Prognostic relevance of prognostic nutritional indices in gastric or gastro-esophageal junction cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.

Background: The Prognostic Nutritional Index (PNI) has become an important predictive tool for assessing patients' nutritional status and immune competence. It is widely used in prognostic evaluations for various cancer patients. However, the prognostic relevance of the Prognostic Nutritional Index (PNI) in gastric or gastro-esophageal junction cancer patients (GC/GEJC) undergoing immune checkpoint inhibitors (ICIs) treatment remains unclear. This meta-analysis aimed to determine the prognostic impact of PNI in this specific patient cohort. Methods: We conducted a thorough literature search, covering prominent databases such as PubMed, Embase, Web of Science, SpringerLink, and the Cochrane Library. The search spanned from the inception of these databases up to December 5, 2023. Employing the 95% confidence interval and Hazard Ratio (HR), the study systematically evaluated the relationship between PNI and key prognostic indicators, including the objective remission rate (ORR), disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) in GC/GEJC patients undergoing ICI treatment. Results: Eight studies comprising 813 eligible patients were selected. With 7 studies consistently demonstrating superior Overall Survival (OS) in the high-Prognostic Nutritional Index (PNI) group compared to their low-PNI counterparts (HR 0.58, 95% CI: 0.47-0.71, P<0.001). Furthermore, the results derived from 6 studies pointed out that the significant correlation between he low-PNI and poorer progression-free survival (PFS) (HR 0.58, 95% CI: 0.47-0.71, P<0.001). Subgroup analyses were performed to validate the robustness of the results. In addition, we conducted a meta-analysis of three studies examining the correlation between PNI and objective response rate/disease control rate (ORR/DCR) and found that the ORR/DCR was significantly superior in the high PNI group (ORR: RR: 1.24, P=0.002; DCR: RR: 1.43, P=0.008). Conclusion: This meta-analysis indicates that the low-PNI in GC/GEJC patients undergoing ICI treatment is significantly linked to worse OS and PFS. Therefore, PNI can serve as a prognostic indicator of post-treatment outcomes in patients with GC receiving ICIs. Further prospective studies are required to assess the reliability of these findings. Systematic review registration: https://inplasy.com/, identifier INPLASY202450133.

A comparative analysis of different reduced-port laparoscopic surgical procedures after non-curative endoscopic resection for early colorectal cancer.

Introduction: Surgery serves as a salvage procedure for non-curative resection of early-stage colorectal cancer under endoscopy. A standard method for performing additional surgery after endoscopic submucosal dissection (ESD) for early colorectal cancer has yet to be established. Aim: To enhance the understanding of different surgical outcomes by discussing additional treatment strategies following non-complete curative endoscopic resection of early colorectal cancer. Material and methods: This retrospective study included 88 patients who were divided into three groups based on the surgical approach: conventional laparoscopic surgery (CLS), single-incision plus one-port laparoscopic surgery (SILS+1), and three-port laparoscopic surgery combined with natural orifice specimen extraction surgery (three-port NOSES). The study aimed to compare the surgical outcomes, safety, and postoperative recovery among these groups. Results: The SILS+1 and three-port NOSES groups demonstrated comparable safety and efficacy to the CLS group in terms of blood loss, complications, number of lymph node dissections, and length of bowel resection. However, the SILS+1 and three-port NOSES groups had advantages in terms of incision length (7.11 ±0.38, 4.24 ±0.33, 3.16 ±0.22, p < 0.001), postoperative pain (4.000 [3.0,5.0], 3.500 [3.0,4.0], 3.000 [3.0,4.0]; p = 0.003), cosmetic result (4.000 [3.8,5.0], 7.000 [7.0,8.0], 7.000 [7.0,8.0]; p < 0.001), and hospital stay (8.000 [7.0,9.0], 7.000 [6.3,8.0.], 7.000 [6.3,8.0]; p = 0.035). Conclusions: Different strategies of reduced-port laparoscopic surgery have been demonstrated to be effective and safe in additional surgery after non-curative ESD. These techniques have shown reduced pain and increased satisfaction among patients. Reduced-port laparoscopic surgery is expected to become the preferred treatment option for these patients.

