Hemodynamic analysis of esophageal varices in patients with liver cirrhosis using color Doppler ultrasound

AIM: To study the portal hemodynamics and their relationship with the size of esophageal varices seen at endoscopy and to evaluate whether these Doppler ultrasound parameters might predict variceal bleeding in patients with liver cirrhosis and portal hypertension.METHODS: One hundred and twenty cirrhotic patients with esophageal varices but without any previous bleeding were enrolled in the prospective study. During a 2-year observation period, 52 patients who had at least one episode of acute esophageal variceal hemorrhage constituted the bleeding group, and the remaining 68 patients without any previous hemorrhage constituted the non-bleeding group. All patients underwent endoscopy before or after color Doppler-ultrasonic examination, and images were interpreted independently by two endoscopists. The control group consisted of 30 healthy subjects, matched to the patient group in age and gender. Measurements of diameter,flow direction and flow velocity in the left gastric vein (LGV) and the portal vein (PV) were done in all patients and controls using color Doppler unit. After baseline measurements, 30 min after oral administration of 75 g glucose in 225 mL, changes of the diameter, flow velocity and direction in the PV and LGV were examined in 60 patients with esophageal varices and 15 healthy controls.RESULTS: The PV and LGV were detected successfully in 115 (96%) and 105 (88%) of 120 cirrhotic patients,respectively, and in 27 (90%) and 21 (70%) of 30 healthy controls, respectively. Among the 120 cirrhotic patients,37 had F1, 59 had F2, and 24 had F3 grade varices. Compared with the healthy controls, cirrhotic group had a significantly lower velocity in the PV, a significantly greater diameter of the PV and LGV, and a higher velocity in the LGV. In the cirrhotic group, no difference in portal flow velocity and diameter were observed between patients with or without esophageal variceal bleeding (EVB). However, the diameter and blood flow velocity of the LGV were significantly higher for EVB (+) group compared with EVB (-) group (P＜0.01).Diameter of the LGV increased with enlarged size of varices.There were differences between F1 and F2, F1 and F3 varices, but no differences between F2 and F3 varices (P = 0.125). However, variceal bleeding was more frequent in patients with a diameter of LGV ＞6 mm. The flow velocity in the LGV of healthy controls was 8.70±1.91 cm/s (n = 21). In patients with liver cirrhosis, it was 10.3±2.1 cm/s (n = 12) when the flow was hepatopetal and 13.5±2.3 cm/s (n = 87) when it was hepatofugal. As the size of varices enlarged, hepatofugal flow velocity increased (P＜0.01) and was significantly different between patients with F1 and F2 varices and between patients with F2 and F3 varices. Variceal bleeding was more frequent in patients with a hepatofugal flow velocity ＞15 cm/s (32 of 52 patients, 61.5%). Within the bleeding group, the mean LGV blood flow velocity was 16.6±2.62 cm/s. No correlation was observed between the portal blood flow velocity and EVB. In all healthy controls, the flow direction in the LGV was hepatopetal, toward the PV. In patients with F1 varices, flow direction was hepatopetal in 10 patients, to-and-fro state in 3 patients, and hepatofugal in the remaining 18. The flow was hepatofugal in 91% patients with F2 and all F3 varices. Changes in diameter of the PV and LGV were not significant before and after ingestion of glucose (PV: 1.41±1.5 cm before and 1.46±1.6 cm after; LGV: 0.57±1.7 cm before and 0.60±1.5 cm after).Flow direction in the LGV was hepatopetal and to-and-fro in 16 patients and hepatofugal in 44 patients before ingestion of glucose. Flow direction changed to hepatofugal in 9 of 16 patients with hepatopetal and to-and-fro blood flow after ingestion of glucose. In 44 patients with hepatofugal blood flow in the LGV, a significant increase in hepatofugal flow velocity was observed in 38 of 44 patients (86%) with esophageal vadces. There was a relationship between the percentage changes in flow velocity and the size of varices. Patients who responded excessively to food ingestion might have a high risk for bleeding. The changes of blood flow velocity in the LGV were greater than those in the PV (LGV: 28.3±26.1%, PV: 7.2±13.2%, P＜0.01), whereas no significant changes in the LGV occurred before and after ingestion of glucose in the control subjects.CONCLUSION: Hemodynamics of the PV is unrelated to the degree of endoscopic abnormalities in patients with liver cirrhosis. The most important combinations are endoscopic findings followed by the LGV hemodynamics.Duplex-Doppler ultrasonography has no value in the identification of patients with cirrhosis at risk of variceal bleeding. Hemodynamics of the LGV appears to be superior to those of the PV in predicting bleeding.

