Aim To explore the mechanism and mate-rial basis of Shenkang injection(SKI)in the treatment of renal fibrosis(RF)by bioinformatics and in vitro experiments.Methods The differentially expressed genes of RF were screened by GEO database.With the help of CMAP database,based on the similarity princi-ple of gene expression profile,the drugs that regulated RF were repositioned,and then the components of SKI potential treatment RF were screened by molecular fin-gerprint similarity analysis.At the same time,the core targets and pathways of SKI regulating RF were predic-ted based on network pharmacology.Finally,it was verified by molecular docking and cell experiments.Results Based on the GEO database,two RF-related data sets were screened,and CMAP was relocated to three common RF therapeutic drugs(saracatinib,da-satinib,pp-2).Molecular fingerprint similarity analysis showed that RF therapeutic drugs had high structural similarity with five SKI components such as salvianolic acid B and hydroxysafflor yellow A.Molecular docking results showed that salvianolic acid B,hydroxysafflor yellow A and other components had good binding abili-ty with MMP1 and MMP13,which were the core targets of SKI-regulated potential treatment of RF.Network pharmacology analysis suggested that the core targets of SKI were mainly enriched in signaling pathways such as Relaxin and AGE-RAGE.Cell experiments showed that SKI could significantly reduce the mRNA expres-sion levels of AGER,NFKB1,COL1A1,SERPINE1,VEGFC in AGE-RAGE signaling pathway and MMP1 and MMP13 in Relaxin signaling pathway in RF model cells,and significantly increase the mRNA expression level of RXFP1.Conclusions SKI can play a role in the treatment of RF by regulating Relaxin and AGE-RAGE signaling pathways,and its material basis may be salvianolic acid B,hydroxysafflor yellow A and other components.

Objective To demonstrate the feasibility of oblique lumbar interbody fusion(OLIF)com-bined with 4-screw fixation for treating two-level lumbar degenerative diseases.Methods An intact finite element model of L3-S1(MO)was constructed and validated.Then,we constructed the M1 model by simulating OLIF surgery at L3/4 and L4/5 segments on the MO model.By attachment of posterior 4-screw or 6-screw fixation to the M1 model,three 4-screw fixation models(M2-M4)and one 6-screw fixation model(M5)were established.The segmental and overall range of motion(ROM)and the peak von Mises stresses of superior endplate,cage,and posterior screw-rod were investigated under each implanted condition.Results Under the motion modes of forward flexion,backward extension,bilateral(left and right)flexion,and left and right rotation,the L3/4 ROM of M2 model and L4/5 ROM of M3 model increased,while the L3/4 and L4/5 ROM of M4 and M5 models significantly decreased compared with those of M1 model.Under all motion modes,the L4 superior endplate in M2 model and the L5 superior endplate in M3 model showed the maximum peak von Mises stress,and the peak von Mises stresses of L4 and L5 superior endplates in M4 and M5 models were close.The L3/4 cage in M2 model and the L4/5 cage in M3 model showcased the largest peak von Mises stress,and the peak von Mises stresses of cages in M4 and M5 models were close.The peak stresses of internal fixation in M2-M5 models were close.Conclusion Four-screw fixa-tion can replace 6-screw fixation in the OLIF surgery for treating two-level degenerative lumbar diseases.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Humans ; Child ; Retrospective Studies ; Thrombocytosis/etiology*

OBJECTIVE: To analyze the clinical characteristics of venous thromboembolism (VTE) in patients with multiple myeloma (MM) and to identify the risk factors of VTE in MM patients. METHODS: 179 newly diagnosed MM (NDMM) patients admitted to The Second Hospital of Shanxi Medical University from January 2014 to December 2020 who were followed up for more than 6 months were collected, and they were divided into VTE group and control group according to whether combined with VTE. The clinical and laboratory data were compared between the two groups. Mann-whitney U test was used for inter-group comparison of measurement data, Chi-square test or Fisher's exact test was used for inter-group comparison of count data, and multivariate logistic regression analysis was performed to explore the risk factors of VTE in MM patients. RESULTS: Compared with control group, the serum albumin (ALB) level in VTE group was significantly lower (P =0.033), the fibrinogen (FIB) level was significantly higher (P =0.016), and the proportion of patients with D-dimer≥2 000 ng/ml was significantly higher than that in the control group (26.3% vs 4.4%, P =0.002). There was a significant difference in M-component type between the two groups (P =0.028), and the proportion of IgG type in VTE group was higher. There were no statistically significant differences between two groups in age, sex, body mass index (BMI), the proportions of patients with hypertension, diabetes, coronary heart disease and cerebral infarction, white blood cell (WBC) count, platelet (PLT) count, liver and kidney function, plasma cells ratio in bone marrow, serum globulin (GLO), lactate dehydrogenase (LDH), β₂-microglobulin (β₂-MG) level, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), prothrombin time (PT), activated partial thromboplastin time (APTT), disease stage, thrombosis prevention and the use of immunomodulators (P >0.05). Multivariate logistic regression analysis showed that FIB level (OR=1.578, 95%CI:1.035-2.407, P =0.034), D-dimer≥2 000 ng/ml (OR=5.467, 95%CI:1.265-23.621, P =0.023) and IgG type (OR=4.780, 95%CI: 1.221-18.712, P =0.025) were independent risk factors for VTE in MM patients. CONCLUSION MM patients are prone to VTE, and FIB level, D-dimer≥2 000 ng/ ml and IgG type are independent risk factors for VTE in MM patients.
Humans ; Venous Thromboembolism ; Multiple Myeloma/complications* ; Risk Factors ; Anticoagulants ; Immunoglobulin G ; Retrospective Studies