Postmastectomy radiotherapy in breast reconstruction: Current controversies and trends.

Breast cancer is the most common cancer among women worldwide. Postmastectomy radiotherapy (PMRT) is an essential component of combined therapy for early-stage, high-risk breast cancer. Breast reconstruction (BR) is often considered for patients with breast cancer who have undergone mastectomy. There has been a considerable amount of discussion about the optimal approach to combining PMRT with BR in the treatment of breast cancer. PMRT may increase the risk of complications and prevent good aesthetic results after BR, while BR may increase the complexity of PMRT and the radiation dose to surrounding normal tissues. The purpose of this review is to give a broad overview and summary of the current controversies and trends in PMRT and BR in the context of the most recent literature available.

Accelerated partial breast irradiation: Current evidence and future developments.

Whole breast irradiation after breast-conserving surgery for early breast cancer has become one of the standard treatment modes for breast cancer and yields the same effect as radical surgery. Accelerated partial breast irradiation (APBI) as a substitute for whole breast irradiation for patients with early breast cancer is a hot spot in clinical research. APBI is characterised by simple high-dose local irradiation of the tumour bed in a short time, thus improving convenience for patients and saving costs. The implementation methods of APBI mainly include brachytherapy, external beam radiation therapy, and intraoperative radiotherapy. This review provides an overview of the clinical effects and adverse reactions of the main technologies of APBI and discusses the prospects for the future development of APBI.

Impact of fast-track surgery-oriented care pathways on perioperative rehabilitation indices in patients undergoing radical prostatectomy for prostate cancer.

OBJECTIVE: This study was conducted to evaluate the effects of Fast-Track Surgery (FTS)-oriented care pathways on perioperative rehabilitation indicators in patients undergoing radical prostatectomy for prostate cancer. METHODS: The clinical data of 120 patients admitted to Sichuan Cancer Hospital & Institute who underwent radical prostatectomy for prostate cancer from September 2020 to October 2022 were collected and retrospectively analyzed. The patients were divided into a control group (n=60, receiving standard care) and an FTS group (n=60 patients receiving FTS-oriented care) according to different nursing methods. The perioperative rehabilitation indices were compared between the groups. RESULTS: The FTS group exhibited shorter hospitalization duration (P=0.001), postoperative anal exhaust time (P=0.012), drain removal time (P=0.007), gastrointestinal recovery time (P=0.008), and a lower total complication rate (P=0.016) compared to the control group. The scores of Visual Analog Scale (VAS) (P=0.001, P=0.003, P=0.015) and Activities of Daily Living (ADL) (P=0.011, P=0.005, P=0.007) at 24, 48, and 72 hours postoperatively were significantly lower in the FTS group than in the control group. Hospitalization cost (P=0.002) and medication expenses (P=0.016) were notably lower in the FTS group. During a 12-month follow-up, the FTS group showed a significantly lower complication rates (3.33%) compared to the control group (18.33%) (P=0.009). CONCLUSION: The application of FTS-oriented nursing pathway in patients undergoing radical prostatectomy for prostate cancer significantly enhances postoperative rehabilitation, reduces pain, lowers hospitalization and medication costs, and improves postoperative quality of life, which contributes positively to the nurse-patient relationship and patient outcome.

Prognostic relevance of platelet lymphocyte ratio (PLR) in gastric cancer patients receiving immune checkpoint inhibitors: a systematic review and meta-analysis.

