Long-Term Follow-Up of a Case of Probable Aspergillus Skull Base Osteomyelitis With Galactomannan Test and Literature Review.

We report a probable case of Aspergillus basicranial infection diagnosed by pathogenic serological examination presenting atypical initial manifestations, and highlight the importance of serological examination to avoid treatment delay and disease management. An 84-year-old diabetic patient presented with right peripheral nerve palsy, intolerable otalgia, hearing loss, dysphagia, hoarseness, and bucking. The patient was diagnosed a probable Aspergillus skull base osteomyelitis with cranial neuritis and meningitis of central nervous system. Galactomannan test was used in combination with 1-3-ß-D-glucan and magnetic resonance imaging to follow-up during the continuous treatment of voriconazole. To date, the patient has remained in clinical remission for over 39 months but the drug cannot be stopped safely.

Cldn4 overexpression promotes penile cavernous smooth muscle cell fibrotic response via the JNK signaling pathway.

BACKGROUND: Erectile dysfunction (ED), defined as the inability to achieve or maintain a penile erection sufficient to satisfy sexual behavior, is prevalent worldwide. AIM: Using previous research, bioinformatics, and experimental confirmation, we aimed to discover genes that contribute to ED through regulating hypoxia in corpus cavernosum smooth muscle cells (CCSMCs). METHODS: We used the Gene Expression Omnibus to acquire the sequencing data of the corpus cavernosum transcriptome for diabetic ED and nerve injury type ED rats. We intersected the common differentially expressed genes. Further verification was performed using single cell sequencing. Real-time quantitative polymerase chain reaction and immunofluorescence were used to investigate whether the differentially expressed genes are found in the corpus cavernosum. We used induced hypoxia to assess cell viability changes, and we developed a lentivirus overexpressing Cldn4 for in vitro and in vivo experiments to measure changes in JNK signaling, fibrosis, hypoxia, and erectile function. OUTCOMES: Our results indicate that targeting the JNK pathway and decreasing local hypoxia may be better options for therapeutic intervention to improve erectile function. RESULTS: We identified Cldn4 and found its expression increased in the corpora cavernosa of the 2 datasets. In addition, we found that hypoxia can increase the expression of Cldn4, activate the JNK signaling pathway, and exacerbate fibrosis in CCSMCs. Cldn4 overexpression in CCSMCs activated the JNK signaling pathway and increased fibrotic protein expression. Last, rat corpus cavernosum overexpressing Cldn4 activated the JNK signaling pathway, increased local fibrosis, and impaired erectile function. CLINICAL IMPLICATIONS: Through bioinformatics and in vitro and in vivo experiments, we found that Cldn4 has a negative effect on ED, and targeting Cldn4 may provide new ideas for ED treatment. STRENGTHS AND LIMITATIONS: Although we have identified Cldn4 as a potential target for ED treatment, we have only conducted preliminary validation on CCMSCs, and we still need to further validate in other cell lines. CONCLUSION: CCSMC hypoxia leads to increased Cldn4, in both nerve injury and diabetic ED rat models, and promotes fibrosis by activating the JNK signaling pathway.

Inhibition of PPP1R15A alleviates osteoporosis via suppressing RANKL-induced osteoclastogenesis.

