Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

OBJECTIVES: To explore the association between GPSM2 expression level and gastric cancer progression and analyze the functional pathways and action mechanism of GPSM2. METHODS: We analyzed GPSM2 expression levels in gastric cancer tumors based on data from the GEPIA database and the clinical data of 109 patients. Public databases enrichment analysis were used to assess the impact of GPSM2 expression level on survival outcomes and the functional pathways and action mechanism of GPSM2. We further observed the effects of GPSM2 knockdown and overexpression on proliferation, migration and apoptosis of MGC803 cells using CCK-8 assay, colony formation assay, flow cytometry and immunoblotting and on the growth of MGC803 cell xenografts in nude mice. RESULTS: Bioinformatic analysis and immunohistochemical staining of the clinical specimens both revealed high GPSM2 expressions in gastric cancer (P<0.01). A high GPSM2 expression was significantly correlated with T3-4 stages, N2-3 stages, a carcinoembryonic antigen (CEA) level ≥5 μg/L, and a carbohydrate antigen (CA) 19-9 level ≥37 kU/L (P<0.05). Cox regression analysis identified high GPSM2 expression as an independent risk factor affecting 5-year survival of the patients (P<0.05). Gene ontology (GO) analysis suggested that GPSM2 was involved in cell cycle regulation. In MGC803 cells, GPSM2 overexpression significantly promoted cell proliferation and G1/S transition and xenograft growth in nude mice. KEGG pathway enrichment analysis indicated that GPSM2 executed its biological functions by regulating the p53 signaling pathway, which was confirmed by the results of immunoblotting experiments showing suppression of p53 signaling pathway activity in GPSM2-over expressing MGC803 cells. CONCLUSIONS GPSM2 is highly expressed in gastric cancer to affect patient prognosis by promoting tumor cell proliferation and G1/S transition possibly via inhibiting the p53 pathway.
Stomach Neoplasms/metabolism* ; Humans ; Cell Proliferation ; Prognosis ; Animals ; Mice, Nude ; Cell Line, Tumor ; Mice ; Apoptosis ; Tumor Suppressor Protein p53/metabolism* ; Cell Movement

Objective:To evaluate the safety and efficacy of ultrasound-guided percutaneous negative pressure suction and minimally invasive rotatory excision technique for the treatment of complex encapsulated lesions.Methods:A total of 48 patients(48 lesions) with complex encapsulated lesions who underwent ultrasound-guided percutaneous negative pressure suction and minimally invasive rotatory excision technique at Xi′an Chest Hospital from January to October 2023 were retrospectively enrolled, including 39 cases of encapsulated abscess, 7 cases of encapsulated effusion, and 2 cases of encapsulated haematoma; the distribution of the bacterial flora of the abscesses were as follows: 24 cases of tuberculous abscess, 14 cases of bacterial abscess, 1 case of bacterial combined bacterial-fungal abscess, and 7 cases of encapsulated effusion were tuberculous pleurisy, and the clinical data were analysed retrospectively. The maximum upper and lower diameters, right and left diameters, and anterior and posterior diameters of the lesions were measured by ultrasound before and after the operation. The patients′ various biochemical indicators (C-reactive protein, white blood cell count, neutrophil count, erythrocyte sedimentation rate) were detected. The intraoperative and postoperative complications, postoperative outcomes, and postoperative clinical symptoms were recorded.Results:Of the 48 patients, 39 were cured and discharged after negative pressure suction and rotatory excision technique, and 9 patients were cured and discharged after surgical incision and drainage of the lesions. The overall effective rate of negative pressure suction and rotatory excision treatment reached 81.25%, and the average number of days of tube placement was (11.81±7.22) days, and the average number of days of follow-up was (35.77±19.39) days. Compared with preoperative values, the upper and lower diameters, the left and right diameters, and the anterior and posterior diameters of the lesions were all reduced after operation [5.80 (4.95, 7.95)cm vs 8.00 (6.00, 11.82)cm, 4.00 (3.25, 5.00)cm vs 5.85 (4.52, 7.65)cm, 1.80 (1.00, 2.90)cm vs 3.40 (2.50, 6.15)cm, all P<0.01]; and postoperative C-reactive protein, white blood cell count and neutrophil count all decreased (all P<0.05). Before operation there were 31 cases of local swelling, 16 cases of pain, 12 cases of activity limitation, 12 cases of fever, 7 cases of chest tightness, and 6 cases of shortness of breath, and during postoperative follow-up, there were 4 cases of local swelling, 5 cases of pain, and 4 cases of activity limitation. The symptoms of fever, chest tightness, and shortness of breath all disappeared, and there was a statistically significant difference between preoperation and postoperation (all P<0.05). There were no adverse events or complications associated with the intraoperative and postoperative follow-up of negative pressure suction and rotatory excision treatment. Conclusions:Ultrasound-guided percutaneous negative pressure suction and invasive rotatory excision technique for the treatment of complex encapsulated lesions can significantly reduce lesion size, reduce inflammatory response and improve patient symptoms, which is a safe, effective and minimally invasive technique.

