Objective:To investigate mevalonic acid(MEV)on reversing the antitumor effects of fluvastatin sodium(FS)on tongue squamous cell carcinoma(TSCC)cells.Methods:TSCC HSC-4 cells were treated with different concentrations of FS and MEV re-spectively or in combination.Cell counting kit-8,flow cytometry,wound healing,immunofluorescence and western blotting assays were conducted to examine cell proliferation,apoptosis and migration capacities,as well as the expression levels of Ras homolog family member A(RHOA),tissue factor(TF)and B-cell lymphoma-2-associated X(BAX)proteins,respectively.Results:FS inhibited HSC-4 cell proliferation and migration,decreased the expression of RHOA and TF,and increased BAX expression.MEV reversed the above antitumor effects of FS and promoted intracellular RHOA and TF expression.Conclusion:MEV reverses the antitumor effects of FS on HSC-4 cells in vitro.

Objective To investigate the expression of HOXB4 gene in patients with myelodysplastic syn-dromes(MDS)and its clinical significance in disease progression.Methods mRNA expression of HOXB4 gene in bone marrow mononuclear cells was detected by real-time fluorescence quantitative PCR(RT-qPCR),and the difference in HOXB4 expression was compared between 49 patients with MDS(MDS group)and 35 patients without MDS(group C).The relationship of mRNA expression of HOXB4 with disease characteristics and clinical prognosis was explored in MDS patients.Results mRNA expression level of HOXB4 gene was higher in MDS group than that in group C(P＜0.05).The patients were divided into a high-and a low-expression group according to the median expression level of HOXB4.Leukocyte count was lower in the high-expression group in the low-expression group at the time of initial diagnosis.The proportion of patients with subtypes of primitive cellular hyperplasia,poor prognostic staging and leukemic transformation was higher in the high-expression group than in the low-expression group.Conclusions mRNA expression level of HOXB4 gene has certain relation with AML transformation in MDS patients.

BACKGROUND:In recent years,increasing studies have shown that low-intensity pulsed ultrasound can promote the healing of acute tendon injuries,but the specific mechanism is still unclear. OBJECTIVE:To observe the effect of low-intensity pulsed ultrasound on early angiogenesis after acute tendon injury,and to detect the regulatory relationship of low-intensity pulsed ultrasound with vascular endothelial growth factor-related signaling pathways,so as to reveal its potential mechanism of action. METHODS:Animal models of acute Achilles tendon injury were established using local injection of type I collagenase for 3 days in SPF male Sprague-Dawley rats aged 8-12 weeks,and were then randomly divided into ultrasound group and control group.In the ultrasound group,low-intensity pulsed ultrasound was treated daily with a small ultrasonic probe with an effective radiation area of 1 cm2 perpendicular to the Achilles tendon.No intervention was performed in the control group.Ultrasound imaging examination was performed 2 weeks later to observe the early healing of the tendon.Hematoxylin-eosin staining and CD31 immunohistochemical staining were performed to observe the changes in the number of blood vessels in the tissues after 1 and 2 weeks of treatment.The expression of vascular endothelial growth factor-related signaling pathway molecules in Achilles tendon tissues was detected by western blot or qRT-PCR. RESULTS AND CONCLUSION:Compared with the control group,the Achilles tendon in the ultrasound group was more continuous,the echo intensity was lower and more uniform,and the tendon thickness was significantly reduced(P<0.05).Hematoxylin-eosin staining and CD31 immunohistochemical staining results showed that after 2 weeks of treatment,the number of new vessels in the ultrasound group was significantly increased compared with the control group(P<0.05).Western blot and qRT-PCR results showed that after 2 weeks of continuous ultrasound intervention,the protein or mRNA expressions of vascular endothelial growth factor,Yes-associated protein,angiopoietin-2 and cysteine-rich angiogenic inducer 61 in the Achilles tendon of the ultrasound group were significantly higher than those of the control group(P<0.05).These finding indicate that low-intensity pulsed ultrasound significantly increases the number of blood vessels in the early stage of acute tendon injury and accelerate tendon healing by up-regulating vascular endothelial growth factor expression.

Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.

Neoadjuvant chemoradiotherapy is a part of the current standard treatment mode for locally advanced rectal cancer,which enables a certain proportion of patients to achieve complete tumor response,improving the surgical resection rate and anal retention rate,and then prolonging the disease-free survival period of patients.MRI is the preferred imaging examination to evaluate the efficacy of neoadjuvant therapy.With the development of functional MRI,quantitative parameters derived from different imaging principles can provide more biological information about tumors,improving the clinical application value of MRI.Multi-parameter MRI combining conventional MRI sequences and functional sequences can more comprehensively evaluate the efficacy of neoadjuvant therapy,which is conducive to developing individualized treatment plans for patients in clinical practice and realize precision medicine.