Osteoporosis results from overactivation of osteoclasts. There are currently few drug options for treatment of this disease. Since the successful development of allosteric inhibitors, phosphatases have become attractive therapeutic targets. Protein phosphatase 1, regulatory subunit 15 A (PPP1R15A), is a stress-responsive protein, which promotes the UPR (unfolded protein response) and restores protein homeostasis. In this study we investigated the role of PPP1R15A in osteoporosis and osteoclastogenesis. Ovariectomy (OVX)-induced osteoporosis mouse model was established, osteoporosis was evaluated in the left femurs using micro-CT. RANKL-stimulated osteoclastogenesis was used as in vitro models. We showed that PPP1R15A expression was markedly increased in BMMs derived from OVX mice and during RANKL-induced osteoclastogenesis in vitro. Knockdown of PPP1R15A or application of Sephin1 (a PPP1R15A allosteric inhibitor in a phase II clinical trial) significantly inhibited osteoclastogenesis in vitro. Sephin1 (0.78, 3.125 and 12.5 µM) dose-dependently mitigated the changes in NF-κB, MAPK, and c-FOS and the subsequent nuclear factor of activated T cells 1 (NFATc1) translocation in RANKL-stimulated BMMs. Both Sephin1 and PPP1R15A knockdown increased the phosphorylated form of eukaryotic initiation factor 2α (eIF2α); knockdown of eIF2α reduced the inhibitory effects of Sephin1 on NFATc1-luc transcription and osteoclast formation. Furthermore, Sephin1 or PPP1R15A knockdown suppressed osteoclastogenesis in CD14+ monocytes from osteoporosis patients. In OVX mice, injection of Sephin1 (4, 8 mg/kg, i.p.) every two days for 6 weeks significantly inhibited bone loss, and restored bone destruction and decreased TRAP-positive cells. This study has identified PPP1R15A as a novel target for osteoclast differentiation, and genetic inhibition or allosteric inhibitors of PPP1R15A, such as Sephin1, can be used to treat osteoporosis. This study revealed that PPP1R15A expression was increased in osteoporosis in both human and mice. Inhibition of PPP1R15A by specific knockdown or an allosteric inhibitor Sephin1 mitigated murine osteoclast formation in vitro and attenuated ovariectomy-induced osteoporosis in vivo. PPP1R15A inhibition also suppressed pathogenic osteoclastogenesis in CD14+ monocytes from osteoporosis patients. These results identify PPP1R15A as a novel regulator of osteoclastogenesis and a valuable therapeutic target for osteoporosis.

Two-dimensional liquid chromatography measurement of meropenem concentration in synovial fluid of patients with periprosthetic joint infection.

Periprosthetic joint infection (PJI) is a catastrophic complication following joint replacement surgery. One potential treatment approach for PJI could be the combination of one-stage revision and intra-articular infusion of antibiotics. Meropenem is one of the commonly used intra-articular antibiotics in our institution. Determining the concentration of meropenem in the joint cavity could be crucial for optimizing its local application, effectively eradicating biofilm infection, and improving PJI treatment outcomes. In this study, we developed a simple, precise, and accurate method of two-dimensional liquid chromatography (2D-LC) for determining the concentration of meropenem in human synovial fluid. The method was then validated based on the guidelines of the Food and Drug Administration and the Chinese Pharmacopoeia. Meropenem showed good linearity in the range of 0.31-25.01 µg/mL (r ≥ .999). Selectivity, intra-day and inter-day precision and accuracy, extraction recovery, and stability validation results were all within the acceptance range. This method has been successfully applied to the determination of synovial fluid samples from PJI patients, providing a useful detection method for meropenem therapeutic drug monitoring (TDM) in PJI patients.

Efficacy and safety of recombinant human anti-SARS-CoV-2 monoclonal antibody injection(F61 injection)in the treatment of patients with COVID-19 combined with renal damage:a randomized controlled exploratory clinical study / 中国感染控制杂志

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Successful Heart Transplantation After Thrombectomy for Acute Ischemic Stroke in a Patient With Heart Failure Complicating With Acute Ischemic Stroke / 中国循环杂志

It remains unclear whether heart transplantation is still feasible on patients who develop neurological complications before surgery and underwent successful neurological treatment.This article reported the diagnosis and treatment process of a heart failure patient complicating with acute ischemic stroke,who underwent successful heart transplantation after thrombectomy for acute ischemic stroke,aiming to provide clinical evidence and decision-making plan on diagnosis and treatment options for this group of patients with severe neurological complications.

Construction of nursing quality evaluation index system for pediatric orthopedics / 中国实用护理杂志

Objective:To construct a representative index system for evaluating pediatric orthopedic nursing quality, providing a basis for hospital pediatric orthopedic nursing quality assessment and monitoring.Methods:From April to July 2023, using the "structure-process-outcome" three-dimensional quality structure model as the theoretical framework, a literature review was conducted, and an item pool was formulated. Through two rounds of Delphi method expert consultations, the hierarchical analysis method was finally employed to determine the indicators and their weights at each level.Results:The effective recovery rates of the questionnaire of the two rounds of expert consultations were 100% (20/20), the authority coefficients of experts were 0.87 and 0.88, the coefficients of variation were 0.00 to 0.27 and 0.00 to 0.24. The Kendell harmony coefficients of the second and third indicators in the two rounds of inquiry were 0.140, 0.166 and 0.192, 0.161(all P<0.05). The final pediatric orthopedic nursing quality evaluation index system included 3 primary indicators, 21 secondary indicators and 83 tertiary indicators. Among the primary indicators, the weight of process quality was the highest at 0.493 4, followed by outcome quality at 0.310 8, and the lowest was structural quality at 0.195 8. In the secondary indicators, "assessment criteria of limb blood circulation" had the highest weight at 0.099 8. Conclusions:The constructed pediatric orthopedic nursing quality evaluation index system covers key aspects and is more operationally feasible. It provides better guidance for nursing interventions and quality control.

