Objective To investigate the effect of basic helix-loop-helix family member E40 (BHLHE40) on the invasion and migration of osteosarcoma (OS) cells, and to explore the role of the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway in the biological behavior of OS mediated by BHLHE40, providing a scientific basis for targeted therapy of OS. Methods On the basis of clinical OS samples and OS cell lines, the expression differences of BHLHE40 between OS and adjacent tissues, as well as those between OS cells and normal osteoblast cell lines, were analyzed. BHLHE40 knockdown OS cells were obtained through shRNA transfection. The effects of BHLHE40 on OS cell proliferation, migration, and invasion were examined using CCK-8, EdU staining, wound healing, and Transwell assays. The involvement of the PI3K/AKT signaling pathway was assessed by Western blotting. Further validation was conducted in vivo experiments. Results The expression of BHLHE40 was significantly higher in OS tissues compared to adjacent tissues. In OS cell lines, BHLHE40 protein expression levels were increased compared to normal osteoblasts, and the cell line with the highest BHLHE40 expression was selected for subsequent knockdown experiments. Compared with the knockdown control group, the BHLHE40 knockdown group exhibited reduced cell viability, EdU-positive cell count, colony number, cell migration, and invasion abilities, along with downregulation of phosphorylated PI3K(p-PI3K)/PI3K and p-AKT/AKT protein expression. The aforementioned functions of BHLHE40 were also reproduced in in vivo experiments. Conclusion BHLHE40 is highly expressed in OS tissues, and its knockdown can significantly inhibit OS cell proliferation, migration, and invasion, while reducing PI3K/AKT signaling pathway activity. This suggests that BHLHE40 could serve as a novel therapeutic target for OS.
Osteosarcoma/metabolism* ; Humans ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Signal Transduction/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Cell Line, Tumor ; Animals ; Neoplasm Invasiveness ; Basic Helix-Loop-Helix Transcription Factors/metabolism* ; Bone Neoplasms/metabolism* ; Mice ; Gene Knockdown Techniques ; Male ; Female ; Mice, Nude

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City,China. Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed. Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52％. The male:female ratio was 2.8:1. 75.3％ of patients were aged between 16 and 60 years old,75.3％ of patients were farmers,and 11.6％ had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity. The typical symptoms of "three red" and"three pain" in patients with HFRS were not obvious.

BACKGROUND:Umbilical cord mesenchymal stem cells(UMSCs)have been proven to have therapeutic effects on cartilage injury,and exosomes are the main carriers for UMSCs to exert therapeutic effects in vivo.Our research group previously found that lncRNA H19 is an important active molecule that mediates the activity of UMSCs-derived exosomes regulating chondrocytes.LncRNA H19 could adsorb miR-29b-3p to promote the proliferation and regeneration of chondrocytes,but its downstream mechanism is still unclear. OBJECTIVE:To reveal the specific mechanism of UMSCs in the treatment of cartilage injury from the perspective of exosomes and lncRNAs,so as to provide a new target for the treatment of cartilage injury. METHODS:UMSCs stably overexpressing lncRNA H19 were constructed.H19-Exos were extracted by ultra-centrifugation.The exosomes were identified by transmission electron microscopy,Nanosight,western blot assay and exosome uptake assay.The effect of miR-29b-3p overexpression and silencing on the TGF-β1/Smad3 pathway was detected by western blot assay,qPCR and dual luciferase reporter gene system.The biological effect of H19-Exos on cartilage regeneration was verified by the specific TGF-β1/Smad3 inhibitor in vitro and in vivo. RESULTS AND CONCLUSION:(1)H19-Exos showed a typical cup shape under an electron microscope,and the particle size was approximately 130 nm.H19-Exos expressed CD63,CD81 and TSG1010.(2)Overexpression of miR-29b-3p could down-regulate the mRNA and protein levels of TGF-β1 and Smad3,while silencing miR-29b-3p could up-regulate the mRNA and protein levels of TGF-β1/Smad3.(3)Dual-luciferase reporter gene system showed that miR-29b-3p had significant differences in the activities of downstream target genes TGF-β1 and Smad3.(4)The osteoarthritis models of rats were successfully established by injection of type II collagenase into the knee joint.H19-Exos significantly promoted cartilage regeneration.The specific TGF-β1/Smad3 inhibitor SB-431542 could block the biological effect of H19-Exos on cartilage regeneration in vitro and in vivo.(5)This study systematically demonstrated the promotion effect of UMSCs-derived exosomes highly expressing lncRNA H19 on cartilage regeneration,and the specific mechanism is that lncRNA H19 promotes cartilage regeneration by targeting miR-29b-3p/TGF-β1/Smad3 pathway.

