OBJECTIVES: To observe the therapeutic effect of spermine in neonatal mouse models of severe hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) infection and explore its therapeutic mechanism in light of regulation of macrophage GBP5/NLRP3 inflammasome pathway. METHODS: Neonatal BALB/c mice (3-5 days old) were divided into control group, EV71 infection group and Spermine treatment group. The mice in the latter two groups received an intraperitoneal injection of 50 μL EV71 suspension (1×10⁶ TCID50 of EV71), followed 3 days later by intraperitoneal injection of 50 μL PBS or 100 μmol/L spermine. GBP5, NLRP3, CXCL10, and TNFSF10 expressions in heart, liver, lung and kidney tissues of the mice were detected using Western blotting and qPCR, and tissue pathologies and macrophage infiltration were assessed with HE staining and immunohistochemistry. In cultured THP-1 and RAW264.7 cells, the effects of EV71 infection, GBP5 siRNA transfection and treatment with spermine or eflornithine on GBP5, NLRP3, CXCL10, and TNFSF10 mRNA expressions were investigated using qPCR. RESULTS: In the neonatal mice, EV71 infection resulted in multiple organ damage, macrophage infiltration and activation of the GBP5/NLRP3 pathway, and spermine treatment significantly improved tissue injuries, reduced macrophage infiltration, and down-regulated the expressions of GBP5, NLRP3 and the inflammatory factors in the infected mice. In THP-1 and RAW264.7 cells, EV71 infection caused significant upregulation of GBP5, NLRP3, CXCL10, and TNFSF10 expressions, which were obviously lowered by spermine treatment. In THP-1 cells, treatment with eflornithine significantly suppressed the reduction of GBP5, NLRP3, CXCL10, and TNFSF10 expressions induced by GBP5 siRNA transfection. CONCLUSIONS Spermine suppressed EV71 infection-induced inflammatory responses by inhibiting GBP5-mediated NLRP3 inflammasome activation, suggesting a new strategy for treatment of severe HFMD.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Mice ; Macrophages/metabolism* ; Enterovirus A, Human ; Mice, Inbred BALB C ; Inflammasomes/metabolism* ; Spermine/therapeutic use* ; Animals, Newborn ; Humans ; Enterovirus Infections ; Hand, Foot and Mouth Disease/drug therapy* ; RAW 264.7 Cells ; Chemokine CXCL10/metabolism*

Objective To analyze the medication rules of traditional Chinese medicine in treating breast cancer based on real-world data mining.Methods Inpatients with breast cancer who received traditional Chinese medicine treatment at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from January 2017 to December 2021 were selected.Python 3.10 software was used to mine traditional Chinese medicine prescription data;SPSS 23.0 software was applied for descriptive analysis,and systematic cluster analysis was performed on high-frequency drugs.Results A total of 3026 consultation records of inpatients with breast cancer were collected.The main traditional Chinese medicine syndrome diagnosis of"predominantly liver depression and Qi stagnation"accounted for 60.94％of the total consultations.A total of 240 kinds of traditional Chinese medicine were used,with a cumulative frequency of 35 462 times.Among them,29 kinds of traditional Chinese medicine such as Danggui,Fuling,Baizhu,Chaihu had a cumulative usage frequency exceeding 300 times.Regarding the four natures of drugs,cold-natured(43.55％),warm-natured(30.05％),and neutral-natured(23.34％)drugs were predominant;In terms of five flavors,sweet(46.12％),bitter(30.91％),and pungent(20.02％)were the main ones.The most frequently used drugs were tonifying herbs(32.77％),followed by heat-clearing herbs(15.96％)and phlegm-resolving herbs(14.71％).Systematic cluster analysis yielded 7 groups of drug combinations.Conclusion In real-world clinical practice,traditional Chinese medicine for breast cancer mainly uses tonifying herbs,reflecting the traditional Chinese medicine principle of"strengthening healthy Qi and cultivating the root"in treating tumors.The four natures and five flavors of drugs follow syndrome differentiation and the combination of cold and heat.The clustered drug combinations have extensive therapeutic effects,covering various syndromes of breast cancer at different stages,which can provide a reference for clinical medication.