Objectives: The prognostic relevance of the platelet-to-lymphocyte ratio (PLR) in gastric cancer (GC) patients undergoing immune checkpoint inhibitor (ICI) treatment remains unclear. This meta-analysis aimed to determine the prognostic impact of PLR in this specific patient cohort. Methods: We searched the PubMed, Cochrane Library, CNKI, and EMBASE databases, including literature published up to September 2023, to investigate the prognostic implications of PLR in patients with gastric cancer undergoing immune checkpoint inhibitor therapy. Outcome measures encompassed overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rates (DCR). Results: Nine studies from seven articles comprising 948 eligible patients were selected. The results revealed a significant correlation between elevated PLR and poorer OS and progression-free survival (PFS) (OS: HR 1.67, 95% CI 1.39-2.00, p < 0.001; PFS: HR 1.51, 95% CI 1.29-1.76, p < 0.001). Subgroup analyses were performed to validate the robustness of the results. Moreover, a meta-analysis of four studies investigating the correlation between the PLR in gastric cancer (GC) patients and the objective response rate/disease control rate (ORR/DCR), showed no significant association between the PLR and ORR/DCR (ORR: RR = 1.01, p = 0.960; DCR: RR = 0.96, p = 0.319). Conclusions: This meta-analysis indicates that elevated PLR in GC patients undergoing ICI treatment is significantly linked to worse OS and PFS. Therefore, PLR can serve as a prognostic indicator of post-treatment outcomes in patients with GC receiving ICIs. Further prospective studies are required to assess the reliability of these findings. Systematic review registration: https://inplasy.com/, identifier INPLASY2023120103.

Unveiling the mechanism of photothermal therapy in acne man-agement: targeting sebaceous gland ferroptosis via umbilical cord mesenchymal stem cell membrane-encapsulated Au-Ag-PDA.

Background: Branched gold and silver nanoparticles coated with polydopamine (Au-Ag-PDA) demonstrate high photothermal conversion efficiency. Utilizing umbilical cord mesenchymal stem cell membranes (MSCM) as an effective drug delivery system, our preliminary studies investigated the suppression of sebum secretion in sebaceous glands using MSCM-coated Au-Ag-PDA nano-particles (Au-Ag-PDA@MSCM) combined with 808 nm laser irradiation, showing potential for dermatological applications in acne treatment. Methods: This study employs proteomic analysis, complemented by subsequent techniques such as Western blotting (WB), small interfering RNA (siRNA), and transmission electron microscopy, to further investigate the differential mechanisms by which Au-Ag-PDA and Au-Ag-PDA@MSCM-mediated photothermal therapy (PTT) suppress sebum secretion. Results: Our proteomic analysis indicated mitochondrial respiratory chain damage in sebaceous gland tissues post-PTT, with further validation revealing ferroptosis in sebaceous cells and tissues. Acyl-CoA Synthetase Long-Chain Family Member 4 (Acsl4) has been identified as a critical target, with Au-Ag-PDA@MSCM demonstrating enhanced ferroptotic effects. Conclusion: These findings significantly advance our understanding of how PTT mediated by Au-Ag-PDA@MSCM nanoparticles reduces sebum secretion and underscore the pivotal role of MSCM in inducing ferroptosis in sebaceous glands, thus providing a robust theoretical foundation for employing PTT via specific molecular pathways in acne treatment.

Self-crosslinking hyaluronic acid hydrogel as an enteroprotective agent for the treatment of inflammatory bowel disease.

The pathological changes in inflammatory bowel disease (IBD) include the disruption of intestinal barrier function and the infiltration of pathogenic microbes. The application of an artificial protective barrier at the site of inflammation can prevent bacterial infiltration, promote epithelial cell migration, and accelerate wound healing. In this study, dopamine-modified hyaluronic acid (HA-DA) was developed as a bioadhesive self-cross-linkable hydrogel, which acted as an enteroprotective agent to promote the healing of inflamed intestinal tissue. The adhesion strength HA-DA to mouse colon was 3.81-fold higher than HA. Moreover, HA-DA promoted Caco-2 cell proliferation and migration as well as had a strong physical barrier effect after gelation. After oral administration, the HA-DA reduced weight loss and attenuated impaired goblet cell function in mice with dextran sodium sulfate-induced IBD. In addition, HA-DA promoted restoration of the epithelial barrier by the upregulation of tight junction proteins. The results reported herein substantiated that self-cross-linkable hydrogel-based enteroprotective agents are a promising approach for the treatment of IBD.

