In recent years， hyperuricemia （HUA） has shown a rapidly increasing incidence and tends to occur in increasingly young people， with a wide range of cardiac， renal， joint， and cancerous hazards and all-cause mortality associations. Western medicine treatment has limitations such as large liver and kidney damage， medication restriction， and easy recurrence. The intestine is the major extra-renal excretion pathway for uric acid （UA）， and the intestinal microecology can be regulated to promote UA degradation. It offers great potential to develop UA-lowering strategies that target the intestinal microecology， which are promising to provide safer and more effective therapeutic approaches. Traditional Chinese medicine （TCM） can treat HUA via multiple targets and multiple pathways from a holistic view， with low toxicity and side effects. Studies have shown that intestinal microecology is a crucial target for TCM in the treatment of HUA. However， its specific mechanism of action has not been fully elucidated. Focusing on the key role of intestinal microecology in HUA， this review explores the relationship between intestinal microecology and HUA in terms of intestinal flora， intestinal metabolites， intestinal UA transporters， and intestinal barriers. Furthermore， we summarize the research progress in TCM treatment of HUA by targeting the intestinal microecology， with the aim of providing references for the development of TCM intervention strategies for HUA and the direction of future research.

Objective:To investigate the role of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) in ferroptosis of mouse dendritic cells (DCs) under simulated sepsis, providing evidence for improving immunosuppression in sepsis caused by wound infection.Methods:This study was an experimental research. The mouse DC line DC2.4 in the logarithmic growth phase (with passages 3-10) was used for the experiments (with each sample size of 3). The sepsis model was established by treating DCs with 1 μg/mL lipopolysaccharide (LPS, same concentration throughout) for 0 (untreated), 6, 12, 24, 48, and 72 h. Western blotting was used to detect the protein expressions of APE1 and anti-ferroptosis proteins glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) in cells, flow cytometry was employed to detect reactive oxygen species (ROS) levels in cells, and live-cell imaging technology was used to measure cell lipid peroxidation levels. DCs successfully transfected with lentivirus containing APE1 short hairpin RNA sequence were divided into APE1-knockdown+phosphate buffer solution (PBS) group and APE1-knockdown+LPS group. DCs successfully transfected with empty lentivirus were divided into empty vector+PBS group and empty vector+LPS group. After stimulation with PBS or LPS and 24 h of culture, corresponding assays were conducted as above. DCs transfected with lentivirus containing APE1 overexpression RNA sequence were divided into APE1-overexpression+PBS group and APE1-overexpression+LPS group. DCs transfected with empty lentivirus were divided into empty vector+PBS group and empty vector+LPS group. After stimulation with PBS or LPS and 24 h of culture, corresponding assays were conducted as above. A total of 88 male C57BL/6J mice aged 6-8 weeks were divided into corn oil+sham injury group, corn oil+cecal ligation and puncture (CLP) group, inhibitor+sham injury group, and inhibitor+CLP group ( n=22) according to the random number table. Mice in the two inhibitor groups were gavaged with APE1 inhibitor E3330 (1 mg/mL in concentration) at 40 mg/kg per day, while mice in the two corn oil groups were gavaged with an equal amount of corn oil daily. Two weeks later, mice in the two CLP groups underwent CLP surgery to establish a sepsis model, while mice in the two sham injury groups underwent sham injury. Sixteen mice from each group were selected to observe survival within 7 d post-surgery. At 24 h post-surgery, CD11c-positive magnetic beads were used to extract spleen DCs from the remaining six mice in each group for corresponding assays ( n=3) as above. Results:Compared with that of LPS treatment at 0 h, APE1 protein expression significantly increased in cells at 6 h of LPS treatment ( P<0.05), APE1 and GPX4 protein expressions significantly decreased at 24, 48, and 72 h of LPS treatment, SLC7A11 protein expression significantly decreased at 24 h of LPS treatment ( P<0.05), while the ROS level in cells ( P<0.05) and cell lipid peroxidation level significantly increased at 24, 48, and 72 h of LPS treatment. After 24 h of culture, the GPX4 protein expression of cells in APE1-knockdown+LPS group was significantly lower than that in APE1-knockdown+PBS group ( P<0.05), while the ROS level in cells ( P<0.05) and cell lipid peroxidation level were significantly higher than those in APE1-knockdown+PBS group and empty vector+LPS group. After 24 h of culture, APE1, SLC7A11, and GPX4 protein expressions of cells in APE1-overexpression+LPS group were significantly higher than those in empty vector+LPS group ( P<0.05), while the ROS level in cells ( P<0.05) and cell lipid peroxidation level were significantly lower than those in empty vector+LPS group. At 24 h post-surgery, APE1 and GPX4 protein expressions of mice cells in inhibitor+CLP group were significantly lower than those in inhibitor+sham injury group and corn oil+CLP group ( P<0.05); the ROS level of mice cells in corn oil+CLP group (12 693±913) was significantly higher than that in corn oil+sham injury group (4 205±805, P<0.05), while the ROS level of mice cells in inhibitor+CLP group (18 085±223) was significantly higher than that in inhibitor+sham injury group (4 381±787) and corn oil+CLP group (with P values all <0.05); the cell lipid peroxidation level of mice in inhibitor+CLP group was significantly higher than that in inhibitor+sham injury group and corn oil+CLP group. Within 7 d post-surgery, the survival ratio of mice in inhibitor+CLP group was significantly lower than that in inhibitor+sham injury group ( χ2=22.67, P<0.05). Conclusions:Under simulated sepsis, the APE1 expression in mouse DCs is decreased, and oxidative stress and ferroptosis are enhanced; knocking down the APE1 exacerbates DC ferroptosis, while APE1 overexpression effectively reduces DC ferroptosis. The inhibition of APE1 expression in DCs is closely associated with poor prognosis in sepsis.

