Objective To induce an NLRP3-/- mouse model of ulcerative colitis(UC)using different concentrations of dextran sulfate sodium(DSS)and different administration times,and to analyze and evaluate the advantages and disadvantages of the preparations to provide a more suitable animal model for the study of UC pathogenesis in humans and the development of therapeutic drugs.Methods Forty-eight male NLRP3-/- specific-pathogen-free mice were divided randomly into blank,2.5％7 d,3％7 d,and 3％5 d groups(n=12 mice per group).UC mouse models were induced using combinations of different concentrations and administration times of DSS.Body weight,DAI(disease activity index)score,hematoxylin and eosin(HE)staining,colon length,and related indicators(interleukin IL-6,tumor necrosis factor(TNF)-α,and tight junction protein(ZO-1))were observed and evaluated.Results(1)UC membrane type was induced in each group with different concentrations and administration times.(2)Mouse body weight decreased,the fecal occult blood became more positive,the DAI score increased,and more mice died with increasing DSS concentration and administration time.(3)Longer administration time and higher concentration of DSS were also associated with more severe damage to the intestinal mucosa,as shown by HE staining.(4)Immunohistochemistry showed that the inflammatory factors TNF-α and IL-6 were increased in the model group compared with the blank control group,while expression of ZO-1 was decreased compared with the blank group.Conclusions(1)Administration of 2.5％or 3％DSS for 7 days or 3％DSS for 5 days can induce UC in NLRP3-/- mice.(2)The combination of DAI score,HE staining,the detection of related indicators,and mouse survival rate indicated that NLRP3-/- mice treated with 3％DSS for 5 days produced the most suitable UC model to study the clinical manifestations and drug treatment of UC.

Objective:To investigate the risk factors and their warning effectiveness for postoperative intestinal barrier dysfunction (IBD) in patients with severe traumatic brain injury (sTBI).Methods:A retrospective cohort study was conducted to analyze the clinical data of 101 patients with sTBI admitted to Wuxi Branch of Zhongda Hospital Affiliated to Southeast University from May 2020 to February 2023, including 63 males and 38 females, aged 21-81 years [(53.4±14.2)years]. All the patients underwent emergency surgery. The patients were divided into IBD group ( n=67) and non-IBD group ( n=34) according to whether or not they had IBD after surgery. The gender, age, basic diseases (hypertension and diabetes), types of intracranial hematoma (subdural, epidural, and intracerebral hematoma), preoperative Glasgow Coma Scale (GCS), cerebral hernia, intraoperative initial intracranial pressure (iICP), operation time, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were recorded in the two groups. Univariate and multivariate binary Logistic regression analyses were conducted to assess the correlations between above-mentioned indicators and incidence of postoperative IBD in sTBI patients and determine the independent risk factors for sTBI. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the warning effectiveness of each risk factor for IBD. Results:The results of the univariate analysis showed that preoperative GCS, cerebral hernia, intraoperative iICP, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were significantly correlated with the incidence of IBD in sTBI patients ( P<0.05 or 0.01), while there were no correlations of IBD with gender, age, basic diseases, types of intracranial hematoma and operation time ( P>0.05). The results of the multivariate binary Logistic regression analysis showed that preoperative GCS≤5 points ( OR=2.49, 95% CI 1.17, 5.32, P<0.05), intraoperative iICP>23 mmHg (1 mmHg=0.133 kPa)( OR=1.20, 95% CI 1.03, 1.39, P<0.05), and initiation time of enteral nutrition>24 hours ( OR=10.03, 95% CI 1.26, 80.21, P<0.05) were highly correlated with postoperative IBD in sTBI patients. The results of the ROC curve analysis showed that intraoperative iICP had the highest warning value (AUC=0.91, 95% CI 0.85, 0.96), followed by preoperative GCS (AUC=0.88, 95% CI 0.82, 0.95), and initiation time of enteral nutrition had the lowest warning value (AUC=0.78, 95% CI 0.69, 0.87). Conclusions:Preoperative GCS≤5 points, intraoperative iICP>23 mmHg, and initiation time of enteral nutrition>24 hours are independent risk factors for postoperative IBD in sTBI patients. The warning value of intraoperative iICP ranks the highest for postoperative IBD in sTBI patients, followed by preoperative GCS, with initiation time of enteral nutrition having the lowest warning value.