The predictors of short and long term urinary continence recovery after laparoscopic radical prostatectomy: a single cancer center report in China.

PURPOSE: To evaluate the predictors for short and long term urinary continence (UC) recovery after laparoscopic radical prostatectomy (LRP) from clinical and oncological variables. METHODS: We retrospectively collected data from 142 prostate cancer patients who underwent LRP between September 2014 and June 2021 at a tumor specialist diagnosis and treatment center in China. The rate of post-prostatectomy incontinence (PPI) was evaluated from immediate and at 3, 6 and 12 mo after LRP, and UC was defined as the use of no or one safety pad. Sixteen clinical and oncological variables were analyzed by univariate and multivariate regression analysis to determine whether they were associated with short (3 mo) or long term (12 mo) UC recovery after LRP. RESULTS: After eliminating patients who were lost to follow-up, 129 patients were eventually included. The mean ± SD age was 68 ± 6.3 years. The UC rates of immediate, 3, 6 and 12 mo after the operation were 27.9%, 54.3%, 75.2% and 88.4%, respectively. Multivariate analyses revealed that membranous urethral length (MUL) was a protective predictor of UC after catheter extraction(P < 0.001), and at 3 mo (P < 0.001), 6 mo (P < 0.001) and 12 mo (P = 0.009) after surgery. CONCLUSION: MUL is a significant independent factor that can contribute to short and long term UC recovery post-LRP, which may assist clinicians and their patients in counseling of treatment.

Successful Treatment of Severe Steroid-Resistant Engraftment Syndrome Following Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia with Emapalumab: A Case Report.

Engraftment syndrome (ES) is an early complication of hematopoietic stem cell transplantation (HSCT) characterized by fever and additional clinical manifestations including rash, diarrhea, lung infiltrates, weight gain, and neurological symptoms. Steroid-resistant ES following HSCT significantly affects the efficacy of transplantation and may even result in patient mortality. As ES essentially represents a cytokine storm induced by engrafted donor cells with interferon-gamma (IFN-γ) playing a central role, we hypothesized that emapalumab (an anti-IFN-γ monoclonal antibody) may be an effective approach to treat steroid-resistant ES. Here, we present a case report of a 14-year-old female patient who received a second haploidentical HSCT due to a relapse of acute myeloid leukemia. Nine days after the transplantation, the patient developed a fever and exhibited a poor response to antimicrobials (ceftazidime/avibactam). A few days later, the patient presented with a new-onset rash, weight gain, and impaired liver function, leading to a diagnosis of ES. Initial immunosuppressive (tacrolimus and mycophenolate mofetil) treatment failed to control the disease. On day 16 post-transplantation, the patient received two infusions of 50 mg of emapalumab. Following the initiation of emapalumab treatment, the patient's fever returned to normal and ES was effectively controlled. This case report demonstrated that emapalumab had a possible efficacy for steroid-resistant ES and provided a novel therapeutic strategy to treat this clinical complication.

Nonsurgical Rhinoplasty: An Updated Systematic Review of Technique, Outcomes, Complications, and Its Treatments.

