The chapter Zhouyu in Guoyu says "Qi of the heaven and the earth moves without losing its order." With lucidity ascending and turbidity descending， Qi moves in a normal state， and Yin and Yang consolidate the foundation of the body. The mutual interference between lucidity and turbidity leads to the disorder of Qi movement， thus causing diseases. It is a pathological state of disorder between ascending and descending， as well as between entering and exiting， gradually evolving into a state of turbidity affecting lucidity and transforming into pathogen， which can be used to interpret and analyze the core of disease pathogenesis. The theory of lucidity and turbidity is connected with the harmony of nutrient and defensive aspects， Qi circulation， and sweat pore associating with Qi movement， and it has common implications with immune responses and nutrient metabolism system， intestinal mucosal barrier function， and mitochondrial energy synthesis. Modern studies have shown that intestinal flora imbalance， bile acid receptor inactivation， macrophage polarization imbalance， epithelial-mesenchymal transition， ferroptosis and other related microscopic pathological mechanisms are involved in the development and progression of ulcerative colitis. By delving into the common meaning of the classic theory of mutual interference between lucidity and turbidity in traditional Chinese medicine and modern medical pathological mechanisms， this paper summarizes the correspondence between the micropathological mechanism and the theory of mutual interference between lucidity and turbidity in the regulation and mamagement of ulcerative colitis. The combined use of sweet and warm medicinal materials consolidates the middle Qi and activates Qi circulation， thus ascending lucidity and descending turbidity. The combined use of pungent medicinal materials for dispersing and bitter medicinal materials for descending simultaneously raises warm and clear Qi. Wind-extinguishing medicinal materials facilitate the ascending of Qi and the opening of sweat pores. Accordingly， turbidity descends and lucidity ascends. The prescriptions incorporating these medication principles are in agreement with the therapeutic approach of following the normal flow of lucidity and turbidity. This paper clarifies the scientific connotation and micropathologic mechanism of ulcerative colitis from the perspective of mutual interference between lucidity and turbidity， providing new theories and prescriptions for the clinical diagnosis， treatment， and prevention of ulcerative colitis.

Objective To gain insights into the biological characteristics of different populations of Culex tritaeniorhynchus within and around the Yellow Sea wetland from the perspective of the occurrence of resistance, we investigated the levels of resistance to deltamethrin and kdr gene mutation in the wetland and its peripheral areas. Methods Specimens were collected from Cx. tritaeniorhynchus populations at two monitoring sites in the Rare Bird National Nature Reserve and Tiaozi Ni Wetland Scenic Area, and also from two populations in Yancheng City and the Liuhe District of Nanjing, and the resistance of these mosquitoes to deltamethrin was determined using the CDC biotest bottle method. For each concentration of deltamethrin assessed, a random subset of exposed specimens was selected for amplification of the kdr gene fragment, followed by Sanger sequencing to identify and analyze resistance-associated mutations. Results The LC50 levels of deltamethrin among mosquitoes from the four populations in Luhe, Yancheng, the Rare Bird National Nature Reserve and the Tiaozi Ni Wetland Scenic Area were 2.048 5, 7.798 2, 3.473 3, and 17.695 5 mg/mL, respectively, with corresponding concentrations of deltamethrin ranging from 0.005 to 5.000,0.050 to 50.000,0.050 to 25.000 and 0.050 to 50.000 mg/mL, respectively. Furthermore, the ranges of the KT50 values were 11.76-107.43, 67.05-216.30,29.77-107.43 and 28.40-329.51 min; the 1-h knockdown rates were 34.58%-99.15%, 9.52%-43.80%, 55.09%-73.01%, and 10.09%-68.07%; and the 24-h mortality rates were 12.15%-67.52%,9.52%-79.56%,13.17%-82.21%, and 11.01%-78.99%, respectively. With respect to kdr gene mutation, we assayed a total of 63,70,59, and 57 mosquitoes for the four populations, for which we detected L1014F mutation frequencies of 14.29%, 35.00%, 20.34%, and 31.58%, respectively, with a majority of these mutations being heterozygous for resistance. In addition, five adult mosquitoes were identified has having synonymous mutations at site 1011[i. e. , AAT(asparagine)mutation to AAC(asparagine)]. Conclusions Our findings revealed the clear resistance of Cx. tritaeniorhynchus to deltamethrin in the Yancheng region of the Yellow Sea wetland, and the resistance phenotype and kdr frequency of Cx. tritaeniorhynchus in the wetland environment were comparable to those of Cx. tritaeniorhynchus in the wetland environment, thereby indicating that the resistance of different populations of Cx. tritaeniorhynchus was homogeneous under the pressure of different insecticide selection within and around the wetland. However, the underlying mechanisms need to be further studied.