Objective To explore clinical effect of different intervertebral fusion devices(cage)in treating postoperative recurrent lumbar disc herniation(LDH).Methods One hundred and forty-two LDH patients with recurrence after simple in-tervertebral disc nucleus pulpoideectomy from January 2019 to January 2021 were retrospectively analyzed.All patients were treated with combined underchannel fixation and interbody fusion and divided into a single anatomical group,two-anatomical group and a single banana group according to types and numbers of implanted cage.There were 51 patients in a single anatom-ical group,included 29 males and 22 females,aged from 39 to 65 years old with an average of(53.74±5.68)years old;body mass index(BMI)ranged from 18.62 to 28.13 kg·m-2 with an average of(22.08±2.15)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 4.0 years with an average of(2.7±0.8)years;5 patients with L3,4,35 patients with L4,5 and 11 patients with L5S1;a single anatomical cage was implanted.There were 46 patients in two-anatomical group,included 25 males and 21 females,aged from 37 to 66 years old with an average of(54.52±6.02)years old;BMI ranged from 18.25 to 28.44 kg· m-2 with an average of(21.74±1.83)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of(2.7±0.9)years;4 patients with L3,4,32 patients with L4,5 and 10 patients with L5S1;two-anatomical cages were im-planted.There were 45 patients in a single banana group,included 22 males and 23 females,aged from 38 to 65 years old with an average of(54.49±6.45)years old;BMI ranged from 18.85 to 28.20 kg·m-2with an average of(21.63±1.59)kg·m-2;the interval between operation and recurrence ranged from 0.5 to 5.0 years with an average of(2.6±1.0)years;3 patients with L3,4,36 patients with L4,5 and 16 patients with L5S1;a single banana cage was implanted.Operation time,intraoperative blood loss,incision length,postoperative incision drainage volume,hospital stay and complications among 3 groups were observed and compared.The height of intervertebral space before and after operation,curvature of lordosis and the postoperative interverte-bral fusion were compared.Visual analogue scale(VAS)and Oswestry disability index(ODI)were used to evaluate degree of lumbar pain and lumbar function before operation,1 and 6 months after operation,respectively.Results All patients among 3 groups were followed up at least 6 months,and no cases were fell out.There were no significant difference in operation time,in-traoperative blood loss,incision length,postoperative incision drainage volume and hospital stay among 3 groups(P＞0.05).At 6 months after operation,the height of intervertebral space in two-anatomical group and a single group were[(11.08±1.78)mm,(10.95±1.62)mm],curvature of lordosis were[(12.05±1.86)°,(11.63±1.57)°],which were higher than those in a sin-gle dissection group(10.14±1.54)mm,(10.92±1.45)°,and the difference were statistically significant(P＜0.05).The inter-body fusion rate between two-anatomical and a banana group(95.65％,95.56％)were higher than that in a single anatomical group(78.43％)at 6 months after operation(P＜0.05).VAS and ODI of lumbar among 3 groups were decreased at 1 and 6 months after operation(P＜0.05).There was no significant difference in complications among 3 groups(P＞0.05).Conclusion The three fusion devices could achieve significant results in treating postoperative recurrence of LDH,but the implantation of two-anatomical cage and a single banana cage are more helpful to maintain the height of intervertebral space and lordosis cur-vature of patients with postoperative recurrence of LDH,and obtain good intervertebral fusion results.

