BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated...BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.展开更多
AIM:To investigate whether nintedanib can inhibit pterygium cells through the fibroblast growth factor receptor 2(FGFR2)/extracellular-signal-regulated kinase(ERK)pathway.METHODS:Human primary pterygium cells were cul...AIM:To investigate whether nintedanib can inhibit pterygium cells through the fibroblast growth factor receptor 2(FGFR2)/extracellular-signal-regulated kinase(ERK)pathway.METHODS:Human primary pterygium cells were cultured in vitro.After treatment with nintedanib,the cell morphology was observed under microscopy,the morphological changes of the nucleus were observed after DAPI staining,apoptosis was analyzed by Annexin-V FITC/PI double staining,and the changes of apoptosis-associated proteins were detected by Western blot.The binding ability of nintedanib to FGFR2 was predicted by molecular docking.Finally,by silencing FGFR2,we explored whether nintedanib inhibited FGFR2/ERK pathway.RESULTS:The results showed that nintedanib inhibited the growth of pterygium cells and caused nuclear pyknosis.The results of Annexin-VFITC/PI double staining showed that nintedanib was able to induce early and late apoptosis of pterygium cells,significantly increasing the expression of apoptosis-associated proteins Bax and cleaved-Caspase3(P<0.05),and reducing the expression of Bcl-2(P<0.05).In addition,nintedanib significantly inhibited ERK1/2 phosphorylation through FGFR2(P<0.05).After silencing the expression of FGFR2,there was no significant difference in the inhibition of ERK1/2 phosphorylation by nintedanib(P>0.05).CONCLUSION:Nintedanib induces apoptosis of pterygium cells by inhibiting FGFR2/ERK pathway.展开更多
AIM:To introduce and evaluate the clinical efficacy of a new technique,the use of viscoelastic substances(VS)to close leaking sclerotomy in 23G microincision vitrectomy,and to observe its effect on the visual acuity a...AIM:To introduce and evaluate the clinical efficacy of a new technique,the use of viscoelastic substances(VS)to close leaking sclerotomy in 23G microincision vitrectomy,and to observe its effect on the visual acuity and intraocular pressure(IOP)of patients.METHODS:Patients who underwent 23G vitrectomy in Ningbo Eye Hospital before the use of VS technique(June 2019 to September 2020)and after the use of VS technique(October 2020 to December 2021)were selected as the subjects of this study.The above cases underwent operation by the same surgeon and were retrospectively analyzed.VS technique was used as the alternative to suturing,in which a small amount of VS was injected at the leaking sclerotomy and then gently massaged to confirm leaking sclerotomy closure.RESULTS:A total of 174 eyes were covered in the study,including 84 eyes in the control group(before the use of VS technique)and 90 eyes in the VS technique group.The number of eyes that needed to be sutured decreased considerably from 42.9%in the control group to 3.3%in the VS technique group,and the proportion of subconjunctival hemorrhage at 1-2d after surgery decreased remarkably from 35.7%in the control group to 2.2%in the VS technique group.No substantial differences in the incidence of mean IOP and low IOP were found between 1-2 and 3-20d after surgery in the VS technique group.No major complications associated with VS technique were identified during the study.CONCLUSION:In 23G microincision vitrectomy,VS technique is a safe,simple,and effective method to close leaking sclerotomy.展开更多
AIM:To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure(ACLF).METHODS:This was a si...AIM:To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure(ACLF).METHODS:This was a single center,prospective cohort study.Eligible,consecutive hospitalized patients received either entecavir 0.5 mg/d or lamivudine 100mg/d.All patients were given standard comprehensive internal medicine.The primary endpoint was survival rate at day 60,and secondary endpoints were reduction in hepatitis B virus(HBV)DNA and alanine aminotransferase(ALT)levels,and improvement in Child-Turcotte-Pugh(CTP)and model for end-stage liver disease(MELD)scores at day 60 and survival rate at week 52.RESULTS:One hundred and nineteen eligible subjects were recruited from 176 patients with severe acute exacerbation of chronic hepatitis B:65 were included in the entecavir group and 54 in the lamivudine group(full analysis set).No significant differences were found in patient baseline clinical parameters.At day 60,entecavir did not improve the probability of survival(P=0.066),despite resulting in faster virological suppression(P<0.001),higher rates of virological response(P<0.05)and greater reductions in the CTP and MELD scores(all P<0.05)than lamivudine.Intriguingly,at week 52,the probability of survival was higher in the entecavir group than in the lamivudine group[42/65(64.6%)vs 26/54(48.1%),respectively;P=0.038].The pretreatment MELD score(B,1.357;95%Cl:2.138-7.062;P=0.000)and virological response at day30(B,1.556;95%Cl:1.811-12.411;P=0.002),were found to be good predictors for 52-wk survival.CONCLUSION:Entecavir significantly reduced HBV DNA levels,decreased the CTP and MELD scores,and thereby improved the long-term survival rate in patients with spontaneous reactivation of hepatitis B presenting as ACLF.展开更多