Objective:To explore the role of conducting a"thematic morning report"based on post-competency in the standardized residents training in hospital in the Intensive Care Unit(ICU).Methods:A total of 60 resident training physicians who participated in the standardized residents training in hospital in the ICU of this hospital from January 2020 to December 2022 were included,and randomly divided into an observation group and a control group,with 30 in each group.The observation group adopted an interactive teaching method of themed morning report based on post-competency,while the control group adopted the traditional teaching method.The assessment results of clinical theoretical knowledge and operational skills of the two groups of resident training physicians under different teaching methods were compared.The 360°assessment method was used to record the multi-directional evaluation of patients or their families,nurses,colleagues,and teaching teachers on the post-competence of resident training physicians(self-learning ability,team collaboration ability,effective communication ability,and learning interest).Results:The assessment scores of clinical theoretical knowledge and practical skills in the observation group after teaching were higher than those in the control group,with statistically significant differences(theoretical assessment:t=2.101,P＜0.05;practical assessment:t=9.647,P＜0.05).The post-competence scores of nurses,colleagues,and teaching teachers on resident training physicians in the observation group were higher than those in the control group after one-month regular training,and the differences were statistically significant(nurses'evaluation of self-learning ability:t=3.182,P=0.002,team collaboration ability:t=3.978,P＜0.05,effective communication ability:t=2.180,P=0.0335,learning interest:t=3.884,P＜0.05;colleagues'evaluation of self-learning ability:t=2.888,P=0.005,team cooperation ability:t=6.816,P＜0.05,effective communication ability:t=3.833,P＜0.05,learning interest:t=4.086,P＜ 0.05;teaching teacher's evaluation of self-learning ability:t=3.429,P=0.001,team cooperation ability:t=3.086,P=0.003,effective communication ability:t=3.493,P=0.001,learning interest:t=3.126,P=0.003).There was a statistically significant difference in the satisfaction scores of patients or their familymembers towards the two groups of resident training physicians(t=3.126,P=0.003).Conclusion:The use of the interactive teaching method of thematic morning report based on post-competency in the standardized residents training in hospital in the ICU can not only improve the theoretical practice and case analysis test scores of resident training physicians,but also improve the post-competence and the satisfaction of patients and their families.

Objective To observe the clinical manifestations of elderly patients with acute infectious purpura fulminant(AIPF)and septic shock caused by Streptococcus pyogenes(GAS),analyze the changes in indicators and treatment processes,and provide clinical references for the diagnosis and treatment of such diseases.Methods A retrospective analysis was conducted on the case data,clinical manifestations,signs,examination indexes and treatment process of an elderly patient who presented with GAS-induced AIPF combined with septic shock and was treated by the department of critical care medicine of Qinghai Provincial People's Hospital on June 17th,2021.This study also involved a discussion on the pathophysiological characteristics and treatment measures for these diseases as well as observation of patient prognosis.Results The 80-year-old male patient,who was previously in good health,underwent knee surgery one year ago and was admitted to the hospital on June 17,2021 due to"pain and swelling of the left face with difficulty opening the mouth for the past 2 days".Upon admission,a complete set of laboratory tests including blood routine,blood biochemistry and coagulation function were conducted.A head CT revealed swelling of the masseter muscle on the left side,subcutaneous exudation of the cheek,non-cyanotic space on the left parapharyngeal space,poor display of eustachian tube opening,and narrow throat.Color ultrasound showed soft tissue swelling and interstitial edema in the left maxillofacial region and eyelid.Six hours after admission,the patient gradually developed purple spots,blood scars and necrosis on the right side neck shoulder and upper chest accompanied by tenderness and high fever mainly on his face.The heart rate fluctuated around 150 times per minute while blood pressure was at 108/71 mmHg(1 mmHg≈0.133 kPa,Metaraminol 6.67 μg·kg-1·min-1).The patient was diagnosed with septic shock and transferred to intensive care unit(ICU)for emergency treatment.With timely comprehensive monitoring in place,the patient received active treatment focused on maintaining respiratory circulation stability.After plasma infusion,early wound treatment,reasonable anti-infection measures as well as inflammation clearance,organ function protection,and supportive therapy,the patient eventually recovered from hospitalization without recurrence after 6 months follow-up.Conclusion The onset of acute GAS infection is characterized by its rapid and severe progression,high mortality,and challenging treatment.However,timely and effective refined comprehensive monitoring,evaluation,and treatment can still yield favorable outcomes.

