ObjectiveTo investigate whether Huanglian Jiedutang （HLJD） and its major active constituents （geniposide， baicalin， and berberine） can inhibit the inflammatory response of BV2 cells under lipopolysaccharide （LPS） stimulation via the high-mobility group protein B1 （HMGB1）/Toll-like receptor 4 （TLR4）/nuclear factor-κB （NF-κB） signaling pathway， and to explore differences in therapeutic efficacy among the three monomers， their combined formula， and HLJD under equal content ratios. MethodsBV2 microglial cells were used as the primary experimental model. Cell viability was assessed using the cell counting kit-8 （CCK-8） method to examine the effects of different concentrations of dimethyl sulfoxide （DMSO， 0.8%， 0.4%， 0.2%， 0.1%， and 0.05%） on cell viability. IncuCyte was employed to monitor the growth of cells under different concentrations of HLJD （200， 100， 50， 25， 12.5， 6.25 mg·L^-1）. Nitric oxide （NO） assay was used to screen the optimal HLJD concentration. High-performance liquid chromatography （HPLC） determined the content of geniposide， baicalin， and berberine in HLJD， and experimental groups were subsequently established according to the relative proportions of these constituents. CCK-8 assay evaluated cell viability under different treatments. Enzyme-linked immunosorbent assay （ELISA） measured levels of inflammatory factors （TNF-α， IL-1β， IL-6， IL-10） in the supernatant. Flow cytometry assessed the effects of treatments on M1-type polarization of BV2 cells. Western blot determined the expression levels of HMGB1， TLR4， and NF-κB-related proteins. ResultsCompared with the blank group， DMSO at concentrations ≤0.2% did not affect cell viability within 48 h. BV2 cell growth plateaued at 24 h after treatment with 200 mg·L^-1 HLJD. Under stimulation with 2 mg·L^-1 LPS， this concentration of HLJD effectively reduced NO release， and 6 h pre-treatment had a stronger inhibitory effect on NO than direct administration. HPLC results showed that 1 mg of HLJD freeze-dried powder contained approximately 24 μg of geniposide， 15 μg of baicalin， and 30 μg of berberine. Based on these ratios， experimental groups were blank， LPS （2 mg·L^-1）， HLJD （200 mg·L^-1）， monomer combination， geniposide （4.8 mg·L^-1）， baicalin （3 mg·L^-1）， and berberine （6 mg·L^-1）. The monomer combination group consisted of all three active constituents dissolved together. LPS and HLJD or its active constituents did not affect cell viability compared with the blank group. LPS significantly increased TNF-α， IL-1β， IL-6， and IL-10 in the supernatant （P<0.01）. HLJD and its active constituents significantly reduced pro-inflammatory factors TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01） while upregulating anti-inflammatory IL-10 （P<0.01）， with the monomer combination showing the strongest effect （P<0.05， P<0.01）. Compared with the blank group， LPS significantly increased the proportion of CD80⁺CD86⁺ （M1-type） BV2 cells （P<0.01）. HLJD and its constituents partially inhibited M1 polarization （P<0.05， P<0.01）， with the monomer combination exhibiting the most pronounced effect （P<0.05， P<0.01）. Compared with the blank group， LPS upregulated HMGB1， TLR4， and NF-κB-related proteins （P<0.01）， whereas HLJD and its active constituents significantly reduced their expression （P<0.05， P<0.01）， with the monomer combination having the strongest regulatory effect （P<0.05， P<0.01）. ConclusionHLJD and its major active constituents （geniposide， baicalin， berberine） can inhibit LPS-induced inflammatory responses in BV2 cells. The combination of the three active constituents demonstrates the most potent anti-inflammatory effect， significantly attenuating M1-type polarization of BV2 cells via the HMGB1/TLR4/NF-κB signaling pathway.

