OBJECTIVE To evaluate the ameliorative effect of Juanbi Tongluo Oral Liquid on sciatic neuronal apoptosis in Type 2 diabetic model mice.METHODS The Type 2 diabetes mouse model was established by feeding with high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin(STZ).The mice were treated with metformin(200 mg·kg-1·d-1),low dose(3.9 g·kg-1·d-1)and high dose(7.8 g·kg-1·d-1)Juanbi Tongluo Oral Liquid for 35 days.The latency of response to thermal stimu-lation was detected by hot plate,and the values of blood glucose insulin and glycosylated hemoglobin were determined.Biochemical kits were used to detect the expression of serum total cholesterol(T-CHO),triglyceride(TG),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px)and oxidation product malondialdehyde(MDA).The expression of tumor cytokine α(TNF-α),interleukin(IL)-1β,IL-6 and IL-10 in serum of mice were detected by ELISA method;the injury of sciatic nerve of model mice was detected by HE staining;the apoptosis of sciatic nerve was detected by TUNEL method;and the expression of neurofilament protein NF-L,apoptosis(cleaved Caspase-3,Caspase-3)and oxidative stress(Nrf2,HO-1)signal pathway proteins in sciatic nerve of model mice were detected by Western blot method.RESULTS High-dose Juanbi Tongluo Oral Liquid shortened the latent period of heat pain response in model mice(P<0.01);downregulated fasting blood glucose and glycated hemoglobin(P<0.01),and upregulated fasting plasma insulin in model mice(P<0.01);downregulated serum T-CHO,TG,and LDL-C levels(P<0.01),upregulated HDL-C levels(P<0.01);downregulated serum pro-inflammatory factors TNF-α,IL-1β and IL-6 levels(P<0.05),upregulated the anti-inflammatory cyto-kine IL-10 level(P<0.01);inhibited sciatic nerve structural damage and apoptosis(P<0.05);downregulated the ratio of cleaved Caspase-3 to Caspase-3 in the apoptosis pathway(P<0.01);upregulated the expression of neurofilament proteins NF-L and NF-H in sciatic nerve tissue(P<0.05,P<0.01);and upregulated the expression of antioxidant stress proteins Nrf2 and HO-1(P<0.01).CONCLUSION Juanbi Tongluo Oral Liquid can improve sciatic neuronal apoptosis of Type 2 diabetic mice,which may be related to its effect on improving oxidative stress and inflammatory stress.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective To investigate the protective effect of curcumin (Cur) against arsenic-induced neuroimmune toxicity and the underlying molecular mechanisms in vivo. Methods Eighty SPF female C57BL/6 mice were randomly assigned to four groups: a control group, an arsenic-treated group, a Cur-treated group and an arsenic+Cur group, with 20 mice in each group. The control group received distilled water; the arsenic-treated group was given 50 mg/L NaAsO₂ in the drinking water; the Cur-treated group was gavaged with 200 mg/kg of curcumin for 45 days; and the arsenic+Cur group received distilled water and was gavaged with 200 mg/kg of curcumin. Y-maze and Morris water maze experiments were conducted to assess the learning and memory ability of the mice. Western blot analysis was used to detect protein levels of blood-brain barrier tight junction proteins zonula occludens protein 1(ZO-1) and claudin 5, T lymphocyte subpopulation CD4 and CD8, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway-related molecules JAK2 and STAT3. Real-time PCR was used to assess the mRNA levels of CD4⁺ T lymphocyte subsets type 1 T helper (Th1), Th2, Th17 and regulatory T cells (Treg) transcription factors and cytokines in hippocampus. Results Compared with the control group, the arsenic-treated group showed a significantly decreased correct rate, increased latency to reach the platform on the third and fifth days, and reduced times of crossing the platform. The expression of ZO-1 and claudin 5 protein decreased significantly, and the protein levels of CD4 and CD8 were up-regulated. The mRNA levels of Th1, Th17, and Treg transcription factor T-box expressed in T cell(T-bet), retinoid-related orphan receptor gamma t(RORγt), and forkhead box protein 3(FOXP3) in the arsenic-treated group were decreased. Th1 and Th17 cytokines interferon γ(IFN-γ) and interleukin 17(IL-17) were markedly decreased. In contrast, the mRNA levels of the Th2 transcription factor GATA binding protein 3(GATA3) and cytokine IL-4 in arsenic-treated group were higher than those in the control group. Furthermore, the protein levels of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) increased. Compared with the arsenic-treated group, the arsenic+Cur group demonstrated a significantly increased correct rate, decreased latency to reach the platform on the third and fifth days, and increased times of crossing the platform. The protein expression levels of ZO-1 and claudin 5 increased significantly, and the protein levels of CD4 and CD8 were down-regulated. The mRNA levels of Th2 transcription factor GATA3 and cytokine IL-4 were decreased. The mRNA levels of Th17 transcription factor RORγt and cytokine IL-17 were markedly increased. Furthermore, the protein levels of p-JAK2 and p-STAT3 decreased. Conclusion Through inhibiting the JAK2/STAT3 signaling pathway, curcumin could improve arsenic-induced decline in learning and memory abilities in mice, reverse the destruction of blood-brain barrier permeability of innate immune system components in arsenic-exposed mice, and antagonize arsenic-induced increase in the number of renal CD4 and CD8 molecule as well as the imbalance of CD4⁺ T lymphocyte subsets (Th1, Th2, Th17 and Treg), ultimately counteracting arsenic-induced neurotoxicity.
Animals ; Janus Kinase 2/genetics* ; STAT3 Transcription Factor/genetics* ; Female ; Curcumin/pharmacology* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Mice ; Arsenic/toxicity*

