OBJECTIVE: To evaluate the early efficacy of local application of tranexamic acid on the osteotomy surface during hallux valgus surgery in reducing postoperative occult blood loss and thus postoperative swelling. METHODS: The data of 40 cases with hallux valgus osteotomy admitted to the Department of Foot and Ankle Surgery of Jishuitan Hospital from July 11, 2022 to October 8, 2022, including 5 males and 35 females were retrospectively analyzed. According to the inclusion and exclusion criteria, 32 cases were finally divided into 16 cases in the observation group (application of tranexamic acid) and 16 cases in the control group (no application of tranexamic acid). The observation group was paired with the control group one by one in accordance with the operation style, and the change in the anterior and posterior diameter of the first metatarsal head, the change in the circumferential diameter of the foot, the length of the first metatarsal midline and the length of the plumbline of the foot measured by postoperative CT were compared between the two groups before and after surgery, in order to evaluate the degree of swelling around the incision after the surgery. The first metatarsal midline and plumb line were measured by reference to the two auxiliary lines that intersect the soft tissue border in the sesamoid bone position to measure the rotation angle of the first metatarsal. A total of three clinicians completed the measurements of these two line segments and interobserver comparisons were performed. RESULTS: By interobserver comparison, the consistency of the length of the midline of the first metatarsal and the plumbline measured by CT was high and could be considered a reliable measurement. After the paired t-test, there was no statistical difference in the amount of changes in the anteroposterior diameter of the first metatarsal before and after surgery between the observation and control groups (P>0.05), and the amount of changes in the circumferential diameter of the foot before and after surgery was smaller in the observation group than in the control group, which was statistically significant (P < 0.05); the length of the midline of the first metatarsal and the plumbline of the foot measured by CT after surgery was smaller in the observation group than in the control group, which was statistically significant (P < 0.05). CONCLUSION Local application of tranexamic acid on the osteotomy surface during hallux valgus osteotomy can relieve postoperative swelling to some extent, which may be related to the fact that tranexamic acid reduces occult blood loss in the postoperative period.
Humans ; Hallux Valgus/surgery* ; Tranexamic Acid/administration & dosage* ; Female ; Male ; Osteotomy/adverse effects* ; Retrospective Studies ; Edema/etiology* ; Adult ; Middle Aged ; Postoperative Complications/prevention & control* ; Antifibrinolytic Agents/administration & dosage*

The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Human keratinocyte growth factor-1 (hKGF-1), a member of the fibroblast growth factor (FGF) family, plays crucial roles in organ development, cell proliferation, wound healing, and tissue repair, representing one of the most effective and specific growth factors for skin repair. However, obtaining recombinant hKGF-1 remains challenging due to its universally low expression efficiency in vitro. This study employs the Bombyx mori baculovirus expression system to establish a technological platform that utilizes the economically important insect Bombyx mori as a bioreactor for high-efficiency and low-cost expression and production of recombinant human keratinocyte growth factor 1 (hKGF-1) protein, ultimately achieving high-level expression of hKGF-1 in Bombyx mori ovary cell line (BmN). In this study, we optimized the hKGF-1 sequence based on the codon preference of baculovirus. By fusing hKGF-1 with polyhedrin (highly expressed in this system) and adding extra promoters and enhancers, we significantly improved the expreesion level of hKGF-1 in Bombyx mori cells. The results demonstrated that the aforementioned strategies significantly enhanced the expression level of hKGF-1 in Bombyx mori cells. SDS-PAGE and Western blotting results revealed that the highest hKGF-1 expression (accounting for 8.7% of total cellular protein) was achieved when the Polh promoter was combined in tandem with the P6.9 promoter and hKGF-1 was fused with a 15-residue polyhedrin fragment for co-expression. The optimal harvest time was determined to be 120 h post transfection. This study achieved the efficient expression of hKGF-1 in Bombyx mori cells, establishing an ideal technological platform for the industrial utilization of recombinant hKGF-1. The developed methodology not only provides valuable technical references for the production of other growth factors and complex proteins, but also demonstrates significant implications for employing silkworms as bioreactors for recombinant human protein expression.
Bombyx/metabolism* ; Animals ; Baculoviridae/metabolism* ; Humans ; Fibroblast Growth Factor 7/biosynthesis* ; Recombinant Proteins/genetics* ; Cell Line ; Genetic Vectors/genetics*

