Exploring the impact of dexmedetomidine on short-term outcomes in critically ill sepsis-associated encephalopathy patients.

OBJECTIVE: Dexmedetomidine has demonstrated potential in preclinical medical research as a protective agent against inflammatory injuries and a provider of neuroprotective benefits. However, its effect on the short-term prognosis of patients with sepsis-associated encephalopathy remains unclear. This study aims to explore the underlying value of dexmedetomidine in these patients. PATIENTS AND METHODS: This study enrolled patients with sepsis-associated encephalopathy from the Medical Information Mart for Intensive Care (MIMIC)-IV database, and they were divided into two groups based on dexmedetomidine therapy during hospitalization. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were utilized to balance the inter-group baseline differences. Kaplan-Meier (KM) curves with log-rank test and subgroup analysis were also employed. The primary outcome was 28-day mortality, and the secondary outcomes were in-hospital mortality, intensive care unit (ICU) stay time, hospital stay time, and the incidence of ventilator-associated pneumonia (VAP). RESULTS: After PSM, 1,075 pairs of patients were matched. In contrast to the non-dexmedetomidine cohort, the dexmedetomidine cohort did not exhibit a shortened ICU [4.65 (3.16, 8.55) vs. 6.14 (3.66, 11.04), p<0.001] and hospital stay duration [10.04 (6.55, 15.93) vs. 12.76 (7.92, 19.95), p<0.001], and there was an elevated incidence of VAP [90 (8.4%) vs. 135 (12.6%), p=0.002]. The log-rank test for the KM curves of dexmedetomidine use and 28-day mortality was statistically significant (p<0.001). The results showed that dexmedetomidine was associated with improved 28-day mortality [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.35-0.61, p<0.001] and in-hospital mortality (HR 0.50, 95% CI 0.37-0.67, p<0.001) after adjusting for various confounders. In the following subgroup analysis, dexmedetomidine infusion was associated with decreased 28-day mortality in most subgroups. CONCLUSIONS: Dexmedetomidine administration was significantly associated with reduced short-term mortality among patients with sepsis-associated encephalopathy in the ICU. However, it also prolonged ICU and hospital stays and increased the incidence of VAP.

[Research progress and prospects of artificial intelligence in diagnosis and treatment of colorectal cancer].

Colorectal cancer is one of the most common malignant tumors worldwide. Due to the heterogeneity in patient outcomes and treatment responses to standard therapy regimens, personalized diagnostic and therapeutic strategies have remained a focus of sustained interest in research. In recent years, with the rapid progression of artificial intelligence (AI) technology in the medical field, an abundance of phased research results has emerged in the decision-making for preoperative, intraoperative, and postoperative diagnostic and therapeutic plans for colorectal cancer, demonstrating great potential for application. This new and efficient solution provides for the personalized evaluations and auxiliary diagnoses and treatments of patients with colorectal cancer. In the future, AI systems may continue to advance towards multimodal, multi-omics, and real-time directions. This paper aims to explore the current state of research on the multi-faceted auxiliary applications of AI in the diagnosis and treatment of colorectal cancer, as well as to present a prospective view of the innovations that AI technology could bring to personalized colorectal cancer treatment in the future and the challenges it may face.

Dietary supplementation of proteases on growth performance, nutrient digestibility, blood characteristics and gut microbiota of growing pigs fed sorghum-based diets.

