Combination of manual lymphatic drainage and Kinesio taping for treating pigmented villonodular synovitis: A case report.

BACKGROUND: Pigmented villonodular synovitis (PVNS) is a benign proliferative disorder that affects the synovial joints, bursae, and tendon sheaths. To date, few studies have reported on the treatment of postoperative pain and edema in patients with PVNS. Herein, we present the case of a woman who developed pain and edema in the left lower limb 1 wk after synovectomy and arthroscopic partial meniscectomy and was unable to walk due to limited flexion and extension of the left knee. CASE SUMMARY: A 32-year-old woman underwent synovectomy and arthroscopic partial meniscectomy successively and was treated with a combination of manual lymphatic drainage (MLD) and kinesio taping (KT) in our hospital to alleviate postoperative pain and edema. The following parameters were assessed at 2 wk post-treatment and 1 wk post-discharge follow up: suprapatellar circumference, infrapatellar circumference, visual analog scale score, knee range of motion, pittsburgh sleep quality index score, hamilton anxiety rating scale (HAMA) score, and hamilton depression rating scale (HAMD) score. After treatment, the postoperative pain and edema in the patient's left knee were effectively relieved, resulting in improved sleep quality and remarkably attenuated HAMA and HAMD scores. CONCLUSION: Combined MLD and KT may be an effective approach for relieving postoperative pain and edema in patients with PVNS.

Dermotoscope assisted diagnosis of adolescent bullous pilomatricoma: six case reports.

BACKGROUND: Pilomatricoma (PM) is a cutaneous benign neoplasm derived from the hair matrix. It clinically presents as a solitary and firm nodule overlying normal epidermis and is usually not easy to be noticed at early stage. Nevertheless, when special bullous lesion occurs in a short time or even ulcerates, preoperative diagnosis by a dermatologist is often challenging especially when the pediatric patients refuse biopsy. CASE PRESENTATION: We present six bullous PM cases and particularly conduct correlation analysis on the dermotoscopy and histopathology detection data. The basic information, medical history, symptoms and lesion morphology results of the patients were also provided. We found that the incidence of bullous PM was higher in females than in males, and most patients were adolescents and the predilection location seem to be consistent in the vaccine injection site. The dermatoscopic features of bullous PM reported were luminous yellow structure below, with gray-blue homogeneous areas and branched capillary. The histological features were consistent with PM, and evident epidermis bullae were above the tumor with extraordinary dilation of lymphangion in the upper dermis. The patients described in this study were Chinese patients in Han population included 4 females and 2 males, coincidentally, they are almost teen-age, respectively are 5,11,17,19,21,22 year-old. CONCLUSIONS: This study reported and analyzed the dermotoscopy and clinical characteristics of bullous PM, dermotoscopy may guide as a rapid and reliable technique in bullous PM diagnosis.

Pyroptosis-related long-noncoding RNA signature predicting survival and immunotherapy efficacy in patients with lung squamous cell carcinoma.

Pyroptosis-related long-noncoding RNAs (PRlncRNAs) play an important role in cancer progression. However, their role in lung squamous cell carcinoma (LUSC) is unclear. A risk model was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression analysis based on RNA sequencing data from The Cancer Genome Atlas database. The LUSC cohort was divided into high- and low-risk groups based on the median risk score. For the prognostic value of the model, the Kaplan-Meier analysis, log-rank test, and Cox regression analysis were performed. A nomogram was constructed to predict the prognosis of patients, using a risk score and clinical parameters such as age, sex, clinical stage, and tumor node metastasis classification (TNM) stage. Afterwards, six common algorithms were employed to assess the invasion of immune cells. The Gene Set Enrichment Analysis (GSEA) was conducted to identify differences between patients at high and low risk. Furthermore, the pRRophetic package was employed to forecast the half-maximal inhibitory doses of prevalent chemotherapeutic drugs, while the tumor immune dysfunction and exclusion score was computed to anticipate the response to immunotherapy. The expression levels of the seven PRlncRNAs were examined in both LUSC and normal lung epithelial cell lines using RT-qPCR. Proliferation, migration, and invasion assays were also carried out to investigate the role of MIR193BHG in LUSC cells. Patients in the low-risk group showed prolonged survival in the total cohort or subgroup analysis. The Cox regression analysis showed that the risk model could act as an independent prognostic factor for patients with LUSC. The results of GSEA analysis revealed that the high-risk group showed enrichment of cytokine pathways, Janus tyrosine kinase/signal transducer and activator of the transcription signalling pathway, and Toll-like receptor pathway. Conversely, the low-risk group showed enrichment of several gene repair pathways. Furthermore, the risk score was positively correlated with immune cell infiltration. Moreover, patients in the high-risk category showed reduced responsiveness to conventional chemotherapeutic medications and immunotherapy. The majority of the long noncoding RNAs in the risk model were confirmed to be overexpressed in LUSC cell lines compared to normal lung epithelial cell lines by in vitro tests. Further studies have shown that downregulating the expression of MIR193BHG may inhibit the growth, movement, and infiltration capabilities of LUSC cells, whereas increasing the expression of MIR193BHG could enhance these malignant tendencies. This study found that PRlncRNAs were linked to the prognosis of LUSC patients. The risk model, evaluated across various clinical parameters and treatment modalities, shows potential as a future reference for clinical applications.