BACKGROUND: For patients looking for temporary results or who do not want surgery, nonsurgical rhinoplasty using filler injections has become increasingly popular. Filler materials and surgical techniques have improved in recent years, but serious complications remain. Therefore, the aim of this systematic review is to summarize the common types of fillers and injection techniques, complications, and treatment to help clinicians perform in a safer and more effective way. METHODS: A systematic review was performed using keywords and Medical Subject Headings search terms. PubMed, Embase, and the Cochrane Library were searched using the appropriate search terms. Data collected from each study included injection materials, location, technique, patient satisfaction and complications, and treatment. RESULTS: From the 1812 studies identified, 30 were included in the systematic review. A total of 9657 patients underwent nonsurgical rhinoplasty, most commonly with hyaluronic acid (HA) (96.76%), followed by calcium hydroxyapatite (CaHA) (1.22%). Overall satisfaction was 99.08%. The overall incidence of complications was 39.11%, with the highest incidence of erythema and swelling (27.95%). Most of the complications are mild, but there are still 0.27% of the patients who have undergone severe complication-an arterial occlusion. CONCLUSIONS: Nonsurgical rhinoplasty is an effective and relatively safe option for improving the profile of the nose, with a short operative time and high patient satisfaction. Most of the complications were mild, but still serious vascular complications such as blindness, skin necrosis, and stroke were as high as 0.27%. A thorough understanding of the anatomy of the nasal vessels and a precise surgical technique is an important basis for prevention. A BULLET POINT LIST: (1) We summarize the common types of fillers and injection techniques, complications, and treatment of complications to guide physicians to perform nonsurgical rhinoplasty in a safer and more effective manner. (2) Out of 1812 studies through the search strategy, 30 articles were included in the systematic review. A total of 9657 patients underwent nonsurgical rhinoplasty. (3) Nonsurgical rhinoplasty is an effective and relatively safe option to improve the profile of the nose, with a short surgical time and high patient satisfaction. (4) Most of the complications were mild, but some severe complications due to the vascular factors such as blindness, skin necrosis, and cerebral infarction need to be vigilant. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

NPTX1 Mediates the Facilitating Effects of Hypoxia-Stimulated Human Adipocytes on Adipose-Derived Stem Cell Activation and Autologous Adipose Graft Survival Rate.

BACKGROUND: Autologous adipose tissue is an ideal material for soft tissue filling and transplantation; however, high volumes of fat absorption over time lead to a relatively low overall survival percentage. The survival and differentiation of adipose-derived stem cells (ADSCs) in the transplanted microenvironment might improve adipose graft survival. Adipocytes have been reported to affect ADSC activation. However, its underlying mechanisms remain unclear. METHODS: Human ADSCs were incubated in a culture medium supplemented with hypoxic or normoxic conditioned culture medium (CM) derived from human adipocytes. Neuronal Pentraxin 1 (NPTX1) was overexpressed or knocked down in human adipocytes using an overexpression vector (NPTX1 OE) or small interfering RNA (siRNA) transfection, respectively. ADSC differentiation and paracrine secretion were assessed. Nude mice were implanted with human adipocytes and ADSCs. The adipose tissue was subsequently evaluated by histological analysis. RESULTS: CM from hypoxic-stimulated human adipocytes significantly facilitated the differentiation ability and paracrine levels of ADSCs. NPTX1 was significantly up-regulated in human adipocytes exposed to hypoxic conditions. In vitro, CM derived from hypoxia-stimulated human adipocytes or NPTX1-overexpressing human adipocytes exposed to normoxia promoted ADSC differentiation and paracrine; after silencing NPTX1, the facilitating effects of hypoxia-treated human adipocytes on ADSC activation were eliminated. Similarly, in vivo, the NPTX1 OE + normoxia-CM group saw improved histological morphology and fat integrity, less fibrosis and inflammation, and increased vessel numbers compared with the OE NC + normoxia-CM group; the adipocyte grafts of the si-NC + hypoxia-CM group yielded the most improved histological morphology, fat integrity, and the most vessel numbers. However, these enhancements of ADSC activation and adipose graft survival were partially abolished by NPTX1 knockdown in human adipocytes. CONCLUSION: NPTX1 might mediate the facilitating effects of hypoxia-stimulated human adipocytes on ADSC activation, thereby improving adipose tissue survival rate after autologous fat transplantation and the effectiveness of autologous fat transplantation through promoting ADSC activation. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Functional Characterization of F3H Gene and Optimization of Dihydrokaempferol Biosynthesis in Saccharomyces cerevisiae.

