Perioperative PD-1/PD-L1 inhibitors for resectable non-small cell lung cancer: A meta-analysis based on randomized controlled trials.

BACKGROUND: PD-1/PD-L1 inhibitors (PI) have shown promising results in both neoadjuvant and adjuvant therapies for resectable non-small cell lung cancer (NSCLC). However, substantial evidence from large-scale studies is still lacking for their use in the perioperative setting (neoadjuvant plus adjuvant). This meta-analysis aims to evaluate the integration of perioperative PI (PPI) with neoadjuvant chemotherapy for resectable NSCLC. METHODS: To identify appropriate randomized controlled trials (RCTs), we thoroughly explored six different databases. The primary endpoint was survival, while the secondary measures included pathological responses and adverse events (AEs). RESULTS: Six RCTs involving 2941 patients were included. The PPI group significantly improved overall survival (OS) (hazard ratio [HR]: 0.62 [0.51, 0.77]), event-free survival (EFS) (HR: 0.57 [0.51, 0.64]), pathological complete response (risk ratio [RR]: 5.81 [4.47, 7.57]), and major pathological response (RR: 2.60 [1.77, 3.82]). Benefits in EFS were seen across all subgroups. OS rates at 12-48 months and EFS rates at 6-48 months were higher in the PPI cohort. Furthermore, the advantages in OS and EFS increased with prolonged survival times. The PPI group also exhibited higher rates of surgery and R0 resections. However, the PPI group experienced more grade 3-5 AEs, serious AEs, and treatment discontinuations due to AEs. CONCLUSIONS: The integration of perioperative PI with neoadjuvant chemotherapy can significantly improve survival and pathological responses for resectable NSCLC. However, the increased incidence of grade 3-5 AEs must be carefully evaluated.

Spatial analysis reveals targetable macrophage-mediated mechanisms of immune evasion in hepatocellular carcinoma minimal residual disease.

Hepatocellular carcinoma (HCC) frequently recurs from minimal residual disease (MRD), which persists after therapy. Here, we identified mechanisms of persistence of residual tumor cells using post-chemoembolization human HCC (n = 108 patients, 1.07 million cells) and a transgenic mouse model of MRD. Through single-cell high-plex cytometric imaging, we identified a spatial neighborhood within which PD-L1 + M2-like macrophages interact with stem-like tumor cells, correlating with CD8+ T cell exhaustion and poor survival. Further, through spatial transcriptomics of residual HCC, we showed that macrophage-derived TGFß1 mediates the persistence of stem-like tumor cells. Last, we demonstrate that combined blockade of Pdl1 and Tgfß excluded immunosuppressive macrophages, recruited activated CD8+ T cells and eliminated residual stem-like tumor cells in two mouse models: a transgenic model of MRD and a syngeneic orthotopic model of doxorubicin-resistant HCC. Thus, our spatial analyses reveal that PD-L1+ macrophages sustain MRD by activating the TGFß pathway in stem-like cancer cells and targeting this interaction may prevent HCC recurrence from MRD.

Functional analysis of a novel nonsense PPP1R12A variant in a Chinese family with infantile epilepsy.

BACKGROUND: Defects in PPP1R12A can lead to genitourinary and/or brain malformation syndrome (GUBS). GUBS is primarily characterized by neurological or genitourinary system abnormalities, but a few reported cases are associated with neonatal seizures. Here, we report a case of a female newborn with neonatal seizures caused by a novel variant in PPP1R12A, aiming to enhance the clinical and variant data of genetic factors related to epilepsy in early life. METHODS: Whole-exome and Sanger sequencing were used for familial variant assessment, and bioinformatics was employed to annotate the variant. A structural model of the mutant protein was simulated using molecular dynamics (MD), and the free binding energy between PPP1R12A and PPP1CB was analyzed. A mutant plasmid was constructed, and mutant protein expression was analyzed using western blotting (WB), and the interaction between the mutant and PPP1CB proteins using co-immunoprecipitation (Co-IP) experiments. RESULTS: The patient experienced tonic-clonic seizures on the second day after birth. Genetic testing revealed a heterozygous variant in PPP1R12A, NM_002480.3:c.2533 C > T (p.Arg845Ter). Both parents had the wild-type gene. MD suggested that loss of the C-terminal structure in the mutant protein altered its structural stability and increased the binding energy with PPP1CB, indicating unstable protein-protein interactions. On WB, a low-molecular-weight band was observed, indicating that the protein was truncated. Co-IP indicated that the mutant protein no longer interacted with PPP1CB, indicating an effect on the structural stability of the myosin phase complex. CONCLUSION: The PPP1R12A c.2533 C > T variant may explain the neonatal seizures in the present case. The findings of this study expand the spectrum of PPP1R12A variants and highlight the potential significance of truncated proteins in the pathogenesis of GUBS.