The m6A methyltransferase METTL3 drives neuroinflammation and neurotoxicity through stabilizing BATF mRNA in microglia.

Persistent neuroinflammation and progressive neuronal loss are defining features of acute brain injury including traumatic brain injury (TBI) and cerebral stroke. Microglia, the most abundant type of brain-resident immune cells, continuously surveil the environment and play a central role in shaping the inflammatory state of the central nervous system (CNS). In the study, we discovered that the protein expression of METTL3 (a m6A methyltransferase) was upregulated in inflammatory microglia independent of increased Mettl3 gene transcription following TBI in both human and mouse subjects. Subsequently, we identified TRIP12, a HECT-domain E3 ubiquitin ligase, as a negative regulator of METTL3 protein expression by facilitating METTL3 K48-linked polyubiquitination. Importantly, selective ablation of Mettl3 inhibited microglial pathogenic activities, diminished neutrophil infiltration, rescued neuronal loss and facilitated functional recovery post-TBI. Using MeRIP-seq and CUT&Tag sequencing, we identified that METTL3 promoted the expression of Basic Leucine Zipper Transcriptional Factor ATF-Like (BATF), which in turn directly bound to a cohort of characteristic inflammatory cytokines and chemokine genes. Enhanced activities of BATF in microglia elicited TNF-dependent neurotoxicity and can also promote neutrophil recruitment through releasing CXCL2. Pharmacological inhibition of METTL3 using a BBB-penetrating drug-loaded nano-system showed satisfactory therapeutic effects in both TBI and stroke mouse models. Collectively, our findings identified METTL3-m6A-BATF axis as a potential therapeutic target for terminating detrimental neuroinflammation and progressive neuronal loss following acute brain injury. METTL3 protein is significantly up-regulated in inflammatory microglia due to the decreased proteasomal degradation mediated by TRIP12 and ERK-USP5 pathways. METTL3 stabilized BATF mRNA stability and promoted BATF expression through the m6A-IGF2BP2-dependent mechanism. Elevated expression of BATF elicits a pro-inflammatory gene program in microglia, and aggravates neuroinflammatory response including local immune responses and peripheral immune cell infiltration. Genetic deletion or pharmaceutically targeting METTL3-BATF axis suppressed microglial pro-inflammatory activities and promoted neurological recovery following TBI and stroke.

Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency.

Apoptotic vesicles (apoVs) play a vital role in various pathological conditions; however, we have yet to fully understand their precise biological effects in rescuing impaired mesenchymal stem cells (MSCs) and regulating tissue homeostasis. Here, we proved that systemic infusion of bone marrow MSCs derived from wild-type (WT) mice effectively improved the osteopenia phenotype and hyperimmune state in ovariectomized (OVX) mice. Importantly, the WT MSCs rescued the impairment of OVX MSCs both in vivo and in vitro, whereas OVX MSCs did not show the same efficacy. Interestingly, treatment with apoVs derived from WT MSCs (WT apoVs) restored the impaired biological function of OVX MSCs and their ability to improve osteoporosis. This effect was not observed with OVX MSCs-derived apoVs (OVX apoVs) treatment. Mechanistically, the reduced miR-145a-5p expression hindered the osteogenic differentiation and immunomodulatory capacity of OVX MSCs by affecting the TGF-ß/Smad 2/3-Wnt/ß-catenin signaling axis, resulting in the development of osteoporosis. WT apoVs directly transferred miR-145a-5p to OVX MSCs, which were then reused to restore their impaired biological functions. Conversely, treatment with OVX apoVs did not produce significant effects due to their limited expression of miR-145a-5p. Overall, our findings unveil the remarkable potential of apoVs in rescuing the biological function and therapeutic capability of MSCs derived from individuals with diseases. This discovery offers a new avenue for exploring apoVs-based MSC engineering and expands the application scope of stem cell therapy, contributing to the maintenance of bone homeostasis through a previously unrecognized mechanism.

In-situ forming carboxymethyl chitosan hydrogel containing Paeonia suffruticosa Andr. leaf extract for mixed infectious vaginitis treatment by reshaping the micro-biota.

