Aim To investigate the possible mechanism of action of Qingjie Huagong decoction(QJHGD)on acute lung injury(ALI)associated with severe acute pancreatitis(SAP)using network pharmacology,and to verify it by animal experiments.Methods The TC-MSP,BATMAN-TCM,ETCM,and SwissTargetPredic-tion databases were searched to obtain the action tar-gets of the blood-entering active ingredients of each drug in the QJHGD.The GeneCard database was searched to obtain SAP-ALI disease targets.The drug targets and disease targets were intersected to obtain common targets.Subsequently,the common targets were analyzed by STRING database and Cytoscape 3.7.1 software for protein interaction network analysis.GO and KEGG enrichment analysis was performed with the help of DAVID database.Finally,the key signa-ling pathways were verified by animal experiments.Results A total of 28 active ingredients were screened out for the treatment of SAP-ALI with 42 common tar-gets.PPI network analysis showed that STAT3,IL-6,and TGFB1 might be core targets;GO and KEGG en-richment analysis mainly involved cell proliferation,PI3K/AKT signaling pathways,etc.Animal experi-ments confirmed that QJHGD could improve the pathol-ogy of pancreas and lung tissues in SAP-ALI rat mod-el,down-regulate the expression levels of α-amylase,lipase,IL-1 β,IL-6,and TNF-α in serum,and down-regulate the expression levels of proteins and mRNAs related to PI3K/AKT1 signaling pathway in lung tis-sues.Conclusion QJHGD synergistically treats SAP-ALI through multi-component,multi-target,and multi-pathway,with a mechanism that may be related to the inhibition of PI3K/AKT signaling pathway activation.

OBJECTIVE: To compare the clinical efficacy between closed reduction combined with semi-circular external fixator and minimally invasive percutaneous plate osteosynthesis (MIPPO) in the treatment of middle anddistal tibia fractures. METHODS: The clinical data of sixty patients with middle and distal tibia fractures admitted between January 2019 and November 2022, were retrospectively analyzed. These patients were categorized into external fixation group (n=30) and internal fixation group (n=30). There were 18 males and 12 females in the external fixation group, with an average age of (49.29±2.35) years old. Among them, 14 patients presented with fractures on the left side, and 16 patients presented with fractures on the right side. Closed reduction, arched wire, and semi-circular external fixator were used for treatment. There were 20 males and 10 females in the internal fixation group, with an average age of (48.96±1.87) years old. Among them, 15 patients presented with fractures on the left side, and 15 patients presented with fractures on the right side. MIPPO technique was used for the treatment. Perioperative parameters, including time injury to surgery, surgical duration, incision length, intraoperative bleeding, time to active activity, and incision healing level, were compared between the two groups. Clinical outcomes were also assessed, including Johner-Wruhs scores, time to minimum pain-adapted full weight-bearing, visual analog scale (VAS), SF-36 scale, and complications. RESULTS: The external fixation group exhibited a significantly shorter incision length (1.36±0.86) cm and lower intraoperative bleeding (10.83±5.73) ml compared to the internal fixation group (12.74±3.12) cm and (86.47±8.90) ml, respectively(P<0.05). The postoperative active activity time (1.50±0.54) days and minimum pain-adapted full weight-bearing activity time(108.87±3.43) days in the external fixation group were slightly delayed than the internal fixation group(1.15±0.98) days and (105.27±3.68) days, respectively(P<0.05). Over a mean postoperative follow-up duration of (6.23±1.89) months, both groups showed improved VAS and SF-36 scale scores. There were no statistically significant differences in VAS and SF-36 scale scores 1, 3, 6 months post-operatively between the two groups(P>0.05). The intraoperative surgical time in the external fixation group (35.42±9.31) minutes was shorter than that in the internal fixation group(74.22±7.81) minutes (P<0.05). There was no intraoperative vascular or nerve injury, nor postoperative skin necrosis in the external fixation group. However, skin necrosis was observed in 6 patientsin the internal fixation group, representing a statistically significant difference (P<0.05). CONCLUSION Both external fixation and plate internal fixation are effective methods for the treatment of middle and distal tibia fractures. External fixation exhibits the advantage of less surgical trauma and a lower incidence of complications.
