Objective To explore the value of droplet digital polymerase chain reaction(ddPCR)in the etiological diagnosis of severe acute pancreatitis(SAP)patients with suspected bloodstream infection(BSI).Methods SAP patients admitted to the department of critical care medicine in a hospital July to September 2022 were enrolled.When BSI was suspected,venous blood was collected for both ddPCR detection and blood culture(BC)with antimi-crobial susceptibility testing(AST)simultaneously.The time required for two detection methods was recorded,and the detection results of ddPCR and BC were compared.The etiological diagnostic efficacy of ddPCR was calculated,and the correlation between the value of pathogen load detected by ddPCR and the level of infection parameters was explored.Results A total of 22 patients were included in the analysis,and 52 venous blood specimens were collec-ted for detection.BC revealed 17 positive specimens(32.7％)and 29 pathogenic strains,while ddPCR showed 41 positive specimens(78.8％)and 73 pathogenic strains.Detection time required for ddPCR was significantly lower than that of BC([0.16±0.03]days vs[5.92±1.20]days,P＜0.001).Within the detection range of ddPCR and taking BC results as the gold standard,the sensitivity and specificity of ddPCR were 80.0％and 28.6％,respective-ly.With the combined assessment of BSI based on non-blood specimen microbial evidence within a week,the sensi-tivity and specificity of ddPCR detection increased to 91.9％and 76.9％,respectively.ddPCR detected resistance genes of blaKPC,blaNDM/IMP,VanA/VanM,and mecA from 19,9,6,and 5 specimens,respectively.Correlation analysis showed a positive correlation between pathogen load and levels of C-reactive protein as well as procalcitonin(r=0.347,0.414,P＜0.05).Conclusion As a supplementary detection method for BC in BSI diagnosis,ddPCR has the advantages of higher sensitivity and shorter detection time,and is worthy of further exploration in clinical application.

Cancer stem cells,a small population of cells with self-renewal and multidirectional differenti-ation potential in tumor tissues,can initiate primary tumors and mediate treatment resistance,tumor re-currence,and metastasis,but the mechanism of how they affect colorectal cancer at the cellular level is unknown.Therefore,in this study,we explored the effect of cancer stem cells and their exosomes on the malignant phenotype of colorectal cancer.First,CD 166+CD44+cancer stem cells(CSCs)were isolated from colorectal cancer tumor tissues,and then cancer stem cell-derived exosomes(CSCexo)and colorec-tal cancer SW480 cell-derived exosomes(Sexo)were extracted by ultracentrifugation.Then,exosomes were subjected to NTA particle size analysis,electron microscopic observation and identification by West-ern blotting.Subsequently,the successfully isolated CSC and CSCexo were co-cultured with colorectal cancer SW480 cells.The apoptosis rate of SW480 cells after co-culture was found to decrease from 20％to about 13％by CCK-8,apoptosis assay(P＜0.01)and the invasive ability was significantly increased(P＜0.001)after co-culture with CSC or CSCexo.In addition,in vivo animal experiments revealed that the tumor growth rate of the S-exo treatment group was slower than that of the CSCexo treatment group,and that CSCexo inhibited the drug efficacy of 5-FU against colorectal cancer tumors.PET/CT imaging,immunohistochemical analysis,and Western blotting experiments showed that CSCexo enhanced the up-take of the glucose analog 18F-FDG and the expression of the glycolytic enzymes HK2,PFKFB2,PKM2,and LDHA in colorectal cancer.In addition,interfering with the expression of glycolytic enzymes with siRNAs blocked the drug resistance induced by CSCexo.In summary,this study demonstrates that color-ectal cancer stem cells deliver exosomes that affect tumor glucose metabolism pathways and promote chemotherapy resistance and invasive ability,revealing the mechanism of formation and dynamic changes in the malignant tumor microenvironment.

Development of extramural health care for chronic wounds is still in its infancy in China, and thus it is urgent and vital to establish a correct concept and practicable principles. The authors reviewed recent domestic and international literature and summarized the following treatment procedures and principles for extramural health care of chronic wounds. (1) The patient needs to do self-assessment of the wound by using available simple methods; (2) The patient consults with professional physicians or nurses on wound care to define the severity and etiology of the non-healing wound; (3) Professionals evaluate the existing treatment strategies; (4) Etiological treatments are given by professionals; (5) Patients buy needed dressings via the more convenient ways from pharmacies, e-commerce platform or others; (6) Professionals provide a standardized and reasonable therapeutic plan based on the patient's wound conditions; (7) Both professionals and the patient pay attention to complications to prevent adverse outcomes; (8) Professionals strengthen the public education on wound care and integrated rehabilitation. This review expected to provide new perspectives on the therapeutic strategies for chronic wounds in an extramural setting.
Humans ; Wound Healing ; Health Facilities ; Delivery of Health Care ; China ; Wounds and Injuries/therapy*