Dynamic trends of ischemic heart disease mortality attributable to high low-density lipoprotein cholesterol: a joinpoint analysis and age-period-cohort analysis with predictions.

AIMS: The purpose of this study was to analyze the dynamic trends of ischemic heart disease (IHD) mortality attributable to high low-density lipoprotein cholesterol (LDL-C). METHODS: Data on IHD mortality attributable to high LDL-C from 1990 to 2021 were extracted from the global disease burden database. Joinpoint software was used to estimate the average annual percentage change (AAPC) in the age-standardized mortality rate (ASMR). An age‒period‒cohort model was used to analyze the impacts of age, period, and cohort on these changes. The Bayesian framework was used to predict IHD mortality attributable to high LDL-C from 2022 to 2040. RESULTS: The overall ASMR of IHD attributable to high LDL-C decreased from 50. 479 per 100,000 people in 1990 to 32.286 per 100,000 people in 2021, and ASMR of IHD attributable to high LDL-C was higher in males than in females. The longitudinal age curves of the overall IHD mortality attributable to high LDL-C showed a monotonic upward trend, especially after 65 years of age. The period and cohort effect relative risk (RR) values of overall IHD mortality attributable to high LDL-C showed a downward trend. The overall ASMR of IHD attributable to high LDL-C is predicted to show a downward trend, and male IHD mortality attributable to high LDL-C is expected to be higher than that of females. CONCLUSION: This study revealed a sustained decrease in IHD mortality attributable to high LDL-C over three decades, with a continued decline expected. Despite this, gender disparities persist, with males experiencing higher mortality rates and elderly individuals remaining a vulnerable group.

Cerastecin Inhibition of the Lipooligosaccharide Transporter MsbA to Combat Acinetobacter baumannii: From Screening Impurity to In Vivo Efficacy.

Acinetobacter baumannii, a commonly multidrug-resistant Gram-negative bacterium responsible for large numbers of bloodstream and lung infections worldwide, is increasingly difficult to treat and constitutes a growing threat to human health. Structurally novel antibacterial chemical matter that can evade existing resistance mechanisms is essential for addressing this critical medical need. Herein, we describe our efforts to inhibit the essential A. baumannii lipooligosaccharide (LOS) ATP-binding cassette (ABC) transporter MsbA. An unexpected impurity from a phenotypic screening was optimized as a series of dimeric compounds, culminating with 1 (cerastecin D), which exhibited antibacterial activity in the presence of human serum and a pharmacokinetic profile sufficient to achieve efficacy against A. baumannii in murine septicemia and lung infection models.

Too much social media? Unveiling the effects of determinants in social media fatigue.

Introduction: With the boom in social media, many people spend a lot of time on these platforms. Among them, some developed negative emotions, such as fatigue, depression, or disinterest in communicating, and used social media temporarily or permanently. Therefore, this study aims to explore the antecedents of social media fatigue, including social media helpfulness, social media self-efficacy, online subjective well-being, social comparison, compulsive social media use, privacy concerns, fear of missing out, and information overload, and to further discuss the determinants of social media fatigue on social anxiety and lurking. Methods: An online questionnaire was distributed to social media users, and 659 valid samples were obtained with the help of a purposive sampling strategy. The data was analyzed by the partial least square (PLS) method. Results: The study found that social media self-efficacy had a significant negative effect on social media fatigue; compulsive social media use, fear of missing out, and information overload had a significant positive effect on social media fatigue; and social media fatigue had a significant positive effect on social anxiety and lurking. Discussion: The research results can be used as a reference for social media marketers and internet service providers in developing business strategies.