Low-tannin sorghum is an excellent energy source in pig diets. However, sorghum contains several anti-nutritional factors that may have negative effects on nutrient digestibility. The impacts of proteases on growth performance, nutrient digestibility, blood parameters, and gut microbiota of growing pigs fed sorghum-based diets were studied in this study. Ninety-six pigs (20.66 ± 0.65 kg BW) were allocated into three groups (eight pens/group, four pigs/pen): (1) CON (control diet, sorghum-based diet included 66.98% sorghum), (2) PRO1 (CON + 200 mg/kg proteases), (3) PRO2 (CON + 400 mg/kg proteases) for 28 d. No differences were observed in growth performance and apparent total tract digestibility (ATTD) of nutrients between CON and PRO1 groups. Pigs fed PRO2 diet had increased (P < 0.05) BW on d 21 and 28, and increased (P < 0.05) average daily gain during d 14-21 and the overall period compared with pigs fed CON diet. In addition, pigs fed PRO2 diet had improved (P < 0.05) ATTD of gross energy, CP, and DM compared with pigs fed CON and PRO1 diets. Pigs fed PRO2 diet had lower (P < 0.05) plasma globulin (GLB) level and higher (P < 0.05) plasma glucose, albumin (ALB) and immunoglobulin G levels, and ALB/GLB ratio than pigs fed CON and PRO1 diets. Furthermore, pigs fed PRO2 diet had decreased (P < 0.05) the relative abundance of Acidobacteriota at the phylum level and increased (P < 0.05) the relative abundance of Prevotella_9 at the genus level. The linear discriminant analysis effect size analysis also showed that pigs fed PRO2 diet had significantly enriched short-chain fatty acid-producing bacteria, such as Subdoligranulum and Parabacteroides. In conclusion, protease supplementation at 400 mg/kg improved the growth performance of growing pigs fed sorghum-based diets, which may be attributed to the improvement of nutrient digestibility, host metabolism, immune status and associated with the altered gut microbiota profiles.

[Chidamide inhibits proliferation and promotes apoptosis of esophageal squamous cell carcinoma cells by inhibiting the PI3K/Akt and ERK1/2 pathways and increasing DNA damage].

OBJECTIVE: To investigate the mechanism mediating the inhibitory effect of chidamide on esophageal squamous cell carcinoma (ESCC) cells. METHODS: ESCC cell lines KYSE-150, KYSE-450 and KYSE-510 were treated with 5, 10, 20, or 40 µmol/L of chidamide, and the changes in cell proliferation, colony-forming capacity, cell apoptosis and cell cycle were assessed using MTT aasay, colony formation experiment and flow cytometry. Western blotting was performed to detect the expression levels of cleaved caspase-3, cleaved PARP, p21, cyclin D1, p-Akt, p-ERK1/2, γH2AX, H3K9ac, and Ki-67. In a nude mouse model bearing subcutaneous ESCC xenografts, the effects of intraperitoneal injection of 20 mg/kg chidamide for 3 days on tumor size and body weight were observed every 3 days, and Ki-67 and CD31 expressions in the tumor tissues were detected using immunohistochemistry. Tubular formation experiment was used to examine the effect of chidamide on tubular formation of human umbilical vein endothelial cells (HUVECs) in vitro. RESULTS: In cultured ESCC cell lines, chidamide significantly inhibited cell proliferation and colony formation (P < 0.05), promoted cell apoptosis, and increased the percentage of G0/G1 phase cells (all P < 0.01). Chidamide obviously up-regulated cleaved caspase-3, cleaved PARP, p21, γH2AX, and H3K9ac and down-regulated cyclin D1, p-Akt and p-ERK1/2, and Ki-67 in the cells (P < 0.01). In the tumor-bearing mouse models, treatment with chidamide significantly reduced the tumor volume (P < 0.05), tumor to body weight ratio (P < 0.01), and the expression levels of Ki-67 and CD31 in the tumors (P < 0.01). Chidamide also significantly inhibited tubule formation in cultured HUVECs (P < 0.05). CONCLUSION: Chidamide inhibits proliferation, induces apoptosis and blocks cell cycle of ESCC cells possibly by inhibiting the PI3K/Akt and ERK1/2 pathways and increasing DNA damage. Chidamide also inhibits subcutaneous tumorigenesis of ESCC cells in mice by inhibiting tumor cell proliferation and angiogenesis.

[Application of a new-type of defecator in the treatment of rectal fecal impaction].