Huanglian Jiedutang （HLJDT）， as a classical formula for clearing heat and removing toxins， has been widely applied in the treatment of various clinical diseases in recent years， particularly during the fire-heat stage of stroke， where it has attracted considerable attention. Based on previous studies， this paper systematically elaborates on the research progress on the active components of HLJDT， its clinical application in ischemic stroke， and advances in studies on its mechanisms of action. Modern pharmacological studies have demonstrated that HLJDT contains multiple active components， including baicalin， geniposide， and berberine. In the treatment of ischemic stroke， these components exert therapeutic effects through multi-target， multi-pathway， and multi-level mechanisms. Clinical studies have shown that HLJDT can increase cerebral blood flow， reduce cerebral infarct volume， and improve post-stroke physical dysfunction in patients with ischemic stroke. Experimental studies have indicated that HLJDT can improve neurological function scores and increase cerebral perfusion in experimental stroke models. In addition， the mechanisms underlying the anti-ischemic stroke effects of HLJDT may be related to anti-inflammatory and antioxidant activities， promotion of angiogenesis， and regulation of amino acid and energy metabolism. Although existing studies have confirmed that HLJDT exhibits multi-target and multi-pathway synergistic therapeutic characteristics， further large-sample randomized controlled trials are still needed to verify its long-term efficacy and to further elucidate the dynamic interaction network among components， targets， and pathways. Combined with network pharmacology and molecular docking analyses， this study further clarifies the synergistic targets of the core components （berberine， baicalin， and geniposide）， providing a theoretical basis for in-depth research and clinical translation of HLJDT in the treatment of ischemic stroke.

During tumor progression, the mechanical properties of the tumor microenvironment play a pivotal regulatory role. As core mechanical indicators, cellular stiffness and extracellular matrix stiffness profoundly influence tumor development through multiple pathways, including cytoskeletal remodeling, activation of signaling pathways, and metabolic regulation. Studies have demonstrated that the tissue stiffness of various solid tumors is significantly higher than that of corresponding normal tissues, while their cellular stiffness exhibits the opposite trend. This mechanical characteristic is also observed in oral squamous cell carcinoma and exerts crucial regulatory effects during tumor progression. This review systematically summarizes the molecular composition and regulatory mechanisms underlying the stiffness of tumor cells and extracellular matrix (ECM). Mainstream stiffness detection technologies such as atomic force microscopy, microfluidic deformation, and real-time deformability cytometry are outlined, with particular emphasis on their applications and limitations in oncology research. This review comprehensively analyzes how mechanical properties regulate key processes in tumor progression, including growth, proliferation, invasion, metastasis, angiogenesis, lymphangiogenesis, drug resistance, and immune escape. This review synthesizes biomechanics-based therapeutic strategies, including: ① targeting the regulation of tumor cell stiffness through cytoskeletal modulators and cholesterol-depleting agents to enhance immune responses; ② reducing ECM stiffness by matrix remodeling enzyme inhibitors, ECM component modulators, or receptor antagonists to improve drug delivery efficiency, and combining with immunotherapy or photothermal therapy for enhanced therapeutic effects; ③ enhancing the mechanical adaptability and anti-tumor activity of immune cells through pharmacological or genetic approaches. This review establishes a robust conceptual framework for developing novel anti-tumor therapeutic strategies and provides insights for future clinical management of oral squamous cell carcinoma.

