-off value of 7 was suggested for remission., (© 2024. The Author(s).)

C-oligosaccharides are found in natural products and drug molecules. Despite the considerable progress made during the last decades, modular and stereoselective synthesis of C-oligosaccharides continues to be challenging and underdeveloped compared to the synthesis technology of O-oligosaccharides. Herein, we design a distinct strategy for the stereoselective and efficient synthesis of C-oligosaccharides via palladium-catalyzed nondirected C1-H glycosylation/C2-alkenylation, cyanation, and alkynylation of 2-iodoglycals with glycosyl chloride donors while realizing the difunctionalization of 2-iodoglycals. The catalysis approach tolerates various functional groups, including derivatives of marketed drugs and natural products. Notably, the obtained C-oligosaccharides can be further transformed into various C-glycosides while fully conserving the stereochemistry. The results of density functional theory (DFT) calculations support oxidative addition mechanism of alkenyl-norbornyl-palladacycle (ANP) intermediate with α-mannofuranose chloride and the high stereoselectivity of glycosylation is due to steric hindrance., (© 2024. The Author(s).)

Objectives: To establish a radiomics model for distinguishing between the benign and malignant mammary gland nodules via combining the features from nodule and mammary regions on DCE-MRI., Methods: In this retrospective study, a total of 103 cases with mammary gland nodules (malignant/benign = 80/23) underwent DCE-MRI, and was confirmed by biopsy pathology. Features were extracted from both nodule region and mammary region on DCE-MRI. Three SVM classifiers were built for diagnosis of benign and malignant nodules as follows: the model with the features only from nodule region (N model), with the features only from mammary region (M model) and the model combining the features from nodule region and mammary region (NM model). The performance of models was evaluated with the area under the curve of receiver operating characteristic (AUC)., Results: One radiomic features is selected from nodule region and 3 radiomic features is selected from mammary region. Compared with N or M model, NM model exhibited the best performance with an AUC of 0.756., Conclusions: Compared with the model only using the features from nodule or mammary region, the radiomics-based model combining the features from nodule and mammary region outperformed in the diagnosis of benign and malignant nodules., 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 Fan, Sun, Xu, Pan and Man.)

Background: Few studies have examined the relationship between perioperative blood transfusion (PBT) and length of hospital stay (LOS) in patients with osteoporotic fractures. This research aims to study the association between PBT and LOS., Methods: This is a retrospective cross-sectional study from the Affiliated Kunshan Hospital of Jiangsu University, Suzhou, China, involving 2357 osteoporotic fractures (OPF) patients who received surgical treatment during hospitalization from January 2017 and March 2022. Multiple linear regression was used to analyze the relationship between PBT and LOS. In the analysis, PBT volume was the dependent variable, whereas LOS was the independent variable. Simultaneously, age, gender, body mass index, hemoglobin, primary diagnosis, American Society of Anesthesiologists, creatinine (Cr), anesthesia, surgical method, and Charlson comorbidity index were included as covariates. The generalized additive model was then used to study nonlinear associations. Two piecewise linear regression exemplary evaluated the inception results for smoothing the curve., Results: Our results proved that PBT was positively correlated with LOS in the fully adjusted model (β, 0.21; 95% CI, 0.04 to 0.37; P < 0.0001). Furthermore, a "U-shape" nonlinear relationship existed between PBT and LOS. When the concentration of PBT was between 0 and 1.5 units, it was manifested as a negative correlation between PBT and LOS. However, there was a positive association between PBT and LOS when PBT levels exceeded 1.5 units., Conclusions: This study demonstrated that PBT and LOS in the OPF population were independent with a nonlinear relationship. These results suggest that PBT may be protective for patients with long LOS. If these findings are confirmed, the LOS in OPF patients can be regulated through appropriate perioperative blood transfusion., (© 2023. The Author(s).)

Objectives: Venetoclax has shown synergism with BCR-ABL1 tyrosine kinase inhibitors (TKIs) in preclinical studies for patients with Philadelphia chromosome-positive (Ph+) leukemias. This combination may suggest a novel treatment strategy for Ph + leukemias., Methods: We conducted a retrospective study to summarize the activity of combining venetoclax and BCR-ABL1 TKI-based therapies in Ph + leukemias., Result: A total of 18 patients with Ph + leukemias were enrolled in this study. At the time of venetoclax and TKI-based therapy, 5 patients were initially diagnosed, with Ph + acute myeloid leukemia (AML) (n = 1) and mixed phenotype acute leukemia (MPAL) (n = 4), 7 patients had chronic myeloid leukemia at blastic phase (CML-BP), and the remaining 6 patients had relapsed or refractory to prior therapy. The overall response rate (ORR) was 88.9% (9 CR, 2 CRi, 4 MLFS, 1 PR), and a major molecular response (MMR) (or better) was achieved in 7 (38.8%) of all patients. With a median follow-up of 7.0 months (range, 2.3-15.6), 15 (83.3%) were in continuous CR at the time of this analysis, with a 1-year OS of 85.6%, 1-year LFS of 76.7%, and 1-year CIR of 22.4%. Moreover, 10 of 18 patients were treated with venetoclax, TKI and hypomethylating agent (HMA) regimens, which also associated with a high ORR rate (6 CR, 1 CRi, 3 MLFS), and can be used for induction or salvage therapy., Conclusion: Venetoclax and TKI-based combination regimens may be a feasible approach for Ph + leukemias, and prospective studies are needed to properly assess the safety, tolerability and efficacy of this regimen.