Free vascularized fibular grafting in treatment of femoral head osteonecrosis / 中国组织工程研究

BACKGROUND:Free vascularized fibular grafting is an effective hip preservation treatment for femoral head osteonecrosis,but its influencing factors are still controversial. OBJECTIVE:To explore the clinical efficacy of free vascularized fibular grafting for femoral head osteonecrosis,and the influence of the etiology and severity of femoral head osteonecrosis on its efficacy. METHODS:Clinical data and clinical efficacy scores of preoperative and postoperative hip joints in 63 patients with femoral head osteonecrosis(73 cases of hip)were enrolled.The subjects were divided into three groups by the etiological classification criteria of femoral head osteonecrosis,including glucocorticoid-associated,alcohol-associated,and idiopathic groups,and also were divided into three groups by the Ficat classification system,including Ficat Ⅱ,Ficat Ⅲ and Ficat Ⅳ groups.The effects of etiological classification and lesion degree on the clinical efficacy of free vascularized fibular grafting for femoral head osteonecrosis were analyzed. RESULTS AND CONCLUSION:(1)The visual analog scale scores in all periods after free vascularized fibular grafting for femoral head osteonecrosis were significantly decreased compared with preoperative data(P<0.001),and Harris scores were significantly increased compared with preoperative data(P<0.001).(2)In the glucocorticoid-associated,alcohol-associated,and idiopathic groups,except the glucocorticoid-associated group,postoperative Harris scores were significantly increased 2 and 3 years after surgery in other groups compared with preoperative data(P<0.05).(3)In the three groups of Ficat Ⅱ,Ficat Ⅲ,and Ficat Ⅳ,the postoperative Harris scores of Ficat Ⅱ and Ficat Ⅲ groups were significantly increased compared with preoperative data(P<0.05),while the difference was not significant in the Ficat Ⅳ group between the preoperative and postoperative data(P>0.05).(4)These results indicate that the clinical effect of free vascularized fibular grafting for the femoral head osteonecrosis is significant,which can reduce hip pain and improve hip joint function.It may not be affected by the etiology,but by the severity of the femoral head osteonecrosis.

Mechanism by which interleukin-1beta regulates the expression of Semaphorin 3A to induce intervertebral disc degeneration / 中国组织工程研究