AIM: To examine the effect of the potential interaction between KIF1 B variants(rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma(HCC) in a high-risk region in China.METHODS: ...AIM: To examine the effect of the potential interaction between KIF1 B variants(rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma(HCC) in a high-risk region in China.METHODS: Three hundred and six patients with HCC and 306 hospital-based control participants residing in the Shunde region of Guangdong Province, China were enrolled. Clinical characteristics were collected by reviewing the complete medical histories from the patient archives, and epidemiological data were collected using a questionnaire and clinical examination. Two single nucleotide polymorphisms(SNPs) of KIF1B(rs17401966 and rs3748578) were chosen for the current study. All subjects were genotypedusing a Taq Man real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions.RESULTS: Smoking, frequent consumption of raw freshwater fish, hepatitis B virus(HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio(OR) = 12.02; 95% confidence interval(95%CI): 6.02-24.00]. No significant association was found between the KIF1 B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption(P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC(OR = 2.36; 95%CI: 1.49-3.74).CONCLUSION: The gene-environment interaction between the KIF1 B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.展开更多
While many controlled irrigation and drainage techniques have been adopted in China, the environmental effects of these techniques require further investigation. This study was conducted to examine the changes of nitr...While many controlled irrigation and drainage techniques have been adopted in China, the environmental effects of these techniques require further investigation. This study was conducted to examine the changes of nitrogen and phosphorus of a flooded paddy water system after fertilizer application and at each growth stage so as to obtain the optimal drainage time at each growth stage. Four treatments with different water level management methods at each growth stage were conducted under the condition of ten-day continuous flooding. Results show that the ammonia nitrogen （ NH4-N ） concentration reached the peak value once the fertilizer was applied, and then decreased to a relatively low level seven to ten days later, and that the nitrate nitrogen （NO^-N） concentration gradually rose to its peak value, which appeared later in subsurface water than in surface water. Continuous flooding could effectively reduce the concentrations of NH^-N , NO3-N, and total phosphorus （TP） in surface water. However, the paddy water disturbance, in the process of soil surface adsorption and nitrification, caused NH]-N to be released and increased the concentrations of NH4-N and NO^-N in surface water. A multi-objective controlled drainage model based on environmental factors was established in order to obtain the optimal drainage time at each growth stage and better guide the drainage practices of farmers. The optimal times for surface drainage are the fourth, sixth, fifth, and sixth days after flooding at the tillering, jointing-booting, heading-flowering, and milking stages, respectively.展开更多
Horizontal wells are commonly used in bottom water reservoirs,which can increase contact area between wellbores and reservoirs.There are many completion methods used to control cresting,among which variable density pe...Horizontal wells are commonly used in bottom water reservoirs,which can increase contact area between wellbores and reservoirs.There are many completion methods used to control cresting,among which variable density perforation is an effective one.It is difficult to evaluate well productivity and to analyze inflow profiles of horizontal wells with quantities of unevenly distributed perforations,which are characterized by different parameters.In this paper,fluid flow in each wellbore perforation,as well as the reservoir,was analyzed.A comprehensive model,coupling the fluid flow in the reservoir and the wellbore pressure drawdown,was developed based on potential functions and solved using the numerical discrete method.Then,a bottom water cresting model was established on the basis of the piston-like displacement principle.Finally,bottom water cresting parameters and factors influencing inflow profile were analyzed.A more systematic optimization method was proposed by introducing the concept of cumulative free-water production,which could maintain a balance（or then a balance is achieved）between stabilizing oil production and controlling bottom water cresting.Results show that the inflow profile is affected by the perforation distribution.Wells with denser perforation density at the toe end and thinner density at the heel end may obtain low production,but the water breakthrough time is delayed.Taking cumulative free-water production as a parameter to evaluate perforation strategies is advisable in bottom water reservoirs.展开更多