Background: Preoperative anxiety management is gaining particular attention in paediatric anaesthesia. Pharmacological and non-pharmacological resorts can be implemented to address this special issue. Despite the various approaches currently used for preoperative sedation in children, the different sedative and anti-anxiety effects between the newly marketed anaesthetic, S-ketamine, and the traditional sedative, midazolam, are still unclear., Methods: This is a patient- and assessor-blinded randomized controlled clinical trial. Participants (n = 110) will receive S-ketamine (0.5 mg/kg) or midazolam (0.08 mg/kg) intravenously administrated at a ratio of 1:1 in the anaesthesia holding area. The primary outcome of this study is the sedative effect evaluated via the change in the modified Yale preoperative anxiety scale. It will be performed at two timepoints: in the pre-anaesthetic holding area before premedication (baseline, marked as T0) and about 5 min after premedication in the operating room without the existence of their guardians (marked as T1). Our secondary objectives include the parent separation anxiety score, postoperative agitation, caregivers' and anaesthesia care providers' satisfaction, and mask compliance., Discussion: This randomized controlled trial is the first study to compare the anti-anxiety effect of intravenous S-ketamine and midazolam. We will provide a new approach for the clinical management of preoperative anxiety in preschool children posted for elective surgery., Trial Registration: ChiCTR2300069998. Registered on 30 March 2023., (© 2023. The Author(s).)

Osteoporosis (OP) is often associated with other complications, such as impaired glucose homeostasis. Vitamin D deficiency is common and has been linked to bone metabolism and the regulation of blood sugar levels. The aim of this study was to evaluate the independent relationship between serum 25-hydroxyvitamin D (25[OH]D) and fasting blood glucose levels (FBG) in a group of patients diagnosed with OP. This is a retrospective cross-sectional study from a prospectively collected database at our tertiary referral center. Consecutive 2084 OP patients who were hospitalization were finally analyzed in this study. FBG is the dependent variable, serum 25(OH)D level of OP patients is exposure variable of this study. There was a linear significantly negative association between serum 25(OH)D and FBG (β, - 0.02; 95% CI - 0.03 to - 0.01; P = 0.0011) in the fully adjusted models. Specifically, when serum 25(OH)D level was less than 23.39 ng/mL, FBG decreased by 0.04 mmol/L for every 1 ng/mL increase of serum 25(OH)D level. When serum 25(OH)D was greater than 23.39 ng/ mL, the negative association was insignificant (P = 0.9616). If the association is confirmed, the clinical management of blood glucose in OP patients with serum 25(OH)D deficiency has instructive implications., (© 2023. The Author(s).)

The purpose of this study was to evaluate the psychometric features of the Chinese version of the developmental dimensional diagnostic interview-short version (3Di-sv). A total sample of 138 children including 79 children with autism spectrum disorder (ASD) and 59 typically developing children completed the 3Di-sv interview. The Chinese version of the 3Di-sv has a good internal consistency (0.94). Test-retest analysis confirmed the instrument's time stability (0.89). The instrument's concurrent validity with the Autism Behavior Checklist (ABC), the Childhood Autism Rating Scale (CARS) and clinical diagnosis was verified; the correlation between total scores was 0.72, 0.82 and 0.90, respectively. The 3Di-sv significantly distinguished between autistic children and non-autistic children in every area of autism symptoms. Optimal cutoffs were derived using receiver operating characteristics curves. Using clinical diagnosis as criterion, overall sensitivity was 98 % and specificity was 90 %. The study determined that the Chinese version of 3Di-sv can well distinguish autistic children from typically developing children., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests. None of the authors received royalties/training fees from 3Di., (Copyright © 2023. Published by Elsevier B.V.)

