Antibiotic-resistant (AR) bacterial wound infections (WIs) impose major burdens on healthcare systems, exacerbated by ineffective therapies and stalled antibiotic development. Phage therapy and phage-derived enzymes have gained traction as potent alternatives, leveraging targeted bactericidal mechanisms to combat AR pathogens. In this review, we summarised the antimicrobial mechanisms of both phage therapy and phage-derived enzymes as antimicrobial therapy, and outlined recent advances in their use for in vitro , in vivo and clinical applications for WI management. In addition, we also highlights recent advancements in their development, driven by genetic engineering, chemical modifications, and artificial intelligence. Finally, we identified the potential barriers and challenges they may encounter in clinical practice and the corresponding strategies to address these issues. The entire review gives us a comprehensive understanding of the latest advances in phages and their derivative enzyme therapies for treating WIs, in the hope that research in this field will continue to improve and innovate, accelerating the transition from the laboratory to application at the bedside and ultimately improving the efficacy of treatment for AR bacterial WIs.
Humans ; Phage Therapy/methods* ; Wound Infection/drug therapy* ; Bacteriophages/enzymology* ; Enzyme Therapy/methods* ; Animals ; Bacterial Infections/therapy*

Objective To discuss the application of therapeutic hemapheresis in clinical therapy and to observe the ad-verse reactions.Methods 126 times of therapeutic hemapheresis were performed in 121 patients by Nangel blood cell sepa-rator.Consumables and apheresis procedures were selected according to different treatment needs of patients.The clinical therapeutic efficacy laboratory indicators and adverse reactions during the treatment process were analyzed,and correspond-ing measures were taken.Results Among 100 patients who underwent platelet rich plasma(PRP)treatment,the success rate of collection was 98％.The average PRP platelet level achieved(981.22±3.55)×109/L,and the average concentration multiple of PRP achieved(4.01±0.52)times.All patients obtain symptomatic relief after treatment with PRP.The level of hemoglobin and red blood cell count of 6 polycythemia vera patients and the level of platelet of 10 essential thrombocythemia patients all decreased after therapeutic hemapheresis combined with hydroxycarbamide,with significant difference(P＜0.05).Five patients with preoperative autologous blood donation have been through the surgery successfully.Out of the 121 patients,10(8.26％)experienced mild adverse reaction(8.26％),15(12.40％)showed bruising and bleeding at puncture site,and 1(0.83％)had pseudoaneurysm.Conclusion Therapeutic hemapheresis has the advantages of good curative effect,high success rate and low incidence of adverse reactions,and can be applied in PRP collection,removal of blood pathological components and preoperative autologous blood donation.

Objective:To analyse the correlation between the lymph nodes, the number of positive lymph nodes, the positive rate of lymph nodes and the long-term prognosis of patients with distal cholangiocarcinoma.Methods:The clinical data and follow-up results of 104 patients with distal cholangiocarcinoma admitted to Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2015 to December 2021 were retrospectively analyzed using a retrospective cohort study. All patients underwent pancreaticoduodenectomy. According to the nature of the patients′ lymph nodes, the number of positive lymph nodes, and the positive rate of lymph nodes, the X-tile software was used to analyze data respectively, and the critical value of SUVmax were determined, and the patients were divided into low-risk group and high-risk group by critical values. Based on this critical value, the patients were divided into low-risk groups and high-risk groups. There were 37 patients in the lymph node positive group and 67 patients in the negative group. In the lymph node positive group, according to the number of positive lymph nodes (the cut-off value=2), they were divided into the low-risk group( n=14), the high-risk group( n=23); grouped according to the lymph node positive rate (the cut off=0.13), and divided into the low-risk group( n=15), and the high-risk group( n=22). After grouping according to different lymph node parameters, the preoperative general data such as age, gender, laboratory examination, etc., the correlation between perioperative complications and long-term prognosis were analyzed. The measurement data conforming to the normal distribution was expressed as mean ± standard deviation( ± s), and the t test was used for comparison between groups; the measurement data that was not normally distributed was expressed as M ( Q1, Q3), and the comparison between groups was performed by the rank sum test. The enumeration data were expressed by the number of cases, and the comparison between groups was performed using the chi-square test. If the total number of cases was less than 50, and Fisher′s exact test was used. The optimal cut-off values for different lymph node parameters were determined using the x-tile 3.6.1 software. Survival curves were calculated and drawn using the Kaplan-Meier method, and the survival rates were compared using the Log-rank test. Results:All patients successfully underwent the operation, 5 patients(4.8%) died during the perioperative period. The median postoperative survival time of lymph node-positive patients and lymph node-negative patients was 17 months and 36 months, respectively, and the overall survival rates at 1, 3, and 5 years were 64.9%, 23.9%, 23.9%, and 81.5%, 49.8%, 41.7%( P=0.003). Among the patients grouped according to the number of positive lymph nodes, the median postoperative survival time of patients in the low-risk group and the high-risk group was 21 months and 17 months, and the 1-, 3-, and 5-year overall survival rates of the two groups were were 77.1%, 42.9%, 42.9% and 58.2%, 13.8%, 13.8%( P=0.284), respectively. Among the patients grouped according to the positive rate of lymph nodes, the median postoperative survival time of the patients in the low-risk group and the high-risk group was 30 months and 15 months, and the 1-, 3-, and 5-year overall survival rates of the two groups were 85.6%, 42.7%, 42.7% and 51.3%, 10.3%, 0.3%( P=0.020), respectively. Conclusions:Radical pancreaticoduodenectomy is the standard procedure for patients with distal cholangiocarcinoma. The prognosis of patients with positive lymph nodes is worse. For patients with positive lymph nodes, the positive rate of lymph nodes is a better predictor of the long-term prognosis compared with the number of positive lymph nodes.