The 1092 bp F3H gene from Trapa bispinosa Roxb., which was named TbF3H, was cloned and it encodes 363 amino acids. Bioinformatic and phylogenetic tree analyses revealed the high homology of TbF3H with flavanone 3-hydroxylase from other plants. A functional analysis showed that TbF3H of Trapa bispinosa Roxb. encoded a functional flavanone 3-hydroxylase; it catalyzed the formation of dihydrokaempferol (DHK) from naringenin in S. cerevisiae. The promoter strengths were compared by fluorescence microscopy and flow cytometry detection of the fluorescence intensity of the reporter genes initiated by each constitutive promoter (FITC), and DHK production reached 216.7 mg/L by the promoter adjustment strategy and the optimization of fermentation conditions. The results presented in this study will contribute to elucidating DHK biosynthesis in Trapa bispinosa Roxb.

Repairing Host Damage Caused by Tobacco Mosaic Virus Stress: Design, Synthesis, and Mechanism Study of Novel Oxadiazole and Arylhydrazone Derivatives.

Tobacco mosaic virus (TMV), as one of the most traditional and extensive biological stresses, poses a serious threat to plant growth and development. In this work, a series of 1-phenyl/tertbutyl-5-amino-4-pyrazole oxadiazole and arylhydrazone derivatives was synthesized. Bioassay evaluation demonstrated that the title compounds (P1-P18) without a "thioether bond" lost their anti-TMV activity, while some of the ring-opening arylhydrazone compounds exhibited superior in vivo activity against TMV in tobacco. The EC50 value of title compound T8 for curative activity was 139 µg/mL, similar to that of ningnanmycin (NNM) (EC50 = 152 µg/mL). Safety analysis revealed that compound T8 had no adverse effects on plant growth or seed germination at a concentration of 250 µg/mL. Morphological observation revealed that compound T8 could restore the leaf tissue of a TMV-stressed host and the leaf stomatal aperture to normal. A mechanism study further revealed that compound T8 not only restored the photosynthetic and growth ability of the damaged host to normal levels but also enhanced catalase (CAT) activity and reduced the content of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in the damaged host, thereby reducing the oxidation damage to the host. TMV-green fluorescent protein (GFP) experiments further demonstrated that compound T8 not only slowed the transmission speed of TMV in the host but also inhibited its reproduction. All of the experimental results demonstrated that compound T8 could reduce the oxidative damage caused by TMV stress and regulate the photosynthetic ability of the host, achieving the ability to repair damage, to make the plant grow normally.

Application of thifluzamide to stem rot in peppers: Infection and control mechanisms of sclerotium rolfsii.

In recent years, the fungal disease 'pepper stem rot', contracted from the soil-borne pathogen sclerotium rolfsii, has been increasing year by year, causing significant losses to the pepper (Capsicum annuum L.) industry. To investigate the infection mechanism of stem rot, the fungus S. rolfsii was used to infect the roots of pepper plants, and was found to affect root morphology and reduce root activity, which subsequently inhibited root growth and development. With fungal infestation, its secretions (oxalic acid, PG and PMG enzyme) were able to break normal tissues in the stem base and induced the burst of the active oxygen, which leads to injury aggravation. Morphological observations of the site of damage at the base of the stem using SEM revealed that the vascular bundles and stomata were completely blocked by hyphae, resulting in a blockade of material exchange in the plant. It was subsequently found that most of the stomata in the leaves were closed, which caused the leaves to lose their ability to photosynthesize, then turned yellow, wilt, shed, and the plant died. Commercialized fungicide thifluzamide with excellent in vitro (EC50 = 0.1 µg/mL) and in vivo curative (EC50 = 29.2 µg/mL) antifungal activity was selected to control the stem rot disease in peppers. The results demonstrated that it was able to suppress the secretion of associated pathogenic factors and reduce the outbursts of reactive oxygen species, thus reducing the damage caused by S. rolfsii at the base of the plant's stem and also enhancing the root activity of the infected plant, thereby promoting root growth. It could also inhibit fungal growth, unblock the vascular bundles and stomata, maintain a balance of material and energy exchange within the plant, and thus restore the damaged plant to its normal growth capacity. All the results will provide an adequate reference for the prevention and control of stem rot disease on peppers with thifluzamide.