Objective:To investigate the value of contrast-enhanced ultrasound (CEUS) as a preoperative planning strategy for lymphaticovenous anastomosis (LVA) in improving the quality of LVA and the outcome of short-term limb volume reduction in patients with secondary upper limb lymphedema.Methods:Patients with breast cancer-related upper extremity lymphedema who underwent LVA at the Department of General Surgery Cancer Center Division of Breast Surgery of Zhejiang Provincial People’s Hospital from August 2021 to August 2023 were enrolled retrospectively. According to whether preoperative ultrasound lymphography was performed, the patients were divided into CEUS assisted group and control group. In the CEUS assisted group, preoperative CEUS lymphography combined with high-frequency ultrasound color Doppler imaging was utilized for precise localization of lymphatic vessels and recipient veins, as well as surgical target planning for LVA. In the control group, preoperative indocyanine green lymphography was employed to guide surgical exploration. Mann-Whitney U test was used to compare the number of LVA surgical exploration incisions per limb and the number of successful anastomoses per limb between the two groups. The success rate of anastomosis (total number of successful anastomoses/total number of surgical exploration incisions) was compared by the chi-square test. The duration of single anastomosis, mean arm circumference, and the difference between preoperative and postoperative mean arm circumference were compared by independent sample t-test. Paired-sample t-test was used to compare the improvement of the mean arm circumference of the operated limb of the two groups after 3 months of follow-up. P < 0.05 was considered statistically significant. Results:A total of 47 female patients were enrolled, including 27 patients in the CEUS assisted group, with an average age of (57.1±9.0) years and a median edema course of 2 years. There were 20 cases in the control group, with an average age of (58.1±9.6) years and a median duration of edema of 2 years. The CEUS group, compared with the control group, exhibited a higher number of surgical exploration incisions per limb [6.0 (4.0, 7.0) cases vs. 5.0 (3.0, 6.0) cases], a greater number of successful anastomoses per limb [5.0 (3.0, 6v0) cases vs. 3.0 (2.0, 3.0) cases], and a significantly increased overall success rate of anastomosis [82.8% (125/151) vs. 61.4% (54/88)]. Additionally, there was a significant increase in the preoperative and postoperative mean arm circumference difference [(6.2±3.3) cm vs. (3.9±1.9) cm]. The duration of single anastomosis was significantly shortened [(57.4±16.0) min vs. (92.8±18.5) min], with statistically significant differences observed in all comparisons (all P < 0.05). The preoperative and postoperative mean arm circumference were compared between the CEUS group [(31.4±4.6) cm vs. (25.3±4.7) cm] and the control group [(31.3±4.3) cm vs. (27.5±3.8) cm], respectively, with statistically significant differences observed in both groups (both P < 0.01). Conclusion:CEUS lymphography, as a preoperative planning strategy for LVA, can significantly increase the number and success rate of LVA anastomosis in patients with secondary upper limb lymphedema, shorten the duration of single anastomosis, and improve the short-term effect of limb volume reduction after LVA.

Objective:To investigate the value of contrast-enhanced ultrasound (CEUS) as a preoperative planning strategy for lymphaticovenous anastomosis (LVA) in improving the quality of LVA and the outcome of short-term limb volume reduction in patients with secondary upper limb lymphedema.Methods:Patients with breast cancer-related upper extremity lymphedema who underwent LVA at the Department of General Surgery Cancer Center Division of Breast Surgery of Zhejiang Provincial People’s Hospital from August 2021 to August 2023 were enrolled retrospectively. According to whether preoperative ultrasound lymphography was performed, the patients were divided into CEUS assisted group and control group. In the CEUS assisted group, preoperative CEUS lymphography combined with high-frequency ultrasound color Doppler imaging was utilized for precise localization of lymphatic vessels and recipient veins, as well as surgical target planning for LVA. In the control group, preoperative indocyanine green lymphography was employed to guide surgical exploration. Mann-Whitney U test was used to compare the number of LVA surgical exploration incisions per limb and the number of successful anastomoses per limb between the two groups. The success rate of anastomosis (total number of successful anastomoses/total number of surgical exploration incisions) was compared by the chi-square test. The duration of single anastomosis, mean arm circumference, and the difference between preoperative and postoperative mean arm circumference were compared by independent sample t-test. Paired-sample t-test was used to compare the improvement of the mean arm circumference of the operated limb of the two groups after 3 months of follow-up. P < 0.05 was considered statistically significant. Results:A total of 47 female patients were enrolled, including 27 patients in the CEUS assisted group, with an average age of (57.1±9.0) years and a median edema course of 2 years. There were 20 cases in the control group, with an average age of (58.1±9.6) years and a median duration of edema of 2 years. The CEUS group, compared with the control group, exhibited a higher number of surgical exploration incisions per limb [6.0 (4.0, 7.0) cases vs. 5.0 (3.0, 6.0) cases], a greater number of successful anastomoses per limb [5.0 (3.0, 6v0) cases vs. 3.0 (2.0, 3.0) cases], and a significantly increased overall success rate of anastomosis [82.8% (125/151) vs. 61.4% (54/88)]. Additionally, there was a significant increase in the preoperative and postoperative mean arm circumference difference [(6.2±3.3) cm vs. (3.9±1.9) cm]. The duration of single anastomosis was significantly shortened [(57.4±16.0) min vs. (92.8±18.5) min], with statistically significant differences observed in all comparisons (all P < 0.05). The preoperative and postoperative mean arm circumference were compared between the CEUS group [(31.4±4.6) cm vs. (25.3±4.7) cm] and the control group [(31.3±4.3) cm vs. (27.5±3.8) cm], respectively, with statistically significant differences observed in both groups (both P < 0.01). Conclusion:CEUS lymphography, as a preoperative planning strategy for LVA, can significantly increase the number and success rate of LVA anastomosis in patients with secondary upper limb lymphedema, shorten the duration of single anastomosis, and improve the short-term effect of limb volume reduction after LVA.