BACKGROUND:Semaphone 3A(Sema3A)is an important neurovascular growth inhibitor.It is not clear how Sema3A is involved in the pathogenesis of discogenic low back pain.Exploring the potential mechanism of Sema3A in intervertebral disc degeneration can provide a new target and theoretical basis for the prevention and treatment of discogenic low back pain. OBJECTIVE:To explore the mechanism of interleukin-1β inhibiting the expression of Sema3A by activating the nuclear factor-κB signaling pathway to induce intervertebral disc degeneration in rats. METHODS:RT-qPCR was used to detect the expression of Sema3A mRNA in normal and degenerative human nucleus pulposus tissues.Nucleus pulposus cells of Sprague-Dawley rats were isolated,cultured,and passaged to the 3rd generation.Then,passage 3 cells were divided into three groups:the blank control group was routinely cultured for 48 hours,the degeneration group was intervened with 10 ng/mL interleukin 1β for 48 hours,and the degeneration+inhibitor group was treated by 5 μmol/L nuclear factor-κB signaling pathway-specific inhibitor BAY11-7082 for 1 hour,followed by interleukin-1β for 48 hours.At the end of the intervention,cell viability was detected by cell counting kit-8,cell apoptosis was detected by Annexin V/FITC staining,mRNA expression of cellular matrix,vascular and neural markers and Sema3A was detected by RT-qPCR,and protein expression of marker proteins,p65 and p-p65 was detected by western blot. RESULTS AND CONCLUSION:RT-qPCR assay showed that the expression of Sema3A mRNA was lower in degenerative human nucleus pulposus tissue than in normal human nucleus pulposus tissue(P＜0.05).Compared with the blank control group,the nucleus pulposus cell viability decreased and the apoptotic rate increased in the degeneration group(P＜0.05);compared with the degeneration group,the nucleus pulposus cell viability increased and the apoptotic rate decreased in the degeneration + inhibitor group(P＜0.05).Compared with the blank control group,mRNA expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was decreased in the degeneration group(P＜0.05),while mRNA expression of CD31 and neurofilament 200 was increased(P＜0.05).Compared with the degeneration group,mRNA expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was elevated in the degeneration+inhibitor group(P＜0.05)and mRNA expression of CD31 and neurofilament 200 decreased(P＜0.05).Compared with the blank control group,the protein expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was decreased in the degeneration group(P＜0.05),and the protein expression of CD31,neurofilament protein 200,p65,and p-p65 was elevated(P＜0.05);compared with the degeneration group,the protein expression of type Ⅱ collagen,polyproteoglycan,and Sema3A was elevated in the degeneration+inhibitor group(P＜0.05),and protein expression of CD31,neurofilament 200,p65,and p-p65 was decreased(P＜0.05).To conclude,interleukin-1β does inhibit the expression of Sema3A by activating the nuclear factor-κB signaling pathway,which can also increase the degradation of extracellular matrix,promote the innervation and angiogenesis in degenerative intervertebral disc,and may be one of potential factors that contribute to intervertebral disc degeneration and discogenic low back pain.

Finite element analysis of interspinous fixation-assisted endoscopic interbody fusion in treatment of severe lumbar spinal stenosis / 中国组织工程研究

BACKGROUND:In clinical application,simple interspinous fixation without additional interbody fusion has similar fixation effects to pedicle screw and rod fusion internal fixation,and can effectively reduce the range of motion of the responsible segment and the stress of the articular process.However,after simple placement of the new interspinous fusion fixation device BacFuse,the stress at the root of the spinous process is relatively concentrated,and the spinous fracture is prone to occur.If an intervertebral fusion cage is inserted in conjunction with interspinous fixation,Von Mises stress can theoretically be dispersed to reduce the risk of spinous fracture.However,there are few studies on biomechanics and finite element analysis. OBJECTIVE:To observe the biomechanical stability of interspinous fixation-assisted endoscopic interbody fusion in the treatment of severe lumbar spinal stenosis. METHODS:The normal finite element model M0 of the L4-L5 segment of the lumbar spine was established by Mimics,Geomagic,Solidworks,and ANSYS software based on the lumbar CT images of a 26-year-old adult male volunteer excluding spinal diseases.On the basis of M0,the immediate model M1 after endoscopic decompression combined with interbody fusion,the interspinous fixation device(BacFuse)model M2 after endoscopic decompression,and the interspinous fixation(BacFuse)model M3 after endoscopic-assisted interbody fusion were established.The same stress was applied to the upper surface of the L4 vertebral body in the four groups,and the lower surface of the L5 vertebral body was fixed and supported.The range of motion and the extreme Von Mises stress of the endplate bone and the posterior ligament complex of the vertebral body were analyzed under six working conditions of flexion,extension,left/right bending,and left/right rotation. RESULTS AND CONCLUSION:(1)Compared with model M0,the range of motion value of model M1 increased significantly under six working conditions.Model M2 and model M3 had a significant reduction in range of motion.(2)Compared with model M0,the maximum stress of the vertebral body in model M1 did not change significantly under the six working conditions.The maximum stress at the rear of the M2 vertebral body increased significantly.(3)Compared with model M1,the maximum stress of model M3 did not change significantly under the six working conditions.Compared with model M2,the maximum stress of model M3 decreased significantly.(4)Compared with the model M0,the extreme Von Mises stress of the L4 and L5 endplates of the model M1 was significantly increased.The extreme Von Mises stress in L4 and L5 endplates of models M2 and M3 decreased slightly.Compared with model M1,the Von Mises stress of the bone under the L4 and L5 endplate of models M2 and M3 was significantly reduced.(5)It is concluded that the implantation of BacFuse can effectively reduce the bone stress under the endplate during simple interbody fusion,decrease the risk of cage subsidence,diminish the risk of facet joint fracture on the decompression side,and provide a good stable environment for interbody fusion.The placement of an intervertebral fusion cage can reduce the stress of the root of the spinous process,which is beneficial to decrease the risk of fracture of the root of the spinous process.