[Objective]To explore the potential mechanism of action of Huangqi Sijunzi Decoction in the treatment of hepatocellular carcinoma(HCC)by network pharmacology combined with bioinformatics methods.[Methods]The bioactive compounds of drugs and their targets were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)database.Differential gene and module gene of HCC were identified by differential analysis and weighted gene co-expression network analysis(WGCNA).On this basis,the network of"Components-targets of Chinese drug"was constructed.Subsequently,the biological function of the target was investigated and protein-protein interaction(PPI)network was constructed to identify key targets for drug therapy of HCC.Finally,the interaction between the target and the compound was explored by molecular docking.[Results]A total of 156 compounds and 227 targets of 5 Chinese drugs were identified,as well as 2 477 and 685 differential genes in The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)datasets,and 2 104 and 2 165 WGCNA association module genes.Then,the Chinese drug component-target network containing 4 drugs,85 compounds and 9 targets was constructed.Biological function analysis showed that the 9 targets were mainly related to cell cycle,p53 signaling pathway and cell senescence.Meanwhile,two core components of kaempferol and quercetin and five core targets of cyclin A2(CCNA2),estrogen receptor alpha(ESR1),cyclin B1(CCNB1),cyclin-dependent kinase 1(CDK1)and topoisomerase Ⅱ alpha(TOP2A)were screened.Molecular docking results showed that the kaempferol and quercetin had stable binding ability to the corresponding core targets.[Conclusion]Huangqi Sijunzi Decoction may play a therapeutic role in HCC by regulating pathways and proteins related with cell cycle.This study provides research ideas and theoretical support for the treatment of HCC with Huangqi Sijunzi Decoction.

Objective:To summarize the relationship between the clinicopathological features and prognosis of immunoglobulin A nephropathy (IgAN) after renal transplantation.Methods:A total of 34 patients with IgAN after renal transplantation confirmed by renal biopsy were enrolled. And another 34 patients with primary IgAN confirmed by initial renal biopsy were adopted as controls. Clinical and pathological features of two groups were compared to explore the relationship between clinicopathological features and prognosis of allograft IgAN.Results:As compared with primary IgAN group, renal function in allograft IgAN group included serum creatinine [(158.5±75.9) vs (84.8±26.8) umol/L], urea nitrogen [(9.7±6.1) vs (5.2±1.4) mmol/L], uric acid [(406.7±87.8) vs (359.0±92.6) umol/L], estimated glomerular filtration rate {(57.4±25.4) vs (91.2±28.6) [ml/(min·1.73m 2)]}. All were statistically significantly higher ( P<0.05) while other parameters showed no differences. Pathologically, the proportion of T1 type (50.0% vs 17.6%) of renal tubular atrophy/interstitial fibrosis was significantly higher in allograft IgAN group than control group ( P<0.05). Furthermore, univariate and multivariate Logistic regression analyses were performed between various pathological parameters and prognosis in allograft IgAN patients. It indicated that the degree of mesangial hyperplasia of patients with transplanted IgAN had a significantly negative impact on the prognosis. Conclusions:The clinicopathological features of patients with allograft IgAN show no difference from those of patients with primary IgAN. And among patients with allograft IgAN, those with severe mesangial hyperplasia often have a worse prognosis.