Objective:This research aimed to study the relationship between preoperative CA19-9/GGT ratio and postoperative long-term survival in patients with distal cholangiocarcinoma.Methods:The clinical data of 121 patients with distal cholangiocarcinoma who underwent radical pancreaticoduodenectomy (PD) at the Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2013 to December 2019 were retrospectively analyzed. The ROC curve was drawn based on the preoperative CA19-9/GGT ratio and postoperative 1-year survival. Using the best cut-off value of CA19-9/GGT ratio, the 121 patients were divided into two groups: the low ratio group (CA19-9/GGT≤0.12, n=53) and the high ratio group (CA19-9/GGT>0.12, n=68). The clinical data of the two groups were compared, and the risk factors of long-term survival were analyzed. Results:There were 72 male and 49 female patients, aged (64.9±9.2) years. When compared with the high ratio group, the low ratio group had significantly less requirement for preoperative jaundice reduction, lower CA19-9, higher GGT, better tumor differentiation, and more patients without lymph node metastasis (all P<0.05). The median follow-up time was 26 months. The 1-, 3- and 5-year survival rates of the low vs. high ratio groups were 89.4% vs. 64.7%, 64.4% vs. 14.1%, 48.7% vs. 14.1%, respectively (all P<0.001). Multivariate analysis showed that CA19-9/GGT ratio>0.12 ( RR=2.802, 95% CI: 1.494-5.256), poor differentiation ( RR=1.855, 95% CI: 1.106-3.111) and lymph node metastasis ( RR=1.891, 95% CI: 1.129-3.169) were independent risk factors for long-term survival ( P<0.05). Conclusion:The ratio of CA19-9/GGT could be used as an index to predict long-term survival of patients with distal cholangiocarcinoma after PD. The smaller the ratio, the better was the long-term prognosis.

Objective:To investigate the infiltration of B10 cells in the anastomotic tissue after choledochojejunostomy by establishing a rat model of choledochojejunostomy.Methods:24 male SPF SD rats aged 6 weeks and weighing 180-200 g were randomly divided into control group, 1-week group, 2-week group and 4-week group, with 6 samples in each group. The rats were killed at different time after operation to obtain the anastomotic tissue and peripheral blood. The changes of anastomotic diameter were measured. The changes of inflammatory factors in peripheral blood were determined by ELISA. Flow cytometry was used to detect the proportion of B10 cells in peripheral blood and tissues around the anastomotic site. The formation of anastomotic scar was evaluated by histopathological section. IL-10 and TGF-β1 gene expression were detected by qPCR. The measurement data with normal distribution were expressed as ( Mean± SD). Analysis of variance was used to compare the measurement data of multiple groups. T test was used to compare the measurement data between the two groups. Results:The diameter of anastomotic stoma gradually narrowed with time after choledochojejunostomy, which was(2.7± 0.3) mm at the 4st week after operation; However, liver function and inflammation index reached the peak at the 2st week after operation, and then gradually returned to normal level; The proportion of B10 cells in peripheral blood did not change significantly in each period after operation, but the infiltration of B10 cells in anastomotic tissue increased significantly, which was significantly higher than that in the control group at the first week after operation [(16.6±4.0)% vs (1.1±0.3)%, P<0.05], and it was still higher than that of the control group at the 4st week after operation [(7.5±1.3)% vs (1.1±0.3)%, P<0.05]; The pathological staining of anastomotic tissue showed that with the passage of time, the infiltration of inflammatory cells in the bile duct wall increased, the proliferation of collagen fibers, the thickening of bile duct wall, and then led to scar formation; Expression of IL-10 and TGF-1β in anastomotic tissue after operation. At the 4st week after operation, IL-10 gene expression was still higher than that of the control group [(1.4±0.6) vs (0.5±0.2), P<0.05], the gene expression of TGF-1β was increased continuously and was higher than that of the control group [(3.9±0.9) vs (0.3±0.2), P<0.05]. Conclusion:The content of B10 cells in the anastomotic tissue of rats after choledochojejunostomy is significantly increased, and the expression of IL-10 gene is high, which may play a role in regulating local scar formation.