Finite element analysis of the influence of lateral collateral ligament injury on ankle stability and talar trochlear cartilage stress in a marathon runner / 中华放射学杂志

Objective:A three-dimensional (3D) finite element model of the ankle joint of marathon runners was constructed to simulate the changes of the lateral collateral ligament (LCL) injury on the stability of the ankle joint and the force distribution of talar talus cartilage during exercise.Methods:The 3D MRI images of the right ankle joint of one marathon runner were acquired and imported into Mimics software in DICOM format for preliminary 3D model reconstruction of the images. The boundary conditions and loads were loaded on the model using Ansys Workbench software, and the ankle joint forces were analyzed by Ansys Workbench for marathon runners in the sports condition, and four kinds of ankle LCL injury finite element models were established, i.e., the normal model of LCL, the injury model of anterior talofibular ligament (ATFL), the injury model of AFTL merged with the calcaneofibular ligament (CFL), and the injury model of AFTL merged with the CFL and the posterior talofibular ligament (PTFL). The peak talus slide cartilage stress and its distribution were observed under the four models, and one-way ANOVA was used to compare the values of talus advancement, and the SNK- q test was used for two-by-two comparisons. Results:In the LCL normal model, the maximum stress peak of the talar slide was 0.21 MPa, which was mainly distributed in the junction area of the anterior medial (MA) and anterior lateral (LA) parts and part of the LA region. In ATFL injury, the peak stress of talar cartilage increased compared with the normal model, with a maximum value of 0.65 MPa, which was mainly distributed in the MA region. In ATFL combined with CFL injury, the peak stress increased, and the peak was mainly distributed in the MA region, and was shifted from the MA to the LA region. In ATFL combined with CFL and PTFL injuries, the peak cartilage stress in the talus slide was up to 2.29 MPa, and the maximum stress was mainly distributed in MA and LA, which had a comparable range of distribution. The anterior talar displacement values were (3.2±0.4), (3.4±0.4), (3.7±0.5), and (6.5±0.7) mm for normal LCL, AFTL injury, AFTL combined with CFL injury, ATFL combined with CFL, PTFL injuries, respectively, with a statistically significant difference ( F=109.08, P<0.001). The anterior talar displacement of ATFL combined with CFL, PTFL injuries was larger than those of normal LCL, AFTL injury, and AFTL combined with CFL injury ( P<0.05). Conclusions:A 3D finite element model is successfully constructed based on 3D MRI of the ankle joint in marathon runners. The peak and range of cartilage stresses in the talar glide change during LCL injury, and the talar glide displaces anteriorly.

A meta-analysis of the efficacy and safety of robotic surgery versus open surgery in the treatment of hilar cholangiocarcinoma / 中华肝胆外科杂志

Objective:To compare the efficacy and safety of robotic surgery and open surgery in the treatment of hilar cholangiocarcinoma.Methods:PubMed, Embase, Cochrane Library, Web of Science, CNKI and Wanfang database were searched to compare the treatment of hilar cholangiocarcinoma by robotic surgery and traditional open surgery. Literatures were searched from the establishment of the database to July 2023. Compare operation time, intraoperative blood transfusion rate, R 0 resection rate, lymph node metastasis rate, postoperative complication rate and hospital stays between the two groups. The combined odds ratio ( OR) and mean difference ( MD) and 95% confidence interval (95% CI) were calculated using RevMan 5.4 software. Results:A total of 4 studies were included, including 267 patients with hilar cholangiocarcinoma. There were 177 males and 90 females, aged (58.8±5.7) years. A total of 267 patients were divided into open surgery group ( n=165) and robotic surgery group ( n=102) according to the surgical formula. The extract results show: operative time ( MD=-103.96, 95% CI: -216.90-8.98, P=0.070) and intraoperative blood transfusion rate ( OR=1.32, 95% CI: 0.43-4.07, P=0.630), R 0 resection rate ( OR=1.41, 95% CI: 0.71-2.81, P=0.330), lymph node metastasis rate ( OR=1.62, 95% CI: 0.46-5.63, P=0.450), postoperative complications ( OR=0.60, 95% CI: 0.28-1.31, P=0.200), and postoperative hospital stay ( MD=2.17, 95% CI: -11.56-15.90, P=0.760). Conclusion:In the treatment of hilar cholangiocarcinoma, robotic surgery is as safe and feasible as open surgery. However, due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

