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Abstract Background Pulmonary hypoperfusion is common in children with congenital heart diseases (CHDs) or pulmonary hypertension (PH) and causes adult pulmonary dysplasia. Systematic reviews have shown that some children with CHDs or PH have mitigated clinical outcomes with COVID-19. Understanding the effects of pulmonary hypoperfusion on postnatal alveolar development may aid in the development of methods to improve the pulmonary function of children with CHDs or PH and improve their care during the COVID-19 pandemic, which is characterized by cytokine storm and persistent inflammation. Methods and results We created a neonatal pulmonary hypoperfusion model through pulmonary artery banding (PAB) surgery at postnatal day 1 (P1). Alveolar dysplasia was confirmed by gross and histological examination at P21. Transcriptomic analysis of pulmonary tissues at P7(alveolar stage 2) and P14(alveolar stage 4) revealed that the postnatal alveolar development track had been changed due to pulmonary hypoperfusion. Under the condition of pulmonary hypoperfusion, the cell–cell communication and axon guidance, which both determine the final number of alveoli, were lost; instead, there was hyperactive cell cycle activity. The transcriptomic results were further confirmed by the examination of axon guidance and cell cycle markers. Because axon guidance controls inflammation and immune cell activation, the loss of axon guidance may explain the lack of severe COVID-19 cases among children with CHDs or PH accompanied by pulmonary hypoperfusion. Conclusions This study suggested that promoting cell–cell communication or supplementation with guidance molecules may treat pulmonary hypoperfusion–induced alveolar dysplasia, and that COVID-19 is less likely to cause a cytokine storm in children with CHD or PH accompanied by pulmonary hypoperfusion. Graphical Abstract

Abstract Background Parkinson’s disease (PD) is a progressive neurodegenerative disease common in aged populations. Classified by Hoehn & Yahr stages, patients are often divided into mild/early stage, moderate/middle stage, and advanced/late stage. With disease progression, PD shows high heterogeneity in each stage. Based on traditional Chinese medicine (TCM) syndrome differentiation theory and our previous works, we found that during the early stage, the main syndrome is Yin deficiency of the liver and kidney; during the moderate stage, the main syndromes are phlegm heat and wind stirring and blood stasis and wind stirring; and during the late stage, the dominant syndromes are deficiency of Yin and Yang and deficiency of Qi and blood. Hence, we proposed a new model of TCM treatment by the stage of PD. Based on Shudi Pingchan formula, an experimental formula of our team, we developed Ziyin Pingchan formula, Jiedu Pingchan formula, and Fuzheng Pingchan formula to treat each stage. This study is designed to evaluate the therapeutic effect of treating Parkinson’s disease by stages using traditional Chinese medicine and to provide an evidence base for forming a standardized scheme of diagnosis and treatment. Methods This study is designed as a multicentre, randomized, double-blind, placebo-controlled clinical trial. Patients will be stratified into 3 subgroups according to Hoehn & Yahr stage; 172, 168, and 72 participants will be required to be in the mild PD, moderate PD, and advanced PD subgroups, respectively, and will be randomized into the treatment or control group at a 1:1 ratio. The mild PD subgroup will receive a 48-week intervention, and the other 2 groups will receive a 24-week intervention. All groups will have a follow-up visit 12 weeks after starting the intervention. The intervention group will receive the Ziyin Pingchan formula, Jiedu Pingchan formula, or Fuzheng Pingchan formula, and the control group will receive the corresponding placebo. The primary outcomes will be the first addition of levodopa for the mild PD subgroup, the duration of the “OFF” period for the moderate PD subgroup, and the Parkinson's Disease Questionnaire (PDQ-39) for the advanced PD subgroup. The secondary outcomes will also be verified by subgroups, including the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Sleep Scale-2 (PDSS-2), scales for Outcomes in Parkinson’s Disease—Autonomic (SCOPA-AUT), and the nonmotor symptom scale (NMSS). Expected outcomes To our knowledge, this is the first trial to combine TCM syndrome differentiation with PD clinical stages and put it into clinical practice. The results of this trial will provide clinical evidence for the therapeutic effect of TCM formulas on PD patients of all stages and help build a new TCM treatment by stage model of PD. Trial registration: This trial is registered at the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ). Registration number: ChiCTR2200056373, Date: 2022–02-04, version 1.