Objective: This study aimed to investigate the viability and safety of a novel defecator in managing rectal fecal impaction. Methods: In a descriptive case series, this new defecator was administered to constipated individuals among the ages of 18 and 80 years who met the diagnostic criteria for rectal fecal impaction and were identified with acute rectal fecal impaction through CT scans. The contraindications for this defecator included: (1) Anal stenosis, acute intestinal obstruction, and intestinal perforation; (2) Concomitant rectal malignant tumors; (3) Coagulation dysfunction, low platelet counts, gastrointestinal bleeding, or other bleeding risks; (4) Patients with severe underlying conditions affecting the heart, brain, lungs, or other systems; (5) Individuals with mental health disorders. Based on these criteria, clinical data from 42 patients with rectal fecal impaction who underwent treatment with the new defecator at Deyang People's Hospital between July 2020 and April 2023 were retrospectively analyzed.The defecator comprises three components: a head, a spiral rod, and a handle, constructed from disposable stainless steel wire. The treatment procedure involves the following steps: The patient assumes a flexed, supine position on their left side with their buttocks slightly protruding from the bed's edge. A transparent sealing bag is affixed to the buttocks, centered around the anus. With gloved hands inserted through the bag's entrance, a cotton ball soaked in liquid paraffin lubricates the anal canal and the head of the defecator's spiral rod. The defecator is then slowly rotated and inserted into the anus, with careful attention to any changes in resistance. Once the spiral rod is fully inserted, the patient is instructed to inhale and defecate while the defecator is slowly withdrawn, carrying the dislodged fecal matter, and depositing it into the sealed bag. This operation is repeated 2 to 3 times, followed by the injection of either 100 ml of 36°C normal saline or 60 ml of liquid paraffin into the rectum. After a 5 to 8-minute wait, the patient assumes a squatting position to expel any remaining feces from the rectum. The study assessed the operation time, single treatment success rate, pain levels during treatment, and the occurrence of complications. Results: All 42 patients successfully underwent treatment with the new defecator device, achieving a single treatment success rate of 100%. The average operation time was 11.0 minutes (range: 9.0 to 13.3 minutes). During treatment, 20 cases (47.6%) reported moderate to severe anal pain, with 1 case (2.4%) experiencing anal fissure bleeding, and 6 cases (14.3%) reporting discomfort such as palpitations and sweating. No serious complications, including rectal perforation, were observed in any case. Conclusion: The new defecator device demonstrates ease of use and safety, making it a feasible option for treating acute rectal fecal impaction.

[Clinical effects of pedicled omental flap transplantation in repairing secondary rejection wounds after brain pacemaker implantation].

Objective: To explore the clinical effects of pedicled omental flap transplantation in repairing secondary rejection wounds after brain pacemaker implantation. Methods: A retrospective observational study was conducted. From January to August 2021, 5 patients with secondary rejection wounds after brain pacemaker implantation who met the inclusion criteria were admitted to the Wound Repair Center of Ruijin Hospital of Shanghai Jiao Tong University School of Medicine, including 3 males and 2 females, aged 56-69 years, with the wound developed at the pulse generator implantation site in the chest in 2 cases, at the connection site of the wire and electrode behind the ear in 2 cases, and at both the chest and the back of the ear in 1 case. All the wounds were repaired by pedicled omental flap transplantation. The wound area after debridement was 2-15 cm2. After operation, the wound healing and related complications (pain, infection, incisional hernia, omental flap necrosis, etc.) were observed. During follow-up, the recurrence of the wound was observed. Results: The wounds of all 5 patients healed within 2 weeks after operation, without related complications. During follow up of 12-18 months, 1 patient got a recurrence of rejection wound behind the left ear 4 months after surgery and eventually had the brain pacemaker removed; the other 4 patients had no recurrence of wounds. Conclusions: Pedicled omental flap transplantation can repair the secondary rejection wounds after brain pacemaker implantation safely and effectively, with few postoperative complications.

A prospective multicentre controlled study of Gaoweikang (Chinese multiherb extract-based tincture) used in high-risk HPV infections.