Objective:To evaluate the accuracy and safety profile of a novel cuboid orientation-guided frontal horn ventriculostomy technique in patients with large hemispheric infarction (LHI).Methods:It was conducted a retrospective cohort study of 48 consecutive LHI patients who underwent the innovative ventriculostomy procedure between time period. Primary outcomes included procedural accuracy (success rates, catheter positioning) and safety indicators (complication rates).Results:All the punctured ventricles were small or of normal size. The success rate of puncture was 100%, the success rate of one-time puncture was 87% (42/48), and the average number of puncture was 1.13 times per case. The ratio of well-positioned tube heads was 87.5% (42/48). The actual angle of the inward deviation of the puncture ranged from -2o to 5o, with an average of 0o±0.3o. The depth of puncture was 7.0-8.0 cm ( 7.3±0.3) cm. The incidence of bleeding around the puncture path was 1.3% (2/48 ) and no massive bleeding occurred. At the 6-month follow-up, one case (2.94%) among the 34 survivors had epilepsy.Conclusions:The cuboid orientation-guided frontal horn ventriculostomy technique demonstrates exceptional procedural accuracy and an excellent safety profile in LHI patients, with high first-pass success rates (87.5%) and minimal complications (4.2% minor hemorrhage). These findings support its clinical adoption for this patient population.

Insulin is an important protein hormone that participates in multiple metabolic pathways.Biosynthetic insulin has been widely used in the treatment of type 1 and type 2 diabetes.Currently,the number of reported cases of insulin overdose both at home and abroad is gradually increasing,and insulin homicide is no longer a means of"committing murder without leaving a trace".At present,there are no systematic protocols for the identification of insulin overdose in the field of forensic medi-cine in China.This article introduces the causes,toxicological characteristics,forensic examination,labo-ratory testing methods and indicator reference of insulin overdose.Based on the identification practice and research results and referring to relevant studies on insulin overdose at home and abroad,this pa-per aims to provide recommendations and references for the formulation of forensic identification guide-lines for insulin overdose cases.

Objective:To explore the effect of Simo decoction improving the low duodenal inflammation and protecting the du-odenal mucosal barrier in rats with functional dyspepsia(FD).Methods:Sixty SD rats were randomly divided into control group(10 rats)and model group(50 rats),and the modeling rats were prepared by multivariate intervention method.After successful modeling,the modeling rats were randomly divided into model group,Simo decoction high-dose,medium-dose,low-dose group and mosapride group,with 10 rats in each group.The high-dose,medium-dose,and low-dose groups of Simo decoction were ga-vage given 5.62 g/kg,2.81 g/kg,and 1.40 g/kg,respectively,and the mosapride group was gavage given 0.305 mg/kg of mosapride,and the control group and model group were gavage given the same amount of distilled water for 14 days.The body weight of rats was observed;gastric emptying rate and small bowel propulsion rate were measured;transmission electron microscopy was used to observe the morphology of duodenal epithelial cells;ELISA detected serum levels of IL-17A and IL-22;Western blot and immunohistochemis-try were used to detect the expressions of protease-activated receptor 2(PAR-2)and tight junction protein(ZO-1,claudin-1)in the duodenum.Results:Compared with the control group,the body weight,gastric emptying rate and small intestinal propulsion rate of the model group were significantly reduced(P<0.01),transmission electron microscopy showed widening of the duodenal epithelial cell space,serum IL-17A and IL-22 levels were significantly increased(P<0.01),the expression of PAR-2 in duodenal tissue was in-creased,and the expressions of ZO-1 and claudin-1 were downregulated(P<0.01).Compared with model group,the gastric emptying rate and small intestinal propulsion rate in Simo decoction high-dose,medium-dose and mosapride group were increased(P<0.05,P<0.01),the contents of IL-17A and IL-22 in serum decreased(P<0.05,P<0.01),and the expression of PAR-2 in duodenal tissues was down-regulated,the expressions of ZO-1 and claudin-1 was significantly increased(P<0.01).The low-dose group of Simo soup could improve weight loss(P<0.01),reduce IL-17A content and PAR-2 expression,and increase ZO-1 and claudin-1 expression(P<0.05,P<0.01),while the effect on other indexes was not obvious.Conclusion:Simo decoction may reduce low-grade duodenal in-flammation to repair the mucosal barrier by down-regulating the levels of IL-17A and IL-22 and the expression of PAR-2,and up-regu-lating the expression of ZO-1 and claudin-1,so as to exert the effect of FD treatment.