Mixed infectious vaginitis poses a serious threat to female reproductive health due to complex pathogenic factors, a long course and easy recurrence. Currently, antibiotic-based treatment methods are facing a crisis of drug resistance and secondary dysbiosis. Exploring effective drugs for the treatment of mixed vaginitis from Paeonia suffruticosa Andr., a natural traditional Chinese medicine with a long history of medicinal use, is a feasible treatment strategy. P. suffruticosa Andr. leaf extract (PLE) has significant anti-bacterial effects due to its rich content of polyphenols and flavonoids. The polyphenols in peony leaves have the potential to make carboxymethyl chitosan form in situ gel. In the current study, PLE and carboxymethyl chitosan were combined to develop another type of natural anti-bacterial anti-oxidant hydrogel for the treatment of mixed infectious vaginitis. Through a series of characterisations, CP had a three-dimensional network porous structure with good mechanical properties, high water absorption, long retention and a slow-release drug effect. The mixed infectious vaginitis mouse model induced by a mixture of pathogenic bacteria was used to investigate the therapeutic effects of CP in vivo. The appearance of the vagina, H&E colouring of the tissue and inflammatory factors (TNF-α, IL-6) confirm the good anti-vaginal effect of CP. Therefore, CP was expected to become an ideal effective strategy to improve mixed infection vaginitis due to its excellent hydrogel performance and remarkable ability to regulate flora.

Endoscopic endonasal resection of symptomatic Rathke's cleft cysts: outcomes of the strategy to maintain the fenestration open.

PURPOSE: The study intends to clarify the optimal endoscopic endonasal surgical strategy for symptomatic Rathke's cleft cysts (RCCs). METHODS: We retrospectively analyzed patients with RCCs that underwent EEA surgery. The strategy for surgical and reconstruction method selection was presented. Patients were split into groups of fenestration open or closed. Pre- and postoperative symptoms, imaging, ophthalmologic, and endocrinologic exams were reviewed. The incidence of complications and the recurrence rates were determined. RESULTS: The 75 individuals were all received primary operations. The fenestration closed group contained 32 cases, while the fenestration open group contained 43 cases. The median follow-up period was 39 months. The three primary complaints were headache (n = 51, 68.00%), vision impairment (n = 45, 60.00%), and pituitary dysfunction (n = 16, 21.33%). Of the 51 patients with preoperative headaches, 48 (94.12%) reported improvement in their symptoms following surgery. Twenty-three out of 45 patients (51.11%) experienced an improvement in visual impairment. Pituitary dysfunction was found improved in 14 out of 16 individuals (87.50%). There was no discernible difference in the rate of symptom alleviation between both groups. There were three patients (3/75, 4.00%) had cyst reaccumulation. One of them (1/75, 1.33%), which needed reoperation, was healed using pterional approach. In term of complications, cerebral infections occurred in two patients (2/75, 2.67%). Both of them recovered after antibiotic treatment. No postoperative cerebrospinal fluid rhinorrhea occurred. One patient (1/75, 1.33%) in the open group experienced epistaxis. There was no persistent hypopituitarism or diabetes insipidus (DI). Analysis of headache related factors showed that the presence of wax like nodules was related to it. CONCLUSION: RCC was successfully treated with endoscopic endonasal surgery with few problems when the fenestration was kept as open as feasible. Preoperative identification of T2WI hypointense nodules may be a potential reference factor for surgical indication.

Oxford Nanopore Technologies (ONT) Full-length Transcriptomics Shows Electroacupuncture ameliorates Lipid Metabolic Disorder through Suppressing Hepatic Pdia3/Perk/Qrich1 Expression in Rats.