Objective:To investigate the effects of stimulator of interferon gene (STING) on ferroptosis mediated by acyl-CoA synthetase long-chain family member 4 (ACSL4) in mouse dendritic cells (DCs) under sepsis, providing a basis for improving the dysregulation of immune response in sepsis caused by factors such as wound infection.Methods:This study was an experimental research. The mouse DC line DC2.4 in the logarithmic growth phase (with passages 3-10) were divided into lipopolysaccharide (LPS) stimulation 0 h (unstimulated) group, LPS stimulation 6 h group, LPS stimulation 12 h group, LPS stimulation 18 h group, and LPS stimulation 24 h group according to the random number table (the same grouping method below), which were cultured with 1 μg/mL LPS (the same concentration below) for the corresponding time. The protein expressions of phosphorylated STING (p-STING), STING, and ACSL4 in cells were determined by Western blotting. DC2.4 successfully transfected with lentivirus containing STING gene small interfering RNA (hereinafter referred to as siSTING) were divided into siSTING+phosphate buffer solution (PBS) group and siSTING+LPS group. DC2.4 successfully transfected with empty lentivirus were divided into empty vector+PBS group and empty vector+LPS group. After being stimulated with PBS or LPS and cultured for 24 hours, the protein expressions of p-STING, STING, and ACSL4 in cells were determined as above. Cell lipid peroxidation degrees were observed using the lipid peroxidation assay kit, and cell apoptosis rates were detected using flow cytometry. The sample numbers in the above cell experiments were all 3. Eighty male C57BL/6J mice aged 6 to 8 weeks were divided into sham surgery+normal saline (NS) group, cecal ligation and puncture (CLP)+NS group, sham surgery+C-176 group, and CLP+C-176 group, with 20 mice in each group. Mice in the two C-176 groups were intraperitoneally injected with C-176, while mice in the two NS groups were intraperitoneally injected with an equivalent volume of NS. One hour later, sham surgery was performed on the mice in the two sham surgery groups, and CLP surgery was performed on the mice in the two CLP groups to establish a sepsis model. At 24 h post-surgery, 10 mice from each group were sacrificed to extract spleen DCs, and protein expression, lipid peroxidation, and apoptosis rates were detected as above ( n=3). Hematoxylin-eosin staining was performed to observe pathological damage in the heart, liver, lung, and kidney tissue. The remaining 10 mice in each group were observed for survival within 7 days after surgery. Results:The protein expressions of p-STING, STING, and ACSL4, as well as the p-STING/STING ratio in DC2.4 in LPS stimulation 24 h group were significantly higher than those in LPS stimulation 0 h group ( P<0.05). After 24 h of culture, the protein expressions of p-STING, STING, and ACSL4 in DC2.4 in siSTING+LPS group and empty vector+PBS group were significantly lower than those in empty vector+LPS group ( P<0.05); the lipid peroxidation degrees of DC2.4 in siSTING+LPS group and empty vector+PBS group were weaker than those in empty vector+LPS group. The apoptosis rates of DC2.4 in empty vector+PBS group, empty vector+LPS group, siSTING+PBS group, and siSTING+LPS group were (15.7±3.0)%, (37.8±2.9)%, (13.1±2.1)%, and (20.6±1.8)%, respectively. The apoptosis rates of DC2.4 in empty vector+PBS group and siSTING+LPS group were significantly lower than that in empty vector+LPS group ( P<0.05). At 24 h post-surgery, the protein expressions of p-STING and ACSL4, and the p-STING/STING ratio in spleen DCs of mice in CLP+NS group were significantly higher than those in sham surgery+NS group and CLP+C-176 group ( P<0.05); the protein expression of STING in spleen DCs of mice in CLP+NS group was significantly higher than that in sham surgery+NS group ( P<0.05); the lipid peroxidation degrees of spleen DCs of mice in CLP+C-176 group and sham surgery+NS group were weaker than that in CLP+NS group. The apoptosis rates of spleen DCs of mice in sham surgery+NS group and CLP+C-176 group were significantly lower than that in CLP+NS group ( P<0.05), and the apoptosis rate of spleen DCs of mice in CLP+C-176 group was significantly higher than that in sham surgery+C-176 group ( P<0.05). Pathological tissue damage in the heart, liver, lung, and kidney of mice in CLP+NS group was significantly worse than that in sham surgery+NS group, while such damage in the above organs of mice in CLP+C-176 group was significantly alleviated compared with that in CLP+NS group. The survival ratio of mice in CLP+NS group within 7 days after surgery was significantly lower than that in sham surgery+NS group ( χ2=8.30, P<0.05). Conclusions:Under sepsis, STING activation in mouse DCs is significant, which enhances ACSL4-mediated ferroptosis. Inhibiting STING activation can significantly reduce ACSL4-mediated ferroptosis level in mouse DCs under sepsis, thereby improving the survival rate of septic mice.

