AIM:To investigate the effects of the Qingfei-Jiedu-Huatan formula(QJHF)on damage to the lung vascular endothelial barrier induced by Klebsiella pneumoniae in mice with severe pneumonia,as well as to elucidate its underlying mechanisms.METHODS:Fifty-one C57BL/6J mice were randomly divided into control group(n=6),model group(n=15),QJHF group(n=15),and ceftriaxone sodium(CRO)group(n=15).Severe pneumonia was in-duced in the mice by a single tracheal intubation with 50 μL of 1×1011 CFU/mL Klebsiella pneumoniae on day 0.Six hours after modeling,the mice in QJHF and CRO groups received their respective treatments,while those in control and model groups were administered an equal volume of saline.All mice were sacrificed on day 3 after the end of gavage.Lung histo-pathological changes were assessed using hematoxylin-eosin(HE)staining.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect CD11b+Ly6g+cells in bronchoalveolar lavage fluid(BALF).Proteomics and network pharma-cology analyses were conducted to elucidate the mechanisms of drug action.Western blot was conducted to assess the ex-pression levels of vascular endothelial cadherin(VE-cadherin),zonula occludens-1(ZO-1),occludin,vascular endothe-lial growth factor(VEGF),P38 mitogen-activated protein kinase(P38),and phosphorylated P38(p-P38)in lung tis-sues.RESULTS:Treatment with QJHF significantly attenuated the symptoms such as mental status and respiratory dis-tress,reduced mortality,mitigated lung tissue lesions,and decreased levels of IL-6,TNF-α,IL-1β,as well as BALF to-tal protein concentration,total cell count and neutrophil content in a mouse model of severe pneumonia(P＜0.05 or P＜0.01).Additionally,QJHF increased the expression of VE-cadherin,ZO-1 and occludin proteins in lung tissues.Pro-teomic analysis demonstrated that QJHF modulated the expression of 129 proteins in the lung tissues of mice suffering from severe pneumonia.Network pharmacology identified 328 potential targets associated with 14 major bioactive components of QJHF and 1 665 genes related to severe pneumonia,with 125 overlapping genes between the two datasets.The construc-tion of a protein-protein interaction(PPI)network,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the regulated proteins and overlapping genes,indicated that QJHF primarily in-fluenced the PI3K-Akt,MAPK and Rap1 signaling pathways,as well as VEGFR.Western blot analysis showed that QJHF significantly inhibited the expression of VEGF and P38 in lung tissues(P＜0.05 or P＜0.01).CONCLUSION:Treatment with QJHF attenuates severe pneumonia in mice,potentially by inhibiting VEGF/P38 signaling to protect the vascular endothelial barrier.

AIM:To investigate the effects of the Qingfei-Jiedu-Huatan formula(QJHF)on damage to the lung vascular endothelial barrier induced by Klebsiella pneumoniae in mice with severe pneumonia,as well as to elucidate its underlying mechanisms.METHODS:Fifty-one C57BL/6J mice were randomly divided into control group(n=6),model group(n=15),QJHF group(n=15),and ceftriaxone sodium(CRO)group(n=15).Severe pneumonia was in-duced in the mice by a single tracheal intubation with 50 μL of 1×1011 CFU/mL Klebsiella pneumoniae on day 0.Six hours after modeling,the mice in QJHF and CRO groups received their respective treatments,while those in control and model groups were administered an equal volume of saline.All mice were sacrificed on day 3 after the end of gavage.Lung histo-pathological changes were assessed using hematoxylin-eosin(HE)staining.Levels of tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),and IL-6 in lung tissues were measured by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect CD11b+Ly6g+cells in bronchoalveolar lavage fluid(BALF).Proteomics and network pharma-cology analyses were conducted to elucidate the mechanisms of drug action.Western blot was conducted to assess the ex-pression levels of vascular endothelial cadherin(VE-cadherin),zonula occludens-1(ZO-1),occludin,vascular endothe-lial growth factor(VEGF),P38 mitogen-activated protein kinase(P38),and phosphorylated P38(p-P38)in lung tis-sues.RESULTS:Treatment with QJHF significantly attenuated the symptoms such as mental status and respiratory dis-tress,reduced mortality,mitigated lung tissue lesions,and decreased levels of IL-6,TNF-α,IL-1β,as well as BALF to-tal protein concentration,total cell count and neutrophil content in a mouse model of severe pneumonia(P＜0.05 or P＜0.01).Additionally,QJHF increased the expression of VE-cadherin,ZO-1 and occludin proteins in lung tissues.Pro-teomic analysis demonstrated that QJHF modulated the expression of 129 proteins in the lung tissues of mice suffering from severe pneumonia.Network pharmacology identified 328 potential targets associated with 14 major bioactive components of QJHF and 1 665 genes related to severe pneumonia,with 125 overlapping genes between the two datasets.The construc-tion of a protein-protein interaction(PPI)network,along with Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of the regulated proteins and overlapping genes,indicated that QJHF primarily in-fluenced the PI3K-Akt,MAPK and Rap1 signaling pathways,as well as VEGFR.Western blot analysis showed that QJHF significantly inhibited the expression of VEGF and P38 in lung tissues(P＜0.05 or P＜0.01).CONCLUSION:Treatment with QJHF attenuates severe pneumonia in mice,potentially by inhibiting VEGF/P38 signaling to protect the vascular endothelial barrier.