BACKGROUND: The incidence of dyslipidemia increases after menopause. Electroacupuncture (EA) has been recommended for menopause-related disease. However, the positive effect on lipid metabolism disorders is still unclear. OBJECTIVES: To investigate the underlying mechanism of EA treatment on lipid metabolism disorders through ONT full-length transcriptome sequencing Methods: Adult female SD rats were randomly divided into Ctrl, sham operation+high-fat feed(Sham+HFD), Ovariectomized+high-fat feed (OVX+HFD), Ovariectomized+high-fat feed + Atorvastatin (OVX+HFD+ATO) and OVX+HFD+EA groups. Periovarian adipose tissue around the bilateral ovaries of rats in the Sham+HFD group was resected. Rats in the OVX+HFD, OVX+HFD+ATO and OVX+HFD+EA groups were subjected to bilateral oophorectomy to prepare the ovariectomized rat model. Treatment was applied to rats in the OVX+HFD+EA group. ST36, PC6, SP6, BL18 and ST40 were the selected acupoints. Daily food intake and body weights of rats were recorded. The samples were collected 30 days after treatment. The serum levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein (HDL-C) were detected to assess the improvement of lipid metabolism disorders. HE and oil red O staining were used to stain the liver tissues. Total RNA was extracted from liver tissues, and its transcriptional changes were determined by high-throughput sequencing. Additionally, RTÁqPCR and immunofluorescence staining were used to verify the crucial signal pathway screened by the ONT fullÁlength transcriptome sequencing. RESULTS: EA treatment resulted in a lowered weight of perirenal fat and liver and a significant improvement in the color of the liver. In addition, EA could improve the lipid profile and hepatic steatosis in OVX+HFD rats. According to fullÁlength transcriptome sequencing, 2292 genes showed differential expression in the OVX+HFD group; of these, 1121 were upregulated and 1171 down-regulated. 609 DEGs were found in the OVX+HFD+EA group compared to the OVX+HFD group; 235 up-regulated and 374 down-regulated. We also found that 77 genes are significantly upregulated after EA intervention through Venn map analysis (including Agtr1a, Pdia3, etc.), which may be the targeted genes for EA treatment of lipid metabolism disorders. Finally, we verified the expression of Pdia3, Perk and Qrich1 levels in liver tissues. HFD feeding could increase the expression of Pdia3 and its downstream signal pathways molecular Perk and Qrich1. But these effects were reversed by EA treatment, the results demonstrated that the expression of pdia3, Perk, as well as Qrich1 of OVX+HFD rats had a decreasing trend after EA treatment. CONCLUSIONS: EA could ameliorate lipid metabolic disorder in OVX+HFD rats. The Pdia3/Perk/Qrich1 signal pathway may play crucial roles in the improvement of lipid metabolism disorder of OVX+HFD rats after EA treatment.

Course and predictors of supportive care needs among colorectal cancer survivors with ostomies: a longitudinal study.

PURPOSE: Although there is a growing emphasis on supportive care for cancer patients, those with colorectal cancer (CRC) who have ostomies require special attention in terms of their physical, psychological, spiritual, and social needs. However, there has been a lack of significant progress in meeting the supportive care needs of CRC survivors with ostomies. To bridge this gap, we conducted a prospective longitudinal study to track the trends in supportive care needs among CRC survivors with ostomies and identify any predictors over 6-month period. METHODS: A prospective longitudinal study was conducted at the wound and stoma clinic of Dalian University Affiliated Xinhua Hospital, focusing on CRC survivors with ostomies. A total of 143 participants completed self-report questionnaires on the 34-item Short-Form Supportive Care Needs Survey (SCNS-SF34-C (Mandarin)) and stoma complications at the first, third, and sixth month after surgery. ANOVA with repeated measure was utilized to assess the course of supportive care needs, with Generalized Estimating Equation (GEE) applied to identify predictors of SCNS. RESULTS: The supportive care needs and five dimensions scores were statistically significant at three time points (P < 0.05). The ratings of patients at the first, third, and sixth month after surgery revealed a decreasing trend in the scores for patient care and support, psychological needs, physical and daily living needs, and health system and information needs. However, the score for sexual needs showed an increased tendency. Higher levels supportive care needs were generally connected with a short duration after ostomy, high income level, resident medical insurance, spouse caregiver, other chronic disease, and stoma complications. CONCLUSIONS: Survivors' supportive care needs showed a dynamic trend over 6 months after surgery. Through three rounds, the primary needs were health system and information needs. It is recommended to integrate interdisciplinary health professionals and establish a comprehensive support and care system to effectively meet the diverse needs at different stages. Priority should be given to individuals with ostomies during the first and third month after surgery, particularly those with higher income levels, employee medical insurance, spouse caregivers, other chronic diseases, and stoma complications.

Intervention of CXCL5 attenuated neuroinflammation and promoted neurological recovery after traumatic brain injury.

Neuroinflammation after traumatic brain injury (TBI) exhibits a strong correlation with neurological impairment, which is a crucial target for improving the prognosis of TBI patients. The involvement of CXCL5/CXCR2 signaling in the regulation of neuroinflammation in brain injury models has been documented. Therefore, the effects of CXCL5 on post-TBI neuroinflammation and its potential mechanisms need to be explored. Following TBI, C57BL/6 mice were administered intraperitoneal injections of a CXCL5 neutralizing antibody (Nab-CXCL5) (5 mg/kg, 2 times/day). Subsequently, the effects on neuroinflammation, nerve injury, and neurological function were assessed. Nab-CXCL5 significantly reduced the release of inflammatory factors, inhibited the formation of inflammatory microglia and astrocytes, and reduced the infiltration of peripheral immune cells in TBI mice. Additionally, this intervention led to a reduction in neuronal impairment and facilitated the restoration of sensorimotor abilities, as well as improvements in learning and memory functions. Peripheral administration of the Nab-CXCL5 to TBI mice could suppress neuroinflammation, reduce neurological damage, and improve neurological function. Our data suggest that neutralizing antibodies against CXCL5 (Nab-CXCL5) may be a promising agent for treating TBI.