Hypoglycemia occurred on hospitalized patients would result in severe complications.So we monitored the blood glucose of hospitalized patients with diabetes in 14 clinical departments from January to December 2013.Tot...Hypoglycemia occurred on hospitalized patients would result in severe complications.So we monitored the blood glucose of hospitalized patients with diabetes in 14 clinical departments from January to December 2013.Totally 105728 cases of blood glucose were monitored and 1374 cases of hypoglycemia were detected.The incidence of hypoglycemia was 1.29%.Among which,317 cases of severe hypoglycemia were detected and the incidence of severe hypoglycemia was 0.29%.The peak periods of hypoglycemia were 0:00~2:00,22:00~24:00,2:00~4:00,8:00~10:00 and 10:00~12:00.The symptomatic hypoglycemia accounted for 47.01%,The asymptomatic hypoglycemia accounted for 52.98%.The incidence of hypoglycemia was 1.49%in medical departments and 0.87%in surgical departments.It is suggested to be vigilant of high risk periods of hypoglycemia,detect and treat asymptomatic hypoglycemia timely and rationally administer antidiabetics to prevent hypoglycemia.展开更多
High concentrations of ammonium nitrogen released from tannery sludge during storage in open air may cause nitrogen pollution to soil and groundwater.To study the transformation mechanism of NH_(4)^(+)-N by nitrifying...High concentrations of ammonium nitrogen released from tannery sludge during storage in open air may cause nitrogen pollution to soil and groundwater.To study the transformation mechanism of NH_(4)^(+)-N by nitrifying functional bacteria in tannery sludge contaminated soils,a series of contaminated soil culture experiments were conducted in this study.The contents of ammonium nitrogen(as NH_(4)^(+)-N),nitrite nitrogen(as NO_(2)^(−)-N)and nitrate nitrogen(as NO_(3)^(−)-N)were analyzed during the culture period under different conditions of pollution load,soil particle and redox environment.Sigmodial equation was used to interpret the change of NO_(3)^(−)-N with time in contaminated soils.The abundance variations of nitrifying functional genes(amoA and nxrA)were also detected using the real-time quantitative fluorescence PCR method.The results show that the nitrification of NH_(4)^(+)-N was aggravated in the contaminated silt soil and fine sand under the condition of lower pollution load,finer particle size and more oxidizing environment.The sigmodial equation well fitted the dynamic accumulation curve of the NO_(3)^(−)-N content in the tannery sludge contaminated soils.The Cr(III)content increased with increasing pollution load,which inhibited the reproduction and activity of nitrifying bacteria in the soils,especially in coarse-grained soil.The accumulation of NO_(2)^(−)-N contents became more obvious with the increase of pollution load in the fine sand,and only 41.5%of the NH_(4)^(+)-N was transformed to NO_(3)^(−)-N.The redox environment was the main factor affecting nitrification process in the soil.Compared to the aerobic soil environment,the transformation of NH_(4)^(+)-N was significantly inhibited under anaerobic incubation condition,and the NO_(3)^(−)-N contents decreased by 37.2%,61.9%and 91.9%under low,medium and high pollution loads,respectively.Nitrification was stronger in the silt soil since its copy number of amoA and nxrA genes was two times larger than that of fine sand.Moreover,the copy numbers of amoA and nxrA genes in the silt soil under the aerobic environment were 2.7 times and 2.2 times larger than those in the anaerobic environment.The abundance changes of the amoA and nxrA functional genes have a positive correlation with the nitrification intensity in the tannery sludge-contaminated soil.展开更多
BACKGROUND Metastatic tumors of the hand are very rare.They are usually late manifestations of massive advanced malignancies.However,a small portion of acrometastases are indications of occult primary cancer.Here,we r...BACKGROUND Metastatic tumors of the hand are very rare.They are usually late manifestations of massive advanced malignancies.However,a small portion of acrometastases are indications of occult primary cancer.Here,we report an extremely rare case in which a scaphoid bone lesion was the initial manifestation and was found to be a metastasis from gastroesophageal junction(GEJ)cancer.CASE SUMMARY A 57-year-old male patient presented with ongoing left wrist pain and swelling after trauma.He was initially misdiagnosed with infection of the scaphoid bone and treated with antibiotics and anti-inflammatory drugs.Further radiographic investigations showed a scaphoid pathological fracture,indicating a metastatic tumor derived from the GEJ and/or right lung malignancies.Gastroscopy failed to identify the pathology of the mass at the GEJ,which grew in an exophytic pattern.A lung puncture biopsy was not performed because the patient refused the procedure.To relieve his wrist pain and obtain a definite pathology,we resected the scaphoid lesion.Based on the clinical and pathological results,the patient was finally diagnosed with multiple metastases of advanced GEJ adenocarcinoma.He underwent chemotherapy and died 6 mo after his initial presentation.CONCLUSION Despite the rareness of the disease,orthopedic surgeons should consider the possibility of metastasis to the bones of the hand when patients complain of persistent and progressive pain in the hand.展开更多