Female ; Male ; Humans ; Middle Aged ; Retrospective Studies ; Tibia ; Treatment Outcome ; Ankle Fractures ; Tibial Fractures/surgery* ; External Fixators ; Pain ; Necrosis

This study aimed to investigate the effects of nanoparticles PLGA-NPs and mesoporous silicon nanoparticles(MSNs) of different stiffness before and after combination with menthol or curcumol on the mechanical properties of bEnd.3 cells. The particle size distributions of PLGA-NPs and MSNs were measured by Malvern particle size analyzer, and the stiffness of the two nanoparticles was quantified by atomic force microscopy(AFM). The bEnd.3 cells were cultured in vitro, and the cell surface morphology, roughness, and Young's modulus were examined to characterize the roughness and stiffness of the cell surface. The changes in the mechanical properties of the cells were observed by AFM, and the structure and expression of cytoskeletal F-actin were observed by a laser-scanning confocal microscope. The results showed that both nanoparticles had good dispersion. The particle size of PLGA-NPs was(98.77±2.04) nm, the PDI was(0.140±0.030), and Young's modulus value was(104.717±8.475) MPa. The particle size of MSNs was(97.47±3.92) nm, the PDI was(0.380±0.016), and Young's modulus value was(306.019±8.822) MPa. The stiffness of PLGA-NPs was significantly lower than that of MSNs. After bEnd.3 cells were treated by PLGA-NPs and MSNs separately, the cells showed fine pores on the cell surface, increased roughness, decreased Young's modulus, blurred and broken F-actin bands, and reduced mean gray value. Compared with PLGA-NPs alone, PLGA-NPs combined with menthol or curcumol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value. Compared with MSNs alone, MSNs combined with menthol could allow deepened and densely distributed surface pores of bEnd.3 cells, increase roughness, reduce Young's modulus, aggravate F-actin band breakage, and diminish mean gray value, while no significant difference was observed in combination with curcumol. Therefore, it is inferred that the aromatic components can increase the intracellular uptake and transport of nanoparticles by altering the biomechanical properties of bEnd.3 cells.
Animals ; Mice ; Menthol/pharmacology* ; Actins/metabolism* ; Endothelial Cells/metabolism* ; Nanoparticles/chemistry*

Objective: To explore the effects of porcine urinary bladder matrix (UBM) on the motility and polarization of bone marrow-derived macrophages in mice, so as to provide evidence for the rational selection of stent in clinical wound repair. Methods: The method of experimental research was used. The microstructure of porcine UBM and absorbable dressing was observed under scanning electron microscope. Polyacrylamide gel electrophoresis was used to observe the protein distribution of the two stent extracts. The primary macrophages were induced from bone marrow-derived cells isolated from six 6-8-week-old male C57BL/6J mice (mouse age, sex, and strain, the same below) and identified. Three batches of macrophages were divided into porcine UBM extract group and absorbable dressing extract group. The cells in each group were cultured with Dulbecco's modified Eagle medium/F12 medium containing the corresponding extracts. The cell migration rate was detected and calculated on 1, 3, and 7 d after scratching by scratch test. The number of migrated cells at 12 and 24 h of culture was detected by Transwell experiment. The percentages of CD206 and CD86 positive cells at 24 h of culture was detected by flow cytometer. The numbers of sample in the above cell experiments were all 3. An incision was prepared on the left and right back of twelve mice, respectively. The left incision of each mouse was included in porcine UBM group and the right incision was included in absorbable dressing group, and the corresponding stents were implanted into the incisions respectively. On post operation day (POD) 7 and 14, the number of inflammatory cells infiltrated in the stent was detected by hematoxylin-eosin staining; the number of F4/80, transforming growth factor-β₁ (TGF-β₁), vascular endothelial growth factor (VEGF), and matrix metalloprotein-9 (MMP-9) positive cells and type Ⅰ collagen deposition in stents were observed by immunohistochemistry; the percentages of F4/80, CD86, and CD206 positive cells were observed by immunofluorescence staining. The numbers of sample in the above animal experiments were all 6. Data were statistically analyzed with analysis of variance for factorial design, analysis of variance for repeated measurement, and independent sample t test. Results: Porcine UBM has a dense basement membrane structure on one side and porous propria containing a fibrous structures on the other. Both sides of the absorbable dressing had three-dimensional porous structure. In the molecular weight range of (50-70)×10³, multiple non-type Ⅰ collagen bands appeared in the lanes of porcine UBM extract, while no obvious bands appeared in the lanes of absorbable dressing extract. It had been identified that mouse bone marrow-derived cells had been successfully induced into macrophages. The cell migration rates in porcine UBM extract group were significantly higher than those in absorbable dressing extract group on 1, 3, and 7 d after scratching (with t values of 15.31, 19.76, and 20.58, respectively, P<0.05). The numbers of migrated cells in porcine UBM extract group were significantly more than those in absorbable dressing extract group at 12 and 24 h of culture (with t values of 12.20 and 33.26, respectively, P<0.05). At 24 h of culture, the percentage of CD86 positive cells in porcine UBM extract group ((1.27±0.19)%) was significantly lower than (7.34±0.14)% in absorbable dressing extract group (t=17.03, P<0.05);the percentage of CD206 positive cells in porcine UBM extract group was (73.4±0.7)%, significantly higher than (32.2±0.5)% in absorbable dressing extract group (t=119.10, P<0.05). On POD 7 and 14, the numbers of inflammatory cells infiltrated in the stents in porcine UBM group was significantly more than those in absorbable dressing group (with t values of 6.58 and 10.70, respectively, P<0.05). On POD 7 and 14, the numbers of F4/80, TGF-β₁, VEGF, and MMP-9 positive cells in the stents in porcine UBM group were significantly more than those in absorbable dressing group (with t values of 46.11, 40.69, 13.90, 14.15, 19.79, 32.93, 12.16, and 13.21, respectively, P<0.05); type Ⅰ collagen deposition in the stents in porcine UBM group was more pronounced than that in absorbable dressing group; the percentages of CD206 positive cells in the stents in porcine UBM group were significantly higher than those in absorbable dressing group (with t values of 5.05 and 4.13, respectively, P<0.05), while the percentages of CD86 positive cells were significantly lower than those in absorbable dressing group (with t values of 20.90 and 19.64, respectively, P<0.05), and more M2-type macrophages were seen in the stents in porcine UBM group and more M1-type macrophages were seen in the stents in absorbable dressing group. Conclusions: Porcine UBM can enhance macrophage motility, induce M2 polarization and paracrine function, create a microenvironment containing growth factors such as TGF-β₁ and MMP-9 tissue remodeling molecules, and promote tissue regeneration and extracellular matrix remodeling in mice.
Mice ; Male ; Animals ; Swine ; Vascular Endothelial Growth Factor A ; Urinary Bladder ; Matrix Metalloproteinase 9 ; Mice, Inbred C57BL ; Macrophages ; Collagen

Animals ; SARS-CoV-2 ; Antibodies, Neutralizing ; Macaca mulatta ; COVID-19/prevention & control* ; Antibodies, Viral ; Vaccines

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objectives: To construct a nomogram incorporating important prognostic factors for predicting the overall survival of patients with colorectal cancer with peritoneal metastases treated with cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC), the aim being to accurately predict such patients' survival rates. Methods: This was a retrospective observational study. Relevant clinical and follow-up data of patients with colorectal cancer with peritoneal metastases treated by CRS + HIPEC in the Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University from 2007 January to 2020 December were collected and subjected to Cox proportional regression analysis. All included patients had been diagnosed with peritoneal metastases from colorectal cancer and had no detectable distant metastases to other sites. Patients who had undergone emergency surgery because of obstruction or bleeding, or had other malignant diseases, or could not tolerate treatment because of severe comorbidities of the heart, lungs, liver or kidneys, or had been lost to follow-up, were excluded. Factors studied included: (1) basic clinicopathological characteristics; (2) details of CRS+HIPEC procedures; (3) overall survival rates; and (4) independent factors that influenced overall survival; the aim being to identify independent prognostic factors and use them to construct and validate a nomogram. The evaluation criteria used in this study were as follows. (1) Karnofsky Performance Scale (KPS) scores