OBJECTIVE: To observe the effect of needle-knife on the chondrocyte apoptosis of knee joint in rabbits with knee osteoarthritis (KOA) based on the CircSERPINE2-miR-1271-5P-E26 specific transformation-related gene (ERG) axis, and to explore the mechanism of needle-knife for KOA. METHODS: Thirty-six New Zealand white rabbits were randomly divided into a normal group, a model group, a needle-knife group and a sham needle-knife group, 9 rabbits in each group. The rabbits in the model group, the needle-knife group and the sham needle-knife group were treated with modified Videman method to prepare KOA model. After successful modeling, the rabbits in the needle-knife group were treated with needle-knife at cord adhesion and nodules near quadriceps femoris tendon and internal and external collateral ligament on the affected knee joint; the rabbits in the sham needle-knife group were treated with sham needle-knife baside the needle insertion point of the needle-knife group (needle-knife was only inserted, without any operation). The treatment was given once a week, 3 times in total. The Lequesne MG behavioral score was used to evaluate the knee joint damage in each group before and after intervention. After intervention, HE staining and transmission electron microscopy were used to observe the cartilage tissue morphology and ultrastructure of chondrocytes in the knee joint in each group; TUNEL method was used to detect the level of chondrocyte apoptosis in the knee joint; real-time fluorescence quantitative PCR was used to detect the expression of CircSERPINE2, miR-1271-5P and ERG mRNA in knee cartilage tissue in each group. RESULTS: After intervention, compared with the normal group, the Lequesne MG behavioral score in the model group was increased (P<0.01). Compared with the model group and the sham needle-knife group, the Lequesne MG behavioral score in the needle-knife group was decreased (P<0.01). In the model group and the sham needle-knife group, the number of chondrocytes and organelles was decreased, the cell nucleus was shrunk, mitochondria was swelling or disappeared; in the needle-knife group, the number of chondrocytes and organelles was increased, the cell nucleus was not obviously shrunk and the mitochondria was not obviously swelling. Compared with the normal group, the level of chondrocyte apoptosis in the model group was increased (P<0.01); compared with the model group and the sham needle-knife group, the level of chondrocyte apoptosis in the needle-knife group was decreased (P<0.01, P<0.05). Compared with the normal group, the expression of CircSERPINE2 and ERG mRNA in the model group was decreased (P<0.01), and the expression of miR-1271-5P mRNA was increased (P<0.01); compared with the model group and the sham needle-knife group, the expression of CircSERPINE2 and ERG mRNA in the needle-knife group was increased (P<0.01), and the expression of miR-1271-5P mRNA was decreased (P<0.01). CONCLUSION Needle-knife could reduce the knee joint damage and chondrocyte apoptosis in KOA rabbits, which may be related to up-regulating the expression of CircSERPINE2 and ERG mRNA, and inhibiting the expression of miR-1271-5P mRNA.
Rabbits ; Animals ; Osteoarthritis, Knee/metabolism* ; Chondrocytes/metabolism* ; Knee Joint/surgery* ; Apoptosis ; MicroRNAs/genetics*