Objective: To explore the effects of three-dimensional (3D) bioprinting gelatin methacrylamide (GelMA) hydrogel loaded with nano silver on full-thickness skin defect wounds in rats. Methods: The experimental research method was adopted. The morphology, particle diameter, and distribution of silver nanoparticles in nano silver solution with different mass concentrations and the pore structure of silver-containing GelMA hydrogel with different final mass fractions of GelMA were observed by scanning electron microscope and the pore size was calculated. On treatment day 1, 3, 7, and 14, the concentration of nano silver released from the hydrogel containing GelMA with final mass fraction of 15% and nano silver with final mass concentration of 10 mg/L was detected by mass spectrometer. At 24 h of culture, the diameters of inhibition zone of GelMA hydrogel containing final mass concentration of 0 (no nano silver), 25, 50, and 100 mg/L nano silver against Staphylococcus aureus and Escherichia coli were detected. Fibroblasts (Fbs) and adipose stem cells (ASCs) were isolated respectively by enzymatic digestion using the discarded prepuce after circumcision from a 5-year-old healthy boy who was treated in the Department of Urology of the Second Affiliated Hospital of Zhejiang University School of Medicine in July 2020, and the discarded fat tissue after liposuction from a 23-year-old healthy woman who was treated in the Department of Plastic Surgery of the Hospital in July 2020. The Fbs were divided into blank control group (culture medium only), 2 mg/L nano sliver group, 5 mg/L nano sliver group, 10 mg/L nano sliver group, 25 mg/L nano sliver group, and 50 mg/L nano sliver group, which were added with the corresponding final mass concentrations of nano sliver solution, respectively. At 48 h of culture, the Fb proliferation viability was detected by cell counting kit 8 method. The Fbs were divided into 0 mg/L silver-containing GelMA hydrogel group, 10 mg/L silver-containing GelMA hydrogel group, 50 mg/L silver-containing GelMA hydrogel group, and 100 mg/L silver-containing GelMA hydrogel group and then were correspondingly treated. On culture day 1, 3, and 7, the Fb proliferation viability was detected as before. The ASCs were mixed into GelMA hydrogel and divided into 3D bioprinting group and non-printing group. On culture day 1, 3, and 7, the ASC proliferation viability was detected as before and cell growth was observed by live/dead cell fluorescence staining. The sample numbers in the above experiments were all 3. Four full-thickness skin defect wounds were produced on the back of 18 male Sprague-Dawley rats aged 4 to 6 weeks. The wounds were divided into hydrogel alone group, hydrogel/nano sliver group, hydrogel scaffold/nano sliver group, and hydrogel scaffold/nano sliver/ASC group, and transplanted with the corresponding scaffolds, respectively. On post injury day (PID) 4, 7, 14, and 21, the wound healing was observed and the wound healing rate was calculated (n=6). On PID 7 and 14, histopathological changes of wounds were observed by hematoxylin eosin staining (n=6). On PID 21, collagen deposition of wounds was observed by Masson staining (n=3). Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, Bonferroni correction, and independent sample t test. Results: The sliver nano particles in nano silver solution with different mass concentrations were all round, in scattered distribution and uniform in size. The silver-containing GelMA hydrogels with different final mass fractions of GelMA all showed pore structures of different sizes and interconnections. The pore size of silver-containing GelMA hydrogel with 10% final mass fraction was significantly larger than that of silver-containing GelMA hydrogels with 15% and 20% final mass fractions (with P values both below 0.05). On treatment day 1, 3, and 7, the concentration of nano silver released from silver-containing GelMA hydrogel in vitro showed a relatively flat trend. On treatment day 14, the concentration of released nano silver in vitro increased rapidly. At 24 h of culture, the diameters of inhibition zone of GelMA hydrogel containing 0, 25, 50, and 100 mg/L nano silver against Staphylococcus aureus and Escherichia coli were 0, 0, 0.7, and 2.1 mm and 0, 1.4, 3.2, and 3.3 mm, respectively. At 48 h of culture, the proliferation activity of Fbs in 2 mg/L nano silver group and 5 mg/L nano silver group was both significantly higher than that in blank control group (P<0.05), and the proliferation activity of Fbs in 10 mg/L nano silver group, 25 mg/L nano silver group, and 50 mg/L nano silver group was all significantly lower than that in blank control group (P<0.05). Compared with the that of Fbs in 0 mg/L silver-containing GelMA hydrogel group, the proliferation activity of Fbs in 50 mg/L silver-containing GelMA hydrogel group and 100 mg/L silver-containing GelMA hydrogel group was all significantly decreased on culture day 1 (P<0.05); the proliferation activity of Fbs in 50 mg/L silver-containing GelMA hydrogel group was significantly increased (P<0.05), while the proliferation activity of Fbs in 100 mg/L silver-containing GelMA hydrogel group was significantly decreased on culture day 3 (P<0.05); the proliferation activity of Fbs in 100 mg/L silver-containing GelMA hydrogel group was significantly decreased on culture day 7 (P<0.05). The proliferation activity of ASCs in 3D bioprinting group show no statistically significant differences to that in non-printing group on culture day 1 (P>0.05). The proliferation activity of ASCs in 3D bioprinting group was significantly higher than that in non-printing group on culture day 3 and 7 (with t values of 21.50 and 12.95, respectively, P<0.05). On culture day 1, the number of dead ASCs in 3D bioprinting group was slightly more than that in non-printing group. On culture day 3 and 5, the majority of ASCs in 3D bioprinting group and non-printing group were living cells. On PID 4, the wounds of rats in hydrogel alone group and hydrogel/nano sliver group had more exudation, and the wounds of rats in hydrogel scaffold/nano sliver group and hydrogel scaffold/nano sliver/ASC group were dry without obvious signs of infection. On PID 7, there was still a small amount of exudation on the wounds of rats in hydrogel alone group and hydrogel/nano sliver group, while the wounds of rats in hydrogel scaffold/nano sliver group and hydrogel scaffold/nano sliver/ASC group were dry and scabbed. On PID 14, the hydrogels on the wound surface of rats in the four groups all fell off. On PID 21, a small area of wounds remained unhealed in hydrogel alone group. On PID 4 and 7, the wound healing rates of rats in hydrogel scaffold/nano sliver/ASC group were significantly higher than those of the other three groups (P<0.05). On PID 14, the wound healing rate of rats in hydrogel scaffold/nano sliver/ASC group was significantly higher than the wound healing rates in hydrogel alone group and hydrogel/nano sliver group (all P<0.05). On PID 21, the wound healing rate of rats in hydrogel alone group was significantly lower than that in hydrogel scaffold/nano sliver/ASC group (P<0.05). On PID 7, the hydrogels on the wound surface of rats in the four groups remained in place; on PID 14, the hydrogel in hydrogel alone group was separated from the wounds of rats, while some hydrogels still existed in the new tissue of the wounds of rats in the other three groups. On PID 21, the collagen arrangement in the wounds of rats in hydrogel alone group was out of order, while the collagen arrangement in the wounds of rats in hydrogel/nano sliver group, and hydrogel scaffold/nano sliver/ASC group was relatively orderly. Conclusions: Silver-containing GelMA hydrogel has good biocompatibility and antibacterial properties. Its three-dimensional bioprinted double-layer structure can better integrate with new formed tissue in the full-thickness skin defect wounds in rats and promote wound healing.
Male ; Rats ; Animals ; Humans ; Hydrogels/pharmacology* ; Bioprinting ; Metal Nanoparticles ; Rats, Sprague-Dawley ; Silver/pharmacology* ; Soft Tissue Injuries ; Anti-Bacterial Agents