AIM:To establish a severe pneumonia mouse model induced by bacterial infection.METHODS:A total of 102 male SPF C57BL/6J mice were randomly divided into a control group and a model group.Klebsiella pneu-moniae was administered via tracheal instillation at a concentration of 5×109 CFU.Mice were euthanized on days 1,2,4,8,and 14 post-infection to assess general condition,body weight,mortality,white blood cell and neutrophil counts,in-flammatory markers,and pathological changes in lung,heart,liver,spleen,kidney,and intestinal tissues.RESULTS:Mice in the model group exhibited symptoms such as dyspnea and huddling from 6 hours to 4 days post-infection,which progressively worsened,accompanied by continuous weight loss(P<0.01).These symptoms gradually resolved between days 5 and 14.Arterial oxygen saturation in the model group dropped to 80.7%from days 1 to 8(P<0.01)but returned to normal from days 9 to 14.A total of 23 model mice died between days 1 and 9,with no deaths thereafter,resulting in a mortality rate of 31.9%(P<0.01).Pathological examination revealed inflammatory cell infiltration,congestion,and ede-ma in lung tissue from days 1 to 2,with continued inflammatory cell infiltration,alveolar structural disorganization from days 4 to 8,and alveolar rupture and fusion by day 14(P<0.05 or P<0.01).Additionally,model mice showed significant increases in neutrophil count,white blood cell count,protein content in bronchoalveolar lavage fluid,total cell count,neutrophil ratio,and levels of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in peripheral blood from days 1 to 8(P<0.05 or P<0.01).No significant pathological changes were observed in heart and liver tissues,while spleen,kidney,and intestinal tissues exhibited notable pathological changes:indistinct boundaries be-tween red and white pulp in the spleen,significant congestion and edema around renal glomeruli,renal tubules,and col-lecting ducts,and extensive inflammatory cell infiltration in the colonic mucosa.CONCLUSION:Tracheal instillation of 5×109 CFU Klebsiella pneumoniae induces severe pathological changes in the lungs of mice,offering a robust model for studying the pathogenesis and treatment of severe pneumonia.