Objective:To investigate the short-term effect of Helicobacter pylori ( HP) eradication on intraoperative bleeding during endoscopic submucosal dissection (ESD) for early gastric cancer. Methods:Patients who underwent ESD for early gastric cancer in Shanghai East Hospital from September 2021 to September 2023 were retrospectively analyzed for endoscopic, pathological and clinical data. The patients with current HP infection were included in the current infection group, and those who underwent eradication therapy within 10 weeks and successfully eradicated were included in the short-term after eradication group. The occurrence of intraoperative bleeding was compared. Results:A total of 345 patients were analyzed, with 156 in the current infection group and 189 in the short-term after eradication group. Compared with the current infection group, short-term after eradication group was effective in reducing the intraoperative bleeding rate [6.3% (12/189) VS 12.8% (20/156), χ2 =4.253, P=0.039] and significantly reduced the duration of operation (29±9 min VS 38±14 min, t=2.667, P=0.008). Intraoperative bleeding was significantly reduced in short-term after eradication group in lesions of the upper 1/3 of the stomach [12.5% (5/40) VS 32.1% (9/28), χ2 =3.887, P=0.049], while there were no significant differences in intraoperative bleeding between the current infection group and the short-term after eradication group in lesions of the middle 1/3 [5.4% (2/37) VS 10.0% (3/30), χ2 =0.506, P=0.477] and lower 1/3 [4.5% (5/112) VS 8.2% (8/98), χ2 =1.231, P=0.267] of the stomach. Conclusion:HP eradication therapy can effectively reduce intraoperative bleeding in ESD and significantly reduce the duration of operation in a short-term. For individuals with early gastric cancer and HP infection, undergoing eradication therapy before ESD is recommended, particularly for lesions situated in the upper 1/3 of the stomach.

Total glucosides of Rhizoma Smilacis Glabrae (RSG) are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T cells. In this study, we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material basis. Our findings revealed significant improvements upon administration of RSG in an imiquimod (IMQ)-induced psoriasis model. These improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema, ulceration, and flaking. By transcriptome sequencing and T-cell flow sorting assay, we identified notable effects of RSG on the modulation of various cellular processes. Specifically, RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G₂ phase cells. Furthermore, RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial cells. Of particular interest, we discovered that β-sitosterol, sitostenone, stigmasterol, smiglanin, and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT cells. In summary, our study highlights the therapeutic potential of RSG in the treatment of psoriasis, attributed to its ability to regulate the Th17/Treg balance. These findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.
Animals ; Mice ; T-Lymphocytes, Regulatory ; Psoriasis/drug therapy* ; Arthritis, Rheumatoid ; Biological Assay ; Glucosides/pharmacology*

ObjectiveTo evaluate the clinical efficacy and adverse effects of Shugan Hewei prescription combined with vonoprazan in the treatment of refractory gastroesophageal reflux disease （RGERD） due to qi depression and phlegm obstruction. MethodEighty RGERD patients who met the inclusion criteria underwent 24-hour pH impedance and high-resolution esophageal manometry and electronic gastroscopy. The 80 patients were randomly assigned to an observation group （Shugan Hewei prescription， one bag each time， twice a day + vonoprazan， 20 mg each time， once a day） and a control group （vonoprazan， 20 mg each time， once a day） by the random number table method. The treatment in both groups lasted for 4 weeks. The clinical efficacy was examined. The scores of TCM symptoms （pharyngeal discomforts such as phlegm obstruction， retrosternal discomfort， and belching）， somatic symptoms， quality of life， and improvement of esophageal mucosa under gastroscopy were observed in both groups before treatment and after treatment for 2 and 4 weeks. ResultSeventy-five patients completed the trial were included in this study， including 38 patients in the observation group and 37 patients in the control group. The total response rate in the observation group was 89.47%（34/38）， which was higher than that （62.16%，23/37） in the control group （χ²=13.014， P<0.01）. After treatment， the scores of esophageal mucous membrane， reflux disease symptoms， TCM symptoms， gastroesophageal reflux disease health-related quality of life scale （GERD-HRQL）， and somatic self-rating scale （SSS） decreased in both groups（P<0.05）. Moreover， the observation group outperformed the control group in alleviating heartburn， acid reflux， throat discomforts， midnight coughing， nausea and dry vomiting， mucousy mouth， and insomnia in the patients with GERD （P<0.05，P<0.01）. However， the two groups showed no statistically significant differences in the improvement of esophageal mucosa after treatment. ConclusionThe combination of Shugan Hewei prescription with vonoprazan was superior to vonoprazan alone in treating RGERD regarding clinical symptoms， physical signs， quality of life， and somatic symptoms， without causing obvious adverse effects.