Controlled interconversion of macrocyclic atropisomers via defined intermediates.

Macrocyclic conformations play a crucial role in regulating their properties. Our understanding of the determinants to control macrocyclic conformation interconversion is still in its infancy. Here we present a macrocycle, octamethyl cyclo[4](1,3-(4,6)-dimethylbenzene)[4]((4,6-benzene)(1,3-dicarboxylate) (OC-4), that can exist at 298 K as two stable atropisomers with C2v and C4v symmetry denoted as C2v-OC-4 and C4v-OC-4, respectively. Heating induces the efficient stepwise conversion of C2v- to C4v-OC-4 via a Cs-symmetric intermediate (Cs-OC-4). It differs from the typical transition state-mediated processes of simple C-C single bond rotations. Hydrolysis and further esterification with a countercation dependence promote the generation of C2v- and Cs-OC-4 from C4v-OC-4. In contrast to C2v-OC-4, C4v-OC-4 can bind linear guests to form pseudo-rotaxans, or bind C60 or C70 efficiently. The present study highlights the differences in recognition behavior that can result from conformational interconversion, as well as providing insights into the basic parameters that govern coupled molecular rotations.

Current application and future perspective of CRISPR/cas9 gene editing system mediated immune checkpoint for liver cancer treatment.

Liver cancer, which is well-known to us as one of human most prevalent malignancies across the globe, poses a significant risk to live condition and life safety of individuals in every region of the planet. It has been shown that immune checkpoint treatment may enhance survival benefits and make a significant contribution to patient prognosis, which makes it a promising and popular therapeutic option for treating liver cancer at the current time. However, there are only a very few numbers of patients who can benefit from the treatment and there also exist adverse events such as toxic effects and so on, which is still required further research and discussion. Fortunately, the clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) provides a potential strategy for immunotherapy and immune checkpoint therapy of liver cancer. In this review, we focus on elucidating the fundamentals of the recently developed CRISPR/Cas9 technology as well as the present-day landscape of immune checkpoint treatment which pertains to liver cancer. What's more, we aim to explore the molecular mechanism of immune checkpoint treatment in liver cancer based on CRISPR/Cas9 technology. At last, its encouraging and powerful potential in the future application of the clinic is discussed, along with the issues that already exist and the difficulties that must be overcome. To sum up, our ultimate goal is to create a fresh knowledge that we can utilize this new CRISPR/Cas9 technology for the current popular immune checkpoint therapy to overcome the treatment issues of liver cancer.

Association between the serum uric acid/serum creatinine ratio and cognitive function in older adults: NHANES in the United States.

Cognitive impairment can potentially become a significant health concern in older adults. However, early effective diagnostic methods are still lacking. Therefore, we utilized the NHANES database in the US to investigate the relationship between serum uric acid to serum creatinine (SUA/SCR) ratio and cognitive impairment. In our study, a total of 3874 participants were included (2001-2002, 2011-2014). Weighted t tests or chi-square tests were utilized to analyze the basic characteristics of the population. Weighted logistic regression analysis, smooth-fit curves, threshold effects, and subgroup analysis were conducted to investigate the correlation between the SUA/SCR and cognitive impairment. In this study, the SUA/SCR was significantly lower in individuals with cognitive impairment. The logistic regression model, after adjusting for all covariates, revealed that the Q2-Q4 were 0.65 (95% CI 0.49, 0.86), 0.60 (95% CI 0.40, 0.90), 0.55 (95% CI 0.39, 0.77) respectively. This indicates that participants in the Q4 had a 45% reduced risk of cognitive impairment. Smooth-fit curves and threshold effect analysis revealed a nonlinear relationship between SUA/SCR and cognitive impairment, with a turning point at 4.13. Subgroup analysis showed no statistically significant differences in the relationship between SUA/SCR and cognitive impairment among different subgroups (P > 0.05). Our findings indicate a negative correlation between the SUA/SCR and the risk of cognitive impairment in the population of adults aged 60 and above in the US. This suggests that the SUA/SCR holds promise as a potential indicator for cognitive impairment.

Wound Healing Complications Associated with Staged Reconstruction after Facial Lentigo Maligna Resection.