Quality of medicinal maltose as a excipient in the production of blood products: a comparative study / 中国输血杂志

【Objective】 To comprehensively compare the quality and filtration efficiency of medicinal maltose between two domestic manufacturers(B, C) and one foreign manufacturer(A), compare their product quality as an excipient for intravenous immunoglobulin(IVIG), so as to determine the feasibility and substitutability of maltose as an excipient for IVIG from different manufacturers. 【Methods】 Quality inspection and comparison of maltose from different manufacturers, small-scale filtration tests, and product quality comparision of IVIG(pH4) were conducted. 【Results】 The comparis on results showed that there was no significant difference in the quality of medicinal maltose between manufacturer B and A, and there was no significant difference in the quality of IVIG (pH4) produced. The quality of manufacturer C did not meet the requirements. 【Conclusion】 There is no significant difference in the quality of medicinal maltose produced by manufacturer B and A, which can be used for the production of IVIG (pH4).

Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

The effect of bivalirudin on coagulation function in male patients with coronary heart disease undergoing percutaneous coronary intervention.

Aim of this study was to explore the effect of bivalirudin on coagulation function with the treatment of percutaneous coronary intervention (PCI) in male coronary heart disease (CHD) patients. There were 90 male CHD cases treated with PCIas study object and were randomly divided into bivalirudin and unfractionated heparin group (n=45). Unfractionated heparin group patients were given unfractionated heparin and bivalirudin group cases were treated with bivalirudin. Activated clotting time (ACT), thrombin time (TT), prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib), platelet count (PLT) were determined and the major adverse cardiovascular events (MACCE) were observed in two group patients. There was no significant (p<0.05) difference with ACT, TT, PT, PLT, APTT and Fib between the two groups before and after 6h, 24h and 72h of operation. The incidence of stent thrombosis and general bleeding with in 24h after PCI in bivalirudin group was lower than in heparin group. After 13 months of follow-up, there was no significant (p<0.05) difference in the incidence of MACCE between the two groups. Compared with the treatment of unfractionated heparin in CHD patients after PCI in 24h, the bivalirudin had more remarkable effect, such as rapid onset, short half-life, lower incidence of thrombosis and bleeding.

An unusual signal transducer GIV/Girdin engages in the roles of adipocyte-derived hormone leptin in liver fibrosis.

Obese patients usually have hyperleptinemia and are prone to develop liver fibrosis. Leptin is intimately linked to liver fibrogenesis, a multi-receptor-driven disease. Gα-Interacting Vesicle-associated protein (GIV) functions as a multimodular signal transducer and a guanine nucleotide exchange factor for Gi controling key signalings downstream of diverse receptors. This study aimed to examine the roles of GIV in leptin-caused liver fibrosis and employed the culture-activated hepatic stellate cells (HSCs) and leptin-deficient mice, respectively. Results indicated that leptin upregulated GIV expression in HSCs. GIV was involved in leptin-induced HSC activation and liver fibrosis. GIV mediated leptin regulation of TIMP1, MMP9, PDGFß receptor and TGFß receptor and was required for leptin stimulating the pathways of Erk1/2, Akt1, and Smad3. GIV was also a mediator for leptin-regulation of Cyclin D1 and Caspase-3 activity but GIV reduced Caspase-3 level independently of leptin in vivo. Erk1/2 signaling, Egr1 and c-Jun were associated with the effect of leptin on GIV expression in HSCs. Leptin-induced Erk1/2 signaling increased Egr1 and p-c-Jun levels and promoted their binding to GIV promoter at the sites between -190 bp and -180 bp and between -382 bp and - 376 bp, respectively. Egr1 knockdown lessened leptin-upregulation of GIV in vitro and in vivo. In human cirrhotic livers, the increase in GIV protein level parallelled with the elevated p-Erk1/2 and Egr1 levels in HSCs. In summary, the unusual signal transducer GIV was identified as an important mediator in leptin-induced liver fibrosis. GIV may have significant implications in liver fibrosis progression of obese patients with hyperleptinaemia.