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

To investigate the effects of streptavidin and dimethylsilicone oil on the detection rate of microscopic lesions under gastroscopy, a total of 353 patients who underwent painless gastroscopy were categorized into the experimental group (given streptavidin combined with sodium bicarbonate, n=176) and the control group (given dimethylsilicone oil combined with sodium bicarbonate, n=177). Clinical indexes such as visual field clarity, examination duration, number of rinses, detection rate of micro lesions, early cancer detection rate and incidence of adverse reactions were recorded in the gastroscopy examination of the two groups. The experimental and control groups were compared in terms of visual field clarity (1.84±0.51 points VS 2.15±0.48 points, t=-5.900), fundus mucus properties (1.04±0.43 points VS 1.46±0.76 points, t=-6.347) and number of rinses (0.76±0.66 times VS 1.18±0.72 times, t=-5.628) with significant differences ( P<0.001). The examination time in the experimental group was slightly higher than that in the control group (10.01±4.40 min VS 8.98±4.22 min, t=2.239, P=0.026). The detection rate of microscopic lesions was significantly higher in the experimental group than that in the control group [97.73%(172/176) VS 91.53%(162/177), χ2=6.665, P=0.010]. There was no significant difference in the detection rate of inflammatory hyperplasia, polyps, precancerous lesions or cancer between the experimental group and the control group ( P>0.05). There was no preoperative drinking discomfort in either group, and 4 cases of intraoperative choking occurred in each of the experimental and the control group with no significant difference ( P>0.999). No postoperative adverse reaction occurred in either group. Taking streptavidin before operation could significantly improve visual field clarity and the detection rate of microscopic lesions, which helps to detect early lesions in stomach.

ObjectiveTo establish a more accurate and sensitive liquid chromatography-ultraviolet (LC-UV) method for the determination of uric acid in rat serum, and compare the results with those of commercial kits, providing a new method for the accurate determination of uric acid in the rat hyperuricemia model induced by potassium oxonate.Methods A hyperuricemia model was established by intraperitoneal injection of potassium oxonate (300 mg/kg) into SPF-grade male SD rats, and the control group was administered an equal amount of 0.5% sodium carboxymethylcellulose solution. Blood samples were collected from the posterior orbital venous plexus and centrifuged to obtain serum samples. After precipitation with 0.1% trifluoroacetic acid-acetonitrile (containing the internal standard 3,4-dihydroxybenzylamine hydrobromide), the supernatant was injected for analysis. Uric acid was separated on a Waters XBridge HILIC column (150 mm×4.6 mm, 3.5 μm) using acetonitrile (containing 0.5% formic acid and 2 mmol/mL ammonium formate) as the organic phase and methanol solution (methanol∶water=1∶1, containing 0.5% formic acid with 2 mmol/L ammonium formate) as the aqueous phase for isocratic elution and detection at 290 nm. Serum samples treated with activated carbon were used as substitute matrices for the methodological verification. Serum uric acid levels in rats with potassium oxonate-induced hyperuricemia were measured using the established LC-UV method and commercially available kits (uricase and phosphotungstic acid methods), and the accuracies of the three methods were compared.Results Serum uric acid showed a good linear relationship (R>0.999) at mass concentration of 10–200 μg/mL in rats, the lower limit of quantification was 10 μg/mL, the accuracy ranged from -2.17% to 2.21%, the intra-batch precision ranged from 0.52% to 1.95%, the inter-batch precision ranged from 3.04% to 4.90%, and the extraction recovery ranged from 83.12% to 89.91%. In the rat model, the results obtained using the commercially available phosphotungstic acid method kit were significantly higher than those of the LC-UV method, and those obtained using the commercially available uricase method kit were significantly lower than those of the LC-UV method, but the LC-UV method showed the best recovery of the spiked sample (95.90%–99.96%).ConclusionThe LC-UV method developed in this study can determine the concentration of uric acid in rat serum with higher accuracy than commercially available kits and is recommended for the determination of serum uric acid in the rat model of hyperuricemia induced by potassium oxonate.