Background: The rates and risk factors for wound complications following staged reconstruction after facial lentigo maligna (LM) resection have not been well described. Objectives: (1) To identify the rate and types of wound complications, including infection, graft necrosis, distal flap necrosis, hematoma, superficial epidermolysis, and seroma among patients undergoing staged reconstruction after resection of LM as documented in the surgeon's clinical notes within 30 days of the procedure. (2) To determine a threshold defect size that may predict the development of wound complications. Design and Outcomes: Retrospective review at an academic medical center of patients who underwent staged reconstruction after facial LM resection over a 5-year period. Results: Ninety-eight patients were identified with a mean age of 69.2 ± 13.6 years; 37% of patients were female. The most common defect sites were the cheek (n = 41; 42%) and nose (n = 22; 22%). Twenty-five of 98 patients (26%) demonstrated complications, with the most common being wound infection (36%) and graft necrosis (24%). Those receiving perioperative antibiotics had lower rates of complication (odds ratio [OR]: 0.36; 95% confidence interval [CI]: 0.13,0.96; p = 0.041). Defects greater than 2.7 cm in maximal diameter had the highest sensitivity for predicting complications. Conclusions: Patients undergoing staged reconstruction after facial LM resection have a high rate of wound complication (26%) and defect size > 2.7 cm may be an important risk factor.

The Impact of Sociodemographic Factors on Rates of Tympanostomy Tube Placement for Pediatric Otitis Media.

Objective: To identify the impact of race, ethnicity, and socioeconomic status (SES) on the rate of tympanostomy tube placement. Study Design: Retrospective medical review and population-level analyses. Setting: Tertiary referral center. Methods: Demographic and population-level characteristics (age, gender, race, insurance status, and ZIP code) compared to the regional, health system, and otolaryngology clinic demographics. Results: Among 38,461 children diagnosed with otitis media (OM) 61.4% were white, 27.4% were black, 32.7% had private insurance, and 18.2% were Hispanic. Among patients seen in the pediatric ear, nose, and throat (ENT) clinics, 70.0% were white, 20.0% were black, 46.6% had private insurance, and 14.9% were Hispanic. Further disparity was noted among those receiving tympanostomy tubes: 75.6% white, 15.6% black, 61.9% private insurance, and 11.7% Hispanic. Higher rates of tube placement were noted for those of white race [odds ratio, OR: 1.96, (95% confidence interval, CI: 1.85-2.04), <.001] and non-Hispanic ethnicity [OR: 1.67, (95% CI: 1.56-1.75), <.001]. Geographically, rates of tube placement were significantly lower in areas with higher deprivation indices, areas with lower proportions of white residents, and areas with the lowest median incomes. These markers correlate strongly with black race and Hispanic ethnicity. Lower rates of tube placement were also seen in majority white locales with higher deprivation indices and lower median incomes. Conclusion: Rates of access to pediatric ENT clinics, and of tube placement, are significantly lower for those of Hispanic ethnicity and black race than for non-Hispanic white children. Higher rates of tube placement were noted among white children and those with private insurance. Lower rates of tube placement were seen in areas of lower SES regardless of racial demographics.

Association between pregnancy loss and depressive symptoms in women: a population-based study.

BACKGROUND: Depression is a common mental disorder with a much higher prevalence in women than in men. Although there has been a gradual increase in research on the association between reproductive health and depression, there is still some inconsistency in the evidence of the relationship between pregnancy loss and depression. This study aimed to investigate the relationship between pregnancy loss and depressive symptoms. METHODS: We analyzed data from the 2007-2020 National Health and Nutrition Examination Survey (NHANES), which included female participants aged 20 to 80 years. Pregnancy loss was determined based on participants' self-reported number of pregnancies and pregnancy outcomes. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9, score ≥ 10). Multivariate logistic regression, smoothed curve fitting, and generalized additive modeling were used to examine the association between pregnancy loss and depression. We also performed sensitivity analyses and subgroup analyses to verify the robustness and specificity of the findings. RESULTS: A total of 12,873 female participants were included in our study, of which 1,595 (12.39%) were categorized as depressed. Multivariate logistic regression results indicated that experiencing a pregnancy loss increased the risk of prevalence of depression in women (for 1 loss: OR = 1.31, 95% CI 1.15,1.50; for 2 or more losses: OR = 1.58, 95% CI 1.38, 1.81). When sensitivity analyses were performed, an association between pregnancy loss and depression was found in both multivariate linear regressions with PHQ-9 scores as a continuous variable and multivariate logistic regressions with a threshold of 5 PHQ-9 scores. The association between pregnancy loss and depression remained stable across subgroups. CONCLUSION: Pregnancy loss correlated with elevated PHQ-9 scores and a heightened risk of depression in adult women across the United States. Focusing on the incidence of adverse pregnancy events in the female population may help prevent or early recognize the onset of depression.