Real-World clinical features and survival outcomes associated with primary gastrointestinal natural killer/T-cell lymphoma from 1999 to 2020.

BACKGROUND: Primary gastrointestinal natural killer (NK)/T-cell lymphoma (PGINKTL) is a rare T-/NK-cell lymphoma subtype, and the clinical features and survival outcomes remain largely unknown. METHODS: To summarize the clinical features and survival outcomes of PGINKTL, PGINKTL cases diagnosed at our hospital from May 1999 to December 2020 were reviewed; and the clinical data, information on treatment strategies, and survival were collected. Survival analysis was performed using the Kaplan-Meier method and multivariable Cox proportional hazards regression. We constructed a nomogram to visualize the survival prediction of PGINKTL. The discriminative ability and calibration of the nomogram for prediction were tested using the concordance index (C-index) and calibration plots. RESULTS: The cohort included 81 cases, the median age was 36 years (range, 7-80 years), and the male-to-female ratio was 1.7:1. The most common clinical symptom at the time of diagnosis was abdominal pain (71.6%). The most common lesion site was the colon (59.3%). During a median follow-up period of 37.7 months, the median overall survival (OS) time of 81 patients was 4.0 months (95% confidence interval [CI], 3.1-4.9 months), and the 2-year OS rate was 30.7% (95% CI, 20.3%-40.1%). The multivariate analyses indicated that patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) score ≥2, serum lactic dehydrogenase (LDH) level ≥ the upper limit normal (ULN), and perforation had worse OS. We used these data to establish a nomogram to predict survival for PGINKTL. The nomogram displayed good accuracy, with a C-index of 0.726. CONCLUSION: The clinical features and poor outcomes of PGINKTL, which is a rare and fatal lymphoma type, are presented. The proposed nomogram provides an individualized estimate of survival for these patients. In the future, the study focused on exploring a better treatment strategy to improve survival is required in PGINKTL.

Curcumol inhibits breast cancer growth via NCL/ERα36 and the PI3K/AKT pathway.

Background: Breast cancer (BC) is the most common malignancy worldwide. ERα36 (ERα66 variant) is expressed in many breast cancer cells, especially highly expressed in tamoxifen (TAM)-resistant cell lines and triple-negative breast cancer, and our previous work revealed that nucleolin (NCL) is a protein target of curcumol. This study is aimed at investigating the effect and mechanism of curcumol on ERα36 positive breast cancer cells, and the relationship between curcumol's target protein NCL and ERα36. Study design: Application of in vivo and in vitro studies to reveal the mechanism of curcumol in inhibiting BC growth and the relationship between curcumol's target protein NCL and ERα36. Methods: The anti-tumor effect of curcumol was quantified via an MTT assay, colony formation and cycle arrest, respectively. The expressions of ERα36, NCL and the proteins involved in PI3K/AKT signaling were evaluated by western blotting. The interaction between two proteins was detected using co-immunoprecipitation (Co-IP) and an immunofluorescence assay. A mouse xenograft model was established to verify the role of ERα36 in breast cancer cells and curcumol's effect on ERα36 positive cancer cells. Results: Curcumol inhibited the cell growth, caused cell cycle arrest, decreased cell cycle related proteins and inactivated the PI3K/AKT pathway in ERα36 positive breast cancer cells. There is a positive correlation between NCL and ERα36 in breast cancer cells. In addition, ERα36 bound to NCL; the two proteins were distributed in the nucleus, cytoplasm and plasma membrane, where their expression was obviously decreased by curcumol. Moreover, NCL silenced by NCL siRNA blocked the cell cycle progress and inhibited the activation of PI3K/AKT in MDA-MB-231 cells, while overexpressed ERα36 increased the expression of NCL, promoted the cell cycle progress and enhanced the activity of PI3K/AKT in MCF-7 cells. NCL knockdown or ERα36 overexpression attenuated the effect of curcumol on breast cancer cells. Conclusion: Curcumol reduced the proliferation of breast cancer cells by targeting NCL/ERα36 and inactivating the PI3K/AKT pathway.