The clinical data from 16 patients who underwent surgery for acute type A aortic dissection under ultra-fast-track anesthesia (UFTA) in the Second Affiliated Hospital of Nanjing Medical University from August 2023 to December 2023 were collected, and the experience of anesthesia management was analyzed and summarized. UFTA strategy was to reduce inflammation and perform multi-organ protection in the perioperative period through cardiopulmonary bypass methods, medications, etc. According to the process of operation, the long-term and short-acting anesthetic drugs were accurately used to achieve the patient′s awakening immediately after the operation. Deep anesthesia extubation, remifentanil infusion techniques, and nasal high-flow ventilation were used to enable patients to be removed from the endotracheal tube with low stress under the premise of safety. All the patients successfully completed anesthesia induction and anesthesia maintenance. The average surgery duration was (413±92) min, the average anesthesia duration was (480±100) min, the cardiopulmonary bypass time was (168±42) min, the cardiac arrest time was (119±36) min, and the deep hypothermic circulatory arrest lasted (24±5) min. Of these patients, 14 underwent deep hypothermic circulatory arrest combined with unilateral cerebral perfusion via the right axillary artery, and 2 underwent deep hypothermic circulatory arrest combined with retrograde cerebral perfusion via the superior vena cava. All the patients had their tracheal tubes removed within 30 min postoperatively, with blood gas analysis and hemodynamics being within or close to normal ranges. The average postoperative intensive care unit stay time was 6 (3, 11) days, and the total length of hospital stay was (23±8) days. The total hospitalization time extended 20 days in 7 patients due to postoperative complications. All the patients recovered and were discharged. In conclusion, the application of UFTA strategy is safe and feasible in the patients with acute type A aortic dissection, allowing for immediate extubation in the operating room.