Abstract Background Minimally invasive surgery for carpal tunnel syndrome has been consistently the mainstay of treatment. In this study, we developed a novel bush hook via a mini-transverse incision at proximal wrist crease to surgically treat carpal tunnel syndrome and our aim was to compare the results with those of mid-palmar small longitudinal incision in carpal tunnel release. Methods This is a retrospective study on patients who received a mini-transverse incision and a novel bush hook or a mid-palmar small longitudinal incision for treatment of carpal tunnel syndrome. The decision to receive either technique was made mainly based on patients' choice. The clinical results were evaluated at 1 week, 1 month, 3 and 6 months postoperatively and compared. Results In total, 58 patients in mini-transverse incision group and 74 in mid-palmar longitudinal incision group were include. The follow-up period was 6.8 ± 1.6 months. The mini-transverse incision group had a significantly smaller incision (4.3 ± 0.4 mm vs. 26.2 ± 1.6 mm), shorter surgical time (7.8 ± 2.6 min vs. 19.7 ± 2.8 min), but not for hospital stay (3.2 ± 1.9 vs. 3.6 ± 2.2 days). Both groups showed significant improvement from baseline level at any time points postoperatively (all P 0.05). In addition, the mini-transverse incision group showed a significantly reduced time to return to the work and activities, tendency to higher rate of excellence and good outcomes and fewer complications. Conclusions This novel technique via a mini-transverse incision and bush hook showed better clinical effectiveness and safety, and can be considered as an alternative for wrist tunnel release after the results are validated by higher-level evidence studies. Evidence level: III.

Abstract Purpose This study aimed to investigate the outcomes of a mini-transverse incision with a bush-hook versus a conventional open incision for carpal tunnel release (CTR). Methods This was a prospective study. The decision to receive either technique (mini-transverse incision with a bush-hook or conventional open incision) was primarily based on patients’ choice. Patients’ symptom severity, functional status, and symptomatic pain were measured at pre-operation, 1 month, and 3 and 6 months postoperatively, and any relevant complications were recorded. Kelly’s scale was used to evaluate the overall clinical efficacy. Results Eighty-nine patients were included in the open CTR group and 85 patients in the mini-transverse incision group. The mini-transverse incision group had a significantly smaller incision (4.4±0.6 vs 44.8±3.7 mm), shorter surgical time (7.8±1.9 vs 21.2±3.4 min), and shorter hospital stay (3.7±1.6 vs 5.9±2.0 days) than did the open CTR group. Both groups showed significant improvements from baseline levels (all P

Abstract Background The incidence of gallbladder carcinoma (GBM) in China has increased in recent years. Here, the functional mechanism of lncRNA TTN-AS1 in GBC was preliminary elucidated. Methods The expression levels of lncRNA TTN-AS1, miR-107, and HMGA1 in tissues and cell lines were assessed by RT-qPCR. Cell proliferation was measured by MTT assays. Cell invasion and migration abilities were evaluated by Transwell assays. The relationship between miR-107 and lncRNA TTN-AS1 or HMGA1 was confirmed by luciferase reporter assay. Results Upregulation of lncRNA TTN-AS1 and downregulation of miR-107 were detected in GBC. Furthermore, the expressions between TTN-AS1 and miR-107 were mutually inhibited in GBC. Functionally, lncRNA TTN-AS1 promoted cell viability and motility in GBC by sponging miR-107. In addition, miR-107 directly targets HMGA1. And HMGA1 can be positively regulated by lncRNA TTN-AS1 in GBC. Furthermore, HMGA1 promoted GBC progression by interacting with lncRNA TTN-AS1/miR-107 axis. Conclusion LncRNA TTN-AS1 acted as a tumor promoter in GBC by sponging miR-107 and upregulating HMGA1.