Cu/Al compound materials,named as copperclad aluminum bus bars,are widely used in heat dissipation of modern engineering.The thermal cycle tests were conducted at 200,250 and 300℃for different cycle times,respectivel...Cu/Al compound materials,named as copperclad aluminum bus bars,are widely used in heat dissipation of modern engineering.The thermal cycle tests were conducted at 200,250 and 300℃for different cycle times,respectively.Effects of thermal cycle temperatures and thermal cycle times on micro structures and mechanical properties of the interface were studied.The results show that the width of bonding layer and bond strength are significantly affected by thermal cycle temperatures and times.Nonetheless,the variety or the quantity of intermediate compounds is scarcely influenced.Al_(2)Cu,Cu_(9) Al_(4)and CuAl were identified on the interface.With the increase in cycle times,grains of the material grew up.However,grains of the interface grew up more apparently than those of Cu and Al.The knowledge may be applied in the establishment of service condition and quality evaluation of material.展开更多
Microporous organic polymers with high surface area are widely used in many applications.Among them,hypercrosslinked polymers have been extensively concerned because of their simple processes and low-cost reagents.How...Microporous organic polymers with high surface area are widely used in many applications.Among them,hypercrosslinked polymers have been extensively concerned because of their simple processes and low-cost reagents.However,due to most state-of-the-art strategies for HCPs based on condensation reactions,the release of small molecules such as hydrochloric acid and methanol involved in such strategies brings about new hazards to environment.Herein,we propose a method of fabrication of hypercrosslinked polymers via self-addition polymerization of divinyl benzene and its crosslinking with polar aromatic molecules.The hypercrosslinked polyDVB-based products are demonstrated by FriedelCrafts addition reaction of double bonds on DVB that can connect adjacent phenyl rings of aromatic molecules to form the crosslinked networks.The HCPDVB-CB obtained in 1-chlorobutane as solvent has a high micropore content and displays high surface area up to 931 m^(2)/g.Following this finding,DVB is used as a novel external crosslinker for knitting polar aromatic molecules.When L-phenylalanine and bisphenol A are used as the aromatic units,the obtained HCP(Phe-DVB)and HCP(BPA-DVB)could reach surface area of 612 and 471 m^(2)/g,and have hydrogen uptake of0.62 wt%and 0.58 wt%at 77 K and 1.13 bar by comparison with HCPDVB-CB having hydrogen uptake of 0.30 wt%,respectively.展开更多
The liquid-crystal assembly of semiflexible-coil diblock copolymers with coil or semiflexible homopolymers is studied by dissipative particle dynamics simulation. Phase diagrams of the blends and orientation ordering ...The liquid-crystal assembly of semiflexible-coil diblock copolymers with coil or semiflexible homopolymers is studied by dissipative particle dynamics simulation. Phase diagrams of the blends and orientation ordering parameters among semiflexible blocks are constructed as a function of chain stiffness and homopolymer volume fraction. For semiflexible-coil/coil blends with varying stiffness of semiflexible blocks, we display the rich phase behaviors of the system transited from coil-coil/coil to rod-coil/coil blends. The disorder- lamellae or lamellae-liquid crystalline transition and ＂dry brush＂ phenomenon induced by coil homopolymers are observed. For semiflexible-coil/semiflexible blends, adding semiflexible homopolymers also leads to a disorder-order transition and even a transition between monolayer and bilayer smectic-A phase. The results demonstrate that blending homopolymers into semiflexible copolymers can induce liquid-crystal assembly and even improve the orientation ordering of semiflexible blocks effectively.展开更多
In this paper,we consider the following problem {-Δu（x）＋u（x）=λ（u^p（x）＋h（x））,x∈R^N,u（x）∈h^1（R^N）,u（x）〉0,x∈R^N,（＊）where λ 〉 0 is a parameter,p =（N＋2）/（N—2）.We will prove that there exi...In this paper,we consider the following problem {-Δu（x）＋u（x）=λ（u^p（x）＋h（x））,x∈R^N,u（x）∈h^1（R^N）,u（x）〉0,x∈R^N,（＊）where λ 〉 0 is a parameter,p =（N＋2）/（N—2）.We will prove that there exists a positive constant 0 〈 A＊ 〈 ＋00such that（＊） has a minimal positive solution for λ∈（0,λ＊）,no solution for λ 〉 λ＊,a unique solution for λ = λ＊.Furthermore,（＊） possesses at least two positive solutions when λ∈（0,λ＊） and 3 ≤ N ≤ 5.For N ≥ 6,under some monotonicity conditions of h we show that there exists a constant 0 〈λ＊＊ 〈 λ＊ such that problem（＊）possesses a unique solution for λ∈（0,λ＊＊）.展开更多
基金Supported by National Natural Science Foundation of China,No.81573695,No.81860894,and No.81674096Ningxia Key Research and Development Plan Project,No.2021BEG03106.