Development of an Online Training System on Pulmonary Aspiration for Clinical Nurses.

Pulmonary aspiration is a particularly problematic condition in patients in hospitals and nursing home. To promote patient safety and prevent serious complications, the nurse's role in preventing and caring for patient at high risk of pulmonary aspiration is crucial. Our team has developed an online training system on pulmonary aspiration for nurses to improve their ability to identify early risk factors, scientifically assess the risk of aspiration, and effectively intervene and manage when pulmonary aspiration occurs. This system was developed via WeChat app, the most popular social media application in China. It has four main functions, such as online training, online assessment, announcement interaction, and learning record. This online training systems offer the benefits of flexible learning time with anytime access, rich resources that are easy to update, and greater cost-effectiveness. This paper presents and discusses the development process of this system.

Nurses' Experiences of Internet + Nursing Service Based on Service Quality: A Qualitative Study.

Internet + Nursing Services began operating from 2019 in China. The Internet+Nursing Service offers convenience to patients with limited mobility. As the application gains traction and order volume increases, guaranteeing service quality becomes the next challenge. Nonetheless, there is still a dearth of study on service quality assurance. In order to investigate nurses' experiences in the service process, this study used a qualitative research approach from the perspectives of the nurses. It is intended to serve as a guide for the creation of Internet+ nursing services. Two primary topics emerged from the analysis: Factors influencing service motivation (Getting Returns, Discontent, Concerns) and Experience of the service process (Trust contributes to smooth service delivery, Nurses' competence affects service quality, Correct assessment of whether the service is available or not, Shortcomings existing in the service process).

Disparities in polysomnography referral in a high-risk cardiac population.

PURPOSE: Obstructive sleep apnea (OSA) is associated with metabolic, cardiovascular, and cerebrovascular comorbidities. Appropriate diagnosis and treatment of OSA might mitigate these comorbidities. This retrospective review sought to assess the impact of sex, age, race, ethnicity, and insurance status on polysomnography (PSG) referral rates. METHODS: An institutional STOP-Bang database of 299,320 patients was filtered for patients admitted to the hospital with an acute cardiac diagnosis between 2015-2020. A cohort of 4,735 patients were risk stratified by STOP-Bang (SB) score and correlations were made between PSG referrals and demographic and clinical variables (sex, age, race, ethnicity, and insurance status). RESULTS: Of the 25.3% of the cohort with high SB scores (5-8) only 21.3% were referred for PSG. Age and female sex were negatively associated with sleep study referrals (p < 0.001). No correlation was found between sleep study referral rates and race or ethnicity. No correlation was found between sleep study referrals and insurance provider. Admitting cardiac diagnosis significantly influenced sleep study referrals with diagnoses of arrhythmias and myocardial infarction being associated with an increased rate of PSG referrals compared to heart failure patients (p < 0.002). CONCLUSIONS: Our study found no significant correlation between PSG referral rates and race, ethnicity, or insurance provider. However, we found low overall rates of PSG referral, with negative correlations between older age and female sex and a high-risk cardiac population. This represents a substantial missed opportunity to identify patients at risk for OSA, obtain a diagnosis, and provider adequate treatment.

Fluorescence Sensing Properties of a Bibranched Cyanostilbene Derivative Containing -NH2 for Trace Water and Picric Acid Determination.