Sodium chloride exacerbates dextran sulfate sodiuminduced colitis by tuning proinflammatory and antiinflammatory lamina propria mononuclear cells through p38/MAPK pathway in mice

AIM To investigate the influence of high salt on dextran sulfate sodium(DSS)-induced colitis in mice and explore the underlying mechanisms of this effect.METHODS DSS and NaC l were used to establish the proinflammatory animal model. We evaluated the colitis severity. Flow cytometry was employed for detecting the frequencies of Th1, macrophages and Tregs in spleen, mesenteric lymph node and lamina propria. The important role of macrophages in the promotion of DSS-induced colitis by NaCl was evaluated by depleting macrophages with clodronate liposomes. Activated peritoneal macrophages and lamina propria mononuclear cells(LPMCs) were stimulated with NaCl, and proteins were detected by western blotting. Cytokines and inflammation genes were analyzed by enzyme-linked immunosorbent assay and RT-PCR, respectively.RESULTS The study findings indicate that NaC l up-regulates the frequencies of CD11b^+ macrophages and CD4^+IFN-γ^+IL-17^+ T cells in lamina propria in DSS-treated mice. CD3^+CD4^+CD25^+Foxp^3+ T cells, which can secrete high levels of IL-10 and TGF-β, increase through feedback in NaCl-and DSS-treated mice. Furthermore, clodronate liposomes pretreatment significantly alleviated DSSinduced colitis, indicating that macrophages play a vital role in NaCl proinflammatory activity. NaCl aggravates peritoneal macrophage inflammation by promoting the expressions of interleukin(IL)-1, IL-6 and mouse inducible nitric oxide synthase. Specifically, high NaCl concentrations promote p38 phosphorylation in lipopolysaccharide-and IFN-γ-activated LPMCs mediated by SGK1. CONCLUSION Proinflammatory macrophages may play an essential role in the onset and development of NaCl-promoted inflammation in DSS-induced colitis. The underlining mechanism involves up-regulation of the p38/MAPK axis.

Toripalimab combined with targeted therapy and chemotherapy achieves pathologic complete response in gastric carcinoma:A case report

BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy.Herein,we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab,Herceptin,and docetaxel,oxaliplatin,calcium folinate,and fluorouracil(FLOT)chemotherapy followed by surgery for human epidermal growth factor receptor 2(HER2)-and programmed deathligand 1(PD-L1)-positive locally advanced gastric carcinoma.We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma.CASE SUMMARY The patient was diagnosed with locally advanced adenocarcinoma of the cardia.Immunohistochemistry of the baseline tissues suggested that the tissues were HER2-(fluorescent in situ hybridization)and PD-L1-positive(combined positive score=1).The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin,toripalimab,and FLOT chemotherapy.The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation(proximal stomach),no clear residual tumor(tumor regression grade 0),no regional lymph node metastasis,and negative upper and lower cut ends.The levels of tumor markers were reduced to normal levels after re-examination.With good postoperative recovery,the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered.After the treatment,the patient was monitored every 3 mo with a follow-up of 12 mo(4 times).As of February 27,2022,he was in a good condition without disease progression.The clinical trial registration number is E2019401.CONCLUSION There are many ongoing studies on neoadjuvant immunotherapy combined with chemotherapy or radiotherapy;however,most of these studies are phase II studies with small cohorts.According to the results of some current studies,these combined regimens have shown promising results in terms of efficacy and safety.However,the clinical efficacy and safety of the neoadjuvant therapies used in these combined regimens need to be confirmed by additional prospective phase III clinical trials,and further exploration of molecular markers for effective populations is required.