文摘BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.
文摘AIM:To investigate whether nintedanib can inhibit pterygium cells through the fibroblast growth factor receptor 2(FGFR2)/extracellular-signal-regulated kinase(ERK)pathway.METHODS:Human primary pterygium cells were cultured in vitro.After treatment with nintedanib,the cell morphology was observed under microscopy,the morphological changes of the nucleus were observed after DAPI staining,apoptosis was analyzed by Annexin-V FITC/PI double staining,and the changes of apoptosis-associated proteins were detected by Western blot.The binding ability of nintedanib to FGFR2 was predicted by molecular docking.Finally,by silencing FGFR2,we explored whether nintedanib inhibited FGFR2/ERK pathway.RESULTS:The results showed that nintedanib inhibited the growth of pterygium cells and caused nuclear pyknosis.The results of Annexin-VFITC/PI double staining showed that nintedanib was able to induce early and late apoptosis of pterygium cells,significantly increasing the expression of apoptosis-associated proteins Bax and cleaved-Caspase3(P<0.05),and reducing the expression of Bcl-2(P<0.05).In addition,nintedanib significantly inhibited ERK1/2 phosphorylation through FGFR2(P<0.05).After silencing the expression of FGFR2,there was no significant difference in the inhibition of ERK1/2 phosphorylation by nintedanib(P>0.05).CONCLUSION:Nintedanib induces apoptosis of pterygium cells by inhibiting FGFR2/ERK pathway.
基金Supported by General Class A of the Zhejiang Medical and Health Science and Technique Plan Project in 2020(No.2020ky288)Zhejiang Provincial Science and Technique Program of Traditional Chinese Medicine(No.2021ZB268)+2 种基金Health Science and Technique Program of Zhejiang Province(No.2021PY073)Yinzhou District Agriculture and Social Development Field Science and Technique Project(No.2021AS0058No.2020AS0080)。
文摘AIM:To introduce and evaluate the clinical efficacy of a new technique,the use of viscoelastic substances(VS)to close leaking sclerotomy in 23G microincision vitrectomy,and to observe its effect on the visual acuity and intraocular pressure(IOP)of patients.METHODS:Patients who underwent 23G vitrectomy in Ningbo Eye Hospital before the use of VS technique(June 2019 to September 2020)and after the use of VS technique(October 2020 to December 2021)were selected as the subjects of this study.The above cases underwent operation by the same surgeon and were retrospectively analyzed.VS technique was used as the alternative to suturing,in which a small amount of VS was injected at the leaking sclerotomy and then gently massaged to confirm leaking sclerotomy closure.RESULTS:A total of 174 eyes were covered in the study,including 84 eyes in the control group(before the use of VS technique)and 90 eyes in the VS technique group.The number of eyes that needed to be sutured decreased considerably from 42.9%in the control group to 3.3%in the VS technique group,and the proportion of subconjunctival hemorrhage at 1-2d after surgery decreased remarkably from 35.7%in the control group to 2.2%in the VS technique group.No substantial differences in the incidence of mean IOP and low IOP were found between 1-2 and 3-20d after surgery in the VS technique group.No major complications associated with VS technique were identified during the study.CONCLUSION:In 23G microincision vitrectomy,VS technique is a safe,simple,and effective method to close leaking sclerotomy.
基金Supported by Grants from the National Key Technology R and D Program,No.2008ZX10005 and No.2009ZX10005
文摘AIM:To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure(ACLF).METHODS:This was a single center,prospective cohort study.Eligible,consecutive hospitalized patients received either entecavir 0.5 mg/d or lamivudine 100mg/d.All patients were given standard comprehensive internal medicine.The primary endpoint was survival rate at day 60,and secondary endpoints were reduction in hepatitis B virus(HBV)DNA and alanine aminotransferase(ALT)levels,and improvement in Child-Turcotte-Pugh(CTP)and model for end-stage liver disease(MELD)scores at day 60 and survival rate at week 52.RESULTS:One hundred and nineteen eligible subjects were recruited from 176 patients with severe acute exacerbation of chronic hepatitis B:65 were included in the entecavir group and 54 in the lamivudine group(full analysis set).No significant differences were found in patient baseline clinical parameters.At day 60,entecavir did not improve the probability of survival(P=0.066),despite resulting in faster virological suppression(P<0.001),higher rates of virological response(P<0.05)and greater reductions in the CTP and MELD scores(all P<0.05)than lamivudine.Intriguingly,at week 52,the probability of survival was higher in the entecavir group than in the lamivudine group[42/65(64.6%)vs 26/54(48.1%),respectively;P=0.038].The pretreatment MELD score(B,1.357;95%Cl:2.138-7.062;P=0.000)and virological response at day30(B,1.556;95%Cl:1.811-12.411;P=0.002),were found to be good predictors for 52-wk survival.CONCLUSION:Entecavir significantly reduced HBV DNA levels,decreased the CTP and MELD scores,and thereby improved the long-term survival rate in patients with spontaneous reactivation of hepatitis B presenting as ACLF.