Objective To investigate the effect and potential mechanisms of α-cyperone(CYP)on Crohn's disease(CD)-like colitis induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS)in mice.Methods The mice were randomly and evenly divided into wild type(WT),TNBS,CYP and 5-aminosalicylic acid(5-ASA)groups,with 10 mice in each group.The symptoms of enteritis,the function and structure of the intestinal barrier,and the expression levels of inflammatory factors,including interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and gamma-interferon(IFN-γ),in the colon were assessed.The lipopolysaccharide(LPS)-induced inflammation model of Caco2 cells was constructed and the cells were divided into Control,LPS and LPS+CYP groups.The expression levels of tight junction protein and inflammatory factors in each group were assessed.Gene Ontology(GO)functional enrichment analysis was conducted to predict the possible pathways of action and potential molecular mechanisms of CYP,and to verify them in vivo and in vitro.Results In the in vivo study,compared with those of the TNBS group,the body mass and colon length of mice in the CYP group and the 5-ASA group were significantly increased,while the disease activity scores and histological inflammation scores were significantly decreased(P＜0.05).The level of lucifcein-glucan isothiocyanate and the bacterial translocation rate(in the liver,the spleen,and mesenteric lymph nodes)were significantly decreased,while the transepithelial electric resistance(TEER)value and the expression levels of zonula occluden protein-1(ZO-1),and claudin-1 were significantly increased(P＜0.05).The expression of inflammatory factors was significantly decreased(P＜0.05).In the in vitro study,compared with those of the LPS group,the TEER value and the expression of ZO-1 and claudin-1 in the Caco2 cells in the LPS+CYP group were significantly increased(P＜0.05).The expression of inflammatory factors was significantly decreased(P＜0.05).Enrichment analysis showed that CYP was correlated with inflammatory response(P＜0.001).Western blot results showed that CYP could significantly reduce the expression of key proteins in toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway in vivo and in vitro(P＜0.05).Conclusion CYP may protect the intestinal barrier by antagonizing the inflammatory response of the intestinal mucosa through regulating the expression of the TLR4/NF-κB signaling pathway,thereby alleviating TNBS-induced CD-like colitis in mice.

To explore the causes and solutions of common faults in the operation of the of Yi Kang A1 series lower limb intelligent feedback training system,and to conduct a comparative study on the structural principle and fault maintenance of the two models.Through the analysis of equipment spasm error,USB disconnection error,inability to access the game,black screen of display,splash screen or no display,standing numerical deviation and proprioceptive numerical deviation and other failure cases,gradually investigate software setting,hardware inspection,sensitivity setting,USB connection testing,game file testing,VGA interface testing,angle sensor testing and pressure sensor testing,etc.,to handle and solve the faults in a timely manner to ensure the equipment in good condition,to improve the normal use rate of equipment and ensure the timely rehabilitation of patients.

Objective The study was conducted to investigate the expression of protein-L-isoaspartate(D-aspartate)O-methyltransferase(PCMT1)in gastric cancer and its effect on the prognosis,and to analyze its potential mechanism.Methods UALCAN,a cancer data analysis platform,was used to conduct online analysis of the expression of PCMT1 in gastric cancer tissues.Through the Database for Annotation,Visualization and Integrated Discovery(DAVID),Gene Ontology(GO)annotation and signaling pathway enrichment by Kyoto Encyclopedia of Genes and Genomes(KEGG)were performed to analyze the possible functions and signaling pathways.A total of 120 patients who underwent radical gastrectomy for gastric cancer between January 2014 and December 2017 in our hospital were enrolled for the study.Immunohistochemical staining was performed to determine the expression of PCMT1 and Ki67 in gastric cancer tissues.Cox regression,Kaplan-Meier curve,and receiver operating characteristic(ROC)curves were used for prognostic analysis of 5-year survival in gastric cancer patients after surgery.Lentivirus was used to construct PCMT1-interfering or PCMT1-overexpressing vectors,which were then used to transfect human gastric cancer cell lines of MGC-803 and HGC-27 cells.The interfering empty vector(sh-NC)group,the interfering PCMT1 vector(sh-PCMT1)group,the overexpressing empty vector(LV-Vec)group,and the overexpressing PCMT1 vector(LV-PCMT1)group were set up.Western blot was performed to determine the protein expression levels of PCMT1,CyclinB1,and CDC20.CCK-8 assay was performed to measure the proliferation of gastric cancer cells.Flow cytometry was performed to determine the cell cycle.MGC-803 cells were injected in four groups of nude mice to construct a subcutaneous xenograft tumor model,with three nude mice in each group.The body mass of the nude mice was measured.The nude mice were sacrificed after 14 days and the tumor volume was monitored.The expression levels of CyclinB1 and CDC20 proteins in the tumor tissues were determined by Western blot assay.Results Analysis with UALCAN showed that PCMT1 was highly expressed in gastric cancer tissues.Moreover,elevated expression was found in gastric tumor tissues of different pathological stages and grades and those with lymph node metastasis(P＜0.05).GO and KEGG enrichment analyses showed that PCMT1 was mainly involved in the signal regulation of mitosis,spindle assembly checkpoints,and cell cycle.The immunohistochemical results showed that PCMT1 and Ki67 were highly expressed in gastric cancer tissues and that they were positively correlated with each other(P＜0.05).Cox multivariate analysis showed that high PCMT1 expression(hazard ratio[HR]=2.921,95％confidence interval[CI]:1.628-5.239)was one of the independent risk factors affecting the 5-year survival rate of gastric cancer patients after surgery.Kaplan-Meier curve showed that patients with high PCMT1 expression had a lower 5-year survival after surgery(16.7％,HR=4.651,95％CI:2.846-7.601)than patients with low PCMT1 expression(70.0％,HR=0.215,95％CI:0.132-0.351)did.The ROC curve showed that PCMT1 had an area under the curve(AUC)of 0.764(95％CI:0.674-0.854)for predicting 5-year patient survival after surgery.Western blot results showed that lentiviral interference or overexpression of PCMT1 cell lines was successfully constructed.The results of CCK-8 showed that the proliferative ability of MGC-803 and HGC-27 cells was weakened with the downregulation of PCMT1,and the overexpression of PCMT1 promoted cell proliferation(P＜0.05).With the interference of PCMT1,the expression of CDC20 protein was decreased,the expression of CyclinB1 protein was increased,and the cell cycle was arrested in the G2/M phase.In contrast,the overexpression of PCMT1 led to the opposite trends(P＜0.05).In the sh-PCMT1 group,the tumor volume and mass were decreased and the expression of CDC20 protein was decreased and the expression of CyclinB1 protein was increased in the tumor tissues of the nude mice(P＜0.05,compared with those of the sh-NC group.In contrast,the LV-PCMT1 group showed the opposite trends(P＜0.05,compared with those of the LV-Vec group).Conclusion The high expression of PCMT1 in gastric cancer tissues is associated with poor prognosis in patients and may affect tumor cell malignant proliferation via regulating spindle checkpoints in the process of mitosis.