Objective:To observe alterations in center retinal thickness (CRT) in patients diagnosed with central retinal artery occlusion (CRAO) before and after undergoing superselective arterial thrombolysis (IAT) treatment.Methods:A retrospective clinical study. From August 2022 to September 2023, 12 patients (12 eyes) diagnosed with CRAO and treated with IAT at the ophthalmology department of Shenzhen Second People's Hospital. Among these patients, there were 8 males (8 eyes) and 4 females (4 eyes), all experiencing unilateral onset. The mean age was (47.00±15.06) years. The mean duration from onset to thrombolysis was (30.00±30.42) h. All eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) assessments; additionally, 6 eyes underwent Fluorescein fundus angiography (FFA). BCVA assessments were conducted using a standard logarithmic chart and transformed into logarithm of the minimum angle of resolution (logMAR) values for statistical analysis. The OCT measured CRT at various locations around the macular fovea (M), including upper (S1, S3), lower (I1, I3), nasal (N1, N3), and temporal (T1, T3) areas at 1 mm and 3 mm distances from the fovea. CRT was defined as the vertical distance between the inner retinal boundary membrane and the inner interface of the retinal pigment epithelial layer. Pre- and post-IAT examinations were performed using the same equipment and methodologies within a 24-hour interval. Changes in CRT at different macular points were compared and observed, while arterial imaging time changes were assessed in 6 eyes that underwent FFA. Paired t-tests were utilized to analyze logMAR BCVA, CRT at different locations, and arterial imaging time pre- and post-treatment. Results:Prior to IAT treatment, the logMAR BCVA for the affected eye was 3.48±1.42, while the arterial imaging time for the 6 eyes undergoing FFA examination was (27.50±5.47) s. After 24 hours, the logMAR BCVA had improved to 2.35±1.59 for the affected eye, with 9 eyes showing varying degrees of BCVA improvement. The arterial imaging time was (24.17±7.28) s post-treatment. The differences in logMAR BCVA and arterial imaging time before and after treatment were found to be statistically significant ( t=2.489, 3.262; P<0.05). Additionally, the comparison of CRT at S3 ( t=2.871), I1 ( t=2.325), and T3 ( t=3.446) before and after treatment yielded statistically significant differences ( P<0.05). Conversely, the comparison of CRT at S1 ( t=1.879), I3 ( t=1.915), N1 ( t=2.001), N3 ( t=1.987), T1 ( t=2.180), and M ( t=-0.490) showed no statistically significant differences ( P>0.05). Conclusions:IAT treatment for CRAO has been shown to be effective in achieving therapeutic effects by reducing CRT in the macular area. However, the short-term improvement in retinal edema in the macular area is limited.

Objective:To investigate the clinical value of multiparameteric quantitative ultrasound combined with a non-invasive prediction model for assessing high-risk steatohepatitis.Methods:One hundred and ninety-four cases with metabolic-associated fatty liver disease (MAFLD) who underwent liver biopsy in Huashan Hospital, Fudan University, from June 2021 to September 2022 were selected. Shear wave elastography (SWE), shear wave dispersion (SWD) imaging, and attenuation imaging (ATI) examinations were conducted in all patients before biopsy. High-risk steatohepatitis was defined as a total activity score of ≥4 in patients with steatohepatitis, hepatocellular ballooning, and liver lobular inflammation based on pathological hepatic steatosis, inflammatory activity, and fibrosis scoring system (SAF), and fibrosis stage≥F2. Binary logistic regression analysis was used to identify the factors influencing high-risk steatohepatitis. A predictive model for diagnosing high-risk steatohepatitis was constructed using R language. The DeLong test was used to compare the area under the curve between groups. Measurement data was compared between groups using the t-test or rank-sum test, and count data were compared between groups using the χ2 test. Results:There were 46 cases (23.7%) with high-risk steatohepatitis. The quantitative ultrasound parameters included elastic modulus ( OR=2.958, 95% CI: 1.889-4.883, P<0.001), dispersion coefficient ( OR=1.786, 95% CI: 1.424-2.292, P<0.001) and attenuation coefficient ( OR=42.642, 95% CI: 3.463-640.451, P=0.004). Serological indexes of fasting blood glucose ( OR=1.196, 95% CI: 1.048-1.392, P=0.011), alanine aminotransferase ( OR=1.012, 95% CI: 1.006-1.019, P<0.001), aspartate aminotransferase ( OR=1.027, 95% CI: 1.014-1.042, P<0.001), γ-glutamyl transferase ( OR=1.008, 95% CI: 1.001-1.017, P=0.041) and HDL cholesterol ( OR=0.087, 95% CI: 0.016-0.404, P=0.003) were the factors influencing its progression. The AUCs of elastic modulus, dispersion coefficient, attenuation coefficient, multiparametric ultrasound model, serological index model, and ultrasound combined with serology model for the diagnosis of high-risk steatohepatitis were 0.764, 0.758, 0.634, 0.786, 0.773 and 0.825, respectively. The results of the DeLong test showed that the ultrasound combined with the serological model was significantly better than the serological index model and the elastic modulus, dispersion coefficient, and attenuation coefficient alone ( P=0.024, 0.027, 0.038 and <0.001). Conclusion:The combination of multiparametric quantitative ultrasound is helpful for the non-invasive diagnosis of high-risk steatohepatitis and possesses great clinical significance.