Abstract Objective The relationship between changes in Chinese visceral adiposity index (CVAI) and cardiometabolic diseases (CMD) in middle-aged and elderly individuals remains unclear. This study aimed to explore whether changes in the CVAI were associated with CMD incidence. Methods This study included 3,243 individuals aged over 45 years from the China Health and Retirement Longitudinal Study. The exposures were changes in the CVAI and cumulative CVAI from 2012 to 2015. Changes in the CVAI were classified using K-means clustering analysis, and the cumulative CVAI was calculated as follows: (CVAI2012 + CVAI2015)/2 × time (2015–2012). Multivariable logistic regression models were used to assess the relationship between different CVAI change classes and CMD incidence. Restricted cubic splines regression was used to assess the dose–response relationship between cumulative CVAI and CMD incidence. To investigate the relationship between combined exposure to each component of CAVI and CMD incidence, a weighted quantile sum regression analysis was employed. Results During the 5 years of follow-up, 776 (24%) incident CMD cases were identified. Changes in CVAI and cumulative CVAI were independently and positively associated with CMD. After adjusting for potential confounders, compared with Class 1, the adjusted ORs (95% CIs) for incident CMD were 1.18 (0.90–1.57) for Class 2, 1.40 (1.03–1.92) for Class 3, and 1.56 (1.04–2.34) for Class 4. When cumulative CVAI was categorized into quartiles, compared with Q1, the adjusted ORs (95% CIs) for incident CMD were 1.30 (1.00–1.70) for Q2, 1.34 (1.01–1.79) for Q3, and 1.63 (1.15–2.31) for Q4. In addition, cumulative CVAI in the overall population exhibited a linear association with CMD (P overall = 0.012, P non-linearity = 0.287), diabetes (P overall = 0.022, P non-linearity = 0.188), and stroke (P overall = 0.002, P non-linearity = 0.978), but showed no significant association with heart disease (P overall = 0.619, P non-linearity = 0.442). Conclusion Participants with higher baseline CVAI level and a change of elevating CVAI level may suffer an increased incidence of CMD. Furthermore, our findings elucidate the underlying mechanisms of the CVAI by highlighting TG as the primary contributor to the observed associations. Long-term CVAI monitoring is of significant importance for early identification and prevention of CMD, with significant implications for clinical practice.

Abstract Background Current evidence suggests that metabolic dysregulation is inextricably linked to both hypertension and osteoporosis, but the correlation between hypertension and osteoporosis is still unclear. Therefore, in this study, we explored the correlation between hypertension and osteoporosis. Methods A total of 37,807 participants from the National Health and Nutrition Examination Survey (1999–2010, 2013–2014, 2017–2018) were enrolled in this population-based cross-sectional study. Hypertension was considered an exposure factor and osteoporosis was considered an outcome factor. Logistic regression and subgroup analysis were used to assess the association between hypertension and osteoporosis. Results A total of 2,523 participants, with a mean age of 68.65 ± 12.21 years, suffered from osteoporosis, and 86.2% were female. Participants with osteoporosis had a greater prevalence of hypertension than participants without osteoporosis (p

Abstract Objective The relationship between changes in Atherogenic Index of Plasma (AIP) and cardiometabolic diseases (CMD) in middle-aged and elderly individuals remains unclear. This study aims to explore the association between changes in AIP and CMD. Methods This study included 3,791 individuals aged over 45 years from CHARLS. Participants were divided into four groups using the K-Means clustering method. Cumulative AIP was used as a quantitative indicator reflecting changes in AIP. Differences in baseline data and CMD incidence rates among these four groups were compared. Multifactorial logistic regression models were used to assess the relationship between changes in AIP and CMD, and subgroup analysis and interaction tests were conducted to evaluate potential relationships between changes in AIP and CMD across different subgroups. Restricted cubic splines (RCS) were used to assess the dose-response relationship between cumulative AIP and CMD. Results Changes in AIP were independently and positively associated with CMD. In males, the risk significantly increased in class4 compared to class1 (OR 1.75, 95%CI 1.12-2.73). In females, changes in AIP were not significantly associated with CMD. Cumulative AIP was positively correlated with CMD (OR 1.15, 95%CI 1.01-1.30), with significant gender differences in males (OR 1.29, 95%CI 1.07-1.55) and females (OR 1.03, 95%CI 0.87-1.23) (p for interaction = 0.042). In addition, a linear relationship was observed between cumulative AIP and CMD in male. Conclusion Substantial changes in AIP may increase the risk of CMD in middle-aged and elderly Chinese males. Dynamic monitoring of AIP is of significant importance for the prevention and treatment of CMD.

Abstract Sexual dimorphism has been observed in the incidence and prognosis of colorectal cancer (CRC), with men generally exhibiting a slightly higher incidence than women. Research suggests that this difference may be attributed to variations in sex steroid hormone levels and the gut microbiome. The gut microbiome in CRC shows variations in composition and function between the sexes, leading to the concept of ‘microgenderome’ and ‘sex hormone–gut microbiome axis.’ Conventional research indicates that estrogens, by promoting a more favorable gut microbiota, may reduce the risk of CRC. Conversely, androgens may have a direct pro-tumorigenic effect by increasing the proportion of opportunistic pathogens. The gut microbiota may also influence sex hormone levels by expressing specific enzymes or directly affecting gonadal function. However, this area remains controversial. This review aims to explore the differences in sex hormone in CRC incidence, the phenomenon of sexual dimorphism within the gut microbiome, and the intricate interplay of the sex hormone–gut microbiome axis in CRC. The objective is to gain a better understanding of these interactions and their potential clinical implications, as well as to introduce innovative approaches to CRC treatment. Graphical Abstract