Objective: To analyze the clinical epidemiological characteristics including composition of pathogens , clinical characteristics, and disease prognosis acute bacterial meningitis (ABM) in Chinese children. Methods: A retrospective analysis was performed on the clinical and laboratory data of 1 610 children <15 years of age with ABM in 33 tertiary hospitals in China from January 2019 to December 2020. Patients were divided into different groups according to age,<28 days group, 28 days to <3 months group, 3 months to <1 year group, 1-<5 years of age group, 5-<15 years of age group; etiology confirmed group and clinically diagnosed group according to etiology diagnosis. Non-numeric variables were analyzed with the Chi-square test or Fisher's exact test, while non-normal distrituction numeric variables were compared with nonparametric test. Results: Among 1 610 children with ABM, 955 were male and 650 were female (5 cases were not provided with gender information), and the age of onset was 1.5 (0.5, 5.5) months. There were 588 cases age from <28 days, 462 cases age from 28 days to <3 months, 302 cases age from 3 months to <1 year of age group, 156 cases in the 1-<5 years of age and 101 cases in the 5-<15 years of age. The detection rates were 38.8% (95/245) and 31.5% (70/222) of Escherichia coli and 27.8% (68/245) and 35.1% (78/222) of Streptococcus agalactiae in infants younger than 28 days of age and 28 days to 3 months of age; the detection rates of Streptococcus pneumonia, Escherichia coli, and Streptococcus agalactiae were 34.3% (61/178), 14.0% (25/178) and 13.5% (24/178) in the 3 months of age to <1 year of age group; the dominant pathogens were Streptococcus pneumoniae and the detection rate were 67.9% (74/109) and 44.4% (16/36) in the 1-<5 years of age and 5-<15 years of age . There were 9.7% (19/195) strains of Escherichia coli producing ultra-broad-spectrum β-lactamases. The positive rates of cerebrospinal fluid (CSF) culture and blood culture were 32.2% (515/1 598) and 25.0% (400/1 598), while 38.2% (126/330)and 25.3% (21/83) in CSF metagenomics next generation sequencing and Streptococcus pneumoniae antigen detection. There were 4.3% (32/790) cases of which CSF white blood cell counts were normal in etiology confirmed group. Among 1 610 children with ABM, main intracranial imaging complications were subdural effusion and (or) empyema in 349 cases (21.7%), hydrocephalus in 233 cases (14.5%), brain abscess in 178 cases (11.1%), and other cerebrovascular diseases, including encephalomalacia, cerebral infarction, and encephalatrophy, in 174 cases (10.8%). Among the 166 cases (10.3%) with unfavorable outcome, 32 cases (2.0%) died among whom 24 cases died before 1 year of age, and 37 cases (2.3%) had recurrence among whom 25 cases had recurrence within 3 weeks. The incidences of subdural effusion and (or) empyema, brain abscess and ependymitis in the etiology confirmed group were significantly higher than those in the clinically diagnosed group (26.2% (207/790) vs. 17.3% (142/820), 13.0% (103/790) vs. 9.1% (75/820), 4.6% (36/790) vs. 2.7% (22/820), χ²=18.71, 6.20, 4.07, all P<0.05), but there was no significant difference in the unfavorable outcomes, mortility, and recurrence between these 2 groups (all P>0.05). Conclusions: The onset age of ABM in children is usually within 1 year of age, especially <3 months. The common pathogens in infants <3 months of age are Escherichia coli and Streptococcus agalactiae, and the dominant pathogen in infant ≥3 months is Streptococcus pneumoniae. Subdural effusion and (or) empyema and hydrocephalus are common complications. ABM should not be excluded even if CSF white blood cell counts is within normal range. Standardized bacteriological examination should be paid more attention to increase the pathogenic detection rate. Non-culture CSF detection methods may facilitate the pathogenic diagnosis.
Adolescent ; Brain Abscess ; Child ; Child, Preschool ; Escherichia coli ; Female ; Humans ; Hydrocephalus ; Infant ; Infant, Newborn ; Male ; Meningitis, Bacterial/epidemiology* ; Retrospective Studies ; Streptococcus agalactiae ; Streptococcus pneumoniae ; Subdural Effusion ; beta-Lactamases