Calcium-activated chloride channels(CaCCs)are a class of channel proteins that trans-port chloride ions activated by intracellular calcium,which play a crucial role in regulating membrane potential,intracellular calcium balance,and cell excitability,particularly in neurons and muscle cells.In the Anoctamin(Ano)family,Ano1 is the most classic CaCC.Targeted modulators of Ano1 have poten-tial therapeutic effects against such diseases as cancer,cystic fibrosis,hypertension,diarrhea,and asthma.Since the discovery of Ano1 in 2008,several methods for screening CaCC-specific modulators have emerged including high-throughput primary screening of fluorescent proteins,electrophysiological patch clamp technique and virtual screening,and identification of small molecule modulators with diverse pharmacological effects.This paper summarizes the principles,advantages and disadvantages of the mainstream screening methods,and reviews the chemical structures and potential applications of Ano1-specific modulators discovered to date.

Objective:To investigate the relationship between age-adjusted Charlson comorbidity index (aCCI) and ischemic stroke in patients with ophthalmic artery occlusion (OAO) or retinal artery occlusion (RAO).Methods:A single center retrospective cohort study. Seventy-four patients with OAO or RAO diagnosed by ophthalmology examination in Shenzhen Second People's Hospital from June 2004 to December 2020 were included in the study. The baseline information of patients were collected and aCCI was used to score the patients' comorbidity. The outcome was ischemic stroke. The median duration of follow-up was 1 796.5 days. According to the maximum likelihood ratio of the two-piecewise COX regression model and the recursive algorithm, the aCCI inflection point value was determined to be 6, and the patients were divided into low aCCI group (<6 points) and high aCCI group (≥6 points). A Cox regression model was used to quantify the association between baseline aCCI and ischemic stroke.Results:Among the 74 patients, 53 were males and 21 were females, with the mean age of (55.22±14.18) (19-84) years. There were 9 patients of OAO and 65 patients of RAO. The aCCI value ranges from 1 to 10 points, with a median of 3 points. There were 63 patients (85.14%, 63/74) in the low aCCI group and 11 patients (14.86%, 11/74) in the high aCCI group. Since 2 patients could not determine the time from baseline to the occurrence of outcome events, 72 patients were included for Cox regression analysis. The results showed that 16 patients (22.22%, 16/72) had ischemic stroke in the future. The baseline aCCI in the low aCCI group was significantly associated with ischemic stroke [hazard ratio ( HR)=1.76, 95% confidence interval ( CI) 1.21-2.56, P=0.003], and for every 1 point increase in baseline aCCI, the risk of future ischemic stroke increased by 76% on average. The baseline aCCI in the high aCCI group had no significant correlation with the ischemic stroke ( HR=0.66, 95% CI 0.33-1.33, P=0.247). Conclusions:aCCI score is an important prognostic information for patients with OAO or RAO. A higher baseline aCCI score predicts a higher risk of ischemic stroke, and the association has a saturation effect.

Objective:To investigate the clinical manifestations and the effect of peroral endoscopic-assisted laryngeal microsurgery for children with laryngeal neurofibroma, and to provide clinical reference for the diagnosis and treatment of this disease. Methods:The clinical data of 4 children with laryngeal tumors admitted to the Department of Otorhinolaryngology, Children's Hospital of Chongqing Medical University from January 2021 to June 2023 were retrospectively analyzed. Laryngeal tumors were removed by peroral endoscopic-assisted laryngeal microsurgery. One case underwent tracheotomy at the same time, and one case was simultaneously performed with laryngeal T tube placement and tracheotomy. Results:Surgical resection is the best treatment for laryngeal neurofibroma, and laryngeal microsurgery should be actively used for patients with surgical indications.This surgical method has the advantages of good efficacy, minimal invasion, aesthetics and preservation of laryngeal function, which not only ensures safety, but also improves the quality of life after surgery, and has the value of development and promotion.
Child ; Humans ; Laryngeal Neoplasms/pathology* ; Laryngoscopy/methods* ; Microsurgery/methods* ; Retrospective Studies ; Quality of Life ; Neurofibroma/diagnosis*

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans ; Male ; Retrospective Studies ; Diabetes Mellitus, Type 2/complications* ; Obesity, Morbid ; Anastomotic Leak/epidemiology* ; Gastrectomy/methods* ; Reoperation/methods* ; Registries ; Laparoscopy/methods* ; Treatment Outcome