OBJECTIVE: The aim of the study was to investigate the safety and antiviral efficacy of a Chinese multiherb extract-based tincture (GWK) on a population of patients with high-risk human papilloma (hrHPV) infections and hrHPV-caused cervical low-grade squamous intraepithelial lesions (LSILs). PATIENTS AND METHODS: Patients with persistent hrHPV infection were enrolled in Group A, including A1 subjects, who received the intervention, and A2 subjects, who received the control. Patients with hrHPV infection causing cervical LSIL were enrolled in Group B, which included B1 subjects, who received the intervention, and B2 subjects, who served as the control. For Groups A1 and B1, hrHPV was tested at 3 months (M3) and 6 months (M6) after the intervention. The side effects were also analyzed. RESULTS: At baseline (D0), a total of 99 patients were enrolled in Group A, with 50 subjects in Group A1 and 49 subjects in Group A2. A total of 91 patients were enrolled in Group B, with 45 subjects in Group B1 and 46 subjects in Group B2. There was no significant difference in the characteristics, including average age, age stratification, and HPV genotype. At M6, both Group A1 and Group B1 had a higher hrHPV clearance rate than the control group (A1/A2: 80.0% vs. 20.4%; B1/B2: 64.4% vs. 15.2%, p<0.001). At M6, the effective rates of Group A1 and Group B1 were 84% (42/50) and 68.9% (31/45), respectively. The side effect rates of Groups A1 and B1 were 11.5% (6/52) and 11.1% (5/45), respectively. Most adverse reactions involved local discomfort, including vulvar erythema, vulvar itch, increased vaginal discharge, cervical bleeding, and mild pain in the lower abdomen. Univariate logistic regression analysis showed that the intervention had an OR of 12 (95% CI 4.431-32.50) for clearing persistent HPV infection (p<0.001). For cervical LSIL, the intervention had an OR of 10.1 for clearing persistent HPV infection (95% CI 3.68-27.7) (p<0.001). CONCLUSIONS: The results of this study suggest that the Chinese multiherb extract-based tincture GWK is safe and well tolerated. Furthermore, this preliminary study showed that this Chinese multiherb extract-based tincture is helpful for promoting HPV clearance in cases of persistent HPV and HPV-induced LSIL.

[A randomized controlled study on the long-term efficacy of intra-cervical lymphatic immunotherapy for adult allergic rhinitis].

Objective: To determine the long-term efficacy and safety of intra-cervical lymphatic immunotherapy (ICLIT) for adult allergic rhinitis (AR) by comparing it with subcutaneous immunotherapy (SCIT). Methods: A total of 100 adult AR patients with dust mite allergy in Department of Otorhinolaryngology, First People's Hospital of Foshan from Feb 2018 to Dec 2019 were randomly divided into two groups, 50 in SCIT group [including 42 males and 8 females, aging (32.55±9.72) years] and 50 in ICLIT group [including 45 males and 5 females, aging (31.33±9.84) years]. The changes in total symptom score (total system score, TSS), nasal symptom score (total nasal symptom score, TNSS), eye symptom score (total ocular scoring system, TOSS), drug score (total medication score, TMS), and quality of life score of the two groups of patients were evaluated before and after treatment, and the adverse reactions of all patients during the treatment period were recorded. The changes in the level of dust mite specific IgE (sIgE) in the serum were evaluated. GraphPad Prism 9.0 software was used for statistical analysis. Results: In the SCIT group, 38 patients completed treatment and follow-up, with a dropout rate of 24%. In the ICLIT group, 48 patients completed treatment and follow-up, with a dropout rate of only 4%. The scores of TSS, TNSS, TOSS, TMS, and quality of life in the ICLIT group before treatment were 32.1±3.0, 27.3±3.1, 4.8±2.8, 2.3±0.9, and 68.1±28.7, respectively; After 36 months of treatment, the scores were 21.8±11.4, 18.1±9.4, 3.7±2.9, 1.3±1.1, and 36.0±26.7, respectively, which were significantly lower than those before treatment (all P<0.001). After 36 months of treatment, the TSS of the ICLIT group improved by 10.3±11.2 compared to before, while the TSS of the SCIT group improved significantly by 21.9±11.0 compared to before, with statistically significant differences between the groups (P<0.001). No serious systemic adverse reactions occurred in both groups of patients. Conclusions: ICLIT treatment for adult AR has long-term efficacy, high safety, and high compliance, but its long-term efficacy is not as good as SCIT. ICLIT can be considered as a new complementary option for AR immunotherapy.

Compound bioengineering protein supplementation improves intestinal health and growth performance of broilers.