Objective:To analyze the risk factors of lymph node metastasis of distal cholangiocarcinoma.Methods:We retrospectively analyzed the clinical data of 123 patients of distal cholangiocarcinoma in Beijing Chaoyang Hospital between Jan 2011 and Dec 2019. All patients underwent pancreatoduodenectomy. The prognosis was evaluated according to the follow-up results. The survival rate was compared by log-rank test. Logistic regression was used to analyze the risk factors for lymph node metastasis.Results:One hundred and twenty-three patients successfully underwent the operations, 6 patients died during the perioperative time. The overall 1-year, 3-year and 5-year survival rates were 75.2%, 41.9% and 31.5%. The median survival time was 44.7 months. Fifty-one patients had lymph node metastasis, and the rate of lymph node metastasis was 41.5%. The median survival time was 55.5 months and 27.5 months for patients without and with lymph node metastasis, respectively. Correspondingly, the survival rates of 1-year, 3-year, 5-year were 83.0%, 50.7%, 42.5% vs. 63.5%, 19.0%, 19.0% ( P=0.000). Multivariate analysis showed that preoperative CA19-9 ( RR=7.064, 95% CI: 2.489-20.051) and portal venous system invasion ( RR=4.610, 95% CI: 1.252-16.972) were independent risk factors for lymph node metastasis. Conclusions:Lymph node metastasis is an important factor affecting the long-term survival of patients with distal cholangiocarcinoma. Preoperative CA19-9 level and portal venous system invasion are independent risk factors for lymph node metastasis.

The number of white blood cells in the leucorrhea microscopic image can indicate the severity of vaginal inflammation. At present, the detection of white blood cells in leucorrhea mainly relies on manual microscopy by medical experts, which is time-consuming, expensive and error-prone. In recent years, some studies have proposed to implement intelligent detection of leucorrhea white blood cells based on deep learning technology. However, such methods usually require manual labeling of a large number of samples as training sets, and the labeling cost is high. Therefore, this study proposes the use of deep active learning algorithms to achieve intelligent detection of white blood cells in leucorrhea microscopic images. In the active learning framework, a small number of labeled samples were firstly used as the basic training set, and a faster region convolutional neural network (Faster R-CNN) training detection model was performed. Then the most valuable samples were automatically selected for manual annotation, and the training set and the corresponding detection model were iteratively updated, which made the performance of the model continue to increase. The experimental results show that the deep active learning technology can obtain higher detection accuracy under less manual labeling samples, and the average precision of white blood cell detection could reach 90.6%, which meets the requirements of clinical routine examination.

Objective:To evaluate the prognosis and related risk factors of distal cholangiocarcinoma after surgical treatment.Methods:The clinical data of 123 patients of distal cholangiocarcinoma in Beijing Chaoyang Hospital between January 2011 and December 2019 were retrospectively analyzed, which including 72 males and 51 females, the average age was (64.9±9.2) years (range from 29 to 84 years). All patients underwent pancreatoduodenectomy. The observation measures contains: (1) Perioperative outcomes; (2) Follow-up outcomes; (3) Risk factors for long-term survival of distal cholangiocarcinoma. Follow-up was carried out to understand the long-term survival of patients, and follow-up method contains the outpatient reexamination and telephone. The deadline of follow-up date was March 2020. The normal distribution data were expressed by ( Mean± SD), and the non-normal distribution data were expressed by M ( P25, P75). Count data were expressed by cases and percentage. Kaplan-Meier method was used to calculate and draw the survival curve. Log-rank test was used to compare the survival rate. Cox proportional risk model was used in multivariate factor analysis. Results:(1) Perioperative outcomes: In our research, all of 123 patients were successfully completed the operations, and 6 patients dead during the perioperative. (2) Follow-up outcomes: The incidence of postoperative complications was 27.6%(34/123). One hundred and twenty-one patients were followed up, the follow-up rate was 98.4%, and the median follow-up time was 41.0 months.The overall 1-year, 2-year, 3-year and 5-year survival rates were 71.8%, 50.5%, 35.5% and 30.2%. And the median survival time was 42.7 months. (3) Risk factors for long-term survival of distal cholangiocarcinoma: Multivariate analysis showed that preoperative CA19-9 ( RR=1.470, 95% CI: 1.028-2.101), portal venous system invasion ( RR=2.020, 95% CI: 1.012-4.035) and tumor differentiation ( RR=1.735, 95% CI: 1.195-2.520) were independent risk factors for the prognosis. Conclusions:Radical pancreatoduodenectomy is the best treatment for distal cholangiocarcinoma. Preoperative CA19-9 level, portal venous system invasion and tumor differentiation are independent risk factors for the prognosis.