We conducted a single-arm, open-label, single-center phase 1 study to assess the safety and efficacy of multicycle-sequential anti-CD19 chimeric antigen receptor (CAR) T-cell therapy in combination with autologous CD19+ feeding T cells (FTCs) and tyrosine kinase inhibitor (TKI) as consolidation therapy in patients under the age of 65 years with de novo Ph-positive CD19+ B-cell acute lymphoblastic leukemia. Participants were given induction chemotherapy as well as systemic chemotherapy with TKI. Afterward, they received a single cycle of CD19 CAR T-cell infusion and another 3 cycles of CD19 CAR T-cell and CD19+ FTC infusions, followed by TKI as consolidation therapy. CD19+ FTCs were given at 3 different doses. The phase 1 results of the first 15 patients, including 2 withdrawals, are presented. The most common adverse events were cytopenia (13/13) and hypogammaglobinemia (12/13). There was no incidence of cytokine release syndrome above grade 2 or immune effector cell-associated neurotoxicity syndrome or grade 4 nonhematological toxicities. All 13 patients achieved complete remission, including 12 patients with a complete molecular response (CMR) at the data cutoff. The relapse-free survival was 84%, and the overall survival was 83% with a median follow-up of 27 months. The total number of CD19-expressing cells decreased with an increasing CMR rate. CD19 CAR T cells survived for up to 40 months, whereas CD19+ FTCs vanished in 8 patients 3 months after the last infusion. These findings could form the basis for the development of an allo-HSCT-free consolidation paradigm. This trial was registered at www.clinicaltrials.gov as #NCT03984968., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: In the literature, scarce data investigate the link between 25-hydroxyvitamin D (25[OH]D) and blood lipids in the osteoporosis (OP) population. 25(OH)D, as a calcium-regulating hormone, can inhibit the rise of parathyroid hormone, increase bone mineralization to prevent bone loss, enhance muscle strength, improve balance, and prevent falls in the elderly. This retrospective cross-sectional study aimed to investigate the association between serum 25(OH)D levels and lipid profiles in patients with osteoporosis, with the objective of providing insight for appropriate vitamin D supplementation in clinical settings to potentially reduce the incidence of cardiovascular disease, which is known to be a major health concern for individuals with osteoporosis., Methods: This is a retrospective cross-sectional study from the Affiliated Kunshan Hospital of Jiangsu University, including 2063 OP patients who received biochemical blood analysis of lipids during hospitalization from January 2015 to March 2022. The associations between serum lipids and 25(OH)D levels were examined by multiple linear regression. The dependent variables in the analysis were the concentrations of serum lipoprotein, total cholesterol (TC), triglycerides (TGs), apolipoprotein-A, lipoprotein A, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol (LDL-C). The independent variable was the concentration of blood serum 25(OH)D. At the same time, age, body mass index, sex, time and year of serum analysis, primary diagnosis, hypertension, diabetes, statins usage, beta-C-terminal telopeptide of type I collagen, procollagen type I N-terminal propeptide were covariates. Blood samples were collected in the early morning after the overnight fasting and were analyzed using an automated electrochemiluminescence immunoassay on the LABOSPECT 008AS platform (Hitachi Hi-Tech Co., Ltd., Tokyo, Japan). The generalized additive model was further applied for nonlinear associations. The inception result for smoothing the curve was evaluated by two-piecewise linear regression exemplary., Results: Our results proved that in the OP patients, the serum 25(OH)D levels were inversely connected with blood TGs concentration, whereas they were positively associated with the HDL, apolipoprotein-A, and lipoprotein A levels. In the meantime, this research also found a nonlinear relationship and threshold effect between serum 25(OH)D and TC, LDL-C. Furthermore, there were positive correlations between the blood serum 25(OH)D levels and the levels of TC and LDL-C when 25(OH)D concentrations ranged from 0 to 10.04 ng/mL. However, this relationship was not present when 25(OH)D levels were higher than 10.04 ng/mL., Conclusions: Our results demonstrated an independent relationship between blood lipids and vitamin D levels in osteoporosis patients. While we cannot establish a causal relationship between the two, our findings suggest that vitamin D may have beneficial effects on both bone health and blood lipid levels, providing a reference for improved protection against cardiovascular disease in this population. Further research, particularly interventional studies, is needed to confirm these associations and investigate their underlying mechanisms., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To examine the psychometric properties of the Chinese version of the Clinically Useful Depression Outcome Scale (CUDOS) in the Chinese patients with major depressive disorder (MDD) using Rasch analysis., Methods: The sample consisted of 283 patients with MDD (69% females). The Rasch model was applied to examine the overall fit of the Chinese version of CUDOS and the fit of the 18 items. Dimensionality, item-model fit, differential item functioning (DIF), reliability, ordering of response category and targeting were tested to examine the psychometric properties of the Chinese version of CUDOS., Results: Rasch analysis demonstrated the unidimensionality of the Chinese version of CUDOS. Of the 18 items, three items (item 4, item 5, item 6) showed misfit in the model. After merging item 4 into item 3 and item 6 into item 5, the overall model fit improved. The person separation index (PSI) was 3.0 and the person reliability coefficient was 0.90. No evidence of significant DIF was found when associated with gender and age. No disordered category and threshold of the rating response were observed, which meant the response category setting was reasonable. The mean ability of person was - 0.53., Conclusion: The results suggested that the Chinese version of CUDOS has acceptable psychometric properties. In order to improve the quality and applicability of the Chinese version of CUDOS, the merging of item 4 into item 3 and item 6 into item 5 are suggested., (© 2023. The Author(s).)

Background: The results of studies exploring the association between serum uric acid (SUA) and bone mineral density (BMD) have been controversial and inconsistent. We thus sought to explore whether SUA levels were independently associated with BMD in patients with osteoporosis (OP)., Methods: This cross-sectional analysis was conducted using prospectively obtained data from the Affiliated Kunshan Hospital of Jiangsu University database pertaining to 1,249 OP patients that were hospitalized from January 2015 - March 2022. BMD was the outcome variable for this study, while baseline SUA levels were the exposure variable. Analyses were adjusted for a range of covariates including age, gender, body mass index (BMI) and a range of other baseline laboratory and clinical findings., Results: SUA levels and BMD were independently positively associated with one another in OP patients. Following adjustment for age, gender, BMI, blood urae nitrogen (BUN), and 25(OH)D levels, a 0.0286 g/cm 2 (β, 0.0286; 95% confidence interval [CI], 0.0193-0.0378, P < 0.000001) increase in BMD was observed per 100 μmol/L rise in SUA levels. A non-linear association between SUA and BMD was also observed for patients with a BMI < 24 kg/m 2 , with a SUA level inflection point at 296 μmol/L in the adjusted smoothed curve., Conclusions: These analyses revealed SUA levels to be independently positively associated with BMD in OP patients, with an additional non-linear relationship between these two variables being evident for individuals of normal or low body weight. This suggests that SUA levels may exert a protective effect on BMD at concentrations below 296 μmol/L in normal- and low-weight OP patients, whereas SUA levels above this concentration were unrelated to BMD., (© 2023. The Author(s).)