In order to design organic small molecule fluorescent materials with multiple sensing, a bibranched -NH2 modified cyanostilbene derivative (AM) was synthesized. It exhibits solvent and aggregation-induced emission effects, with a solid-state quantum yield of 28%, which is seven times higher than that in THF. The synthesized sample AM demonstrated high sensitivity to trace water via a fluorescence "turn-off" response, achieving a low detection limit of 0.41 µM in THF and 0.80 µM in EtOH. AM also exhibits a "turn-off" response to picric acid, attributed to the photo-induced electron transfer effect it induces. The recognition of picric acid by AM demonstrates specificity and resistance to interference from nitro explosives, with a detection limit of 300 ppb and a linear relationship (R2 = 0.9981) at the range of 0-4 equivalents AM. Such acid recognition can facilitate the design of qualitative test papers and safety inks. Additionally, AM can function as a temperature sensor with a linear relationship (R2 = 0.9976) within the temperature range of 25-110 °C. Leveraging these unique characteristics, a series of methods were proposed for the direct quantitative determination of trace water in nonaqueous solvents, picric acid, and temperature.

Relationships between body image, dyadic coping and post-traumatic growth in breast cancer patients: a cross-sectional study.

Background: The diagnosis and treatment of cancer triggers not only a negative psychological response for the patient, but also a positive psychological outcome. Positive dyadic coping, as a form of coping for mental health outcomes, can maintain or reestablish internal stability between the patient and his or her spouse, resulting in positive physical and psychological changes. However, there is a paucity of research on body image, dyadic coping, and post-traumatic growth in breast cancer patients. The purpose of this study was to explore the relationship and pathways between body image, dyadic coping, and post-traumatic growth in breast cancer patients. Methods: A cross-sectional study was conducted from November 2022 to November 2023 at a tertiary care hospital in Wuxi, Jiangsu, China. This study was conducted among 154 breast cancer patients treated at the Affiliated Hospital of Jiangnan University, all of whom completed demographic and clinical information questionnaires, Body image self-rating questionnaire for breast cancer (BISQ-BC), Dyadic Coping Inventory (DCI) and Post Traumatic Growth Inventory (PTGI). A Pearson correlation analysis was used to explore the relationship between body image, dyadic coping, and post-traumatic growth. Structural equation modeling was used to analyze the path relationships among the three and to explore the mediating role of dyadic coping. Results: The level of body image was negatively correlated with post-traumatic growth (r = -0.462, p < 0.01); and the level of body image was negatively correlated with dyadic coping (r = -0.308, p < 0.01). And dyadic coping was positively associated with post-traumatic growth (r = 0.464, p < 0.01). The structural equation modeling results supported the mediation model with the following model fit indices, chi-square to degrees of freedom ratio (χ2/df = 2.05), goodness of fit index (GFI = 0.93), comparative fit index (CFI = 0.99), canonical fit index (NFI = 0.93), incremental fit index (IFI = 0.99), non-canonical fit index (TLI = 0.99) and the root mean square of the difference in approximation error (RMSEA = 0.03). Body image and dyadic coping directly affected post-traumatic growth (ß = -0.33, p < 0.05; ß = 0.43, p < 0.05). And body image indirectly influenced post-traumatic growth through dyadic coping (ß = -0.17, p < 0.05). Conclusion: Interconnections between body image, dyadic coping, and post-traumatic growth in breast cancer patients. A preliminary validation of the mediating role of dyadic coping between body image and post-traumatic growth, body image can have an impact on dyadic coping, which in turn can have an impact on post-traumatic growth. Whereby higher levels of dyadic coping in patients may also be associated with higher levels of post-traumatic growth, whereas body image disturbance may impede levels of post-traumatic growth.

Prescription Data Mining and Network Pharmacology Study of 1152 Patients with Rectal Prolapse Using Traditional Chinese Medicine.