Objective:To study the clinical characteristics and management strategies of late bleeding after laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of 58 patients with post-pancreaticoduodenectomy hemorrhage (PPH) admitted to the Department of Hepatobiliary Surgery of the Second Hospital of Hebei Medical University from March 2018 to March 2022 were retrospectively analyzed, including 42 males and 16 females, aged (61.88±11.02) years old. According to the occurrence of intra-abdominal erosion factors (e.g., pancreatic fistula, biliary fistula, gastrointestinal anastomotic fistula, intra-abdominal abscess), patients were divided into the erosion group ( n=42) and non-erosion group ( n=16). All patients underwent standard lymphadenectomy. Clinical data including the PPH time-point, occurrence of rebleeding, and treatment outcomes were accessed. The management strategies of PPH in the two groups of patients were analyzed. Results:The PPH time-point in the erosion group and non-erosion patients was 8.00 (5.00, 19.25) d and 21.50 (12.75, 26.75) d, respectively ( P=0.001). PPH can occurred within one month after surgery in both erosion and non-erosion groups. In the erosion group, 31 cases (73.81%, 31/42) were treated by re-operation, two (4.76%, 2/42) by interventional radiology and nine (21.43%, 9/42) with conservative protocol, respectively. In the non-erosion group, five cases (31.25%, 5/16) were treated by re-operation, seven (43.75%, 7/16) by interventional radiology and four (25.00%, 4/16) with conservative protocol, respectively. The incidence of re-bleeding is higher in the erosion group [47.6% (20/42) vs 12.5% (2/16), P<0.05]. Clinical manifestations, sites and severity of bleeding, and treatment outcomes were also different in the erosion and non-erosion groups (all P<0.05). Conclusions:The occurrence of intra-abdominal erosion factors can affect the clinical characteristics and treatment strategy of late bleeding after laparoscopic pancreaticoduodenectomy. Surgery remains the treatment of choice for post-pancreaticoduodenectomy hemorrhage either as an urgent or last resort.

Objective:To evalte a novel laparoscopic splenic artery ligation plus devascularization (LSALD) vs. laparoscopic splenectomy and devascularization (LSD) for the treatment of portal hypertention. Methods:From Jan 2014 to Dec 2019, 50 patients undergoing LSALD and 30 patients receiving LSD . We compared the safety and feasibility between LSALD and LSD groups by analyzing the patients′ blood routine, liver function before and after operation, intraoperative condition, postoperative recovery and prognosis.Results:The operation time[(181±72)min vs.(284±72)min , t=-6.205, P<0.01], intraoperative blood loss[(100±50)ml vs.( 700±86 ml), t=-5.166, P<0.01]and blood transfusion rate (28% vs.67%, χ 2=11.471, P<0.01)in LSALD group were significantly more favorite than those in LSD group ( P<0.05). The postoperative exhaust in the LSALD group was earlier than that in the LSD group (2 d vs.3 d, Z=2.361, P<0.05) though the WBC and blood platelet count was higher in LSD group ( P<0.05). Portal vein thrombosis occurred in 10 cases in LSD group and 6 cases in LSALD group (χ 2=5.757, P<0.05). Conclusion:Compared with laparoscopic splenectomy combined with periesophagogastric devascularization, laparoscopic splenic artery ligation combined with periesophagogastric devascularization is less traumatic, helping quick recovery and lower rate of post-op portal vein thrombosis.

Objective:To evaluate the safety and effectiveness of clinical application of " variable diameter measurable pancreatic duct" in laparoscopic pancreaticoduodenectomy (LPD).Methods:A retrospective study was conducted at the Second Hospital, Hebei Medical University Liver Surgical Team from July 2019 to July 2020 using the " HongShi single stitch" method of pancreatic duct to jejunum anastomosis on 147 patients who underwent LPD. According to the type of pancreatic duct, the patients were divided into having normal pancreatic ducts (the normal group, n=61) and those having " variable diameter measuring pancreatic duct" (the variable diameter group, n=86). The perioperative data and postoperative complications were compared and analyzed. Results:There were 89 males and 58 females, aged (56.7±1.5) years. There were no significant differences in age, gender and body mass index between groups ( P>0.05). For the variable diameter group, the diameter of the divided pancreatic stump was (3.2±0.1) mm, and the depth of internal pancreatic duct stenting was (4.7±0.2) cm. However, it could not be measured accurately in the normal group. The incidence of postoperative pancreatic fistula rate was significantly lower in the variable diameter group than the normal group [2.32% (2/61) vs. 11.47% (7/86), P=0.023]. Conclusion:The variable diameter measurement of pancreatic duct was safe and effective in choosing patients to undergo LPD.