Objective To investigate the application effect of postural gravity traction combined with floss and titanium clip pulley external traction in endoscopic submucosal dissection(ESD)for early intestinal lesions.Methods A total of 100 patients with early colorectal lesions admitted to the Affiliated Hospital of Jiangsu University from January 2022 to September 2024 were selected as the research subjects and divided in-to the observation group and the control group,with 50 cases in each group.The control group underwent con-ventional intestinal ESD treatment,while the observation group used positional gravity traction combined with dental floss and titanium clips to form pulley external traction in ESD treatment.Clinical data including opera-tion time,number of submucosal injections,intraoperative blood loss,lesion resection effect,complication inci-dence,and hospital stay were compared between the two groups.Results The total operation time in the ob-servation group was shorter than that in the control group,and the total number of submucosal injections was less than that in the control group,with statistically significant differences(P<0.05).There were no signifi-cant differences in intraoperative blood loss,complete resection rate,complication incidence,en bloc resection rate,and hospital stay between the two groups(P>0.05).For lesions≤1 cm or>5 cm in size,there were no significant differences in operation time,complete resection rate and en bloc resection rate between the two groups(P>0.05).For lesions>1-3 cm or>3-5 cm in size and laterally spreading lesions,significant differences were observed in operation time,number of submucosal injections,complete resection rate,and en bloc resection rate between the two groups(P<0.05).For pedunculated polyps,there were no significant differences in the number of submucosal injections,complete resection rate and en bloc resection rate between the two groups(P>0.05),but the operation time differed significantly(P<0.05).Conclusion Postural gravity traction combined with dental floss and titanium clip to form pulley external traction is simple to oper-ate in ESD for early intestinal lesions.It can maintain a clear field of view,shorten operation time,reduce the incidence of complications,and is safe and effective.

Objective To explore the protective effect of L-carnitine on myocardial systolic dysfunction in sepsis and its underlying mechanism.Methods A mouse sepsis model was established by cecal ligation and puncture(CLP).Ten-week-old male SPF-grade C57BL/6 mice(body weight 20～30 g)were randomly divided into 5 groups via random number table:Sham group,Sepsis group,L-carnitine group,L-carnitine+Etomoxir(Eto)group,and Eto group.Echocardiography assessed cardiac function,ELISA measured serum creatine kinase isoenzyme MB(CK-MB)levels,and 72-hour survival rates were recorded to evaluate L-carnitine's effects on cardiac function.Cardiomyocytes were isolated,and a cell microtensiometer was used to detect cardiomyocyte contractile function and calcium transients.Myocardial tissues were collected from each group,and ELISA was used to determine the contents of triglyceride(TG),free fatty acid(FFA),and adenosine triphosphate(ATP).An in vitro sepsis model was constructed by stimulating HL-1 cardiomyocytes with lipopolysaccharide(LPS)for 12 hours,which was divided into 5 groups:control(CTRL)group,LPS group,L-carnitine group,L-carnitine+Eto group,and Eto group.ELISA was used to detect the contents of TG,FFA,and ATP as well as the activity of carnitine palmitoyltransferase 1A(CPT1A)in cardiomyocytes.A cellular energy metabolism analysis system was employed to measure fatty acid oxidation capacity,and Western blot was used to detect the protein expression of CPT1A in cardiomyocytes.BODIPY-FL-C16(green fluorescently labeled palmitic acid)was utilized to detect the distribution of fatty acids in the cytoplasm and mitochondria via immunofluorescence technology,thereby observing the ability of cells to transport fatty acids into mitochondria.Results Compared with the Sham group,cardiac function was significantly impaired in the Sepsis group,as evidenced by decreased ejection fraction and mean arterial pressure(P<0.05),along with