Objective:To explore the effect of NOD-like receptor thermal protein 3 ( NLRP3) knockout in γ-aminobutyric acid (GABA)-ergic neurons in the hippocampal CA1 area on improving cognitive dysfunction in mice after traumatic brain injury (TBI). Methods:Forty-eight healthy male NLRP3 flox/flox mice weighing 25-28 g were randomly divided into 4 groups ( n=12): sham-operated+control virus group (SV group), sham-operated+ NLRP3 specific knockout group (SG group), TBI+control virus group (TV group), TBI+ NLRP3 specific knockout group (TG group). TBI in the TV and TG groups was established by free-fall method, while surgical procedures such as scalp incision and cranial window opening without impact were given to the SV and SG groups. Adenovirus was injected into the hippocampal CA1 area of SG and TG groups 21 d before TBI to induce NLRP3 specific knockout in GABA-ergic neurons in the hippocampal CA1 area; empty virus was injected into the CA1 area of SV and TV groups. Cognitive function was evaluated using novel object recognition test 30 and 31 d after TBI, and learning and memory functions were assessed using Morris water maze test 32-36 d after TBI. Field potentials in the hippocampal CA1 area were recorded during novel object recognition 31 d after TBI. After behavioral tests, these mice were sacrificed. Immunofluorescent staining was used to detect the fluorescent intensity of microtubule-associated protein2 (MAP2), glutamic acid decarboxylase 67 (GAD67), and postsynaptic density protein 95 (PSD95) in the hippocampal CA1 area, as well as percentage of pyroptosis-associated inflammatory factor interleukin-18 (IL-18)/GAD67 double-positive neurons in total GAD67 positive neurons. Results:Compared with the SV and SG groups, the TV and TG groups had decreased novel object recognition index, decreased number of platform crossings during the experimental period, increased escape latency on day 3 and day 4 of the training period in Morris water maze test, decreased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, decreased fluorescent intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, increased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Compared with the TV group, the TG group had increased novel object recognition index, increased number of platform crossings in Morris water maze test, decreased escape latency during the training period, increased θ and γ oscillation power in the hippocampal CA1 area during novel object recognition, increased fluorescence intensity of MAP2, GAD67, and PSD95 in the hippocampal CA1 area, decreased percentage of IL-18/GAD67 double-positive neurons, with significant differences ( P<0.05). Conclusion:Specific inhibition of NLRP3 expression in GABA-ergic neurons in the hippocampal CA1 area can improve cognitive dysfunction in mice after TBI, whose mechanism may be related to inhibited GABA-ergic neuronal pyroptosis in the hippocampal CA1 area.

Polygoni multiflori radix praeparata is a processed product of Polygoni multiflori radix(Polygonum multiflorum Thunb.),and its main components include stilbene glycosides,anthraquinones,flavonoids,alkaloids,phenolic acids,etc.It has antioxidant,antianemic,anti-tumor,hypoglycemic,anti-inflammatory effects,etc,and is widely used in clinical practice.The processing technology is mainly stewinging with black bean juice,steaming,processing for 9 times and braising and simmering.After processing,the color deepens and the content of composition changes.By consulting domestic and foreign literature,the research on Polygoni multiflori radix praeparata is not comprehensive enough compared with Polygoni multiflori radix.Therefore,this paper mainly summarizes the processing technology,chemical composition and pharmacological activity of Polygoni multiflori radix preparata reported in the past 20 years,and provides a reference for further development of Polygoni multiflori radix preparata.

Pelvic floor dysfunction(PFD)is a common clinical problem that can lead to bladder and bowel dysfunction such as urinary incontinence,urinary retention,fecal incontinence,pelvic organ prolapse,and sexual dysfunction.Pelvic floor rehabilitation aids are essential tools in the treatment of PFD.However,there is limited understanding of the efficacy and mechanisms of these aids,and there is a lack of standardized guidelines for selecting appropriate aids for different types of PFD.To assist patients in choosing suitable pelvic floor rehabilitation aids to their needs,it is necessary to summarize the existing types,mechanisms,and applications of these aids.Based on their mechanisms and target functions,pelvic floor rehabilitation aids can be mainly categorized into 3 main types.The first type includes aids that improve pelvic floor function,such as vaginal dumbbells,vaginal tampons,and vaginal dilators,which aim to strengthen pelvic floor muscles and enhance the contractility of the urethral,vaginal,and anal sphincters,thereby improving incontinence symptoms.The second type consists of aids that mechanically block the outlet,such as pessaries,urethral plugs,incontinence pads,incontinence pants,anal plugs,and vaginal bowel control systems,which directly or indirectly prevent incontinence leakage.The third type includes aids that assist in outlet drainage,such as catheters and anal excreta collection devices,which help patients effectively expel urine,feces,and other waste materials,preventing incontinence leakage.By summarizing the existing pelvic floor rehabilitation aids,personalized guidance can be provided to patients with PFD,helping them select the appropriate aids for their rehabilitation needs.

Objective To establish an immortalized tree shrew corneal stromal cells(CSCs)line and to study its response to virus infection.Methods Primary tree shrew CSCs were isolated and cultured by the tissue block adhesion method.CSCs were then transfected with a lentivirus carrying the SV40T gene and monoclonal cells were selected for passage culture.The characteristics of the CSCs were investigated by morphological observation and compared with 40 generations until the 50 generations or more,immunofluorescence identification of vimentin and SV40T genes,karyotype examination,and cell proliferation curve.The CSCs were infected with herpes simplex virus-1(HSV-1)(McKrae strain),Zika virus(ZIKV,GZ01 strain),Dengue virus typeⅡ,and H1N1(PR8).Results The immortalized tree shrew CSCs after＞50 passages appeared spindle-shaped with good cell morphology and structure compared with 40 generations.Positive immunofluorescence expression of vimentin and SV40T genes.The cell growth curve showed that the cells were in logarithmic-phase growth on days 4～5 and grew vigorously.The number of chromosomes in the primary cells was stable at 62,while immortalized CSCs had 64 chromosomes at P21 and P56.The virus titer results showed that the immortalized tree shrew CSCs were sensitive to HSV-1(McKrae strain),ZIKV(GZ01 strain),Dengue virus typeⅡ,and H1N1(PR8),with virus titers of 1.32×105,5.62×106,2.69×107,and 7.76×104 CCID50/mL,respectively.Conclusions The immortalized tree shrew CSCs were established successfully,suggesting that this cell line is suitable for studies of the mechanisms of HSV,ZIKV,Dengue virus,and influenza A virus infection in relation to corneal diseases and antiviral drugs.

Objective:To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB).Methods:This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children′s Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children′s Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher′s exact test.Results:Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P=0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs.40% (25/62), P=0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion:ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.