【Objective】 To study the effects of gestational diabetes (GDM) on morphological structure of brain tissue and microribonucleotide (miRNA) expression profile in neonatal mice, and to provide a new research target for the prevention and treatment of abnormal neurodevelopment in GDM progeny. 【Methods】 The pregnant mice were divided into model group and control group,each group consisted of 10 mice. The model group mice established a GDM model by injecting streptozotocin to measure fasting blood glucose (FPG) and random blood glucose (GLU) at different times. Successful molded mice were randomly divided into model group A and model group C, and control mice were divided into control group B and control group D, with 5 mice in each group. The newborn mice in groups A and B were used for hippocampal tissue GeneChip detection and brain morphology structure observation, and group C and D newborn mice were used for qRT-PCR detection of hippocampus tissue expression differences to verify the differentially expressed genes of miRANs obtained by GeneChip screening. After giving birth, the neonatal mice were sacrificed by decapitation, and the brain tissue was dissected to observe the overall morphological structure. The structural changes of hippocampus were observed under HE chromogenic microscope. The Agilent mouse miRNA oligonucleotide gene chip was used to detect the miRNA expression profile of mouse hippocampus, screen differential miRNAs and predict their target genes, and conduct GO analysis and signal transduction pathway analysis of target genes. The relative expression levels of the screened miRNAs were verified by qRT-PCR. 【Results】 Compared with the control group, the GLU increased significantly from the 3rd day after drug administration in the model group (P<0.01). Macroscopic observation of control group B mice had normal brain morphology and structure, smooth appearance, clear gyrus, close arrangement of hippocampus cell structure, uniform staining and complete structure; in model group A, the number of hippocampus cells decreased, loose arrangement and deep staining. In the initial screen of miRNA microarray, there were 11 differentially expressed miRNAs between control and model groups, all of which were downregulated miRNAs, including let-7b-5p、miR-130b-3p、miR-181c-5p、miR-181d-5p、miR-3099-3p、miR-3470a、miR-3473a、miR-3473b、miR-500-3p、miR-532-5p、miR-7047-5p(P<0.05). Two miRNAs (miR-3473b, miR-7047-75p) and 5 target genes (MAPK3, MAPK11, MAPK14, CALM3, AKT3). The relative expression of miR-3473b and miR-7047-5p in model group C were lower than that in control group D (t=19.13 and 6.24, P<0.05), and the validation results were consistent with the microarray test results. 【Conclusion】 Compared with the offspring of normal pregnant mice, GDM offspring mice have abnormal development of brain structure and damage of hippocampal nerve cells, and there are a large number of abnormal expression of miRNAs in hippocampal tissue. Differentially expressed miRNAs can be used as research targets for prevention and treatment of GDM offspring neurodevelopmental abnormalities.

〓 Objectives: To analyze the pathological and clinical features of nasal respiratory epithelial adenomatoid hamartoma（REAH）, and summarize the diagnostic points, to improve the experience of diagnosis and treatment. Methods:The clinical data of 16 patients with REAH were analyzed retrospectively. The clinical manifestations, pathological features, imaging features, surgical treatment and prognosis were summarized. Results:16 cases of REAH were studied, 10 cases（62.50%） were associated with sinusitis, 1 case（6.25%） was associated with inverted papilloma, 1 case（6.25%） was associated with hemangioma. 5 cases（31.25%） had a history of nasal sinus surgery, including 1 case with 3 times of nasal sinus surgery, 1 case with 2 times of nasal sinus surgery, 3 cases with 1 time of nasal sinus surgery; 10 cases（62.50%） occurred in the bilateral olfactory cleft, 2 cases（12.50%） in the unilateral olfactory cleft, 3 cases（18.75%） in the unilateral middle turbinate, 1 case（6.25%） in the nasopharynx. All 16 patients were pathologically diagnosed as REAH. In the patients with lesions located in bilateral olfactory fissures, symmetrical widening of olfactory fissures and lateral displacement of middle turbinate were observed on preoperative sinus CT. The average width of bilateral olfactory fissures was （9.9±2.70） mm. The ratio of wide to narrow olfactory cleft was 1.21 ± 0.19. There was no significant difference in Lund-Mackay score between the two sides（P>0.05）. All patients underwent surgery under general anesthesia and nasal endoscopy. The follow-up period ranged from 1 to 66 months, and no recurrence occurred. Conclusion:Preoperative diagnosis of REAH is facilitated by the combination of clinical manifestations and endoscopic and imaging features. Endoscopic complete resection can achieve a good therapeutic effect.
Humans ; Nasal Polyps/complications* ; Retrospective Studies ; Paranasal Sinuses/pathology* ; Adenoma ; Endoscopy/methods* ; Hamartoma/surgery*