文摘AIM: To examine the effect of the potential interaction between KIF1 B variants(rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma(HCC) in a high-risk region in China.METHODS: Three hundred and six patients with HCC and 306 hospital-based control participants residing in the Shunde region of Guangdong Province, China were enrolled. Clinical characteristics were collected by reviewing the complete medical histories from the patient archives, and epidemiological data were collected using a questionnaire and clinical examination. Two single nucleotide polymorphisms(SNPs) of KIF1B(rs17401966 and rs3748578) were chosen for the current study. All subjects were genotypedusing a Taq Man real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions.RESULTS: Smoking, frequent consumption of raw freshwater fish, hepatitis B virus(HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio(OR) = 12.02; 95% confidence interval(95%CI): 6.02-24.00]. No significant association was found between the KIF1 B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption(P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC(OR = 2.36; 95%CI: 1.49-3.74).CONCLUSION: The gene-environment interaction between the KIF1 B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.
基金supported by the National Natural Science Foundation of China (Grant No. 50839002)the National Key Technologies R&D Program of China during the Eleventh Five-Year Plan Period (Grant No.2006BAD11B06)the Jiangsu Province Graduate Cultivation Innovative Project (Grant No.CXZZ11_0453)
文摘While many controlled irrigation and drainage techniques have been adopted in China, the environmental effects of these techniques require further investigation. This study was conducted to examine the changes of nitrogen and phosphorus of a flooded paddy water system after fertilizer application and at each growth stage so as to obtain the optimal drainage time at each growth stage. Four treatments with different water level management methods at each growth stage were conducted under the condition of ten-day continuous flooding. Results show that the ammonia nitrogen （ NH4-N ） concentration reached the peak value once the fertilizer was applied, and then decreased to a relatively low level seven to ten days later, and that the nitrate nitrogen （NO^-N） concentration gradually rose to its peak value, which appeared later in subsurface water than in surface water. Continuous flooding could effectively reduce the concentrations of NH^-N , NO3-N, and total phosphorus （TP） in surface water. However, the paddy water disturbance, in the process of soil surface adsorption and nitrification, caused NH]-N to be released and increased the concentrations of NH4-N and NO^-N in surface water. A multi-objective controlled drainage model based on environmental factors was established in order to obtain the optimal drainage time at each growth stage and better guide the drainage practices of farmers. The optimal times for surface drainage are the fourth, sixth, fifth, and sixth days after flooding at the tillering, jointing-booting, heading-flowering, and milking stages, respectively.
文摘Horizontal wells are commonly used in bottom water reservoirs,which can increase contact area between wellbores and reservoirs.There are many completion methods used to control cresting,among which variable density perforation is an effective one.It is difficult to evaluate well productivity and to analyze inflow profiles of horizontal wells with quantities of unevenly distributed perforations,which are characterized by different parameters.In this paper,fluid flow in each wellbore perforation,as well as the reservoir,was analyzed.A comprehensive model,coupling the fluid flow in the reservoir and the wellbore pressure drawdown,was developed based on potential functions and solved using the numerical discrete method.Then,a bottom water cresting model was established on the basis of the piston-like displacement principle.Finally,bottom water cresting parameters and factors influencing inflow profile were analyzed.A more systematic optimization method was proposed by introducing the concept of cumulative free-water production,which could maintain a balance（or then a balance is achieved）between stabilizing oil production and controlling bottom water cresting.Results show that the inflow profile is affected by the perforation distribution.Wells with denser perforation density at the toe end and thinner density at the heel end may obtain low production,but the water breakthrough time is delayed.Taking cumulative free-water production as a parameter to evaluate perforation strategies is advisable in bottom water reservoirs.