Acupuncture Points ; Acupuncture Therapy ; Depression/therapy* ; Humans ; Interleukin-2 ; Neoplasms/therapy* ; Sertraline ; Treatment Outcome

OBJECTIVE Cerebral ischemia or ischemic stroke is due to insufficient blood supply to the brain, which causes hypoxia or ischemia in some areas. This work aimed to quantify the minerals and heavy metals in Qishiwei Zhenzhu pill in vivo and in vitro, analyze its effect on the types and abundance of intestinal flora, and study its mechanism on inflammation and apoptosis pathways as a treatment for cerebral ischemia. METHODS Microwave digestion and induc?tively coupled plasma mass spectrometry (ICP-MS) were used to determine the minerals and heavy metals in 10 batches of Qishiwei Zhenzhu pill in vitro. With the use of the middle cerebral artery obstruction (MCAO) model, ICP-MS was applied to determine the content of minerals and heavy metals in hepatic portal vein blood, abdominal aortic blood, brain, liver, kidney, hair, urine and feces at different time periods. On this model, the ileum, cecum, and colon tissues were tested for intestinal pathology, and 16S rRNA was used for sequencing. Species taxonomy, α diversity, and spe?cies microbial composition and structure analysis were also performed. Polymerase chain reaction and Western blotting were employed to determine the mRNA and protein expression of p38 MAPK, caspase-3, IL-1β and TNF-α in the isch?emic brain tissues of rats. RESULTS The average content of heavy metals in the 10 batches of Qishiwei Zhenzhu pill samples is in the descending order Hg>Cu>Pb. Significant differences in the metal elements are found among Qishiwei Zhenzhu pill from different manufacturers but not among the different batches of the same manufacturer. An extremely low content of heavy metals are absorbed into the blood or accumulated in the brain, liver, kidney, and other tissues. Stool is the main excretion route of minerals and heavy metals from Qishiwei Zhenzhu pill. This medicine helps repair the intestinal mucosa in MCAO rats. At the phylum level, it can regulate the abundance of Firmicutes and Proteobacteria in the intestinal flora of rats with cerebral ischemia. At the genus level, it can adjust the abundance of Escherichia Shigella. At the species level, it can adjust the abundance of Lactobacillus yoelii and Lactobacillus reuteri. Cluster classification results show that Qishiwei Zhenzhu pill can improve the intestinal flora of rats with cerebral ischemia, reduce the mRNA and protein expression of caspase-3 and IL-1βin rat brain tissues, and have a tendency to decrease the mRNA expres?sion of p38 MAPK and TNF-α. CONCLUSION Quantifying the minerals and heavy metals in Qishiwei Zhenzhu pill in vivo and in vitro will help improve their quality standards. Minerals and heavy metals are mainly excreted in feces, accumu?late in extremely low levels in various tissues, and do not damage the intestinal mucosa. The effective material basis of Qishiwei Zhenzhu pill in treating cerebral ischemia may be related to their Li, Cr, and Cd elements. These pills can improve the environment of intestinal flora, and their mechanism of treatment for cerebral ischemia may be related to the down-regulation of IL-1βinflammatory factor and inhibition of cell apoptosis.