The clinical data of a child with perianal necrotizing fasciitis admitted to the Department of Pedia-trics of Guangzhou First People′s Hospital were retrospectively analyzed.The child, girl, more than 5 months old, the clinical features of the onset of fever and diarrhea, only 10 days after the onset, the child′s skin progressed from redness and swelling to perianal skin and soft tissue ulcers, fat liquefaction, visible rectum exposure.After surgical incision, thorough debridement and drainage and selection of sensitive antibiotics, the child recovered and was discharged.Perianal necrotizing fasciitis is a rare necrotizing soft tissue infection caused by a variety of bacterial infections.Because its early performance is difficult to distinguish, the symptoms are serious, and the mortality rate is high.It should been pain attention in clinical work.

Objective To investigate the bacterial resistance profile of clinical isolates collected in the hospitals across Chuzhou in 2016. Methods Antimicrobial susceptibility testing was carried out by Kirby-Bauer method. The data were analyzed using WHONET 5.6 software according to CLSI 2015 breakpoints. Results A total of 5 465 clinical isolates were collected during 2016, of which gram positive organisms and gram negative organisms accounted for 25.9％ (1 416/5 465) and 74.1％ (4 049/5 465), respectively. Prevalence of MRSA was 37.6％ among S. aureus and the prevalence of MRCNS was 78.1％ in CNS. All Staphylococcus, E. faecalis and E. faecium isolates were sensitive to vancomycin and linezolid. The prevalence of extended spectrum-lactamases (ESBLs) positive strains was 51.2％ in E. coli, 23.4％ in Klebsiella spp. (K. pneumoniae and K. oxytoca), and 23.6％ in P. mirabilis isolates, respectively. The Enterobacteriaceae strains were highly sensitive to carbapenems. The percentage of the P. aeruginosa isolates resistant to the antimicrobials tested was lower than 30％. The percentage of the Acinetobacter strains resistant to meropenem and imipenem was 65.6％ and 67.4％, respectively. Conclusions The situation of antibiotic resistance is still very serious, especially multi-drug or pan-drug resistant strains, which is of great concern.

Objective To analyze the diagnostic value of endoscopic ultrasonography(EUS)for staging of early gastric cancer(EGC)and its influential factors. Methods Clinical information of 120 EGC patients admitted from February 2009 to January 2016 was reviewed. Diagnostic accuracy and the influencing factors of EUS for the invasive depth were analyzed by comparing the results of preoperative EUS and the pathology. Results Thirty-six patients were over-staged by EUS,and 10 patients were under-staged among 120 EGC patients. The accuracy, sensitivity, specificity of EUS for the submucosal invasion were 61.67%(74/120),58.33%(14/24),62.50%(60/96)respectively. The accuracy, sensitivity and specificity for protruded EGCs(Type I)diagnosis were 74.36%(29/39), 50.00%(6/12), 85.19%(23/27) respectively;these three variables were 59.02%(36/61),83.33%(5/6),56.36%(31/55)respectively for flat EGCs(Type Ⅱ), and 45.00%(9/20), 50.00%(3/6), 42.86%(6/14)respectively for excavated EGCs(Type Ⅲ). The univariate factor results showed that differentiated degree, location and endoscopic morphology of the tumor were possible influential factors for over-stage. Multivariate factor results showed that flat type(OR=3.667,95%CI:1.086-12.386,P<0.05)and excavated type(OR=6.552,95%CI:1.421-30.218,P<0.05)were independent risk factors. Gender,age and tumor maximum diameter were not factors influencing the diagnostic accuracy of EUS. Conclusion The EUS shows higher clinical value for diagnosing the invasive depth in EGC. Tumor differentiated degree, location and endoscopic morphology may be the influencing factors for diagnostic accuracy of EUS. Flat type and excavated type may lead to over-staging.