文摘Hypoglycemia occurred on hospitalized patients would result in severe complications.So we monitored the blood glucose of hospitalized patients with diabetes in 14 clinical departments from January to December 2013.Totally 105728 cases of blood glucose were monitored and 1374 cases of hypoglycemia were detected.The incidence of hypoglycemia was 1.29%.Among which,317 cases of severe hypoglycemia were detected and the incidence of severe hypoglycemia was 0.29%.The peak periods of hypoglycemia were 0:00~2:00,22:00~24:00,2:00~4:00,8:00~10:00 and 10:00~12:00.The symptomatic hypoglycemia accounted for 47.01%,The asymptomatic hypoglycemia accounted for 52.98%.The incidence of hypoglycemia was 1.49%in medical departments and 0.87%in surgical departments.It is suggested to be vigilant of high risk periods of hypoglycemia,detect and treat asymptomatic hypoglycemia timely and rationally administer antidiabetics to prevent hypoglycemia.
基金supported jointly by Natural Science Foundation of Hebei Province(D2020504003)National Key Research and Development Program of China(No.2019YFC1805300).
文摘High concentrations of ammonium nitrogen released from tannery sludge during storage in open air may cause nitrogen pollution to soil and groundwater.To study the transformation mechanism of NH_(4)^(+)-N by nitrifying functional bacteria in tannery sludge contaminated soils,a series of contaminated soil culture experiments were conducted in this study.The contents of ammonium nitrogen(as NH_(4)^(+)-N),nitrite nitrogen(as NO_(2)^(−)-N)and nitrate nitrogen(as NO_(3)^(−)-N)were analyzed during the culture period under different conditions of pollution load,soil particle and redox environment.Sigmodial equation was used to interpret the change of NO_(3)^(−)-N with time in contaminated soils.The abundance variations of nitrifying functional genes(amoA and nxrA)were also detected using the real-time quantitative fluorescence PCR method.The results show that the nitrification of NH_(4)^(+)-N was aggravated in the contaminated silt soil and fine sand under the condition of lower pollution load,finer particle size and more oxidizing environment.The sigmodial equation well fitted the dynamic accumulation curve of the NO_(3)^(−)-N content in the tannery sludge contaminated soils.The Cr(III)content increased with increasing pollution load,which inhibited the reproduction and activity of nitrifying bacteria in the soils,especially in coarse-grained soil.The accumulation of NO_(2)^(−)-N contents became more obvious with the increase of pollution load in the fine sand,and only 41.5%of the NH_(4)^(+)-N was transformed to NO_(3)^(−)-N.The redox environment was the main factor affecting nitrification process in the soil.Compared to the aerobic soil environment,the transformation of NH_(4)^(+)-N was significantly inhibited under anaerobic incubation condition,and the NO_(3)^(−)-N contents decreased by 37.2%,61.9%and 91.9%under low,medium and high pollution loads,respectively.Nitrification was stronger in the silt soil since its copy number of amoA and nxrA genes was two times larger than that of fine sand.Moreover,the copy numbers of amoA and nxrA genes in the silt soil under the aerobic environment were 2.7 times and 2.2 times larger than those in the anaerobic environment.The abundance changes of the amoA and nxrA functional genes have a positive correlation with the nitrification intensity in the tannery sludge-contaminated soil.
基金Natural Science Foundation of Zhejiang Province,No.LQ19H060002 and No.LQ19H160041Medical and Health Science and Technology Project of Zhejiang Province,No.2018KY089.
文摘BACKGROUND Metastatic tumors of the hand are very rare.They are usually late manifestations of massive advanced malignancies.However,a small portion of acrometastases are indications of occult primary cancer.Here,we report an extremely rare case in which a scaphoid bone lesion was the initial manifestation and was found to be a metastasis from gastroesophageal junction(GEJ)cancer.CASE SUMMARY A 57-year-old male patient presented with ongoing left wrist pain and swelling after trauma.He was initially misdiagnosed with infection of the scaphoid bone and treated with antibiotics and anti-inflammatory drugs.Further radiographic investigations showed a scaphoid pathological fracture,indicating a metastatic tumor derived from the GEJ and/or right lung malignancies.Gastroscopy failed to identify the pathology of the mass at the GEJ,which grew in an exophytic pattern.A lung puncture biopsy was not performed because the patient refused the procedure.To relieve his wrist pain and obtain a definite pathology,we resected the scaphoid lesion.Based on the clinical and pathological results,the patient was finally diagnosed with multiple metastases of advanced GEJ adenocarcinoma.He underwent chemotherapy and died 6 mo after his initial presentation.CONCLUSION Despite the rareness of the disease,orthopedic surgeons should consider the possibility of metastasis to the bones of the hand when patients complain of persistent and progressive pain in the hand.