NO/ET-1比值及Hcy水平与OSAHS患者认知功能障碍的相关性分析

目的探讨血清同型半胱氨酸(Hcy)和一氧化氮NO与内皮素-1(ET-1)比值对阻塞型睡眠呼吸暂停低通气综合征(OSAHS)患者认知功能障碍的诊断效能,为干预OSAHS患者并发认知功能障碍提供新的临床依据。方法选取OSAHS患者86例(OSAHS组)及健康体检者50例(对照组)。OSAHS组患者又分为认知障碍组和认识正常组。比较两组血清Hcy及NO/ET-1水平,应用蒙特利尔认知评估量表(MoCA)评估OSAHS组轻度认知功能障碍发生情况,分析OSAHS组患者血清Hcy、NO/ET-1水平与认知功能的相关性。结果 OSAHS伴认知障碍患者血清Hcy水平高于认知正常组,NO/ET-1水平低于认知正常组(P<0.05)。OSAHS认知障碍组呼吸暂停低通气指数(AHI)、睡眠时间高于认知正常组,最低动脉血氧饱和度(LSaO2)低于认知正常组(P<0.05)。MoCA评分与AHI、睡眠时间呈负相关,与LSaO2呈正相关。血清Hcy水平与MoCA总分及其亚项得分均呈负相关(P<0.05),NO/ET-1与MoCA总分及其亚项评分均呈正相关(P<0.05),Hcy与NO/ET-1呈负相关(P<0.05)。血清Hcy及NO/ET-1水平预测OSAHS患者认知功能障碍的ROC曲线下面积分别为0.708(95%CI:0.599,0.816)、0.739(95%CI:0.618,0.859)。结论血清Hcy、NO/ET-1是OSAHS患者认知功能障碍形成的影响因素,Hcy水平与认知损害程度呈负相关,NO/ET-1与认知损害程度呈正相关。

Preparation of magnetic resonance probes using one-pot method for detection of hepatocellular carcinoma

AIM: To prepare the specific magnetic resonance(MR) probes for detection of hepatocellular carcinoma(HCC) using one-pot method.METHODS: The carboxylated dextran-coated nanoparticles were conjugated with anti-α-fetoprotein(anti-AFP) or anti-glypican 3(anti-GPC3) antibodies through 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/N-hydroxysuccinimide(EDC/NHS)-mediated reaction to synthesize the probes.The physical and chemical properties of the probes were determined by transmission electron microscopy(TEM) and dynamic light scattering, and the relaxivity was compared to uncombined ultrasmall superparamagnetic iron oxide nanoparticles(USPIONs) using a 1.5T clinical MR scanner.The binding efficiency of the antibodies to nanoparticles was measured with an ultravioletvisible spectrophotometer.In addition, the probes were incubated with targetable cells in vitro.RESULTS: The superparamagnetic MR probes(antiGPC3-USPION probe and anti-AFP-USPION probe) were synthesized using one-pot method.Their mean hydrodynamic diameter was 47 nm with a broader slight size distribution.The coupling efficiency of carboxylated dextran-coated ultrasmall superparamagnetic iron oxide(USPIO) with anti-GPC3 or anti-AFP antibody was 15.9% and 88.8%, respectively.Each of the USPIO nanoparticles may bind 3 GPC3 antibodies or 12 AFP antibodies.The statistical analysis showed no significance(P > 0.05) in shortening the T1 and T2 values when comparing the USPIO-AFP or USPIOGPC3 to USPIO.Analysis of TEM images revealed that anti-GPC3-USPION probes and anti-AFP-USPION probes could specifically enter into the Hep G2 cell by combining with the GPC3 receptors or AFP receptors, whereas the Hep G2 cell sample incubated with USPIONs showed no or few nanoparticles in the cytoplasm.CONCLUSION: The synthesized probes using one-pot method can be used for in vitro experimental study and have potential clinical application in MR imaging for detection of hepatocellular carcinomas.

Effects of soil moisture regimes on growth and photosynthesis of the riparian plant Bolboschoenus planiculmis

Plants distributed in riparian regions experience frequent episodes of flooding and drought between years, and hence, riparian plants need to be floodand drought-tolerant. Riparian plants possess various traits to survive flooding, while their sensitivity to drought has received less attention. To investigate the growth and photosynthetic responses of a riparian species (Bolboschoenus planiculmis) to flooding and drought, plants of this species were subjected to 60-d flooding or drought stress under greenhouse conditions. Growth and photosynthetic traits were measured at the end of the treatments. As well, we determined the efficiency of photosynthetic apparatus in mature leaves. Plants of B. planiculmis adequately adjusted their growth and photosynthetic traits under both flooding and drought conditions. Flooding did not affect the above-ground growth of B. planiculmis. Increased growth of roots and rhizomes and the generation of new tubers suggested a high ability of below-ground lateral growth by capturing resources under flooding conditions. Enhanced photosynthetic capacity, retained leaf pigment concentrations and chlorophyll a fluorescence capacity indicated photosynthetic adaptation to flooding. In contrast, drought significantly decreased the above-ground growth of B. planiculmis, especially the leaves, thereby minimizing water loss due to transpiration. Its increased root to shoot ratio and "phalanx" asexual propagation pattern might enhance soil water uptake ability. Although the functional leaves of B. planiculmis could retain their leaf pigment concentrations, as well as photosynthesis and chlorophyll a fluorescence, the total biomass of plants decreased, which may be a consequence of the reduced leaf area, suggesting adverse effects by drought. Therefore, both growth and photosynthetic responses of B. planiculmis are likely to contribute to the ability of this species to thrive in riparian regions, but remain susceptive to drought.