Background: Despite widespread acknowledgment of the impact of stressful life events on suicide risk, the understanding of the psychological mechanisms underlying the relationship between stressful life events and suicide risk in major depressive disorder (MDD) remain unclear. This study aim to examine whether the distress tolerance mediates the relationship between the stressful life events and suicide risk in patients with MDD., Methods: A cross-sectional study was carried out among 125 Chinese patients with MDD, mean age was 27.05 (SD=0.68) and 68.8% were females. The 17-item Hamilton Depression Rating scale (HAMD-17), the validated Chinese version of the Mini International Neuropsychiatric Interview (MINI) suicide module, Life Events Scale (LES) and Distress Tolerance Scale (DTS) were utilized to evaluate depressive symptoms, stressful life events, levels of distress tolerance, and suicide risk, respectively. Mediation analyses was used to test the mediation effect of distress tolerance on the relationship between stressful life events and suicide risk., Results: The ratio of suicide risk in patients with MDD was 75.2%. Pearson correlation analysis showed that stressful life events were positively correlated with suicide risk(r=0.182, p<0.05). Stressful life events(r=-0.323, p<0.01) and suicide risk(r=-0.354, p<0.01) were negatively correlated with distress tolerance. Mediation analyses showed that the direct path from stressful life events to suicide risk was not significant (B= 0.012, 95% confidence interval (CI) [-0.017, 0.042]). Stressful life events affected suicide risk indirectly through distress tolerance (B= 0.018, 95% CI [0.007, 0.031]), and the mediating effect accounted for 60.0% of the total effect., Conclusion: Distress tolerance completely played a mediating role between stressful life events and suicide risk. Further suicide prevention and intervention strategies should focus on increasing levels of distress tolerance in patients with MDD., (© 2023. The Author(s).)

In obese patients, non-alcoholic fatty liver (NAFLD) is common. However, whether there is a connection between the gut microbiota and the onset of NAFLD in obese people is yet unknown. Using quantitative real-time PCR, the microbiota of feces of the eligible 181 obese individuals was identified to compare the differences in gut microbiota between obesity with NAFLD and simple obesity. According to the findings, the gut dominant microbiota was similar between obesity with NAFLD and simple obesity. Nonetheless, compared to the simple obesity group, the quantity of Faecalibacterium prausnitzii colonies was much lower in the obesity with the NAFLD group. Bacteroides were present in greater than 65% of both groups. Bacteroides , Clostridium leptum , and Clostridium butyricum accounted for more than 80% of the cases in the obesity with NAFLD group, whereas Bacteroides , Clostridium butyricum , and F. prausnitzii accounted for more than 80% of the cases in the simple obesity group. We look for potential contributing variables to obesity-related NAFLD and potential prevention measures for obese people. Based on a multi-factor logistic regression analysis, lymphocytes may be a risk factor for obesity with NAFLD while F. prausnitzii may be a protective factor. Additionally, F. prausnitzii is positively impacted by Bacteroides , Clostridium leptum , Clostridium butyricum , and Eubacterium rectale , yet adversely impacted by Enterobacteriaceae. Notably, lymphocytes and F. prausnitzii may help determine whether obese patients would develop NAFLD., 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 Jin and Xu.)

In this study, novel bioavailable selenium nanoparticles with controllable particle size and low toxicity were developed. With selenium modified zein nanoparticles (zein NPs) in-situ, dispersed nano-selenium particles with different structure were formed simultaneously. The particle size, zeta potential, morphology and binding mechanism of synthesized zein-selenium nanoparticles (zein-Se NPs) were systematically discussed. Selenium was considered to be combined with OH and -CO-NH- groups of zein. The selenium in the complex particles presented an amorphous structure with zero valence. The cytotoxicity of zein-Se NPs was significantly lower than that of sodium selenite, even exhibited a growth-promoting effect on normal liver cells (L-02), and were proven to be orally absorbed by organisms in vivo experiments. The difference in particle structure had certain effects on cytotoxicity and oral targeting. The complex particles obtained by this method were anticipated be further used as food fortifiers or medicines., 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.)