were used to quantitatively assess the quality of life of the study patients. The lower the score, the worse the patient's condition. (2) A peritoneal cancer index (PCI) was calculated by dividing the abdominal cavity into 13 regions, the highest score for each region being three points. The lower the score, the greater is the value of treatment. (3) Completeness of cytoreduction score (CC), where CC-0 and CC-1 denote complete eradication of tumor cells and CC-2 and CC-3 incomplete reduction of tumor cells. (4) To validate and evaluate the nomogram model, the internal validation cohort was bootstrapped 1000 times from the original data. The accuracy of prediction of the nomogram was evaluated with the consistency coefficient (C-index), and a C-index of 0.70-0.90 suggest that prediction by the model was accurate. Calibration curves were constructed to assess the conformity of predictions: the closer the predicted risk to the standard curve, the better the conformity. Results: The study cohort comprised 240 patients with peritoneal metastases from colorectal cancer who had undergone CRS+HIPEC. There were 104 women and 136 men of median age 52 years (10-79 years) and with a median preoperative KPS score of 90 points. There were 116 patients (48.3%) with PCI≤20 and 124 (51.7%) with PCI>20. Preoperative tumor markers were abnormal in 175 patients (72.9%) and normal in 38 (15.8%). HIPEC lasted 30 minutes in seven patients (2.9%), 60 minutes in 190 (79.2%), 90 minutes in 37 (15.4%), and 120 minutes in six (2.5%). There were 142 patients (59.2%) with CC scores 0-1 and 98 (40.8%) with CC scores 2-3. The incidence of Grade III to V adverse events was 21.7% (52/240). The median follow-up time is 15.3 (0.4-128.7) months. The median overall survival was 18.7 months, and the 1-, 3- and 5-year overall survival rates were 65.8%, 37.2% and 25.7%, respectively. Multivariate analysis showed that KPS score, preoperative tumor markers, CC score, and duration of HIPEC were independent prognostic factors. In the nomogram constructed with the above four variables, the predicted and actual values in the calibration curves for 1, 2 and 3-year survival rates were in good agreement, the C-index being 0.70 (95% CI: 0.65-0.75). Conclusions: Our nomogram, which was constructed with KPS score, preoperative tumor markers, CC score, and duration of HIPEC, accurately predicts the survival probability of patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy.
Male ; Humans ; Female ; Middle Aged ; Peritoneal Neoplasms/secondary* ; Nomograms ; Cytoreduction Surgical Procedures/adverse effects* ; Hyperthermic Intraperitoneal Chemotherapy ; Quality of Life ; Hyperthermia, Induced ; Prognosis ; Combined Modality Therapy ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Colorectal Neoplasms/pathology* ; Retrospective Studies ; Survival Rate

General recommendations regarding surgical techniques are not always appropriate for all Peyronie's disease (PD) patients. Therefore, the purpose of this study was to investigate the effects of plication procedures in PD patients with severe penile curvature and the effects of early surgical correction in patients who no longer have progressive deformities. The clinical data from 72 patients who underwent plication procedures were analyzed in this study. Patients were divided into Groups A and B according to the curvature severity (≤60° or >60°) and Groups 1 and 2 according to the duration of disease stabilization (≥3 months or <3 months). At the 1-year follow-up, 90.0% (36/40) and 90.6% (29/32) patients reported complete penile straightening, and 60.0% (24/40) and 100.0% (32/32) patients reported penile shortening in Groups A and B, respectively. No curvature recurrence occurred in any patient, and no significant differences were observed in postoperative International Index of Erectile Function-Erectile Function domain (IIEF-EF), erectile pain, sensitivity, or suture knots on the penis whether such outcomes were grouped according to the curvature severity or the duration of stabilization. However, the duration from symptom onset to surgical management in Group 1 was significantly longer than that in Group 2 (mean ± standard deviation [s.d.]: 20.9 ± 2.0 months and 14.3 ± 1.2 months, respectively, P < 0.001). The present study showed that the plication procedures seemed to be an effective choice for the surgical treatment of PD patients with severe penile curvature. In addition, the early surgical treatment seemed to benefit those patients who already had no erectile pain and no longer exhibited progressive deformity.