FNDC5 prevents oxidative stress and neuronal apoptosis after traumatic brain injury through SIRT3-dependent regulation of mitochondrial quality control.

Mitochondrial dysfunction and oxidative stress are important mechanisms for secondary injury after traumatic brain injury (TBI), which result in progressive pathophysiological exacerbation. Although the Fibronectin type III domain-containing 5 (FNDC5) was reported to repress oxidative stress by retaining mitochondrial biogenesis and dynamics, its possible role in the secondary injury after TBI remain obscure. In present study, we observed that the level of serum irisin (the cleavage product of FNDC5) significantly correlated with the neurological outcomes of TBI patients. Knockout of FNDC5 increased the lesion volume and exacerbated apoptosis and neurological deficits after TBI in mice, while FNDC5 overexpression yielded a neuroprotective effect. Moreover, FNDC5 deficiency disrupted mitochondrial dynamics and function. Activation of Sirtuin 3 (SIRT3) alleviated FNDC5 deficiency-induced disruption of mitochondrial dynamics and bioenergetics. In neuron-specific SIRT3 knockout mice, FNDC5 failed to attenuate TBI-induced mitochondrial damage and brain injuries. Mechanically, FNDC5 deficiency led to reduced SIRT3 expression via enhanced ubiquitin degradation of transcription factor Nuclear factor erythroid 2-related factor 2 (NRF2), which contributed to the hyperacetylation and inactivation of key regulatory proteins of mitochondrial dynamics and function, including OPA1 and SOD2. Finally, engineered RVG29-conjugated nanoparticles were generated to selectively and efficiently deliver irisin to the brain of mice, which yielded a satisfactory curative effect against TBI. In conclusion, FNDC5/irisin exerts a protective role against acute brain injury by promoting SIRT3-dependent mitochondrial quality control and thus represents a potential target for neuroprotection after TBI.

Analysis of nearly 3000 archaeal genomes from terrestrial geothermal springs sheds light on interconnected biogeochemical processes.

Terrestrial geothermal springs are physicochemically diverse and host abundant populations of Archaea. However, the diversity, functionality, and geological influences of these Archaea are not well understood. Here we explore the genomic diversity of Archaea in 152 metagenomes from 48 geothermal springs in Tengchong, China, collected from 2016 to 2021. Our dataset is comprised of 2949 archaeal metagenome-assembled genomes spanning 12 phyla and 392 newly identified species, which increases the known species diversity of Archaea by ~48.6%. The structures and potential functions of the archaeal communities are strongly influenced by temperature and pH, with high-temperature acidic and alkaline springs favoring archaeal abundance over Bacteria. Genome-resolved metagenomics and metatranscriptomics provide insights into the potential ecological niches of these Archaea and their potential roles in carbon, sulfur, nitrogen, and hydrogen metabolism. Furthermore, our findings illustrate the interplay of competition and cooperation among Archaea in biogeochemical cycles, possibly arising from overlapping functional niches and metabolic handoffs. Taken together, our study expands the genomic diversity of Archaea inhabiting geothermal springs and provides a foundation for more incisive study of biogeochemical processes mediated by Archaea in geothermal ecosystems.

[Application and significance of prone position in the treatment of patients with severe pneumonia in intensive care unit].