Objective: The present study aimed to equate the 9-item Patient Health Questionnaire (PHQ-9) and 7-item Generalized Anxiety Disorder Scale (GAD-7) to the Hospital Anxiety and Depression Scale (HADS) depression and anxiety subscales (HADS-D,HADS-A) respectively in patients with major depressive disorder (MDD) and generate crosswalks of raw scores., Methods: As it is a single group design that adopts common-person equating method, a total of 460 patients with MDD completed the PHQ-9, GAD-7 and HADS at the same time. Rasch analysis was used to filter out invalid participants, investigate the psychometric properties of test items and participants, link the PHQ-9 and HADS-D as well as GAD-7 and HADS-A, and produce conversion tables respectively. The differences between original scores and converted scores were analyzed to validate the crosswalks., Result: 401 samples of depression part and 396 samples of anxiety part were left for final samples. Both the PHQ-9 / HADS-D and GAD-7 / HADS-A combined analysis adequately fit the unidimensional Rasch model, demonstrated acceptable reliability and item-person targeting and showed no disordering category. Slight differential item functioning across gender was found in item PHQ9 and item GAD6. The crosswalks were generated and verified to be validity., Limitations: The results might be restricted to patients with MDD recruited in a single mental health center., Conclusion: The PHQ-9, GAD-7 and HADS depression and anxiety subscales were successfully linked, producing conversion tables that could be used for directly converting raw score from one instrument to the other., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background & Aims: Numerous studies have evaluated the effects of dietary protein on specific health outcomes. The aim of our umbrella review was to summarize the existing evidence between the intake of dietary proteins and multiple health outcomes, and assess their strength and validity., Methods: Our study was registered at PROSPERO (No. CRD42021255938). We systematically searched PubMed, Embase, and Web of Science databases from inception to May 18, 2021, to identify relevant systematic reviews and meta-analyses of observational studies. The validated "A Measurement Tool to Assess Systematic Reviews" for assessing the methodological quality of included systematic reviews was utilized. For each association, we estimated the summary effect size using fixed and random effects methods, and the 95% confidence and prediction intervals. We also evaluated heterogeneity, evidence of small-study effects, and excess significance bias., Results: Overall, 16 articles with 58 meta-analyses were included. All studies were categorized as over moderate quality. On employing the random-effects model, fourteen (24.1%) meta-analyses were found to be significant at P < 0.05, whereas only one (1.7%) remained significant at P < 10 -6 . Twenty-two (37.9%) meta-analyses had large or very large heterogeneity. Evidence of small-study effects and excess significance bias was found for three (5.2%) meta-analyses, respectively. One meta-analysis was supported by highly suggestive evidence, indicating that a 5% increase in energy intake from animal protein was associated with 12% higher risk of type 2 diabetes (95% confidence interval [CI]: 1.08-1.17). Of note, the intake of animal and plant proteins had different health effects on type 2 diabetes, all-cause mortality, and risk of cardiovascular disease mortality., Conclusions: Although the intake of dietary protein was associated with certain health outcomes, the strength of evidence was limited for most outcomes. Moreover, the source of dietary protein is an important factor that requires better consideration in future studies., Competing Interests: Conflicts of Interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Objectives: The objective of this research was to verify the psychometric characteristics of the Chinese Adaptation of self-report HAMD-6., Methods: Outpatients and inpatients who met the DSM-5 criterion for major depressive disorder (MDD) were evaluated by the Chinese self-report HAMD-6, seventeen items of Hamilton Depression Rating Scale (HAMD-17), Patient Health Questionnaire Depression Scale (PHQ-9) and Improved Clinical Global Impression Scale (iCGI-S). The internal consistency reliability, retest reliability, criterion validity and construct validity of the Chinese self-report HAMD-6 were tested. Pearson correlation coefficient was used to assess the correlativity between the total score and the item scores. By drawing the Receiver Operating Characteristics (ROC) curve, the best cut-off value, sensitivity and specificity of Chinese Adaptation self-report HAMD-6 were obtained., Results: Cronbach's alpha coefficient of the Chinese self-report HAMD-6 was 0.91, and the intra-group correlation coefficient (ICC) of retest reliability was 0.81(P < 0.01). The Spearman correlation coefficients of the Chinese self-report HAMD-6, Chinese clinician version of HAMD-6, PHQ-9 and HAMD-17 were 0.86, 0.81 and 0.86, respectively (all P < 0.01). Results of the confirmatory factor analysis (CFA) supported a unidimensional construct. In addition, HAMD-17 ≤ 7 and iCGI-S= 1 were taken as the remission criteria for depression disorder, and the ROC curves of the Chinese self-report HAMD-6 were plotted with a cut-off value of 3/4, the specificity and sensitivity were 0.85/0.92 and 0.96/0.93 respectively., Conclusion: These results suggested that the abbreviated Chinese self-report HAMD-6 has good reliability and validity among the Chinese population. This study suggested that the remission cut-off value of the scale is 3/4., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We studied an amorphous solid dispersion of berberine with absorption enhancer sodium caprate (Huang-Gui solid dispersion preparations, HGSD). A therapeutic effect of HGSD was revealed in mice with type 2 diabetes mellitus and palmitate-induced injury to MIN6 β-cells. HGSD treatment (150 mg/kg) improved glucose metabolism and decreased β-cell apoptosis in diabetic mice. Furthermore, the effective component of HGSD berberine significantly attenuated the palmitate-induced decrease in MIN6 β-cells viability and insulin secretion. Moreover, molecular docking analysis and Western blotting showed that berberine decreased cell apoptosis and expression of group VIA phospholipase A 2 (iPLA 2 ), p38 mitogen-activated protein kinase (p38 MAPK), and caspase-3. These data suggest that HGSD treatment protected β-cells via inhibiting the iPLA 2 /p38 MAPK pathway., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Purpose: Generation of cGMP via NO-sensitive soluble guanylyl cyclase (sGC) has been implicated in the regulation of renal functions. Chronic kidney disease (CKD) is associated with decreased NO bioavailability, increased oxidative stress and oxidation of sGC to its haem-free form, apo-sGC. Apo-sGC cannot be activated by NO, resulting in impaired cGMP signalling that is associated with chronic kidney disease progression. We hypothesised that sGC activators, which activate apo-sGC independently of NO, increase renal cGMP production under conditions of oxidative stress, thereby improving renal blood flow (RBF) and kidney function., Experimental Approach: Two novel sGC activators, runcaciguat and BAY-543, were tested on murine kidney. We measured cGMP levels in real time in kidney slices of cGMP sensor mice, vasodilation of pre-constricted glomerular arterioles and RBF in isolated perfused kidneys. Experiments were performed at baseline conditions, under L-NAME-induced NO deficiency, and in the presence of oxidative stress induced by ODQ., Key Results: Mouse glomeruli showed NO-induced cGMP increases. Under baseline conditions, sGC activator did not alter glomerular cGMP concentration or NO-induced cGMP generation. In the presence of ODQ, NO-induced glomerular cGMP signals were markedly reduced, whereas sGC activator induced strong cGMP increases. L-NAME and ODQ pretreated isolated glomerular arterioles were strongly dilated by sGC activator. sGC activator also increased cGMP and RBF in ODQ-perfused kidneys., Conclusion and Implication: sGC activators increase glomerular cGMP, dilate glomerular arterioles and improve RBF under disease-relevant oxidative stress conditions. Therefore, sGC activators represent a promising class of drugs for chronic kidney disease treatment., Linked Articles: This article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc., (© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Pathogenic bacteria infections have posed a threat to human health worldwide. Nanomaterials with natural enzymatic activity provide an opportunity for the development of new antibacterial pathways. We successfully constructed iron phosphate nanozyme-hydrogel (FePO 4 -HG) with the traits of positive charge and macropores. Interestingly, FePO 4 -HG displayed not only peroxidase-like activity under acidic bacterial infectious microenvironment but also superoxide dismutase-catalase-like synergistic effects in neutral or weak alkaline conditions, thus protecting normal tissues from the peroxidase-like protocol with exogenous H 2 O 2 damage. Furthermore, the positive charge and macropore structure of FePO 4 -HG could capture and restrict bacteria in the range of ROS destruction. Obviously, FePO 4 -HG exhibited excellent antibacterial ability against MRSA and AREC with the assistance of H 2 O 2 . Significantly, the FePO 4 -HG + H 2 O 2 system could efficiently disrupt the bacterial biofilm formation and facilitate the glutathione oxidation process to rapid bacterial death with low cytotoxicity. Moreover, FePO 4 -HG was unsusceptible to bacterial resistance development in MRSA. Animal experiments showed that the FePO 4 -HG + H 2 O 2 group could efficiently eliminate the MRSA infection and present excellent wound healing without inflammation and tissue adhesions. With further development and optimization, FePO 4 -HG has great potential as a new class of antibacterial agents to fight antibiotic-resistant pathogens.