Objective To assess the diagnostic value of serum soluble mannose receptor (sMR) for hepatic fibrosis in patients with chronic hepatitis B (CHB).Methods Fifty patients with CHB undergoing liver biopsy in the Department of Infectious Diseases , Taizhou Hospital of Zhejiang Province from November 2016 to October 2018 were enrolled, including 28 males and 22 females.According to the stage of liver fibrosis, there were 15 cases without fibrosis (S0 group), 12 cases of mild fibrosis (S1-2 group), and 15 cases of moderate-severe fibrosis ( S3-4 group).Twenty healthy subjects (12 males and 8 females) were recruited as controls.Enzyme linked immunosorbent assay (ELISA) was used to detect the serum hyaluronic acid (HA), laminin (LN), procollagen type ⅢN-terminal peptide (PⅢP), collagen type IV (CIV) and sMR in all groups.One-way ANOVA, Spearman correlation analysis and receiver operating characteristic (ROC) curve were used to analyze the data.Results The serum levels of sMR, HA, LN, CIV and PⅢP in S3-4 group were significantly higher than those in S 0 group ( t＝10.20, 4.69, 8.94, 2.35 and 4.34, respectively; all P＜0.05) and S1-2 group (t＝5.77, 4.23, 7.88, 2.71 and 3.43, respectively; all P＜0.05); and serum sMR level in S1-2 group was higher than that in S0 group ( t ＝6.23, P ＜0.05). Spearman rank correlation demonstrated that serum sMR level was positively correlated with the degree of liver fibrosis (r＝0.860, P＜0.01).ROC curve analysis showed that when 228.69 ng／mL was taken as cut-off value of sMR, its specificity and sensitivity for diagnosis of hepatic fibrosis were 93.3%and 88.6%, respectively.The diagnostic efficacy of sMR was significantly better than that of HA , LN, CIV and PⅢP (Z＝3.179, 3.467, 5.241 and 3.567, respectively; all P＜0.05).When 345.80 ng／mL was taken as cut-off value of sMR, the specificity and sensitivity for diagnosis of moderate to severe hepatic fibrosis were 85.7%and 86.7%, respectively; and its diagnostic efficacy was better than that of HA , CIV and PⅢP (Z＝2.253, 2.475 and 2.092, all P ＜0.05).Conclusion Serum sMR level is associated with the progression of liver fibrosis, it may be used as a new serological marker for non-invasive assessment of liver fibrosis.

Objective To introduce the detailed surgical procedure of parachute-like-suture double-pouch pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy (LPD),and to study its clinical results.Methods A retrospective study was conducted on 31 patients who underwent parachute-like-suture double-pouch pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy between January 2016 and June 2018 in our department.Results Of 31 patients who underwent total laparoscopic pancreaticoduodenectomy,5 patients underwent two-dimensional (2D) LPD and 26 underwent three-dimensional (3D) LPD.Total mesopancreas excision (TMpE) was performed in 12 patients,including 2 patients combined with PV-SMV segmental resection and reconstruction.The mean operative duration,and mean estimated blood loss,post-operative hospital stay were 412.8 ± 102.4 min,462.8 ± 396.7 ml,14.7 ± 8.9 d,respectively.The operating time of parachute-like-suture double-pouch pancreaticojejunostomy was 29.7 ± 6.8 min (20 ～45 min).Post-operative complications occurred in 8 patients (25.8％),3 of whom suffered from more than two types of complications.There were 2 patients (6.5％) with postoperative B/C grade pancreatic fistula,4 patients with postoperative biliary leakage (12.9％),3 patients with delayed gastric emptying (9.7％),1 patient with portal vein thrombosis (3.2％) and 1 patient with peritoneal effusion (3.2％).One patient died during perioperative period due to gastrointestinal hemorrhage.Conclusions Parachute-like-suture double-pouch pancreaticojejunostomy in laparoscopic pancreaticoduodenectomy was a simple,convenient,reliable method.It is worthy of clinical promotion and further studied.