Currently, antimicrobial peptides (AMPs) are of growing interest as potential substitutes for antibiotic growth promoters in animal production. The present study was conducted to evaluate the effects of dietary supplementation of bioengineering artificial Parasin I protein (API) and artificial plectasin protein (APL) (named as compound bioengineering protein, CBP) on growth performance and intestinal health of broilers. A total of 450 one-day-old Arbor Acres male healthy broilers were randomly allotted to 5 dietary groups with 10 replicates of 9 individuals in each replicate and supplemented with 0, 250, 500, 750, and 1,000 mg/kg CBP for 6 wk. Dietary CBP supplementation increased (P < 0.01) body weight (6 wk), average daily gain (0-6 wk), and average daily feed intake (3-6 wk and 0-6 wk). CBP addition enhanced antioxidant capacity, which was accompanied by the higher (P < 0.05) activity of serum total antioxidant capacity (T-AOC) (750 mg/kg), jejunal glutathione peroxidase (750 mg/kg), and T-AOC (500 and 1,000 mg/kg). Dietary CBP addition improved intestinal health, reflecting by the increased (P < 0.05) villus height to crypt depth ratio in the duodenum, the upregulated (P < 0.01) mRNA levels of claudin-1 (500 and 750 mg/kg) in the ileum, the downregulated (P < 0.01) mRNA expression of occludin (500 mg/kg) in the duodenum and claudin-1 (500 mg/kg) and occludin (500 and 750 mg/kg) in the jejunum, and the upregulated mRNA expression of (P < 0.01) mucin2 (MUC2) (1,000 mg/kg) in the duodenum. In addition, CBP upregulated (P < 0.01) IL-10 (1,000 mg/kg) in duodenum and ileum, and downregulated (P < 0.05) the mRNA expression of IL-6 (750 and 1,000 mg/kg), interferon-γ (1,000 mg/kg) in the jejunum and TNF-α (250 mg/kg) in the ileum. Furthermore, dietary CBP increased (P < 0.01) the abundance of total bacteria and Lactobacillus (500 and 750 mg/kg), and reduced (P < 0.05) the abundance of Escherichia coli (750 mg/kg) in the cecum. In conclusion, CBP supplementation enhances the antioxidant capacity, intestinal health, immune function, and ameliorates the gut microflora population, thus improving the growth performance of broilers. Dietary supplementation of 750 mg/kg CBP exhibits a better beneficial effect.

The Biocompatibility Analysis of Artificial Mucin-Like Glycopolymers.

The ocular surface is covered by a tear film consisting of an aqueous/mucin phase and a superficial lipid layer. Mucins, highly O-glycosylated proteins, are responsible for lubrication and ocular surface protection. Due to contact lens wear or eye disorders, lubrication of the ocular surface can be affected. Artificial glycopolymers which mimic natural mucins could be efficient in ophthalmic therapy. Various neutral, positively, and negatively charged mucin-mimicking glycopolymers were synthesized (n = 11), cultured in different concentrations (1%, 0.1%, and 0.01% w/v) with human corneal epithelial cells (HCE), and analyzed by various cytotoxicity/viability, morphology, and immunohistochemistry (IHC) assays. Six of the eleven glycopolymers were selected for further analysis after cytotoxicity/viability assays. We showed that the six selected glycopolymers had no cytotoxic effect on HCE cells in the 0.01% w/v concentration. They did not negatively affect cell viability and displayed both morphology and characteristic markers as untreated control cells. These polymers could be used in the future as mucin-mimicking semi-synthetic materials for lubrication and protection of the ocular surface.

[Importance of comprehensive management of anastomotic site after ultra-low anal sphincter-preservation surgery].

Intersphincteric resection (ISR) surgery increases the rate of anal sphincter preservation in patients with ultra-low rectal cancers. However, the anastomotic site of ISR surgery is at risk for structural healing complications such as anastomotic leakage, anastomotic dehiscence, secondary anastomotic stenosis, chronic presacral sinus, rectovaginal fistula, and rectourethral fistula, which can lead to a persistent defunctioning ostomy or a secondary permanent colostomy. This article systematically describes the preoperative high-risk factors and characteristics of anastomotic site structural healing complications after ISR surgery, as well as the management of the anastomotic site during various stages including hospitalization, from discharge to one month after surgery, from one month after surgery to before stoma reversal, and after stoma reversal. This is to provide a clearer understanding of the risks associated with the anastomotic site at different stages of the healing process and to timely detect and actively manage related complications, thereby reducing the rate of permanent colostomy and truly achieving the dual goals of "survival benefit" and "quality of life improvement" in ISR surgery.