Background: Maternal smoking during pregnancy may be associated with low birth weight (LBW) in offspring and global risk estimates have not been summarized previously. We aimed to systematically explore evidence regarding maternal smoking and the LBW risk in offspring globally and examine possible causes of heterogeneity across relevant studies., Methods: Comprehensive search of PubMed, Ovid Embase, Ovid Medline (R), and Web of science from inception until October 2021 was carried out. A random-effects meta-analysis was used to estimate the pooled odds ratio (OR) and corresponding 95% confidence interval (CI). Restricted cubic spline analysis with three knots was used to further examine the dose-response relationship., Results: Literature searches yielded 4940 articles, of which 53 met inclusion criteria (comprising 55 independent studies). Maternal smoking during pregnancy was significantly associated with the risk of LBW in offspring (OR = 1.89, 95% CI = 1.80-1.98). Furthermore, an obvious dose-response relationship between the amount of cigarettes daily smoked in pregnancy and the risk of LBW in offspring was observed. The results of subgroup analyses indicated that the risk of maternal smoking on LBW was larger in more recently conducted studies (P = 0.020) and longer period of active smoking during pregnancy (P = 0.002). No evidence of publication bias was found., Conclusions: In summary, maternal smoking in pregnancy was significantly associated with a higher risk of LBW in offspring on a global scale. The risk of maternal smoking on infant LBW seems to be increasing over time, and was higher with longer smoking duration throughout pregnancy and more cigarettes smoked daily., (© 2022. Children's Hospital, Zhejiang University School of Medicine.)

Objective: To explore the role of chidamide, decitabine plus priming regimen in the salvage treatment of relapsed/refractory acute myeloid leukemia., Methods: A clinical trial was conducted in relapsed/refractory acute myeloid leukemia patients using chidamide, decitabine, cytarabine, idarubicin, and granulocyte-colony stimulating factor, termed CDIAG, a double epigenetic priming regimen., Results: Thirty-five patients were recruited. Three patients received 2 treatment cycles. In 32 evaluable patients and 35 treatment courses, the completed remission rate (CRR) was 42.9%. The median OS time was 11.7 months. The median OS times of responders were 18.4 months, while those of nonresponders were 7.4 months (P = 0.015). The presence of RUNX1 mutations was associated with a high CRR but a short 2-year OS (P = 0.023) and PFS (P = 0.018) due to relapse after treatment. The presence of IDH mutations had no effect on the remission rate (80.0% vs . 73.3%), but showed a better OS (2-year OS rate: 100.0% vs . 28.9%). Grade 3/4 nonhematological adverse events included pneumonia, hematosepsis, febrile neutropenia, skin and soft tissue infection and others., Conclusion: The double epigenetic priming regimen (CDIAG regimen) showed considerably good antileukemia activity in these patients. Adverse events were acceptable according to previous experience. The study was registered as a clinical trial., Clinical Trial Registration: https://clinicaltrials.gov/, identifier:NCT03985007., 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 Yin, Wan, Zhang, Zhang, Bai, Zhou, Xu, Chen, Qian, Qiu, Chen, Tang, Wu, Zhang, Sun and Xue.)