BACKGROUND: It has been confirmed that high-frequency chest wall oscillatory (HFCWO) is a new type of auxiliary sputum discharge device. However, up to now, the specific therapeutic effect of HFCWO is still uncertain. This study aimed to compare the changes of the sputum volume before and after the treatment of HFCWO, and to investigate the effect of HFCWO on lung function and arterial blood gas analysis after single port video-assisted thoracoscopic surgery lobectomy (S-VATS). METHODS: A total of 90 patients with S-VATS lobectomy were collected in the Second Affiliated Hospital of Soochow University from January 2017 to December 2017, which were randomly divided into the experimental group with HFCWO (n=45) and the control group (n=45) with routine clapping, respectively. The sputum volume of the two groups was measured 5 days before operation. Lung function and arterial blood gas analysis was measured before and 7th days after surgery. RESULTS: The sputum volume was higher in the experimental group than that of the control group after surgery, there was statistically significant difference for the first three days (P<0.05). There was no statistically significant difference between the two groups in forced expiratory volume in one second (FEV₁), forced vital capacity (FVC) and oxygen partial pressure (PaO₂) before surgery (P>0.05); Compared with those before surgery, FEV₁, FVC and PaO₂ decreased in both groups after surgery (P<0.05); However, FEV₁, FVC and PaO₂ in the experimental group were higher than those in the control group (P<0.05); There was no statistically significant difference in preoperative and postoperative partial pressure of carbon dioxide (PaCO₂) between the two groups (P>0.05). CONCLUSIONS HFCWO can significantly increase the amount of sputum excretion, improve lung function and alleviate hypoxia status after S-VATS lobectomy. This study provides a promising approach for HFCWO toward hypoxia status after S-VATS lobectomy.
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Adult ; Aged ; Case-Control Studies ; Female ; Forced Expiratory Volume ; High-Frequency Ventilation ; Humans ; Lung ; physiopathology ; surgery ; Lung Neoplasms ; physiopathology ; surgery ; Male ; Middle Aged ; Pneumonectomy ; Respiratory Function Tests ; Thoracic Surgery, Video-Assisted ; Thoracic Wall ; surgery ; Young Adult

Objective To evaluate the application value of ultrasound in vascularization of different artificial bones . Methods A total of 15 New Zealand rabbits were utilized for model establishment of classic segmental bone defect in bilateral radius . Recombinant human bonemorphogenic protein-2 ( rhBMP-2 ) coralline hydroxyapatite(CHA) and CHA were implanted into left and right limbs . Each CHA was divided into 4 equal parts which were examined with conventional ultrasonography and contrast-enhanced ultrasonography( CEUS ) on 3 d ,7 d ,11 d ,15 d ,30 d and 45 d respectively . CEUS quantitative was performed by time-intensity curve(TIC) ,which parameters including the basic intensity(BI) ,peak intensity (PI) ,increased signal intensity ( ΔSI) and time to peak ( TTP) . Then the results were analyzed and compared to pathology . Results Within the same duration ,the vascularization degree in rhBMP-2 group was stronger than that in the ordinary group with advanced vascularization time . Positive correlation was detected between ΔSI and time of both groups ( r =0 .938 ,0 .890 ;P =0 .000) ,and negative correlation was found between BI/PI or TTP and time ( BI/PI: r = -0 .798 ,-0 .899 ; P = 0 .000 ;TTP= r -0 .874 ,-0 .868 ;P = 0 .000 ) . No statistical significance was observed among four observation points of both CHA ,which indicated no obvious difference in vascularization degree of each observation point . Conclusions The structure of bone graft can be clearly displayed by conventional ultrasound ,and CEUS is able to show the early blood perfusion in two CHA grafts and to accurately evaluate the difference of CHA microvascular growth before and after rhBMP-2 application . The combination of these two techniques is a promising approach of evaluating bone graft vascularization in clinical practice .

Objective To compare the biomechanical stability of 4 internal fixations in treatment of acetabular fracture of the lower anterior column through finite element analysis.Methods One normal adult male pelvis was subjected to 0.7mm thin-section CT scanning and 379 CT pictures were obtained.Finite element modeling software was used to establish internal fixation models for acetabular fracture of the lower anterior column,including lag screws (A),anterior column reconstruction plate (B),subcutaneous plate not crossing the pubic symphysis (C) and subcutaneous plate crossing the pubic symphysis (D).Finite element analysis was carried out to compare the biomechanical differences among the 4 internal fixation models which were subjected to the same loading conditions at both standing and sitting positions.Results At standing and sitting positions,the maximum displacement and the mean node displacement of fracture lines were the greatest in group A (0.558 mm and 0.462 ±0.092 mm at standing;0.634 mm and 0.473 ±0.108 mm at sitting),the smallest in group D (0.512 mm and 0.425 ±0.083 mm at standing;0.031 mm and 0.025 ± 0.004 mm at sitting),and in between in group B (0.513 mm and 0.432 ±0.085 mm at standing;0.630 mm and 0.466 ± 0.109 mm at sitting) and in group C (0.514 mm and 0.433 ± 0.085 mm at standing;0.627 mm and 0.464 ± 0.107 mm at sitting).At both standing and sitting positions,the maximum stress at the fracture line was the greatest in group D (10.519 MPa and 24.879 MPa),the smallest in group A (3.254 MPa and 8.954 MPa),and in between in group B (4.873 MPa and 9.431 MPa) and in group C (4.384 MPa and 10.128 MPa).Conclusions In treatment of acetabular fracture of the lower anterior column,subcutaneous plate crossing the pubic symphysis may result in the greatest biomechanical stability,lag screws the smallest biomechanical stability,and anterior column reconstruction plate and subcutaneous plate not crossing the pubic symphysis the moderate biomechanical stability.