Analysis of effect of preoperative renal insufficiency on clinical prognosis of heart transplant recipients / 器官移植

Objective To evaluate the effect of renal insufficiency before heart transplantation on perioperative death, complications and long-term survival, and to compare the differences between preoperative serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) in preoperative risk assessment. Methods Clinical data of 1 095 heart transplant recipients were retrospectively analyzed. According to preoperative Scr level, all recipients were divided into the Scr < 133 μmol/L(n=980), Scr 133-176 μmol/L (n=83) and Scr≥177 μmol/L groups (n=32). According to preoperative eGFR, all recipients were divided into eGFR≥90 mL/(min·1.73m2) (n=436), eGFR 60-89 mL/(min·1.73m2) (n=418) and eGFR < 60 mL/(min·1.73m2) groups (n=241). Clinical prognosis of postoperative renal function, perioperative and long-term outcomes of recipients were compared among different groups. The effect of eGFR and Scr level on renal function injury and long-term survival after heart transplantation was assessed. Results With the increase of preoperative Scr level, the proportion of recipients undergoing postoperative continuous renal replacement therapy (CRRT) was increased, the proportion of recipients receiving postoperative mechanical circulatory support was elevated, the incidence of postoperative complications was increased, the duration of mechanical ventilation and intensive care unit(ICU) stay was prolonged, and the in-hospital fatality was increased. The differences among three groups were statistically significant (all P < 0.05). With the decrease of preoperative eGFR, the proportion of recipients receiving postoperative CRRT was increased, the proportion of recipients using postoperative intra-aortic balloon pump (IABP) was elevated, the duration of mechanical ventilation and ICU stay was prolonged, and the in-hospital fatality was increased. The differences among three groups were statistically significant (all P < 0.05). Scr≥177 μmol/L was an independent risk factor for postoperative death [adjusted hazard ratio (HR) 3.64, 95% confidence interval (CI) 1.89-6.99, P < 0.01]. Among different groups classified by Scr and eGFR, the cumulative incidence rate of postoperative renal function injury and long-term survival rate were statistically significant among three groups (all P < 0.05). In patients with preoperative Scr < 133 μmol/L, the cumulative incidence rate of postoperative long-term renal function injury was significantly increased with the decrease of preoperative eGFR (P < 0.01). There was no significant difference in postoperative long-term survival rate among patients stratified by different eGFR (P > 0.05). Conclusions Renal insufficiency before heart transplantation is associated with poor perioperative and long-term prognosis. Preoperative Scr and eGFR are the independent risk factors for postoperative renal function injury. Scr yields low sensitivity in the assessment of preoperative renal function, whereas it has high accuracy in predicting perioperative death risk. And eGFR is a more sensitive parameter to evaluate preoperative renal function, which may identify early-stage renal functional abnormality and take effective measures during early stage to reduce adverse effect on prognosis.

The effect of Jiegeng decoction on lipopolysaccharide-induced acute lung injury in mice based on metabolomics / 药学学报

One of the traditional prescriptions for treating lung diseases, Jiegeng decoction (JGT), is still unknown in terms of its chemical makeup and mechanism. In this study, Q-Exactive-Orbitrap MS technology was used to identify the chemical constituents of JGT, and metabolomics was used to examine the effect of JGT on metabolites in the lung tissue of mice with acute lung injury (ALI) model. The potential biomarkers were screened by fold change (FC) > 1.5 or FC < 0.67 and P < 0.05, and enriched for metabolic pathways. A total of 40 compounds, including triterpenoid saponins, flavonoids and glycosides, were identified by mass spectrometry analysis of JGT. All animal experiments were approved by the Experimental Animal Ethics Committee of Tianjin University of Traditional Chinese Medicine (No. TCM-LAEC2021106). The results showed that JGT improved the lung coefficient, and lung tissue morphology of mice with ALI, lowered the levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in bronchoalveolar lavage fluid (BALF), and reduced myeloperoxidase (MPO) content in lung tissue. The metabolomic results showed that JGT could regulate 22 metabolites associated with ALI, among which leukotriene D4, docosapentaenoic acid, hypoxanthine, L-5-oxoproline, and other metabolites were mainly associated with the body′s inflammatory response and oxidative stress, and were enriched in the pathways of glutathione metabolism, purine metabolism, and primary bile acid biosynthesis. This study analyzed the potential mechanism of JGT in the treatment of ALI through metabolomics, providing an important theoretical basis for the clinical application of JGT.