elevated levels of the cardiac injury marker CK-MB(P<0.05).Treatment with L-carnitine significantly improved myocardial function,restored blood pressure in septic mice,and increased their survival rate from 12.50%to 81.25%(P<0.05).Compared with the Sham group,the contractile function and calcium transients of acutely isolated single cardiomyocytes were significantly reduced in the Sepsis group(P<0.05),while L-carnitine treatment remarkably restored the contractile function and calcium release capacity of septic cardiomyocytes(P<0.05).Both in vivo and in vitro experiments showed that TG and FFA levels were significantly increased(P<0.05),and ATP levels was significantly decreased(P<0.05)in the Sepsis and LPS groups—effects significantly reversed by L-carnitine treatment.Compared with the CTRL group,the basal oxidation rate and maximum oxidation capacity of fatty acids in cardiomyocytes of the LPS group were significantly reduced(P<0.05),and L-carnitine treatment notably improved these indicators.Compared with the CTRL group,the expression and activity of CPT1A in cardiomyocytes of the LPS group were significantly decreased(P<0.05),while L-carnitine treatment significantly increased the expression and activity of CPT1A(P<0.05).In LPS group cardiomyocytes,green fluorescently labeled palmitic acid primarily formed numerous granular/clumpy aggregates in the cytoplasm with minimal mitochondrial colocalization.In the L-carnitine group,the green fluorescent granules in the cytoplasm of cardiomyocytes were smaller,and colocalization with mitochondria was increased.However,the L-carnitine+Eto group exhibited similar phenomena to the LPS group.In addition,both in vivo and in vitro experiments demonstrated that treatment with the CPT1A inhibitor Eto reversed the effect of L-carnitine.Compared with the L-carnitine group,the ATP content in the L-carnitine+Eto group was significantly decreased(P<0.05),while the FFA content was significantly increased(P<0.05).Conclusion L-carnitine facilitates fatty acid entry into mitochondria for β-oxidation via a CPT1A-dependent mechanism,thereby ameliorating fatty acid oxidation dysfunction in septic cardiomyocytes and improving myocardial contractile function.

Objective To analyze the medication rules of traditional Chinese medicine in treating breast cancer based on real-world data mining.Methods Inpatients with breast cancer who received traditional Chinese medicine treatment at the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from January 2017 to December 2021 were selected.Python 3.10 software was used to mine traditional Chinese medicine prescription data;SPSS 23.0 software was applied for descriptive analysis,and systematic cluster analysis was performed on high-frequency drugs.Results A total of 3026 consultation records of inpatients with breast cancer were collected.The main traditional Chinese medicine syndrome diagnosis of"predominantly liver depression and Qi stagnation"accounted for 60.94％of the total consultations.A total of 240 kinds of traditional Chinese medicine were used,with a cumulative frequency of 35 462 times.Among them,29 kinds of traditional Chinese medicine such as Danggui,Fuling,Baizhu,Chaihu had a cumulative usage frequency exceeding 300 times.Regarding the four natures of drugs,cold-natured(43.55％),warm-natured(30.05％),and neutral-natured(23.34％)drugs were predominant;In terms of five flavors,sweet(46.12％),bitter(30.91％),and pungent(20.02％)were the main ones.The most frequently used drugs were tonifying herbs(32.77％),followed by heat-clearing herbs(15.96％)and phlegm-resolving herbs(14.71％).Systematic cluster analysis yielded 7 groups of drug combinations.Conclusion In real-world clinical practice,traditional Chinese medicine for breast cancer mainly uses tonifying herbs,reflecting the traditional Chinese medicine principle of"strengthening healthy Qi and cultivating the root"in treating tumors.The four natures and five flavors of drugs follow syndrome differentiation and the combination of cold and heat.The clustered drug combinations have extensive therapeutic effects,covering various syndromes of breast cancer at different stages,which can provide a reference for clinical medication.