Background: Skin pruritus is a common complication in patients with uremia. When the hemodialysis time of patients is extended, and the probability of skin pruritus is greater. Patients often have the symptoms of skin pruritus intolerable, affecting the normal sleep and normal life of patients. The patients with uremic pruritus often constant scratching and pruritus skin, resulting in broken skin, and further symptoms such as infection, and subsequent skin shedding, prurigo nodularis, and other adverse complications, aggravating the patient's condition. Some patients will experience symptoms such as depression and insomnia due to skin pruritus, and simply scratching the skin lead to infection. Severely affected patients may even show suicidal tendency, endangering the physical and mental health of patients, and it is needed to give the effective treatment to patients. Hemodialysis is a common treatment for uremic pruritus, which can effectively relieve the pruritus symptoms of patients. The drugs can also relieve the symptoms and improve the degree of pruritus in patients. And some studies show that traditional Chinese medicine UCG combined with HFH in the treatment of uremic pruritus has a very good effect, Therefore, this study will systematically evaluate the clinical efficacy and safety of UCG combined with HFH and HFH alone in the treatment of uremic pruritus., Methods: Use computer to search English and Chinese databases, English databases include: PubMed, Web of Science, EMbase, The Cochrane Library. Chinese databases include: CNKI, CBM, WanFang Data and VIP databases, collecting the RCT on the clinical effectiveness and safety of UCG combined with HFH and HFH alone in the treatment of uremic pruritus. The retrieval time is from the beginning of each database to May 1, 2021. In order to improve the retrieval rate of the literature, the references cited in the included research are also collected and screened. Set Chinese and English as the search language. Two members of the research group independently collected, included and excluded the literatures. In case of disagreement, consulting the third party to assist in the judgment. For the literature with missing data, the original author should be contacted as far as possible to obtain complete data. Two evaluators evaluate the bias risk of included studies according to the Cochrane Handbook bias risk assessment tool for RCT. RevMan 5.3 software is used for statistical analysis and the forest plot is drawn to show the outcome indicators and funnel plot is drawn to show the publication bias., Results: This study evaluates the advantages and disadvantages of traditional Chinese medicine UCG combined with HFH and HFH alone in the treatment of uremic pruritus through the clinical effectiveness and safety-related indicators., Conclusion: This study will give a positive conclusion on the efficacy and safety of uremic clearance granule in the treatment of uremic pruritus, and the research results will be published in professional journals in the form of academic papers, thus benefiting more patients., Ethics and Dissemination: This study belongs to meta-analysis and all data comes from academic papers published publicly in formal academic journals, so there are no ethical issues involved in this study and no ethical review or approval is required., Osf Registration Number: DOI 10.17605/OSF.IO/W8P5G., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

N 6 -methyladenosine (m 6 A) methylation is the most prevalent internal modification of post-transcriptional modifications in mRNA, tRNA, miRNA, and long non-coding RNA in eukaryotes. m 6 A methylation has been proven to be involved in plant resistance to pathogens. However, there are no reports on wheat ( Triticum aestivum ) m 6 A transcriptome-wide map and its potential biological function in wheat resistance to wheat yellow mosaic virus (WYMV). To the best of our knowledge, this study is the first to determine the transcriptome-wide m 6 A profile of two wheat varieties with different resistances to WYMV. By analyzing m 6 A-sequencing (m 6 A-seq) data, we identified 25,752 common m 6 A peaks and 30,582 common m 6 A genes in two groups [WYMV-infected resistant wheat variety (WRV) and WYMV-infected sensitive wheat variety (WSV)], and all these peaks were mainly enriched in 3' untranslated regions and stop codons of coding sequences. Gene Ontology analysis of m 6 A-seq and RNA-sequencing data revealed that genes that showed significant changes in both m 6 A and mRNA levels were associated with plant defense responses. Kyoto Encyclopedia of Genes and Genomes analysis revealed that these selected genes were enriched in the plant-pathogen interaction pathway. We further verified these changes in m 6 A and mRNA levels through gene-specific m 6 A real-time quantitative PCR (RT-qPCR) and normal RT-qPCR. This study highlights the role of m 6 A methylation in wheat resistance to WYMV, providing a solid basis for the potential functional role of m 6 A RNA methylation in wheat resistance to infection by RNA viruses., 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 Zhang, Wang, Hu, Chen, Liu, Gao, Zhang, He, Jin, Xu, Chen and Yang.)