Colorectal cancer(CRC)is a malignant tumor formed in the colon or rectum,usually caused by uncontrolled growth and division of normal cells in the body.Cell apoptosis,pyroptosis,and necroptosis are key pathways of cell death in colorectal cancer.The comprehensive treatment strategy includes the synergistic effect of cell death inducers with chemotherapy,immunotherapy,and targeted therapy.Traditional Chinese medicine plays an important role as an adjuvant therapy in regulating cell death.The combination of traditional Chinese and western medicine has shown significant effects in precancerous lesions,improving efficacy,reducing adverse reactions,and reducing drug resistance.Although the research on the mechanism of cell death is not yet sufficient,emphasizing the unique characteristics of traditional Chinese medicine,clarifying the anti-tumor mechanism of traditional Chinese medicine,and achieving modern scientific internationalization of integrated traditional Chinese and western medicine treatment for colorectal cancer have become future research directions.This article will comprehensively review the molecular mechanisms of cell apoptosis,pyroptosis,and necroptosis from the perspective of combining traditional Chinese and Western medicine,as well as their regulatory role in the treatment of colorectal cancer.

Coronary heart disease is a common cardiovascular disease.Intravascular imaging plays an important role in the management of coronary artery disease.In contemporary clinical practice,intravascular ultrasound(IVUS)and optical coherence tomography(OCT)are widely used.Near-infrared spectroscopy(NIRS)has attracted much attention due to the advantage of being able to sensitively identify lipid components.In recent years,NIRS is still being explored,although some applications have been reported.Lipids play an important role in the assessment of atherosclerotic plaque stability,which further affects the progression and prognosis of coronary heart disease.Therefore,this article will review the current application of NIRS in the diagnosis and treatment of coronary heart disease.It further provides an imaging basis for clinical disease diagnosis and treatment,evaluation and the development of multimodal technology.

Objective:To investigate the role of hypoxia-induced angiopoietin-like protein 4 (ANGPTL4) expression in experimental choroidal neovascularization (CNV).Methods:Twenty-seven SPF male C57BL/6J mice aged 6-8 weeks were selected.Eighteen of the mice were used to establish a laser-induced CNV model.On the 7th day after laser photocoagulation, success of the modeling was verified using optical coherence tomography angiography (OCTA) and fundus fluorescein angiography (FFA). The retinal pigment epithelium (RPE)-choroid-sclera complex was extracted for protein analysis before modeling and on the 3rd and 7th days after modeling.The relative expression levels of ANGPTL4 and vascular endothelial growth factor (VEGF) at different time points were detected by Western blot.Additionally, frozen sections of mouse eyeballs on day 7 after modeling were prepared and the expression and cellular localization of ANGPTL4 were observed by immunofluorescence.RF/6A cells, derived from monkey choroidal retinal endothelial cells, were treated with 200 μmol/L cobalt chloride (CoCl 2) in the culture medium for 0, 3, 6, and 12 hours.RF/6A cells were also divided into a normal control group, a hypoxia group, and a hypoxia+ si-ANGPTL4 group, and cells were transfected with a plasmid containing si-ANGPTL4 sequence.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot, and the differences in tube formation among the groups were observed by tube formation assay.A total of 27 male C57BL/6J mice were randomly divided into CNV group, CNV+ si-NC group, and CNV+ si-ANGPTL4 group, with 9 mice in each group.In the CNV+ si-NC and CNV+ si-ANGPTL4 groups, si-NC and si-ANGPTL4 were respectively injected into the vitreous cavity after the CNV model was established.Fluorescence leakage in mice was observed by FFA, and the length, thickness and area of CNV was observed using OCTA and immunofluorescence staining of choroidal flat mounts.The relative expression levels of ANGPTL4 and VEGF proteins in each group were detected by Western blot.All animal experiments were conducted in accordance with ARVO Statement on the Use of Animals in Ophthalmic and Vision Research.The experimental protocol was approved by the Affiliated Hospital of Nantong University (No.S20220822-902). Results:Before modeling and on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 protein were 1.00±0.00, 1.58±0.05, and 1.90±0.04, respectively, and the relative expression levels of VEGF protein were 1.00±0.00, 1.31±0.05, and 1.84±0.04, respectively, with statistically significant overall differences ( F=528.934, 390.424, both P<0.05). Among them, on the 3rd and 7th days after modeling, the relative expression levels of ANGPTL4 and VEGF proteins were significantly higher in CNV group than in the control group (all P<0.05). The tissues of each layer of the retina were clear in the control group, while neovascularization could be seen growing under the retinal neuroepithelial layer in the CNV group.Compared with the control group, ANGPTL4 expression was significantly increased and colocalized with vascular endothelial cells in the CNV group.After CoCl 2 treatment of RF/6A cells for 3, 6, and 12 hours, the relative expression levels of ANGPTL4 and VEGF proteins were higher than at 0 hour, with statistically significant differences (all P<0.05). Compared with the control group, the relative ANGPTL4 protein expression was increased in the hypoxia group and significantly decreased in the hypoxia+ si-ANGPTL4 group, showing statistically significant differences (both P<0.05). The number of tube formations in the control group, hypoxia group, and hypoxia+ si-ANGPTL4 group were 12.67±1.53, 19.64±1.56, and 17.01±1.04, respectively, with a statistically significant overall difference ( F=33.091, P<0.01). The number of tube formations increased in the hypoxia group and hypoxia+ si-ANGPTL4 group compared with the control group, and the number of tube formations decreased in the hypoxia+ si-ANGPTL4 group compared with the hypoxia group, with statistically significant differences (all P<0.05). Relative expression levels of ANGPTL4 and VEGF proteins were significantly lower in the CNV+ si-ANGPTL4 group than those in the CNV group (both P<0.05). The CNV area was significantly lower in the CNV+ si-ANGPTL4 group than in the CNV group and CNV+ si-NC group (both P<0.05). Conclusions:Hypoxia-induced ANGPTL4 promotes experimental CNV formation in vivo and in vitro.Inhibiting ANGPTL4 can reduce CNV formation and leakage.