Objective:To evaluate the differential expression of blood routine in different types of infection and the diagnostic value of C-reactive protein (CRP), procalcitonin (PT), ferritin (SF) and lactate dehydrogenase (LDH) in bacterial and mycoplasma pneumonia and their early warning value in severe cases.Method:A total of 627 patients, including 176 cases of bacterial pneumonia, 275 cases of mycoplasma pneumonia, 176 cases of viral infection and 180 cases of normal control were collected from May 2018 to December 2019 in children′s Hospital Affiliated to Capital Institute of Pediatrics. The mycoplasma pneumonia group was divided into mild group (151 cases) and severe group (124 cases) according to the results of lavage fluid RNA-examination. All patients received completed blood routine test at the first day of admission, patients in bacteria group and Mycoplasma group received the examination of four inflammatory indicators. The Kruskal-Wallis test was used to analyze the differences in blood routine results between different infection groups, and the differences of inflammatory indexes between bacterial group and Mycoplasma mild and severe group. The receiver operating characteristic (ROC)-curve method was used to analyze the predictive value of inflammatory indexes between different infection groups.Results:There were significant differences in leukocyte count, neutrophil, lymphocyte and monocyte percentage between bacterial pneumonia, mycoplasma pneumonia, viral infection and normal control group ( P<0.05). The differences of four inflammatory indexes in bacterial group, mild Mycoplasma group and severe group were statistically significant ( P<0.05). The rest of the index (CRP, PCT, LDH, SF and white blood cell count) were P<0.05 (CRP: area under curve [AUC] 0.799; PCT: AUC 0.579; LDH: AUC 0.651; SF: AUC 0.854), in mild and severe mycoplasma group, except WBC, by ROC-curves analysis. The AUC value of the area under the curve of CRP and SF is high, and the sensitivity and specificity at the diagnostic critical point are high, which has great diagnostic value (CRP: diagnostic critical point 12.55 mg/L, sensitivity 0.719, specificity 0.755; SF: diagnostic critical point 176.02 μg/L, sensitivity 0.765, specificity 0.960). ROC curve results also showed that of PCT, White blood cell and neutrophil percentage had the diagnostic value in bacterial infection and mycoplasma infection, P<0.05 (PCT: AUC 0.658; leukocyte: AUC 0.804; neutrophil: AUC 0.630). Leukocyte count is the best differential index (diagnostic critical point 9.585×10 9/L, sensitivity 0.778, specificity 0.698), PCT has higher sensitivity at the diagnostic critical point of 0.55 μg/L, but the specificity is slightly lower (diagnostic critical point of 0.55 μg/L, sensitivity 0.862, specificity 0.366). Conclusions:PCT and leukocyte count can be used as the preferred inflammatory indexes to distinguish bacterial and mycoplasma infection. CRP, LDH, PCT and SF can be used as early warning indexes to evaluate severe mycoplasma infection.

Cholesterol is an important lipid component in the body, which not only participates in the formation of cell membranes, but also is the raw material for the synthesis of bile acids and steroid hormones. Low density lipoprotein receptor (LDLR) is involved in cholesterol metabolism and plays an important role in maintaining the cholesterol homeostasis of organism cells. The expression of LDLR is precisely regulated by transcription, post-transcription and post-translation, and the imbalance of ldlr expression will lead to the occurrence and development of many diseases. In this paper, the molecular regulation mechanism of LDLR, the damage of target organs caused by the imbalance of LDLR expression and the research and development progress of drugs targeting LDLR are reviewed, which provides theoretical basis for further understanding of the progress of diseases related to lipid metabolism disorder and new insights for developing drugs targeting LDLR with more effective and less side effects.