Biphasic Fermentation of Trapa bispinosa Shells by Ganoderma sinense and Characterization of Its Polysaccharides and Alcoholic Extract and Analysis of Their Bioactivity.

BACKGROUND: Trapa bispinosa shells (TBs) and its flesh (TBf) have been recognized for their medicinal properties, including antioxidant, antitumor, and immunomodulatory effects. Despite these benefits, TBs are often discarded as waste material, and their applications remain to be further explored. METHODS: In this study, we optimized the solid-state fermentation process of Ganoderma sinense (GS) with TBs using a response surface experiment methodology to obtain the fermented production with the highest water extract rate and DPPH free radical scavenging activity. We prepared and characterized pre-fermentation purified polysaccharides (P1) and post-fermentation purified polysaccharides (P2). Alcoholic extracts before (AE1) and after (AE2) fermentation were analyzed for active components such as polyphenols and flavonoids using UPLC-QTOF-MS/MS (ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry). Mouse macrophages (RAW 264.7) were employed to compare the immune-stimulating ability of polysaccharides and the antioxidant activity of AE1 and AE2. RESULTS: Optimal fermentation conditions comprised a duration of 2 days, a temperature of 14 °C, and a humidity of 77%. The peak water extract yield and DPPH free radical scavenging rate of the water extract from TBs fermented by GS were observed under these conditions. The enhanced activity may be attributed to changes in the polysaccharide structure and the components of the alcoholic extract. The P2 treatment group indicated more secretion of RAW 264.7 cells of NO, iNOS, IL-2, IL-10, and TNF-α than P1, which shows that the polysaccharides demonstrated increased immune-stimulating ability, with their effect linked to the NF-кB pathway. Moreover, the results of the AE2 treatment group indicated that secretion of RAW 264.7 cells of T-AOC and T-SOD increased and MDA decreased, which shows that the alcoholic extract demonstrated enhanced antioxidant activity, with its effect linked to the Nrf2/Keap1-ARE pathway. CONCLUSIONS: Biphasic fermentation of Trapa bispinosa shells by Ganoderma sinense could change the composition and structure of the polysaccharides and the composition of the alcoholic extract, which could increase the products' immunomodulatory and antioxidant activity.

Prediction of pulmonary infection in patients with severe myelitis by NPAR combined with spinal cord lesion segments.

Objectives: To investigate the risk factors of pulmonary infection in patients with severe myelitis and construct a prediction model. Methods: The clinical data of 177 patients with severe myelitis at admission from the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2022 were retrospectively analyzed. The predicting factors associated with pulmonary infection were screened by multivariate logistic regression analysis, and the nomogram model was constructed, and the predictive efficiency of the model was evaluated, which was verified by calibration curve, Hosmer-Lemeshow goodness-of-fit test and decision curve analysis. Results: Of the 177 patients with severe myelitis, 38 (21.5%) had pulmonary infection. Multivariate logistic regression analysis showed that neutrophil percentage to albumin ratio (NPAR) (OR = 6.865, 95%CI:1.746-26.993, p = 0.006) and high cervical cord lesion (OR = 2.788, 95%CI:1.229-6.323, p = 0.014) were independent risk factors for pulmonary infection, and the combined nomogram could easily predict the occurrence of pulmonary infection, with a C-index of 0.766 (95% CI: 0.678-0.854). The calibration curve, Hosmer-Lemeshow goodness-of-fit test (χ2 = 9.539, p = 0.299) and decision curve analysis showed that the model had good consistency and clinical applicability. Conclusion: The nomogram model constructed based on NPAR combined with high cervical cord lesion at admission has good clinical application value in predicting pulmonary infection in patients with severe myelitis, which is conducive to clinicians' evaluation of patients.

Insights into the role of the N6-methyladenosine reader IGF2BP3 in the progression of oral squamous cell carcinoma and its connection to cell-cycle control.