Bombyx mori nucleopolyhedrovirus (BmNPV) is extremely harmful to the silk industry. The polyhedrin, which encodes the polyhedrin (Polh), can be expressed at ultra-high levels and form occlusion bodies in the nucleus, embedding the progeny virus within it. However, the detailed mechanism by which polyhedrin is transported into the host cell nucleus remains unknown. Clarifying the nuclear import mechanisms of viral proteins can help us develop better prevention and treatment measures against baculoviruses. This study employed molecular cloning, co-immunoprecipitation, and immunofluorescence to analyze in detail the expression pattern of the highly expressed polyhedrin in the very late stage of the virus, and further revealed that the host protein importin α participates in the nuclear import of polyhedrin through protein interactions. This study provides a reference for further elucidating the nuclear import mechanisms of the baculovirus proteins including polyhedrin that can enter the nucleus.
Nucleopolyhedroviruses/metabolism* ; Active Transport, Cell Nucleus ; Animals ; Bombyx/virology* ; alpha Karyopherins/metabolism* ; Cell Nucleus/metabolism* ; Viral Structural Proteins/metabolism* ; Occlusion Body Matrix Proteins

Objective:To investigate the prognosis and the factors that influence it in patients with non-gastric gastrointestinal stromal tumors (GISTs) who are at low risk of recurrence.Methods:This was a retrospective cohort study. Clinicopathologic and prognostic data from patients with non-gastric GISTs and at low risk of recurrence (i.e., very low-risk or low-risk according to the 2008 version of the Modified NIH Risk Classification), who attended 18 medical centers in China between January 2000 and June 2023, were collected. We excluded patients with a history of prior malignancy, concurrent primary malignancy, multiple GISTs, and those who had received preoperative imatinib. The study cohort comprised 1,571 patients with GISTs, 370 (23.6%) of whom were at very low-risk and 1,201 (76.4%) at low-risk of recurrence. The cohort included 799 (50.9%) men and 772 (49.1%) women of median age 57 (16–93) years. Patients were followed up to July 2024. The prognosis and its influencing factors were analyzed. Receiver operating characteristic curves for tumor diameter and Ki67 were established, and the sensitivity, specificity, area under the curve (AUC) and optimal cut-off value with 95% confidence intervals were calculated. Propensity score matching was implemented using the 1:1 nearest neighbor matching method with a matching tolerance of 0.02.Results:With a median follow-up of 63 (12–267) months, the 5- and 10-year overall survival (OS) rates of the 1,571 patients were 99.5% and 98.0%, respectively, and the 5- and 10-year disease-free survival (DFS) rates were 96.3% and 94.4%, respectively. During postoperative follow-up, 3.8% (60/1,571) patients had disease recurrence or metastasis, comprising 0.8% (3/370) in the very low-risk group and 4.7% (57/1,201) in the low-risk group. In the low-risk group, recurrence or metastasis occurred in 5.5% (25/457) of patients with duodenal GISTs, 3.9% (25/645) of those with small intestinal GISTs, 9.2% (6/65) of those with rectal GISTs, and 10.0% (1/10) of those with colonic GISTs. Among the 60 patients with metastases, 56.7% (34/60) of the metastases were located in the abdominal cavity, 53.3% (32/60) in the liver, and 3.3% (2/60) in bone. During the follow-up period, 13 patients (0.8%) died of disease. Receiver operating characteristic curves were plotted for tumor diameter and Ki67 and assessed using the Jordon index. This showed that the difference in DFS between the two groups was statistically significant when the cutoff value for tumor diameter was 3.5 cm (AUC 0.731, 95% CI: 0.670–0.793, sensitivity 77.7%, specificity 64.1%). Furthermore, the difference in DFS between the two groups was statistically significant when the cutoff value for Ki67 was 5% (AUC 0.693, 95% CI: 0.624–0.762, sensitivity 60.7%, specificity 65.3%). Multifactorial analysis revealed that tumor diameter ≥3.5 cm, Ki67 ≥5%, and R1 resection were independent risk factors for DFS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). Furthermore, age >57 years, Ki67 ≥5%, and R1 resection were also independent risk factors for OS in patients with non-gastric GISTs at low risk of recurrence (all P<0.05). We also grouped the patients according to whether they had received postoperative adjuvant treatment with imatinib for 1 or 3 years. This yielded 137 patients in the less than 1-year group, 139 in the 1-year plus group; and 44 in both the less than 3 years and 3-years plus group. After propensity score matching for age, tumor diameter, Ki67, and resection status, the differences in survival between the two groups were not statistically significant (all P>0.05). The 10-year DFS and OS were 87.5% and 95.5%, respectively, in the group treated with imatinib for less than 1 year and 88.5% and 97.8%, respectively, in the group treated for more than 1 year. The 10-year DFS and OS were 89.6% and 92.6%, respectively, in the group treated with imatinib for less than 3 years and 88.0% and 100.0%, respectively, in the group treated with imatinib for more than 3 years. Conclusion:The overall prognosis of primary, non-gastric, low recurrence risk GISTs is relatively favorable; however, recurrences and metastases do occur. Age, tumor diameter, Ki67, and R1 resection may affect the prognosis. For some patients with low risk GISTs, administration of adjuvant therapy with imatinib for an appropriate duration may help prevent recurrence and improve survival.