Renal arteriolar tone depends considerably on the dilatory action of nitric oxide (NO) via activation of soluble guanylyl cyclase (sGC) and cGMP action. NO deficiency and hypoxia/reoxygenation are important pathophysiological factors in the development of acute kidney injury. It was hypothesized that the NO-sGC-cGMP system functions differently in renal afferent arterioles (AA) compared with efferent arterioles (EA) and that the sGC activator cinaciguat differentially dilates these arterioles. Experiments were performed in isolated, perfused mouse glomerular arterioles. Hypoxia (0.1% oxygen) was achieved by using a hypoxia chamber. Phosphodiesterase 5 (PDE5) and sGC subunits were considerably expressed on the mRNA level in AA. PDE5 inhibition with sildenafil, which blocks cGMP degradation, diminished the responses to ANG II bolus application in AA, but not significantly in EA. Vasodilation induced by sildenafil in ANG II-preconstricted vessels was stronger in EA than AA. Cinaciguat, an NO- and heme-independent sGC activator, dilated EA more strongly than AA after N G -nitro-l-arginine methyl ester (l-NAME; NO synthase inhibitor) treatment and preconstriction with ANG II. Cinaciguat-induced dilatation of l-NAME-pretreated and ANG II-preconstricted arterioles was similar to controls without l-NAME treatment. Cinaciguat also induced dilatation in iodinated contrast medium treated AA. Furthermore, it dilated EA, but not AA, after hypoxia/reoxygenation. The results reveal an important role of the NO-sGC-cGMP system for renal dilatation and that EA have a more potent sGC activated dilatory system. Furthermore, AA seem to be more sensitive to hypoxia/reoxygenation than EA under these experimental conditions.

In this study, two isomeric impurities were identified in cefotiam hydrochloride injection preparation and were characterized. Column-switching HPLC-MS and NMR techniques were used to identify the impurity 1 as the Δ3(4) isomers of cefotiam. Using software-based calculations, it was predicted that neither of the isomeric impurities was embryotoxic. This study provides a reference for the production, storage, and quality control of cefotiam and related cephalosporin antibiotics., 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 Tian, Chong, Liu, Han, Hu, Yao and Xu.)

Objective: To investigate the target delivery properties of RC48-ADC, a novel antibody drug conjugate (ADC) comprising cytotoxic monomethyl auristatin E (MMAE) and an anti-human epidermal growth factor receptor 2 (HER2) antibody tethered via valine-citrulline linker, in vitro and in vivo., Materials and Methods: Dissociation rate of MMAE from RC48-ADC was used as an estimate of its stability in serum. Cytotoxicity of the antibody and RC48-ADC towards multiple cell lines was measured. Subcellular distribution of the drug was determined by fluorescence imaging. The mechanism of lysosome targeting was verified. Endocytic pathways of RC48-ADC were assessed by the cellular fluorescence intensity of fluorescently-labelled drugs. Intracellular and extracellular distribution of MMAE was analysed after RC48-ADC or MMAE administration to characterize MMAE release. The serum and tumour concentration of MMAE was compared after tail-vein injection of RC48-ADC into tumour-bearing mice., Results: RC48-ADC was highly stable in human serum. HER2-overexpressed cell line SK-BR-3 proliferation was stronger when suppressed by RC48-ADC than by the naked antibody. Both RC48-ADC and naked antibody were internalized via caveolae-mediated and clathrin-mediated endocytosis and concentrated in lysosomes. Higher HER2 expression was associated with enhanced uptake and intracellular release of conjugated MMAE; free MMAE could kill tumour cells via the bystander effect. Although serum RC48-ADC concentration was higher than that in tumours, exposure of MMAE in tumours was ~200 times higher than in serum, which rationalized the reduced toxicity of RC48-ADC., Conclusions: In vitro and in vivo experiments confirmed the targeted transport and release of RC48-ADC; it could selectively deliver MMAE to the targeted HER2-positive cell or tumour tissue, which could reduce off-target toxicity and enhance anti-tumour potency in humans.

The invasion and egress are two key steps in lytic cycle vital to the propagation of Toxoplasma gondii infection, and phosphorylation is believed to play important roles in these processes. However, the phosphoproteome of T. gondii at these two stages has not been characterized. In this study, we profiled the phosphoproteome of tachyzoites at the stages of "just invading" (JI) and "prior to egress" (PE) based on iTRAQ quantitative analysis, in which a total of 46 phosphopeptides, 42 phosphorylation sites, and 38 phosphoproteins were detected. In the comparison of PE vs. JI, 10 phosphoproteins were detected with their phosphorylation level significantly changed, and four of them were demonstrated to be significantly down-regulated at the transcriptional level. Bioinformatic analysis of these identified phosphoproteins suggested that phosphorylation-mediated modulation of protein function was employed to regulate the pathway of toxoplasmosis and metabolism and cellular processes correlated with tachyzoite's binding, location, and metabolism, and thus play vital roles in the parasite lytic cycle. Moreover, cytoskeletal network (CN)-associated Inner Membrane Complex (IMC1, IMC4, IMC6 and IMC12), Intravascular Network (IVN)-related GRAs (GRA2, GRA3, GRA7 and GRA12), and Parasitophorous Vacuole Membrane (PVM)-localized ROP5 were shown to be enriched at the central nodes in the protein interaction network generated by bioinformatic analysis, in which the phosphorylation level of IMC4, GRA2, GRA3, and GRA12 were found to be significantly regulated. This study revealed the main cellular processes and key phosphoproteins crucial for the invasion and egress of T. gondii , which will provide new insights into the developmental biology of T. gondii in vitro and contribute to the understanding of pathogen-host interaction from the parasite perspective., 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 © 2020 He, Xu, Pan, Wang, Peng and Liu.)