The genome of oral squamous cell carcinoma (OSCC) has been extensively characterized via bulk sequencing, revealing a multitude of genetic changes. The gene IGF2BP3, which encodes for the insulin-like growth factor 2 mRNA-binding protein 3, has been observed to be highly expressed in several types of cancer. This finding suggests that IGF2BP3 may play a significant role in the initiation and advancement of cancer. Nevertheless, the mechanisms by which IGF2BP3 contribute to OSCC are yet to be fully understood. In this study, we have observed that IGF2BP3 exhibits overexpression in OSCC. Based on our findings from bulk sequencing analysis, we have concluded that IGF2BP3 could potentially serve as a biomarker for predicting poor prognosis in OSCC. Moreover, it has been demonstrated that IGF2BP3 exhibits a significant association with the initiation and advancement of tumors both in vivo and in vitro. The evaluation of IGF2BP3 expression levels in relation to the cell cycle stage was conducted using single-cell RNA sequencing data. Tumor cells characterized by elevated IGF2BP3 expression demonstrated a higher percentage of cells in the G2/M transition phase. This study presents new findings indicating that the molecular target IGF2BP3 can serve as a prognostic indicator for tumors and has an impact on the development and progression of OSCC by influencing the regulation of the cell cycle.

A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models.

Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease with a high mortality rate. Putative drug targets in IPF have failed to translate into effective therapies at the clinical level. We identify TRAF2- and NCK-interacting kinase (TNIK) as an anti-fibrotic target using a predictive artificial intelligence (AI) approach. Using AI-driven methodology, we generated INS018_055, a small-molecule TNIK inhibitor, which exhibits desirable drug-like properties and anti-fibrotic activity across different organs in vivo through oral, inhaled or topical administration. INS018_055 possesses anti-inflammatory effects in addition to its anti-fibrotic profile, validated in multiple in vivo studies. Its safety and tolerability as well as pharmacokinetics were validated in a randomized, double-blinded, placebo-controlled phase I clinical trial (NCT05154240) involving 78 healthy participants. A separate phase I trial in China, CTR20221542, also demonstrated comparable safety and pharmacokinetic profiles. This work was completed in roughly 18 months from target discovery to preclinical candidate nomination and demonstrates the capabilities of our generative AI-driven drug-discovery pipeline.

Perturbations in gut and respiratory microbiota in COVID-19 and influenza patients: a systematic review and meta-analysis.

Objectives: Coronavirus disease-19 (COVID-19)/influenza poses unprecedented challenges to the global economy and healthcare services. Numerous studies have described alterations in the microbiome of COVID-19/influenza patients, but further investigation is needed to understand the relationship between the microbiome and these diseases. Herein, through systematic comparison between COVID-19 patients, long COVID-19 patients, influenza patients, no COVID-19/influenza controls and no COVID-19/influenza patients, we conducted a comprehensive review to describe the microbial change of respiratory tract/digestive tract in COVID-19/influenza patients. Methods: We systematically reviewed relevant literature by searching the PubMed, Embase, and Cochrane Library databases from inception to August 12, 2023. We conducted a comprehensive review to explore microbial alterations in patients with COVID-19/influenza. In addition, the data on α-diversity were summarized and analyzed by meta-analysis. Results: A total of 134 studies comparing COVID-19 patients with controls and 18 studies comparing influenza patients with controls were included. The Shannon indices of the gut and respiratory tract microbiome were slightly decreased in COVID-19/influenza patients compared to no COVID-19/influenza controls. Meanwhile, COVID-19 patients with more severe symptoms also exhibited a lower Shannon index versus COVID-19 patients with milder symptoms. The intestinal microbiome of COVID-19 patients was characterized by elevated opportunistic pathogens along with reduced short-chain fatty acid (SCFAs)-producing microbiota. Moreover, Enterobacteriaceae (including Escherichia and Enterococcus) and Lactococcus, were enriched in the gut and respiratory tract of COVID-19 patients. Conversely, Haemophilus and Neisseria showed reduced abundance in the respiratory tract of both COVID-19 and influenza patients. Conclusion: In this systematic review, we identified the microbiome in COVID-19/influenza patients in comparison with controls. The microbial changes in influenza and COVID-19 are partly similar.