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Objective: To detect the percentages of CD8⁺Treg cells in the nasal mucosa and peripheral blood of chronic rhinosinusitis (CRS) and to explore their correlation with eosinophilic infiltration. Methods: Thirty-three chronic rhinosinusitis with polyp (CRSwNP), 26 chronic rhinosinusitis without polyp (CRSsNP) and 27 control patients who were collected with the nose mucosal tissue and peripheral blood in the Third Affiliated Hospital of Sun Yat-sen University from March 2017 to October 2018 were selected, including 59 males and 27 females, aging from 18 to 72 years. Hematoxylin and eosin (HE) staining was used to observe the number of eosinophils in the nasal tissues and to classify the CRS into eosinophilic CRS (ECRS) and non-eosinophilic CRS (Non-ECRS). Flow cytometry was used to detect the percentages of CD4⁺ and CD8⁺T cells in lymphocytes of nasal mucosa and peripheral blood. The percentages of CD8⁺Foxp3⁺Treg cells, CD8⁺Foxp3^-IL-10⁺Treg cells, CD8⁺IFN-γ⁺T cells (Tc1), CD8⁺IL-4⁺T cells (Tc2) and CD8⁺IL-17A⁺T cells (Tc17) in lymphocytes of nasal mucosa and peripheral blood were also tested. Besides, the percentages of Foxp3⁺TGF-β⁺Treg cells and Foxp3⁺IL-10⁺Treg cells in CD8⁺T cells were determined. All data were represented by M (IQR). GraphPad 7.0 and SPSS 16.0 were used for illustration and statistical analysis. Results: The percentage of CD8⁺T cells (37.75%(17.35%)) was higher than that of CD4⁺T cells (4.72%(4.29%)) in nasal mucosa (Z=-5.70, P<0.001), while lower (23.60%(9.33%)) than that of CD4⁺T cells (44.05% (10.93%)) in peripheral blood (t=9.72, P<0.001). CRSwNP patients possessed the highest Tc2 (1.82% (1.22%)) and Tc17 (1.93% (2.32%)) percentages than CRSsNP (Tc2: 0.84% (0.79%); Tc17: 0.54% (1.04%)) and control (Tc2: 1.09% (0.92%); Tc17: 0.47% (0.51%), both P<0.05) patients. While, CRSwNP patients possessed the lowest CD8⁺Foxp3⁺Treg cells percentage (0.10% (0.32%)) than CRSsNP (0.43% (1.45%)) and control (0.48% (0.83%), Z value was -2.24, -2.22, respectively, P value was 0.025, 0.027, respectively). The percentages of Foxp3⁺TGF-β⁺Treg cells and Foxp3⁺IL-10⁺Treg cells of CD8⁺T cells in nasal mucosa in CRSwNP were also lower than controls (Z value was 1.46, 0.49, respectively, both P=0.001). Moreover, the percentage of CD8⁺Foxp3^-IL-10⁺Treg cells of CD8⁺T cells was decreased in nasal mucosa of CRSwNP patients (0.14% (0.28%)) when compared with that of CRSsNP (0.89% (0.81%), Z=0.61, P=0.03). ECRS patients had the lower percentages of CD8⁺Foxp3⁺Treg cells (0.07% (0.44%)) and CD8⁺Foxp3^-IL-10⁺Treg cells (0.13% (0.21%)) than Non-ECRS patients (CD8⁺Foxp3⁺Treg cells: 0.53% (0.75%); CD8⁺Foxp3^-IL-10⁺Treg cells: 0.29% (0.76%), t value was 2.14, 2.78, respectively, both P<0.05). The percentage of CD8⁺Foxp3⁺Treg cells and the ratio of CD8⁺Foxp3^-IL-10⁺T per CD8⁺T cells were negatively correlated with the percentage of eosinophils in CRS patients(R² value was 0.56, 0.78, respectively, both P<0.001). There was no significant difference in the distribution of CD8⁺Fxop3⁺Treg cells and CD8⁺Fxop3^-IL-10⁺Treg cells in peripheral blood among different groups. Conclusion: The percentages of CD8⁺Treg cells decrease in CRSwNP patients, especially in ECRS patients, which are opposite to that of Tc2 and Tc17, and negatively correlate with the eosinophils percentage. This indicates that the decrease in the ratio of CD8⁺Treg cell may be associated with the immune-imbalance and eosinophilic infiltration in nasal mucosa of CRS patients.
CD8-Positive T-Lymphocytes ; Chronic Disease ; Female ; Humans ; Male ; Nasal Polyps/complications* ; Rhinitis/complications* ; Sinusitis/complications* ; T-Lymphocytes, Regulatory

Objective: To analyze the dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture, Yunnan province, and provide information support for the clinical use of HIV-1 DNA quantitative detection. Methods: The HIV infection cases in recent infection cohort from Dehong Center for Disease Control and Prevention during 2009-2018 were selected as study subjects. The dynamic curve of HIV-1 DNA load varrying with time was generated and logistic regression analysis was conducted to identify the risk factors for HIV-1 load in the recent follow up after ART and statistical analysis was performed by using SPSS 17.0. Results: Among the 113 HIV infection cases detected from the recent infection cohort, the recent HIV infection rate were 49.6%(56/113) males, sexual transmission cases and drug injection transmission cases accounted for 53.1% (60/113), 80.5% (91/113) and 19.5% (22/113), respectively. The dynamic changes curve showed that HIV-1 DNA load was relatively high (>800 copies /10⁶ PBMCs) before ART, and droped rapidly (<400 copies /10⁶ PBMCs) after ART for 1 year. However, HIV-1 DNA load decreased insignificantly from the second year of ART, and remained to be 269 copies/10⁶ PBMCs after ART for 6 years. Univariable logistic regression analysis indicated that OR (95%CI) of CD8, CD4/CD8 and HIV-1 DNA load were 1.00 (1.00-1.00), 0.30 (0.09-1.05) and 1.01 (1.00-1.01), respectively. Multivariable logistic regression analysis showed that OR value of HIV-1 DNA load base was 1.00 (1.00-1.01). Conclusions: HIV-1 DNA load decreased significantly in the first year of ART, then remained stable for years. HIV-1 DNA load base was the key factor associated with the decrease of HIV-1 DNA load, the lower the HIV-1 DNA load base, the lower HIV-1 DNA load. Therefore, earlier ART can contribute to the decrease of HIV-1 DNA load.
China/epidemiology* ; DNA/therapeutic use* ; HIV Infections/drug therapy* ; HIV Seropositivity ; HIV-1/genetics* ; Humans ; Male ; Viral Load