Erectile Dysfunction/surgery* ; Humans ; Male ; Patient Satisfaction ; Pelvic Pain ; Penile Induration/surgery* ; Penis/surgery* ; Retrospective Studies ; Treatment Outcome

OBJECTIVE: To analyze the clinical characteristics and long-term prognosis of patients with primary bone lymphoma (PBL). METHODS: The clinical data of 21 patients with PBL treated in our center from 2005 to 2018 were analyzed retrospectively, the clinical characteristics and the factors affecting prognosis of the patients were analyzed. RESULTS: The median age of all the 21 newly diagnosed PBL patients was 40(12-71) years old. Ostealgia was the initial symptom in most of the patients (19/21,90.5%). 42.9%(9/21) of the patients showed single bone lesion only. 571% (12/21) of the patients showed diffuse large B cell lymphoma. 28.6% (6/21) of the patients showed anaplastic large cell lymphoma and 9.5% (2/21) of the patients showed T cell lymphoblastic lymphoma. All the patients received chemotherapy (CHOP or CHOP like regimen, 33.3% plus rituximab) with or without radiotherapy and/or autologous hematopoietic stem cell transplantation (ASCT). 18 patients achieved clinical remission (including 15 for CR and 3 for PR). The median follow-up time was 48 months. The 5-year overall survival rate and progression-free survival rate of the patients were was 67.5% and 63.7%, respectively. The single factors analysis showed that ASCT was the important prognostic factor of PFS, while the single or multiple bone lesion was the factors affecting OS of the patients. There were no statistical differences with the effects of age, sex, stage, ECOG score, LDH level, B symptoms and radiotherapy for the prognosis of patients. CONCLUSION Diffuse large B cell lymphoma is the most common pathological type of PBL. Chemotherapy is the main treatment, which can be combined with radiotherapy and/or ASCT. The ASCT and the number of bone lesion are the factors for long time survival of the patients.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cyclophosphamide ; Disease-Free Survival ; Doxorubicin ; Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Middle Aged ; Prednisone ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Transplantation, Autologous ; Vincristine

Objective:To evaluate the safety and efficacy of endoscopic retrograde biliary drainage (ERBD) for acute obstructive suppurative cholangitis (AOSC) in the elderly.Methods:A retrospective analysis was performed on the clinical data of AOSC patients admitted to the First Affiliated Hospital of Xinjiang Medical University from January 2018 to January 2020. Patients aged 75 years and over ( n=49) were assigned to the elderly group and patients under 75 years old were assigned to the control group ( n=63). General data, American Society of Anesthesiologists (ASA) grading, procedure-related indicators, incidence of postoperative complications and mortality were compared. Results:There were significant differences in age (82.6±5.1 years VS 64.6±4.5 years, t=19.98, P<0.001), albumin levels (29.1±5.9 g/L VS 34.6±8.8 g/L, t=-3.94, P<0.001) and ASA grade ( χ2=8.37, P=0.015) in the elderly group and the control group . The elderly group were accompanied by more basic diseases, i.e. hypertension [57.14% (28/49) VS 34.9% (22/63), χ2=5.51, P=0.019], coronary heart disease [55.1% (27/49) VS 27.0% (17/63), χ2=9.14, P=0.003], chronic obstructive pulmonary diseases/asthma [24.5% (12/49) VS 6.3% (4/63), χ2=7.41, P=0.006]. There were no significant differences in the operation time (31.4±8.1 min VS 30.4±8.0 min, t=-0.61, P=0.543) or hospital stay (6.1±1.7 days VS 5.7±1.4 days, t=1.35, P=0.182). The incidences of postoperative complications were 14.3% (7/49) in the elderly group and 12.7% (8/63) in the control group, showing no significant difference ( χ2=0.06, P=0.807). No ERBD-related death was observed in either group during hospital stay. Conclusion:For elderly patients with AOSC over 75 years old, emergency ERBD, which can quickly relieve the disease, is safe and effective. Advanced age is not an absolute contraindication for emergency ERBD.