[Structural changes of the frontal cortex in depressed mice are associated with decreased expression of brain-derived neurotrophic factor].

OBJECTIVE: To investigate the changes in gray matter volume in depressive-like mice and explore the possible mechanism. METHODS: Twenty-four 6-week-old C57 mice were randomized equally into control group and model group, and the mice in the model group were subjected to chronic unpredictable mild stimulation (CUMS) for 35 days. Magnetic resonance imaging was performed to examine structural changes of the grey matter volume in depressive-like mice. The expression of brain-derived neurotrophic factor (BDNF) in the grey matter of the mice was detected using Western blotting and immunofluorescence staining. RESULTS: Compared with the control mice, the mice with CUMS showed significantly decreased central walking distance in the open field test (P < 0.05) and increased immobile time in forced swimming test (P < 0.05). Magnetic resonance imaging showed that the volume of the frontal cortex was significantly decreased in CUMS mice (P < 0.001, when the mass level was greater than or equal to 10 756, the FDRc was corrected with P=0.05). Western blotting showed that the expression of mature BDNF in the frontal cortex was significantly decreased in CUMS mice (P < 0.05), and its expression began to decrease after the exposure to CUMS as shown by immunofluorescence staining. The volume of different clusters obtained by voxel-based morphometry (VBM) analysis was correlated with the expression level of mature BDNF detected by Western blotting (P < 0.05). CONCLUSION: The decrease of frontal cortex volume after CUMS is related with the reduction of mature BDNF expression in the frontal cortex.

[CIC-rearranged sarcoma: a clinicopathological analysis of four cases].

Objective: To investigate the clinicopathological features and differential diagnosis of CIC-rearranged sarcoma (CRS). Methods: Five CRSs of 4 patients (2 biopsies of pelvic cavity and lung metastasis from case 4) diagnosed in the First Affiliated Hospital of Nanjing Medical University were enrolled from 2019 to 2021. All cases were evaluated by clinical presentation, H&E, immunohistochemical staining and molecular analysis and the related literature was reviewed. Results: There were one male and three females, the age at diagnosis ranged from 18 to 58 (mean 42.5) years. Three cases were from the deep soft tissues of the trunk and one case from the skin of foot. Grossly, the tumor size ranged from 1 to 16 cm. Microscopically, the tumor was arranged in nodules or solid sheets. The tumor cells were typically round or ovoid, with occasional spindled or epithelioid morphology. The nuclei were round to ovoid with vesicular chromatin and prominent nucleoli. Mitotic figures were brisk (>10/10 HPF). Rhabdoid cells were seen in four of five cases. Myxoid change and hemorrhage were observed in all samples and two cases showed geographic necrosis. Immunohistochemically, CD99 was variably positive in all samples, while WT1 and TLE-1 were positive in four of five samples. Molecular analysis showed CIC-rearrangements in all cases. Two patients succumbed within 3 months. One had mediastinal metastasis 9 months after surgery. One underwent adjuvant chemotherapy and remained tumor-free 10 months after diagnosis. Conclusions: CIC-rearranged sarcoma is uncommon and shows aggressive clinical course with dismal prognosis. The morphological and immunohistochemical characteristics can largely overlap with a variety of sarcomas; hence, knowledge of this entity is vital to avoid potential diagnostic pitfalls. Definitive diagnosis requires molecular confirmation of CIC-gene rearrangement.

[Genetic susceptibility to drug-induced liver injury].

Drug-induced liver injury (DILI) risk prediction, diagnosis establishment, clinical management, and all other aspects are facing great challenges. Although the current understanding of its pathogenesis is still incomplete, research over the past 20 years has shown that genetic susceptibility may play an important role in the occurrence and development of DILI. In recent years, pharmacogenomics studies have further revealed the association between human leukocyte antigen (HLA) genes, some non-HLA genes, and hepatotoxicity from certain drugs. However, due to the lack of well-designed, prospective, large-sample cohort validation and low positive predictive values, there may still be some way to go before the current results can be truly translated into clinical practice for precise prediction and prevention of DILI risk.