Objective:To investigate the perioperative adverse events and complications of flow-diverter devices in the treatment of unruptured intracranial aneurysms.Methods:This is a retrospective case series study. The clinical and imaging data of 174 patients with unruptured intracranial aneurysms treated with flow-diverter devices in the Department of Neurointervention, Department of Neurology, the First Medical Center of Chinese People′s Liberation Army General Hospital from January 2020 to January 2024 were retrospectively analyzed. There were 63 males and 111 females, with an age of (53.9±11.4) years (range:23 to 76 years).The occurrence, development and outcome of perioperative complications and related adverse events during treatment were collected and analyzed. The degree of aneurysm embolization was evaluated using the O′Kelly-Marotta (OKM) grading system,with OKM grade C and D as successful occlusion.Results:A total of 187 flow-diverter devices (from 7 different brands) were implanted in 174 patients (with 294 aneurysms). Of these, 151 cases involved standalone stent embolization, 26 cases involved stent embolization combined with coil assistance, and 5 cases involved the use of two flow-diverter devices simultaneously. Twenty-nine cases (16.7%,29/174) suffered intraoperative adverse events, including 10 cases of poor stents deployment, 3 cases of stents migration into the aneurysm sac, 1 cases of abnormal guidewire movement, 4 cases of ischemic events. Complications occurred in 10 patients (5.7%, 10/174), and neurological deficits occurred in 5 patients (2.9%, 5/174). A total of 129 patients completed follow-up for more than 12 months after surgery. There were 117 aneurysms with OKM grade D and 22 with OKM grade C, showing a satisfactory healing rate of 77.7% (139/179).Conclusion:The effect of flow-diverter devices in the treatment of intracranial aneurysms is satisfactory, but complications and adverse events cannot be ignored, especially the relatively high incidence of perioperative adverse events, which requires neurointerventional physicians to be vigilant.

Objective:To evaluate the effectiveness of surgical methods for correcting pollybeak deformity in Chinese rhinoplasty.Methods:A retrospective chart review was conducted for patients who underwent pollybeak correction between January 2021 and December 2022 at the Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University. Individualized correction was tailored based on the etiology and severity of the nasal deformity of each patient, involving techniques such as resection of the anterior part of the nasal septum, reconstruction of nasal tip support, reconstruction of the middle part of the nasal vault, and excision of skin in the upper region of the nasal tip. A modified classification system for pollybeak deformity, the supratip fullness rating scale (SFRS), was developed to evaluate supratip fullness (0-3 points, with higher scores indicating more apparent deformity). The patients aesthetic outcomes were assessed by surgeons using the visual analogue scale (VAS) (0-10 points, with higher scores indicating more apparent deformity), and patient self-assessed using the rhinoplasty outcome evaluation (ROE) questionnaire (0-100 points, with higher scores indicating higher satisfaction). The measurement data of normal distribution was expressed as Mean±SD and analyzed by paired t-test; the measurement data of non-normal distribution was expressed as M( Q1, Q3) and analyzed by Wilcoxon signed rank test. Results:In a cohort study of 53 rhinoplasty patients (7 male, 46 female; age range 19-45 years, mean 29 years), comprising 15 primary and 38 secondary surgeries, nasal tip deformities were evaluated. Deformities were classified as mild (5 cases), moderate (25 cases), and severe (23 cases). Over a follow-up period of 6-17 months (mean 9.5 months), significant aesthetic improvements in the nasal tip region were observed. The SFRS scores decreased from 2(2, 3) preoperatively to 0(0, 0) postoperatively ( Z = -6.58, P < 0.001), and VAS scores decreased from 7.47±1.73 to 1.79±1.67 ( t = -25.61, P < 0.001). High patient satisfaction was indicated by a mean ROE score of 82.45±11.55. No significant complications, such as nasal tip ptosis, skin necrosis, or scar hyperplasia, were reported. Conclusion:Selecting an appropriate surgical method based on the severity and cause of pollybeak deformity can achieve satisfactory outcomes. Post-operative patients exhibit significant aesthetic improvement in the upper nasal tip area, resulting in high patient satisfaction.