Objective:To investigate the efficacy and toxicity of oxaliplatin reintroduction combined with raltitrexed as second-line che-motherapy after the first-line oxaliplatin-based chemotherapy in advanced colorectal cancer patients. Methods:The 48 evaluable pa-tients with advanced colorectal cancer following disease progression prior to the first-line chemotherapy were treated with oxaliplatin and raltitrexed (raltitrexed 3 mg/m2 ivgtt d1, oxaliplatin 100-130 mg/m2 ivgtt d1, q21d). All 48 patients were divided into two groups:Group A, non-oxaliplatin-based regimens as the first-line chemotherapy, 20 cases;Group B, oxaliplatin-based regimens as the first-line chemotherapy, 28 cases. Each group was evaluated every two cycles. Results:The response rates (RR) of Groups A and B were 30.0%(6/20) and 32.1%(9/28), the disease control rates (DCR) were 80.0%(16/20) and 75.0%(21/28), the median progression free survival time (mPFS) was 6.5 and 7.0 months, and the median overall survival time (mOS) was 10 and 13 months, respectively. No statistical sig-nificance was observed between the two groups in their RR, CR, mPFS, and mOS (P=0.264, 0.514, 0.713, 0.788), respectively. The most common adverse effects observed wereⅠ-Ⅱgrades of bone marrow suppression, aminotransferase abnormality, and digestive toxici-ties. The incidence of neurotoxicity (Ⅰ-Ⅱgrades) between the two groups was similar. Conclusion:Instead of irinotecan combined with raltitrexed, oxaliplatin reintroduction combined with raltitrexed for second-line chemotherapy after the first-line oxaliplatin-based chemotherapy in advanced colorectal cancer patients is feasible.

Objective Toinvestigate the molecular characteristics including antibiotic resistance,strain type,serotype,virulence,biofilm formation of Streptococcus pneumoniae isolated from Shanghai adult patients.Methods A total of 37 non-repetitive S.pneumoniae isolates causing community acquired and hospital acquired infections of adults were collected from Shanghai Huashan Hospital from January 2011 to December 2013.The inhibitory zone diameter or minimum inhibitory concentrations (MICs) of 9 antimicrobial agents (penicillin,vancomycin,erythromycin,clindamycin,levofloxacin,cefprozi,ceftriaxone,cefotaxime and linezolid) were determined by Kirby-bauer (K-B) method or Etest method;Serotypes were tested by polymerase chain reaction (PCR) and S.pneumoniae antisera agglutination;Genomic characteristics of different serotype strains were determined by pulsed field gel electrophoresis (PFGE)method;Multilocus sequence types (MLST) was used for strain type;Semi quantitative biofilm formation test was used for the biological membrane formation.Ten main pneumococcal virulence genes (cbpA,pspA,cps2A,lytA,nana,pavA,piaA,ply,psaA and spxB) were detected by PCR and gel electrophoresis.Statistical analysis was performed using Stata software and association statistics were tested using Fisher's exact test.Results The most frequent serotypes were 19F (13.5％),23 F (13.5％),14 (10.8％),19A (10.8％).The penicillin resistance rate was 64.9％.Serotypes 19 F,19A and 23 F were significantly associated with penicillin resistance (x2 =5.89,P =0.015) and the isolates belonged to these serotypes were all multi-drug resistant (MDR).ST81 and ST271 showed high resistance rates to several antibiotics including penicillin (x2 =4.57,P =0.033).Biofilm formation was significantly associated with serotypes 19A (x2 =5.55,P =0.018) and strain type ST320 (x2 =4.33,P =0.037),but not associated with penicillin resistance (x2 =0.16,P =0.686).Virulence gene lytA,pavA,ply,psaA,spxB were found in all isolates.Conclusions Penicillin resistance rate of S.pneumoniae in adult is rising.Specific serotype,epidemic clone and antibiotic resistance are closely related,and can provide the basis for the infection control.The virulence factors such as PspA will be the new targets for vaccine development to reduce S.pneumoniae infection in the future.