基金financially supported by the National Natural Science Foundation of China(No.51201107)。
文摘Cu/Al compound materials,named as copperclad aluminum bus bars,are widely used in heat dissipation of modern engineering.The thermal cycle tests were conducted at 200,250 and 300℃for different cycle times,respectively.Effects of thermal cycle temperatures and thermal cycle times on micro structures and mechanical properties of the interface were studied.The results show that the width of bonding layer and bond strength are significantly affected by thermal cycle temperatures and times.Nonetheless,the variety or the quantity of intermediate compounds is scarcely influenced.Al_(2)Cu,Cu_(9) Al_(4)and CuAl were identified on the interface.With the increase in cycle times,grains of the material grew up.However,grains of the interface grew up more apparently than those of Cu and Al.The knowledge may be applied in the establishment of service condition and quality evaluation of material.
基金National Key R&D Program of China(No.2017YFC1600404)Natural Science Foundation of Shandong Province(No.ZR2013BM011)+1 种基金supported by Open Projects Fund of Shandong Key Laboratory of Carbohydrate Chemistry and Glycobiology,Shandong University(No.2019CCG02)Shandong Key Laboratory of Fluorine Chemistry and Chemical Engineering Materials,and Science and Technology Bureau of Jinan(No.2021GXRC105)。
文摘Microporous organic polymers with high surface area are widely used in many applications.Among them,hypercrosslinked polymers have been extensively concerned because of their simple processes and low-cost reagents.However,due to most state-of-the-art strategies for HCPs based on condensation reactions,the release of small molecules such as hydrochloric acid and methanol involved in such strategies brings about new hazards to environment.Herein,we propose a method of fabrication of hypercrosslinked polymers via self-addition polymerization of divinyl benzene and its crosslinking with polar aromatic molecules.The hypercrosslinked polyDVB-based products are demonstrated by FriedelCrafts addition reaction of double bonds on DVB that can connect adjacent phenyl rings of aromatic molecules to form the crosslinked networks.The HCPDVB-CB obtained in 1-chlorobutane as solvent has a high micropore content and displays high surface area up to 931 m^(2)/g.Following this finding,DVB is used as a novel external crosslinker for knitting polar aromatic molecules.When L-phenylalanine and bisphenol A are used as the aromatic units,the obtained HCP(Phe-DVB)and HCP(BPA-DVB)could reach surface area of 612 and 471 m^(2)/g,and have hydrogen uptake of0.62 wt%and 0.58 wt%at 77 K and 1.13 bar by comparison with HCPDVB-CB having hydrogen uptake of 0.30 wt%,respectively.
基金financially supported by the National Natural Science Foundation of China(No.21674082)
文摘The liquid-crystal assembly of semiflexible-coil diblock copolymers with coil or semiflexible homopolymers is studied by dissipative particle dynamics simulation. Phase diagrams of the blends and orientation ordering parameters among semiflexible blocks are constructed as a function of chain stiffness and homopolymer volume fraction. For semiflexible-coil/coil blends with varying stiffness of semiflexible blocks, we display the rich phase behaviors of the system transited from coil-coil/coil to rod-coil/coil blends. The disorder- lamellae or lamellae-liquid crystalline transition and ＂dry brush＂ phenomenon induced by coil homopolymers are observed. For semiflexible-coil/semiflexible blends, adding semiflexible homopolymers also leads to a disorder-order transition and even a transition between monolayer and bilayer smectic-A phase. The results demonstrate that blending homopolymers into semiflexible copolymers can induce liquid-crystal assembly and even improve the orientation ordering of semiflexible blocks effectively.
基金supported by the National Natural Science Foundation of China(No.11201132)Scientific Research Foundation for Ph.D of Hubei University of Technology(No.BSQD12065)supported by the Science Research Project of Hubei Provincial Department of education(No.d200614001)
文摘In this paper,we consider the following problem {-Δu（x）＋u（x）=λ（u^p（x）＋h（x））,x∈R^N,u（x）∈h^1（R^N）,u（x）〉0,x∈R^N,（＊）where λ 〉 0 is a parameter,p =（N＋2）/（N—2）.We will prove that there exists a positive constant 0 〈 A＊ 〈 ＋00such that（＊） has a minimal positive solution for λ∈（0,λ＊）,no solution for λ 〉 λ＊,a unique solution for λ = λ＊.Furthermore,（＊） possesses at least two positive solutions when λ∈（0,λ＊） and 3 ≤ N ≤ 5.For N ≥ 6,under some monotonicity conditions of h we show that there exists a constant 0 〈λ＊＊ 〈 λ＊ such that problem（＊）possesses a unique solution for λ∈（0,λ＊＊）.