Objectives: To evaluate the feasibility and preliminary clinical results of transcatheter pulmonary valve replacement (TPVR) with the domestically-produced balloon-expandable Prizvalve system. Methods: This is a prospective single-center observational study. Patients with postoperative right ventricular outflow tract (RVOT) dysfunction, who were admitted to West China Hospital of Sichuan University from September 2021 to March 2023 and deemed anatomically suitable for TPVR with balloon-expandable valve, were included. Clinical, imaging, procedural and follow-up data were analyzed. The immediate procedural results were evaluated by clinical implant success rate, which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitationResults: A total of 5 patients were included, with 4 males, aged 14 to 37 years. The initial diagnosis included Tetralogy of Fallot (2 cases), truncus arteriosus (1 case), pulmonary atresia (1 case) and subaortic stenosis (1 case, prior Ross procedure). Four patients underwent RVOT reconstruction with homograft or artificial conduit, and one patient was treated with trans-annular patch technique. The indications of TPVR included RVOT obstruction and regurgitation (3 cases), isolated obstruction (1 case), and isolated regurgitation (1 case). Of the 4 patients with varying severity of ROVT obstruction, the average preprocedural peak jet velocity of RVOT was 3.5 m/s, and the average peak pressure gradient was 50.0 mmHg. Except for one patient, who had previously been implanted with a covered Cheatham-Platinum (CP) stent due to severe stenosis of the main pulmonary artery, other patients underwent pre-stenting with a covered CP stent before TPVR. Clinical implant success was achieved in all of the 5 patients, and there was no serious periprocedural complications. The average trans-pulmonary peak jet velocity and peak pressure gradient derived from postprocedural echocardiography was 2.3 m/s and 21.2 mmHg, respectively. All patients experienced significant symptom relief after the procedure. All patients completed 3-month follow-up, and 4 completed 6-month follow-up. There was no case of infectious endocarditis during follow-up. All patients were graded as NYHA functional class one at the latest follow-up. Conclusions: TPVR using the domestically-produced balloon-expandable Prizvalve system is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable landing-zone anatomy. The safety, effectiveness, and long-term valve durability of the Prizvalve system deserve further research.
Male ; Humans ; Pulmonary Valve/surgery* ; Heart Valve Prosthesis/adverse effects* ; Heart Valve Prosthesis Implantation ; Constriction, Pathologic/surgery* ; Prospective Studies ; Ventricular Outflow Obstruction/surgery* ; Treatment Outcome ; Cardiac Catheterization/methods* ; Transcatheter Aortic Valve Replacement