OBJECTIVE: To investigate the effect of prone position on the prognosis of patients with severe pneumonia in intensive care unit (ICU). METHODS: A retrospective cohort study was conducted. The patients with severe pneumonia admitted to the ICU of Qingdao Municipal Hospital from May 2022 to August 2023 were enrolled. The general information, etiology, underlying diseases, vital signs and laboratory indicators at ICU admission, clinical treatment and prognosis during ICU hospitalization were collected. The above clinical data of patients with different prognosis were compared. Multifactorial Logistic regression analysis was used to screen the related factors affecting survival during ICU in patients with severe pneumonia. The change in oxygenation index (PaO2/FiO2) of patients with severe pneumonia were observed at 1 hour before the first prone position, 1 hour after the first prone position, and 1 hour after the end of the first prone position. The effect of prone position on oxygenation in patients with severe pneumonia was analyzed. Spearman correlation analysis was used to investigate the correlation between the duration to first prone position and the change in the PaO2/FiO2 before and after prone position in patients with severe pneumonia. RESULTS: Finally, a total of 144 patients with severe pneumonia were enrolled, 45 survived and 99 died during ICU hospitalization, with a mortality of 68.8%. Compared with the survival group, the patients in the death group were older [years old: 81.00 (70.75, 86.00) vs. 71.00 (60.50, 81.50), P < 0.01], the proportion of pre-existing lung disease, heart rate (HR), respiratory rate (RR), blood lactic acid (Lac) and the ratio of continuous renal replacement therapy (CRRT) were higher [ratio of pre-existing lung disease: 23.2% (23/99) vs. 8.9% (4/45), HR (bpm): 99.61±22.47 vs. 91.49±18.76, RR (times/min): 22.50 (19.75, 29.25) vs. 20.00 (17.50, 24.50), Lac (mmol/L): 2.00 (1.55 , 3.25) vs. 1.60 (1.20, 1.95), CRRT ratio: 25.3% (25/99) vs. 6.7% (3/45), all P < 0.05], and the proportion of prone position was lower [41.4% (41/99) vs. 68.9% (31/45), P < 0.01]. Multifactorial Logistic regression analysis showed that age [odds ratio (OR) = 0.946, 95% confidence interval (95%CI) was 0.912-0.980, P = 0.002] and Lac (OR = 0.563, 95%CI was 0.340-0.930, P = 0.025) were negatively correlated with survival during ICU hospitalization in severe pneumonia patients, while prone position was positively correlated with survival (OR = 2.551, 95%CI was 1.067-6.095, P = 0.035), indicating that prone position was beneficial for improving ICU prognosis in severe pneumonia patients. The results of PaO2/FiO2 at different time points in prone position showed that PaO2/FiO2 at 1 hour of the first prone position in the patients with severe pneumonia was significantly higher than that at 1 hour before the first prone position [mmHg (1 mmHg ≈ 0.133 kPa): 146.69 (113.92, 257.25) vs. 111.75 (70.15, 212.20), P < 0.01], indicating that the prone position had a relevant effect on the improvement of oxygenation in patients. Spearman correlation analysis showed that the duration of the first prone position in patients with severe pneumonia was significantly and positively correlated with the improvement of oxygenation at 1 hour of the first prone position (r = 0.565, P < 0.001). CONCLUSIONS: The prone position is a therapeutic measure that can independently influence the prognosis of patients with severe pneumonia during ICU hospitalization. The prone position effectively improves oxygenation in patients with severe pneumonia and the first change in oxygenation in patients is related to the duration of the prone position.

Microbial communities are thermally more sensitive in warm-climate lizards compared with their cold-climate counterparts.

Environmental temperature affects the composition, structure, and function of the gut microbial communities in host animals. To elucidate the role of gut microbiota in thermal adaptation, we designed a 2 species × 3 temperatures experiment, whereby we acclimated adult males of two agamid lizard species (warm-climate Leiolepis reevesii and cold-climate Phrynocephalus przewalskii) to 20, 28, and 36°C for 2 weeks and then collected their fecal and small-intestinal samples to analyze and compare the microbiota using 16S rRNA gene amplicon sequencing technology. The fecal microbiota displayed more pronounced interspecific differences in microbial community than the small-intestinal microbiota in the two species occurring in thermally different regions. The response of fecal and small-intestinal microbiota to temperature increase or decrease differed between the two species, with more bacterial taxa affected by acclimation temperature in L. reevesii than in P. przewalskii. Both species, the warm-climate species in particular, could cope with temperature change by adjusting the relative abundance of functional categories associated with metabolism and environmental information processing. Functional genes associated with carbohydrate metabolism were enhanced in P. przewalskii, suggesting the contribution of the fecal microbiota to cold-climate adaptation in P. przewalskii. Taken together, our results validate the two hypotheses tested, of which one suggests that the gut microbiota should help lizards adapt to thermal environments in which they live, and the other suggests that microbial communities should be thermally more sensitive in warm-climate lizards than in cold-climate lizards.

Pre-coating cRGD-modified bovine serum albumin enhanced the anti-tumor angiogenesis of siVEGF-loaded chitosan-based nanoparticles by manipulating the protein corona composition.

Chitosan-based nanoparticles inevitably adsorb numerous proteins in the bloodstream, forming a protein corona that significantly influences their functionality. This study employed a pre-coated protein corona using cyclic Arg-Gly-Asp peptide (cRGD)-modified bovine serum albumin (BcR) to confer tumor-targeting capabilities on siVEGF-loaded chitosan-based nanoparticles (CsR/siVEGF NPs) and actively manipulated the serum protein corona composition to enhance their anti-tumor angiogenesis. Consequently, BcR effectively binds to the nanoparticles' surface, generating nanocarriers of appropriate size and stability that enhance the inhibition of endothelial cell proliferation, migration, invasion, and tube formation, as well as suppress tumor proliferation and angiogenesis in tumor-bearing nude mice. Proteomic analysis indicated a significant enrichment of serotransferrin, albumin, and proteasome subunit alpha type-1 in the protein corona of BcR-precoated NPs formed in the serum of tumor-bearing nude mice. Additionally, there was a decrease in proteins associated with complement activation, immunoglobulins, blood coagulation, and acute-phase responses. This modification resulted in an enhanced impact on anti-tumor angiogenesis, along with a reduction in opsonization and inflammatory responses. Therefore, pre-coating of nanoparticles with a functionalized albumin corona to manipulate the composition of serum protein corona emerges as an innovative approach to improve the delivery effectiveness of chitosan-based carriers for siVEGF, targeting the inhibition of tumor angiogenesis.