Objective To investigate the effect of dexmedetomidine (Dex)combined with ischemic preconditioning on liver ischemic reperfusion injury in rats in order to explore its possible mechanism. Methods Sixty healthy male SD rats weighing (251 ±18)g,were randomly (random number)divided into five groups (n =12 in each):sham-operation group (Group S:operation without ischemia), ischemia-reperfusion group (Group IR:hepatic pedicle occlusion for 30 min and reperfusion for 6 h), dexmedetomidine preconditioning group (Group Dex: dexmedetomidine 25 μg/kg was given intra-peritoneally at 30 min before operation),ischemic preconditioning group (Group IP:10 min ischemia,10 min reperfusion,followed by hepatic IR)and Dex combined with ischemic preconditioning group (Group Dex +IP:Dex 25μg/kg was given intra-peritoneally at 30 min befor operation,10 min ischemia and 10 min reperfusion was given followed by hepatic IR).The hepatic inflow of blood stream was occluded for 30 min by Pringle maneuver to establish hepatic ischemic reperfusion injury (HIRI)rat model.At the end of reperfusion for 6 h,the concentration of ALT,AST and LDH (lactate dehydrogenase)in serum were measured.The liver histological changes were examined after HE staining.The liver cell apoptosis were examined by TUNEL. The expression of heme oxygenase-1 were examined by Westeren blot and immunohistochemistry.H2 O2 and GSH (r-glutamylcysteinylglycine ) in liver tissue were detected by spectrophotometer.Differences among the groups were analyzed by one-way analysis of variance (ANOVA) and Student-Newman-Keul test by using SPSS version 17.0 software.Differences were considered significant at P <0.05.Results Serum concentrations of ALT,AST and LDH in group IR,Dex,IP and Dex +IP were significantly higher than those in group S (P =0.000).And those biomarkers in group Dex,IP and Dex +IP,were significantly lower than those in group IR (P =0.000).Furthermore,those biomarkers in group Dex +IP,were significantly lower than those in group Dex and IP (P =0.000).There were no significant difference in the serum concentrations of ALT and AST between group Dex and IP (P =0.550, 0.771),and the serum level of LDH in group Dex was significantly lower than that in group IP (P =0.000).The liver histopathological score and apoptosis index were the lowest in group S and the highest in group IR,and those in group Dex and group IP were significantly lower than those in group IR (P =0.000),and those in group Dex +IP were significantly lower than those in group Dex and group IP (P =0.000),and there were no significant difference between group Dex and IP (P =0.704,0.661 ).The expression score of HO-1 was the lowest in group S and the highest in group Dex +IP,and that in group Dex and group IP was significantly lower than that in group Dex +IP (P =0.000,0.002),and that in group IR was significantly lower than that in group Dex and group IP (P =0.000),and there was no significant difference between group Dex and IP (P =0.099).In respect of H2 O2 level and GSH level in liver tissue, compared with group S,the H2 O2 levels in groups IR,Dex,IP and Dex +IP were significantly higher (P=0.000,0.000,0.000,0.001)while the GSH levels were significantly lower (P =0.000).Compared with group IR,the H2 O2 level in group Dex,IP and Dex +IP was significantly lower than that in group IR while the GSH level was significantly higher (P =0.000 ).The H2 O2 level in group Dex +IP was significantly lower than that in group Dex and IP while the GSH level was significantly higher (P =0.000).There were no significant difference between group Dex and IP (P =0.480,0.667).Conclusions Both of dexmedetomidine and ischemic preconditioning can protect liver from ischemia reperfusion injury in rats to some extent,and the combined application of two gives better effects,which is attributed to the increasing expression of HO-1 to a certain extent.

Congenital hypertrophic pyloric stenosis(CHPS)is a common gastrointestinal congenital mal-formation in neonate and small infants.Pyloromyotomy is an effective method for treatment of CHPS,including several methods.Traditional open pyloromyotomy for the patient's body injury is serious,such as accident of an-esthesia,postoperative infection,skin scar;laparoscopic pyloromyotomy can cause the pylorus muscle incision uncomplete,invasive operation damage,etc.Endoscopic pyloromyotomy for neonatal has some advantages:a lit-tle injury,no scars,simple operation,less complications,quicker recovery of feeding.Endoscopic mucosal pyloro-myotomy may be a new method of treatment,needing further exploration and research.