Objective:To investigate the surgical effect of pedicled upper lip mucosal flap in repairing nasal septal mucosal defects after rhinoplasty.Methods:A retrospective analysis was performed from January 2016 to October 2022, the clinical data of patients with nasal septal mucosal defects after rhinoplasty were collected in the Department of Plastic and Aesthetic (Burn) Surgery at the Second Xiangya Hospital of Central South University. The pedicled upper lip mucosal flap was utilized for repair based on the patient’s medical history and wound condition. The pedicle of the flap was designed 1 cm adjacent to the frenulum of the upper lip, and an appropriate flap was incised based on the size of the wound, with dissection performed up to the superficial layer of the orbicularis oris muscle. The dissection establishes an upper lip tunnel that connects the gingival-buccal groove to the nasal cavity. The pedicled upper lip mucosal flap was elevated and transposed into the nasal cavity via the upper lip tunnel. The position of the flap was adjusted to ensure complete coverage and fixation of the nasal septal defect wound using 5-0 absorbable suture. The visual analogue scale (VAS) and the nasal obstruction symptom evaluation (NOSE) scale were utilized to facilitate patients’ satisfaction evaluation and assessment of nasal obstruction symptoms before surgery and at 6 months post-surgery. The VAS total score was 10 points, with higher scores indicating greater levels of patient satisfaction. The NOSE scale comprises of 5 items, each assigned a score ranging from 0 to 4, denoting absence of symptoms, very mild presence, moderate intensity, relatively severe manifestation, and highly severe indication respectively. The measurement data of VAS and NOSE scores before surgery and at 6 months post-surgery was expressed by Mean±SD, using paired t-test. The score distribution of the NOSE scale was represented by the number of cases, using Mann-Whitney U test. Results:The study included a total of 15 female patients, with an average age of (27.6±2.9) years (ranging from 23 to 33 years). Eleven cases presented with preoperative cartilage exposure, and the size of tissue defect ranged from 0.9 cm×0.5 cm to 1.5 cm×0.7 cm. Nine patients had a history of smoking. Skin grafting was performed in 9 patients, while nasal mucosal metastasis was observed in 8 patients. The dimensions of the flap varied from 4.0 cm×1.2 cm to 7.0 cm×1.5 cm. The postoperative recovery was satisfactory, with successful survival of the skin flaps and no occurrences of infection, hematoma, wound dehiscence, or flap necrosis. The average duration of follow-up was (8.2±2.1) months (ranging from 6 to 12 months). The postoperative VAS score (7.73±0.88) was significantly higher compared to the preoperative score (1.86±0.74) ( P<0.01). Additionally, the postoperative NOSE score (4.66±1.71) showed a significant decrease from the preoperative score (10.73±2.68), with a statistically significant difference ( P<0.01). Among them, after surgery items of stuffy or unbreathable nose (2 cases vs. 15 cases), nasal obstruction (1 case vs. 14 cases), and feeling that the nose was not enough to breathe during exercise or exertion (4 cases vs. 14 cases) scored≥2 points were significantly less than those before operation (all P<0.01). Conclusion:The utilization of pedicled upper lip mucosal flap in the reconstruction of severe nasal septal mucosal defects following rhinoplasty has proven to be highly effective. The postoperative satisfaction of patients is remarkably high, the ventilation function exhibits significant improvement, and no severe complications are observed.

Objective:To investigate the clinical characteristics and survival prognosis of patients with triple/quad-class exposed relapsed or refractory multiple myeloma(RRMM).Methods:The clinical data of patients with triple/quad-class exposed RRMM from eight centers in Shanxi Province between May 2017 and May 2024 were retrospectively analyzed.Overall survival(OS)and progression-free survival(PFS)were analyzed using the Kaplan-Meier method,and factors affecting survival were examined by the Cox proportional hazards model and Log-rank test.Results:Among the 112 patients with triple-class exposure,16 were quadruple-class exposed.The detection rates of high-risk cytogenetic abnormalities and extramedullary lesions in patients with triple-class exposure were 57.1%and 36.6%,respectively,while those in patients with quadruple-class exposure were 87.5%and 62.5%,respectively.The median PFS and OS of patients with triple-class expos-ure were 5.6 months and 12.2 months,respectively,while those of patients with quadruple-class exposure were 9.4 months and 16.9 months,respectively.Cox model analysis showed that extramedullary lesions and multi-line treatment(≥3 lines)were independent risk factors for the survival of patients with triple-class exposed RRMM(P<0.05).Previous autologous stem cell transplantation,subsequent con-ventional drug treatment,and B-cell maturation antigen(BCMA)chimeric antigen receptor T-cell(CAR-T)treatment were protective factors(P<0.05).After triple-class drug resistance,the Log-rank test verified that BCMA CAR-T treatment significantly prolonged the median PFS of patients compared to conventional drug treatment(9.4 months vs.5.2 months,P=0.026 9),whereas the difference in OS was not statistic-ally significant(16.9 months vs.7.9 months,P=0.263 4).Conclusions:Patients with triple/quad-class exposed RRMM have a poor prognosis,and BCMA CAR-T cell therapy can improve survival in patients with triple-class drug-resistant RRMM.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.