Hepatic progenitor cell-originated ductular reaction facilitates liver fibrosis through activation of hedgehog signaling.

Background: It is poorly understood what cellular types participate in ductular reaction (DR) and whether DR facilitates recovery from injury or accelerates hepatic fibrosis. The aim of this study is to gain insights into the role of hepatic progenitor cell (HPC)-originated DR during fibrotic progression. Methods: DR in liver specimens of PBC, chronic HBV infection (CHB) or NAFLD, and four rodent fibrotic models by different pathogenic processes was evaluated. Gli1 expression was inhibited in rodent models or cell culture and organoid models by AAV-shGli1 or treating with GANT61. Results: Severity of liver fibrosis was positively correlated with DR extent in patients with PBC, CHB or NAFLD. HPCs were activated, expanded, differentiated into reactive cholangiocytes and constituted "HPC-originated DR", accompanying with exacerbated fibrosis in rodent models of HPC activation & proliferation (CCl4/2-AAF-treated), Μdr2-/- spontaneous PSC, BDL-cholestatic fibrosis or WD-fed/CCl4-treated NASH-fibrosis. Gli1 expression was significantly increased in enriched pathways in vivo and in vitro. Enhanced Gli1 expression was identified in KRT19+-reactive cholangiocytes. Suppressing Gli1 expression by administration of AAV-shGli1 or GANT61 ameliorated HPC-originated DR and fibrotic extent. KRT19 expression was reduced after GANT61 treatment in sodium butyrate-stimulated WB-F344 cells or organoids or in cells transduced with Gli1 knockdown lentiviral vectors. In contrast, KRT19 expression was elevated after transducing Gli1 overexpression lentiviral vectors in these cells. Conclusions: During various modes of chronic injury, Gli1 acted as an important mediator of HPC activation, expansion, differentiation into reactive cholangiocytes that formed DR, and subsequently provoked hepatic fibrogenesis.

Apoptotic vesicles are required to repair DNA damage and suppress premature cellular senescence.

It is well known that DNA damage can cause apoptosis. However, whether apoptosis and its metabolites contribute to DNA repair is largely unknown. In this study, we found that apoptosis-deficient Fasmut and Bim- /- mice show significantly elevated DNA damage and premature cellular senescence, along with a significantly reduced number of 16,000 g apoptotic vesicles (apoVs). Intravenous infusion of mesenchymal stromal cell (MSC)-derived 16,000 g apoVs rescued the DNA damage and premature senescence in Fasmut and Bim-/- mice. Moreover, a sublethal dose of radiation exposure caused more severe DNA damage, reduced survival rate, and loss of body weight in Fasmut mice than in wild-type mice, which can be recovered by the infusion of MSC-apoVs. Mechanistically, we showed that apoptosis can assemble multiple nuclear DNA repair enzymes, such as the full-length PARP1, into 16,000 g apoVs. These DNA repair components are directly transferred by 16,000 g apoVs to recipient cells, leading to the rescue of DNA damage and elimination of senescent cells. Finally, we showed that embryonic stem cell-derived 16,000 g apoVs have superior DNA repair capacity due to containing a high level of nuclear DNA repair enzymes to rescue lethal dose-irradiated mice. This study uncovers a previously unknown role of 16,000 g apoVs in safeguarding tissues from DNA damage and demonstrates a strategy for using stem cell-derived apoVs to ameliorate irradiation-induced DNA damage.

Is There an Optimal Time Window of Placement of Intracranial Pressure (ICP) Monitor for Elderly Patients With Severe Traumatic Brain Injury? An 11-Year Institutional Cohort Study With Restricted Cubic Spline Analysis.