Objectives: To evaluate the feasibility and preliminary clinical results of transcatheter pulmonary valve replacement (TPVR) with the domestically-produced balloon-expandable Prizvalve system. Methods: This is a prospective single-center observational study. Patients with postoperative right ventricular outflow tract (RVOT) dysfunction, who were admitted to West China Hospital of Sichuan University from September 2021 to March 2023 and deemed anatomically suitable for TPVR with balloon-expandable valve, were included. Clinical, imaging, procedural and follow-up data were analyzed. The immediate procedural results were evaluated by clinical implant success rate, which is defined as successful valve implantation with echocardiography-assessed pulmonary regurgitationResults: A total of 5 patients were included, with 4 males, aged 14 to 37 years. The initial diagnosis included Tetralogy of Fallot (2 cases), truncus arteriosus (1 case), pulmonary atresia (1 case) and subaortic stenosis (1 case, prior Ross procedure). Four patients underwent RVOT reconstruction with homograft or artificial conduit, and one patient was treated with trans-annular patch technique. The indications of TPVR included RVOT obstruction and regurgitation (3 cases), isolated obstruction (1 case), and isolated regurgitation (1 case). Of the 4 patients with varying severity of ROVT obstruction, the average preprocedural peak jet velocity of RVOT was 3.5 m/s, and the average peak pressure gradient was 50.0 mmHg. Except for one patient, who had previously been implanted with a covered Cheatham-Platinum (CP) stent due to severe stenosis of the main pulmonary artery, other patients underwent pre-stenting with a covered CP stent before TPVR. Clinical implant success was achieved in all of the 5 patients, and there was no serious periprocedural complications. The average trans-pulmonary peak jet velocity and peak pressure gradient derived from postprocedural echocardiography was 2.3 m/s and 21.2 mmHg, respectively. All patients experienced significant symptom relief after the procedure. All patients completed 3-month follow-up, and 4 completed 6-month follow-up. There was no case of infectious endocarditis during follow-up. All patients were graded as NYHA functional class one at the latest follow-up. Conclusions: TPVR using the domestically-produced balloon-expandable Prizvalve system is safe and feasible for the treatment of patients with post-surgical RVOT dysfunction and suitable landing-zone anatomy. The safety, effectiveness, and long-term valve durability of the Prizvalve system deserve further research.
Male ; Humans ; Pulmonary Valve/surgery* ; Heart Valve Prosthesis/adverse effects* ; Heart Valve Prosthesis Implantation ; Constriction, Pathologic/surgery* ; Prospective Studies ; Ventricular Outflow Obstruction/surgery* ; Treatment Outcome ; Cardiac Catheterization/methods* ; Transcatheter Aortic Valve Replacement