Objective To study the feasibility of laparoscopic pancreaticoduodenectomy ( LPD) in the treatment of pancreatic head cancer, and to analyze the short-term postoperative outcomes. Methods The clinical data of 57 patients with pancreatic head cancer who underwent laparoscopic pancreaticoduode-nectomy from April 2015 to November 2017 in the Second Hospital of Hebei Medical University were retro-spectively analyzed. Results Of the 57 patients, conversion to open surgery was required in 2 patients, and major venous resection and reconstruction were performed in 9 patients, including 8 end-to-end anastomosis, and 1 synthetic graft interposition. Total pancreatectomy was carried out in 4 patients. For the remaining 53 patients, pancreaticojejunal mucosal anastomoses were carried out in 50 patients, and sleeve pancreaticojeju-nostomy in 3 patients. The mean operative time and operative blood loss were 497 (240～720) min and 435 (50～3 000 ) ml, respectively. The mean postoperative hospital stay was 17. 7 ( 6. 0 ～59. 0 ) days. Postoperative complications were detected in 26. 3% (15/57) of patients, which included delayed gastric emptying (DGE) in 4 patients, Grade B pancreatic fistula (PF) in 4 patients, biliary fistula ( BF) in 2 patients, postpancreatectomy hemorrhage ( PPH) in 2 patients, intraabdominal infection in 1 patient and pulmonary infection in 2 patients. All the patients with DGE recovered with conservative treatment and they were discharged home. Reoperation was only required in the two patients with PPH. One patient died after the operation. The postoperative pathological results revealed pancreatic duct adenocarcinoma in 53 patients, adenosscale carcinoma in 1 patient and neuroendocrine carcinoma in 3 patients. The maximum and minimum tumor sizes were 7. 0 cm×5. 0 cm×3. 5 cm and 2. 5 cm×1. 5 ×1. 0 cm, respectively. The mean lymph nodes harvest and positive lymph node retrieval were 14(1～60) and 0. 7(0～3), respectively. Negative resection margins were obtained in 84. 2% (48/57) of patients. This study was censored on December 31, 2017. The follow-up for these patients ranged between 1 to 32 months. Mortality occurred in 21 patients, including 1 patient with a ruptured aneurysm 2 months after operation, 2 patients with GI bleeding 2 and 9 months respectively after operation, 1 patient with severe pulmonary infection and 17 patients with cancer recurrence with survival varying from 2 to 21 months. 35 patients were still alive. Conclusion Laparoscopic pancreaticoduodenectomy is a safe and feasible procedure for pancreatic head cancer.

Objective To understand the basic situation of healthcare-associated infection(HAI)management and prevention and control of multidrug-resistant organism(MDRO)infection in medical institutions in Hubei Province.Methods Questionnaires were used to investigate the basic situation of HAI management and MDRO infection in 47 tertiary and secondary hospitals in Hubei Province.Results 47 hospital were enrolled in this study,HAI management full-time staff was allocated with a median of 0.90/250 beds;in 2015,the isolation rates of methicillin-resistant Staphylococcus aureus,carbapenem-resistant Enterobacteriaceae,carbapenem-resistant Pseudomonas aeruginosa,carbapenem-resistant Acinetobacter baumannii,and vancomycin-resistant Enterococcus were 39.13%,4.13%,19.44%,63.60%,and 2.77%respectively.47 hospitals all carried out surveillance on MDROs,28(59.57%)hospitals were installed HAI monitoring system software,could directly obtain data through collecting with the laboratory system.The diagnosis of MDRO infection was mainly based on the combined diagnosis by HAI full-time personnel and clinicians(26 hospitals,55.32%).44(93.62%)hospitals regularly convened coordination meeting on prevention and control of MDROs,in 2015,hand hygiene compliance rate were 10.0%-89.2%by self-inspection;42(89.36%)hospitals routinely prescribed isolation orders for patients with MDRO infection,33(70.21%)hospitals conducted environmental clean and disinfection twice a day,24(51.06%)hospitals performed personal protection by using complete set of protective equipment.Conclusion This investigation is helpful for understanding the general situation of HAI management in medical institutions,as well as the detection and control of MDROs in this area,and make continual improvement on the problems and weakness found in the investigated project,so as to promote the development of HAI management in this area.