Objective:To analyze the value and significance of surgical operation in the treatment of pancreatic carcinoma with portal venous system invasion.Methods:The clinical data of 66 patients of pancreatic carcinoma with portal venous system invasion admitted in Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2011 to December 2018 were retrospectively analyzed. Vascular resection and reconstruction was used on all patients who underwent radical resection for pancreatic carcinoma (portal vein system invasion group). The operation procedure was made according to the location of the pancreatic carcinoma, and the vascular reconstruction procedure was made according to the type and location of portal venous system invasion. The intraoperative and perioperative situation of the patients were analyzed. Then 129 patients of pancreatic carcinoma without portal venous system invasion in the same period were selected as the control group, and the long-term prognosis between the two groups was compared.Results:The operation was successfully in 66 patients. According to the location of the pancreatic carcinoma, 55 patients underwent pancreatoduodenectomy, 8 patients underwent total pancreatoduodenectomy and 3 patients underwent distal pancreatectomy. According to the type and location of portal venous system invasion, 43 patients underwent allogeneic vascular replacement, 16 patients underwent segmental resection with end-to-end anastomosis, and 7 patients underwent wedge resection with primary closure. There was no perioperative death in this group. The incidence of postoperative complications was 28.8%(19/66), and the incidence of biochemical fistula was 9.1%(6/66), intraperitoneal infection was 7.6%(5/66), intraperitoneal hemorrhage was 4.5%(3/66), delayed gastric emptying was 4.5%(3/66), pancreatic fistula of Grade C was 1.5%(1/66) and biliary fistula was 1.5%(1/66). All the patients were discharged successfully, and the postoperative hospital stay was (20.8±9.7) days. 65 patients were followed up, and the follow-up rate was 98.5%. The median survival time of portal venous system invasion group and control group was 13 months and 22 months, respectively. The overall 1-year, 2-year and 3-year survival rates of portal venous system invasion group and control group were 53.3%, 30.4%, 23.4% and 73.1%, 45.8% and 40.1%, respectively ( P=0.006). Conclusions:Prognosis of pancreatic carcinoma patients with portal venous system invasion was poor, but it was safe and feasible to perform surgery for such patients. During the operation, different ways of venous reconstruction can be used according to the specific situation of venous invasion.

Objective:To evaluate the prognosis and related risk factors in patients who underwent surgical resection for pancreatic cancer with portal vein invasion.Methods:The clinical data of 66 patients with pancreatic cancer with portal vein invasion who underwent pancreatic combined with vascular resection and reconstruction at the Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital Affiliated to Capital Medical University between January 2011 and December 2018 were retrospectively studied. There were 30 males and 36 females. Their age ranged from 35 years to 81 years, with a mean of 61.5 years. Post-operative survival outcomes were evaluated on follow-up, and the related risk factors for prognosis were analyzed. Kaplan-Meier method was used to construct survival curves, and the survival rates were compared by the log-rank test. Multivariate Cox regression was used to analyze prognostic factors.Results:All 66 patients successfully underwent the operations. There was no perioperative death. The postoperative complication rate was 28.8% (19/66). Sixty-five patients were followed up (follow-up rate 98.5%, 65/66). The overall 1-, 2- and 3-year survival rates were 53.3%, 30.4%, 23.4%, respectively, with a median survival of 13 months. Multivariate analysis showed that preoperative CA19-9 >400 U/ml ( RR=1.871, 95% CI: 1.123-3.117) and depth of venous invasion ( RR=1.713, 95% CI: 1.072-2.736) were independent risk factors of prognosis. The higher the preoperative CA19-9, and the deeper the venous invasion, the worse was the prognosis. Conclusion:Long-term prognosis of pancreatic carcinoma patients with portal vein invasion was poor. Preoperative CA19-9 >400 U/ml and depth of vascular invasion were the main risk factors of prognosis for patients with pancreatic carcinoma and portal vein invasion after surgical resection.