A 59-year-old male patient with local sinus tract formation due to residual foreign body was admitted to the Second Affiliated Hospital of Zhejiang University College of Medicine on December 17, 2018. The examination showed that the residual foreign body was the component of a sticky cloth implanted when the patient underwent appendectomy 27 years ago. Hypertrophic scar developed at the right-lower abdominal incision for appendectomy 23 years ago and the secondary infection after cicatrectomy resulted in non-healing of the wound. The chronic refractory wound healed completely after surgical treatment in our hospital after this admission. The postoperative pathological examination revealed local inflammatory granuloma. This case suggests that chronic refractory wound is likely to form when secondary infection occurs following the surgical procedure near the implant, and aggressive surgery is an effective way to solve this problem.
Abdomen ; Abdominal Cavity ; Cicatrix, Hypertrophic ; Coinfection ; Foreign Bodies/surgery* ; Humans ; Male ; Middle Aged

Wound repair is a highly coordinated and mutually regulated complex process involving various kinds of cells, extracellular matrices and cytokines. A variety of growth factors play an important regulatory role in wound healing, and it is critical to achieve effective delivery and sustained function of growth factors. In recent years, the application of biomaterials in tissue engineering has shown great potential, and the effective delivery of growth factors by biomaterials has attracted increasing attention. Based on this, this paper introduces the mechanism of related growth factors in the process of wound healing, focusing on the recent progress of biomaterial delivery of growth factors to accelerate wound healing, in order to provide new enlightenment for clinical wound treatment.
Biocompatible Materials/metabolism* ; Extracellular Matrix/metabolism* ; Intercellular Signaling Peptides and Proteins/therapeutic use* ; Tissue Engineering ; Wound Healing

Objective:To investigate the efficacy and safety of comprehensive therapy in the treatment of advanced unresectable hepatocellular carcinoma.Methods:Clinical data of 34 patients with primary liver cancer admitted to Peking Union Medical College Hospital from Nov 2018 to Dec 2020 initially evaluated as unresectable were treated firstly by combined therapy and then underwent reevaluation for further management.Results:A total of 34 patients completed the integrative treatment, and no serious adverse events occurred. Among them, 6 patients were evaluated as partial remission, and underwent successful tumor resection, tumors in 7 patients were stable, and 21 patients suffered from disease progression.Conclusion:After comprehensive therapy, unresectable tumors in some patients could reduce and be rendered resection.

Objective: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) with the novel Prizvalve^® system in treating severe aortic stenosis. Methods: This is a single-center, prospective, single-arm, observational study. A total of 11 patients with severe aortic stenosis with high risk or inappropriate for conventional surgical aortic valve replacement (SAVR) were included, and TAVI was achieved with the Prizvalve^® system between March 2021 and May 2021 in West China Hospital. Transthoracic echocardiography (TTE) was performed immediately after prosthesis implantation to evaluate mean transaortic gradient and maximal transaortic velocity. The device success rate was calculated, which was defined as (1) the device being delivered via the access, deployed, implanted and withdrawn, (2) mean transaortic gradient<20 mmHg (1 mmHg=0.133 kPa) or a maximal transaortic velocity<3 m/s post TAVI, and without severe aortic regurgitation or paravalvular leak post TAVI. TTE was performed at 30 days after the surgery, and all-cause mortality as well as the major cardiovascular adverse events (including acute myocardial infarction, disabling hemorrhagic or ischemic stroke) up to 30 days post TAVI were analyzed. Results: The age of 11 included patients were (78.1±6.3) years, with 8 males. A total of 10 patients were with NYHA functional class Ⅲ or Ⅳ. Devices were delivered via the access, deployed, implanted and withdrawn successfully in all patients. Post-implant mean transaortic gradient was (7.55±4.08) mmHg and maximal transaortic velocity was (1.78±0.44) m/s, and both decreased significantly as compared to baseline levels (both P<0.05). No severe aortic regurgitation or paravalvular leak was observed post TAVI. Device success was achieved in all the 11 patients. No patient died or experienced major cardiovascular adverse events up to 30 days post TAVI. Mean transaortic gradient was (9.45±5.07) mmHg and maximal transaortic velocity was (2.05±0.42) m/s at 30 days post TAVI, which were similar as the values measured immediately post TAVI (both P>0.05). Conclusions: TAVI with the Prizvalve^® system is a feasible and relatively safe procedure for patients with severe aortic stenosis and at high risk or inappropriate for SAVR. Further clinical studies could be launched to obtain more clinical experience with Prizvalve^® system.
Aged ; Aged, 80 and over ; Aortic Valve ; Aortic Valve Stenosis/surgery* ; Heart Valve Prosthesis ; Heart Valve Prosthesis Implantation ; Humans ; Male ; Prospective Studies ; Transcatheter Aortic Valve Replacement/methods* ; Treatment Outcome