Mesh-related visceral complications caused by mesh erosion after tension-free inguinal hernia repair are one kind of rare long-term complications, but they are easily neglected. Interval time from initial hernia repair to mesh-related visceral complications by preperitoneal and laparoscopic repair is short. Rutkow and transabdominal preperitoneal repair have the highest reported rate. Lichtenstein has the longest interval time and the lowest reported rate. The most frequently eroded organs are sigmoid colon, bladder and small intestine. The common clinical manifestations of sigmoid colon erosion are hematochezia, abdominal wall fistula and colitis, hematuria and recurrent urinary tract infection in bladder erosion cases, intestinal obstruction and abdominal wall fistula in intestinal erosion case, sigmoid-bladder fistula and intestinal-bladder fistula in multiple organ erosion cases. Resection or repair of corresponding organs with mesh removal have good efficacies in most patients. The authors summarize and analyze researches on mesh-related visceral complications after tension-free inguinal hernia repair from 1994 to 2021, review their advances, in order to raise awareness of such complications in clinicians.

【Objective】 To investigate the effect of optimized preoperative hemoglobin (Hb) level on clinical outcome in patients undergoing coronary artery bypass grafting (CABG). 【Methods】 Retrospective analysis was performed on patients who were selected to receive CABG from April 2020 to August 2021 in our hospital. Preoperative basic data, perioperative blood transfusion volume, blood transfusion rate, acute liver function impairment, renal function impairment (AKI), ICU stay, length of hospital stay, and in-hospital mortality of patients, meeting the inclusion criteria, were collected. According to the perioperative red blood cell transfusion, the optimal preoperative Hb threshold was calculated by receiver operating characteristic curve (ROC). According to the threshold, all patients were divided into two groups, and the blood transfusion volume and clinical outcomes of the two groups were compared to evaluate the predictive value of the optimal threshold of Hb. 【Results】 A total of 915 patients who met the inclusion criteria were enrolled in the study. The optimal threshold for predicting red blood cell transfusion rate by calculating preoperative Hb value by ROC curve was 118 g/L for males and 116g/L for females. Group A: Hb≤ threshold (n=293) was divided into the red blood cell transfusion group A1 and the red blood cell non-transfusion group A2. Group B: Hb>threshold (n=622) was divided into the red blood cell non-transfusion group B1 and no red blood cell non-transfusion group B2. The risk factors for perioperative red blood cell transfusion were age (OR=1.033 874, 95%CI 1.000 4-1.068 3, P<0.01), gender (female) (OR=3.268 5, 95%CI 2.353 1-4.540 0, P<0.01), BMI (OR=0.927 8, 95%CI 0.883 3-0.974 4, P<0.01), chronic renal insufficiency (CKD) (OR=2.041 1, 95%CI 1.347 8-3.091 0, P<0.01). Preoperative Hb≤ threshold (OR=3.517 4, 95%CI 2.502 1-4.944 7, P<0.01) was an independent risk factor for perioperative red blood cell transfusion. Perioperative red blood cell transfusion in patients with preoperative anemia further increases the incidence of postoperative complications (acute liver injury, AKI) and length of ICU stay. 【Conclusion】 Preoperative Hb≤ threshold can effectively predict perioperative red blood cell transfusion in patients with CABG, and increase the risk of postoperative acute liver injury, AKI, prolonged ICU stay and hospital stay. Optimizing the preoperative Hb level in CABG patients, increasing the Hb level to 118 g/L in males and 116 g/L in females can reduce the incidence of perioperative red blood cell transfusion and postoperative complications.