Objective:To investigate the prognosis and safety of ripretinib in the treatment of patients with advanced gastrointestinal mesenchymal stromal tumors (GISTs) and to analyze the relationship between blood concentrations of this drug and prognosis.Methods:In this retrospective study, we investigated the effects of ripretinib in patients with advanced GISTs. The inclusion criteria comprised: (1) daily oral administration of ripretinib scheduled; and (2) uninterrupted treatment for at least 1month, with a stable and relatively fixed daily dosage maintained for a minimum of 2 weeks. Exclusion criteria comprised concurrent use of other tyrosine kinase inhibitors and presence of significant organ dysfunction. We retrospectively identified 79 patients with advanced GISTs who had received ripretinib across seven medical centers, namely Jiangsu Provincial Hospital, Jiangsu Cancer Hospital, Nanjing Drum Tower Hospital Affiliated to Nanjing University, Sir Run Run Shaw Hospital of Zhejiang University, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and the General Hospital of the People's Liberation Army, from 1 June 2021 to 31 March 2024. The cohort included 48 men and 31 women, 19 of whom had received ripretinib as second-line, 13 as third-line, and 47 as fourth-line therapy. Two peripheral venous blood samples were obtained from each participant and high-performance liquid chromatography-tandem mass spectrometry used to determine peak (Cmax) and trough (Cmin) concentrations of ripretinib. Machine learning methodologies, specifically the K-nearest neighbor algorithm combined with the Gridsearch CV strategy, were employed to establish the threshold for Cmin. We analyzed adverse reactions, treatment efficacy, median progression-free survival (mPFS), and the relationship between drug blood concentration and selected clinical parameters.Results:In the entire cohort, the Cmin and Cmax of ripretinib were 467 ± 360 μg/L and 986 ± 493 μg/L, respectively. Notably, female patients and individuals in the high-dose group exhibited significantly higher values for both Cmin and Cmax (both P<0.05). However, variations in drug concentrations associated with the line of ripretinib therapy, treatment efficacy, disease progression, and presence of selected specific genetic mutations were not significantly associated with values of Cmin and Cmax ( P>0.05). Among the 79 patients with advanced GISTs receiving ripretinib, reported adverse reactions included alopecia (53, 67.09%), hand–foot syndrome (24, 30.38%), fatigue (22, 27.85%), and myalgia (21, 26.58%). Two patients (2.53%) had grade III complications, both classified as hand–foot syndrome. The correlation between Cmax and adverse reactions was not statistically significant ( P > 0.05). By the time of the latest follow-up, five deaths (6.3%) had occurred within the cohort. The mPFS for the group was 16.3 months, with a mPFS of 14.4 months for those receiving standard dosage and 7.0 months for those receiving escalating dosage. Among the 65 patients treated with standard doses of ripretinib, those with Cmin exceeding a threshold of 450 μg/L exhibited a significantly longer mPFS (18.0 months vs.13.7 months; P < 0.05). Conclusion:In China, patients with advanced GISTs exhibit a notable tolerance to ripretinib, with no evidence for a correlation between adverse reactions and Cmax for the drug. Additionally, a Cmin exceeding 450 μg/L may be associated with an extended mPFS.

Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Objective To develop a pressure swing adsorption oxygen generating device that is workable at altitudes of 0 to 7000 meters.Methods The three-bed molecular sieve oxygen production process was adopted.The switching time of air circuit solenoid valve and the rotation speed of the compression pump were taken as controllable variables.The performance of the oxygen generating device was tested in a normal atmospheric environment and a low-pressure environment corresponding to altitudes of 0 to 7000 meters.The optimal values of controllable oxygen generating parameters corresponding to 10 low-pressure environments(89.9,79.7,69.7,65.0,62.0,57.7,53.8,47.6,43.0,41.0 kPa)were obtained.Results The oxygen concentration could reach 94％,oxygen flow rate was 9 L/min and oxygen outlet pressure stood at 44 kPa in a normal atmospheric environment(altitude 416 meters),compared with 94％,6.3 L/min and 30 kPa in a low-pressure environment of 41 kPa(altitude 7000 meters).Conclusion The oxygen generating device can meet the oxygen needs of two persons within the altitude range of 0 to 7000 meters.

Objective:To investigate the value of CT imaging radiomics in predicting the therapeutic effect of extracorporeal shock wave lithotripsy (ESWL) for pancreatic duct stones.Methods:The clinical data of 167 patients with pancreatic duct stones treated with ESWL in the Department of Gastroenterology, the First People's Hospital of Hangzhou, Westlake University from July 2016 to January 2023 were retrospectively analyzed. Patients were divided into complete lithotripsy group (stone diameter ≤3 mm, n=94) and incomplete lithotripsy group (stone diameter>3 mm, n=73), according to the size of the largest residual stone after the first ESWL treatment. ITK SNAP software was used to delineate the images of pancreatic duct stones, and the artificial intelligence tool kit developed by United Shadow Company was used to extract the image radiomics characteristics. The pancreatic duct stone data set was randomly assigned into the training set ( n=118) and the test set ( n=29) in the ratio of 8∶2, and the absolute maximum normalization treatment was used, followed by peacekeeping selection through the minimum absolute contraction and selection operator (Lasso) to calculate the CT image radiomics score, and the logistic regression classifier was used to construct the ESWL treatment effect prediction model of pancreatic duct stones. Receiver operating characteristic curves (ROC) were plotted, and the area under the curve (AUC) and sensitivity, specificity, and accuracy were calculated to assess the performance of the prediction model. Decision curve analysis was used to evaluate the clinical value of CT radiomics score in the diagnosis of ESWL for pancreatic duct stones. Results:A total of 2 287 imaging radiomics characteristics were extracted, and 11 optimal imaging radiomics characteristics were finally screened by Lasso regression dimensionality reduction to establish a prediction model for ESWL treatment effect of pancreatic duct stones. The AUC values of the training set and the test set were 0.89 and 0.87, respectively, and the sensitivity, specificity, and accuracy were 82% and 79%, 82% and 82%, 82% and 80%, respectively. The AUC value in the independent validation set was 0.90, and the sensitivity, specificity, and accuracy were 78%, 90%, and 85%, respectively. The results of decision curve analysis showed that when the probability of ESWL efficacy in the diagnosis of pancreatic duct stones with CT image radiomics score was >0.05, the use of CT image radiomics score in the diagnosis of ESWL efficacy in pancreatic duct stones was more beneficial to patients in clinical practice than not.Conclusions:The treatment effect of ESWL for pancreatic duct stones can be predicted by CT imaging radiomics model.

Purpose/Significance To analyze the current situation and problems of the development of digital health in China,and to explore how to promote the innovative development of digital health.Method/Process The current situation and main problems of digital health are studied and analyzed by the method of literature research and network survey,and the paths of the innovative development of digital health are devised based on case analysis.Result/Conclusion Digital technology has become the key to breaking down multiple barriers to digital health development.The paper puts forward the specific path of"sharing and cooperative governance platform-indus-trial security system-intelligent supervision mechanism"and the digital technology-based countermeasures to promote innovative devel-opment of the industry.