Severe traumatic brain injury (sTBI) is a prominent contributor to both morbidity and mortality in the elderly population. The monitoring of intracranial pressure (ICP) is crucial in the management of sTBI patients. Nevertheless, the appropriate timing for the placement of ICP monitor in elderly sTBI patients remains uncertain. To determine the optimal timing for the placement of ICP monitor in elderly sTBI patients, in this retrospective cohort study, we collected data from elderly patients (> 65 years) who suffered sTBI and received ICP monitors at Tangdu Hospital, The Fourth Military Medical University, between January 2011 and December 2021. To examine the relationship between the time of ICP monitor placement and in-hospital mortality, we conducted a multi-variate-adjusted restricted cubic spline (RCS) analysis. Additionally, logistic regression analysis was applied to further analyze the influencing factors contributing to early or late ICP monitor placements. A total of 283 eligible elderly TBI patients were included in the current analysis. The in-hospital mortality rate was 73 out of 283 (26%). The RCS analysis demonstrated an inverted U-shaped curve in the relationship between the timing of ICP monitor placement and in-hospital mortality. For the elderly sTBI patient cohort, 6 h was identified as the crucial moment for the treatment strategy. In addition, the protective time window for ICP placement was less than 4.92 h for the GCS 3-5 group, and less than 8.26 h for the GCS 6-8 group. However, the clinical benefit of ICP placement decreased gradually over time. The relationship between ICP placement and in-hospital mortality was non-linear, exhibiting an inverted U-shaped curve in elderly patients with sTBI. For elderly patients with sTBI, early (≤ 6 h) ICP placement was associated with reduced in-hospital mortality. The clinical benefit of ICP placement decreased beyond the optimal time window.

Identify CTBP1-DT as an immunological biomarker that promotes lipid synthesis and apoptosis resistance in KIRC.

Recently, mounting evidence has highlighted the essential function of the C-terminal binding protein-1 divergent transcript (CTBP1-DT) in malignancies. However, its role in kidney renal clear cell carcinoma (KIRC) remains largely unknown. Our study aimed to identify the potential function of CTBP1-DT in KIRC. RT-qPCR, Kaplan-Meier survival analysis, Cox regression analysis, and nomogram analysis were utilized to determine the expression and effects of CTBP1-DT on survival. The subcellular localization of CTBP1-DT was determined using RNA fluorescence in situ hybridization (FISH). To investigate the functions of CTBP1-DT in regulating KIRC cell proliferation, migration, invasion, lipid synthesis, and apoptosis, we conducted CCK8, EdU, Transwell, and Oil Red O staining and cell apoptosis staining assays. The relationships between CTBP1-DT and the tumor microenvironment were investigated with multiple bioinformatics analysis algorithms and databases, including CYBERSORT, TIMER2, Spearman correlation test, tumor mutation burden (TMB), microsatellite instability (MSI), and immunophenoscore (IPS). According to our results, CTBP1-DT is a lncRNA located in the nucleus that is significantly upregulated in KIRC and is correlated with better clinical outcomes. Downregulating CTBP1-DT inhibited cell viability, migration, invasion, and lipid synthesis but triggered cell apoptosis. Additionally, we explored the potential effect of CTBP1-DT in regulating immune cell infiltration in KIRC and other malignancies. Furthermore, CTBP1-DT could be used to predict the effectiveness of targeted drugs and immune checkpoint inhibitors. In conclusion, we identified CTBP1-DT as a potential immunological biomarker and discovered the potential role of CTBP1-DT in regulating lipid synthesis and apoptosis resistance.

Restoring long-lasting midface volume in the Asian face with a hyaluronic acid filler: A randomized controlled multicenter study.

BACKGROUND: Hyaluronic acid (HA) filler treatment is a minimally-invasive alternative to surgery to volumize the cheeks. HAVOL (Restylane® Volyme) is a flexible HA filler suited to contouring and volumizing the midface. METHODS: This randomized, evaluator-blinded, no-treatment controlled study evaluated effectiveness and safety of HAVOL for correction of midface volume deficit and midface contour deficiency in Chinese subjects. In total 111 subjects were randomized to HAVOL and 37 to no treatment (control). The primary endpoint was response, on the blinded evaluator-assessed Medicis Midface Volume Scale (MMVS), at 6 months after last injection for the treatment group and 6 months after randomization for controls, where response was defined as ≥1-point improvement from baseline on both sides of the face. RESULTS: HAVOL was superior to no treatment at 6 months, meeting the primary objective: 76% versus 8% MMVS responders, a difference of 68% (CI: 55.7%-79.4%, p < 0.0001). These effects were sustained in 51% at 12 months after last injection. A majority (≥96%) had improved aesthetic appearance of midface fullness at Month 1 (using the Global Aesthetic Improvement Scale [GAIS]), effects which remained in ≥80% up to 12 months. Volume change captured by 3D photography increased after 1 month to 3.6 mL (close to the total injected volume of 3.4 mL), and remained stable through 12 months. Over 97% reported satisfaction with results after treatment with HAVOL. Additionally, HAVOL was well tolerated, with no unanticipated related adverse events. CONCLUSIONS: This study showed that HAVOL is effective and well tolerated for midface treatment in a Chinese population.