BACKGROUND: In recent years, the incidence of rectal prolapse has increased significantly due to the sedentary lifestyle and irregular eating habits of modern life. However, there is a lack of clinical studies on the treatment of rectal prolapse with traditional Chinese medicine (TCM) with a large sample size. Therefore, this study investigated the characteristics of rectal prolapse treatment formulas and then studied the network pharmacology of their core therapeutic drugs, which can help to provide a reference for the treatment and postoperative care of rectal prolapse patients. OBJECTIVE: This study aimed to explore the prescription characteristics and the mechanism of action of core drugs in the treatment of rectal prolapse in Chinese medicine through data mining and bioinformatics techniques. METHODS: We collected the diagnosis and treatment information of patients with rectal prolapse from January 2014 to September 2021 in the electronic case database of Nanjing Hospital of TCM, mined the patient information and prescription features using R, screened the active ingredients of the core pairs of drugs and disease drug intersection targets using TCMSP and GnenCard databases, and constructed a Protein-protein interaction (PPI) network using STRING and Cytoscape, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the intersecting targets were performed using Metascape and R. RESULTS: We found that prolapse is easy to occur in people over 50 years old, preferably in autumn and winter. Commonly used therapeutic Chinese medicines include Glycyrrhiza glabra, Radix angelicae sinensis, Radix astragali, Atractylodes macrocephala, and Pericarpium citri reticulatae, which are mostly deficiency tonic medicines, warm in nature, and belong to spleen meridian. The core therapeutic medicinal pair was "Bupleuri radix-Cimicifugae rhizoma". There were 190 common targets of Bupleuri radix and Cimicifugae rhizoma, and 71 intersection targets of the drug pair and prolapse. The main components of the core drugs for the treatment of prolapse may be quercetin, kaempferol, Stigmasterol, etc, and the core targets may be CASP3, AKT1, HIF1A, etc. The total number of GO entries for the intersection targets of "Bupleuri radix-Cimicifugae rhizoma" and diseases was 3495, among which the molecular functions accounted for the largest proportion, mainly Pathways in cancer, IL-18 signaling pathway, etc. KEGG enriched pathway analysis yielded 168 results, and the major pathways were pathways in cancer, lipid and atherosclerosis, IL-17 signaling pathway, etc. Conclusion: This study adopted real-world research methodology and used data mining and bioinformatics technology to mine the medication law of rectal prolapse and its core drug action mechanism from the clinical information of Chinese medicine.

Limited debridement combined with ReCell® Techniques for deep second-degree burns.

BACKGROUND: The purpose of this article is to introduce a method that combines limited debridement and ReCell® autologous cell regeneration techniques for the treatment of deep second-degree burn wounds. METHOD: A total of 20 patients suffered with deep second-degree burns less than 10% of total body surface area (TBSA) who were admitted to our department, from June 2019 to June 2021, participated in this study. These patients first underwent limited debridement with an electric/pneumatic dermatome, followed by the ReCell® technique for secondary wounds. Routine treatment was applied to prevent scarring after the wound healed. Clinical outcomes were scored using the Vancouver Scar Scale (VSS). RESULTS: All wounds of the patients healed completely. One patient developed an infection in the skin graft area and finally recovered by routine dressing changes. The average healing time was 12 days (range: 10-15 days). The new skin in the treated area was soft and matched the colour of the surrounding normal skin and the VSS score ranged from 3~5 for each patient. Of the 20 patients, 19 were very satisfied and 1 was satisfied. CONCLUSIONS: This article reports a useful treatment method that combines electric dermatome-dependent limited debridement and the ReCell® technique for the treatment of deep second-degree burn wounds. It is a feasible and effective strategy that is easy to implement and minimally invasive, and it is associated with a short healing time, mild scar formation and little damage to the donor skin area.

Cerastecins inhibit membrane lipooligosaccharide transport in drug-resistant Acinetobacter baumannii.

Carbapenem-resistant Acinetobacter baumannii infections have limited treatment options. Synthesis, transport and placement of lipopolysaccharide or lipooligosaccharide (LOS) in the outer membrane of Gram-negative bacteria are important for bacterial virulence and survival. Here we describe the cerastecins, inhibitors of the A. baumannii transporter MsbA, an LOS flippase. These molecules are potent and bactericidal against A. baumannii, including clinical carbapenem-resistant Acinetobacter baumannii isolates. Using cryo-electron microscopy and biochemical analysis, we show that the cerastecins adopt a serpentine configuration in the central vault of the MsbA dimer, stalling the enzyme and uncoupling ATP hydrolysis from substrate flipping. A derivative with optimized potency and pharmacokinetic properties showed efficacy in murine models of bloodstream or pulmonary A. baumannii infection. While resistance development is inevitable, targeting a clinically unexploited mechanism avoids existing antibiotic resistance mechanisms. Although clinical validation of LOS transport remains undetermined, the cerastecins may open a path to narrow-spectrum treatment modalities for important nosocomial infections.