OBJECTIVE: To retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

OBJECTIVE: To analyze the gene mutation characteristics and survival time of patients with newly diagnosed acute myeloid leukemia (AML) based on next-generation sequencing(NGS) gene detection. METHODS: A retrospective analysis was conducted on the clinical data of 92 patients with AML (non APL) admitted to our hospital from January 2018 to May 2022. AML related genes tested were using NGS, the mutation characteristics and survival time of AML patients were analyzed. RESULTS: Among the 92 patients, 41 were males and 51 were females. A total of 38 types of gene mutations were detected. Six-two patients carried at least one gere mutation, while no gene mutations were detected in 30 patients. In the group with favourable prognosis (n =14), the frequencies of higher gene mutations were NRAS, KIT (21.43%, n =3), KRAS (14.29%, n =2). In the group with intermediate prognosis (n =64), the gene mutation frequencies from high to low were DNMT3A (18.75%, n =12), NPM1 (17.19%, n =11), IDH2, FLT3-ITD, CEBPA (12.50%, n =8), TET2 (10.94%, n =7). In the poor prognosis group (n =14), ASXL1, TP53, EZH2, NRAS had higher gene mutation frequency than others(14.29 %, n =2 ). Statistical analysis revealed that KIT had a relative hotspot of mutations in the intermediate-risk group, and DNMT3A had a relative hotspot of mutations in the high-risk group (P < 0.05). The correlation analysis of genes with high mutation rates in different prognostic groups, such as NRAS, KIT, IDH2, DNMT3A, NPM1, and FLT3-ITD, with prognosis found that KIT was a factor affecting OS (P < 0.05), while no significant differences were observed for the others(P >0.05). CONCLUSION The frequency of gene mutations is high in AML patients, 67.4% of the patients carried at least one gene mutation. The mutation frequency varies among different genes in patients with different karyotypes, and there are obvious dominant mutations. KIT and DNMT3A can be used as factors for evaluating the prognosis of AML.
Humans ; Leukemia, Myeloid, Acute/genetics* ; Nucleophosmin ; Mutation ; Prognosis ; Retrospective Studies ; Male ; Female ; High-Throughput Nucleotide Sequencing ; Middle Aged ; DNA Methyltransferase 3A ; Adult ; Aged ; Survival Analysis ; Proto-Oncogene Proteins c-kit/genetics*