Change of SPARC expression after chemotherapy in gastric cancer

Objective:The expression of tumor biomarkers may change after chemotherapy. However, whether secreted protein acidic and rich in cysteine(SPARC) expression changes after chemotherapy in gastric cancer(GC) is unclear. This study investigated the influence of chemotherapy on SPARC expression in GC.Methods: Immunohistochemistry was used to analyze SPARC expression in 132 GC cases(including 54 cases with preoperative chemotherapy and 78 cases without preoperative chemotherapy). SPARC expression of postoperative specimens with and without preoperative chemotherapy was assessed to analyze the influence of chemotherapy on SPARC expression.Results: SPARC was highly expressed in GC compared with the desmoplastic stroma surrounding tumor cells and noncancerous tissues. High SPARC expression was correlated with invasion depth, lymph node, and TNM stage. After chemotherapy, a lower proportion of high SPARC expression was observed in patients with preoperative chemotherapy than in the controls. For 54 patients with preoperative chemotherapy, gross type, histology, depth of invasion, lymph node, TNM stage, and SPARC expression were related to overall survival. Further multivariate analysis showed that lymph node, histology, and SPARC expression after chemotherapy were independent prognostic factors.Conclusion: SPARC expression may change after chemotherapy in GC. SPARC expression should be reassessed for patients with GC after chemotherapy.

A delayed stage-structure brucellosis model with interaction among seasonality, time-varying incubation and density-dependent growth

In this paper,a class of brucellosis transmission model with seasonal alternation,density-dependent growth,stage-structure,maturation delay,time-varying incubation is established.The basic reproduction number Ro is derived,by which we find that the brucellosis is uniformly persistent if R_(0)>1,while the disease-free periodic solution is globally attractive if R_(0)<1.The theoretical results are illustrated by numerical simulation,from which we find that the brucellosis transmission would be overestimated(or underestimated)if we ignore the influence of time-varying incubation or maturation delay.If density-dependent growth of animals is ignored,the risk of brucellosis may be far underestimated,the extinction of brucellosis can be obtained by numerical simulation under the same conditions.Seasonality significantly affects the long-term dynamic behavior of brucellosis,and the inconsistency of parameter periods results in complex dynamic behavior.

Influence of nicorandil combined with creatine phosphate sodium on serum cell factors and cardiac function in patients with STEMI

Objective: To observe the influence of nicorandil combined with creatine phosphate sodium on serum BNP, CK-MB, cTnl, SOD, MMP-9 and cardiac function in patients with STEMI. Methods: A total of 60 patients with STEMI were randomly divided into observation group (30 cases) and control group (30 cases). Observation group: nicorandil combined with creatine phosphate sodium;control group: patients were treated only by nicorandil. Recording and comparing the levels of BNP, CK-MB, cTnl, SOD, MMP-9 and cardiac function before and after treatment. Results: (1) Before treatment, there was no statistically significant difference in the serum BNP, CK-MB, cTnl, SOD, MMP-9 levels between the two groups. After treatment, compared with the same group before treatment, the serum BNP, CK-MB, cTnl, MMP-9 levels of the two groups were significantly lower, the serum SOD level of the two groups were significantly higher, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups. (2) Before treatment, there was no statistically significant difference in LVEF, WMSI, CI between the two groups. After treatment, compared with the same group before treatment, the WMSI of the two groups were significantly lower, the LVEF and CI of the two groups were significantly higher, and those levels of observation group were significantly better than the control group, there was significant difference between the two groups. Conclusion: Nicorandil combined with creatine phosphate sodium for patients with STEMI can perfect the levels of serum BNP, CK-MB, cTnl, SOD, MMP-9 and be beneficial to protect their cardiac function.

Nitrogen addition frequency and propagule pressure influence Solidago canadensis invasion into native plant community

Introduction:Propagule pressure(i.e.,the number of propagules)has long been recognized to play an essential role in plant invasion.But it is not clear whether propagule pressure influences the invasion of exotic plants into native plant communities when different frequencies of nitrogen are added.Method:We established an experiment with three plant communities that included native plant communities alone(four grasses,two legumes and two forbs)or native plant communities with one or five invasive plants,Solidago canadensis,under three frequencies of nitrogen addition(no addition or low or high addition with the same amount).Results:High propagule pressure significantly enhanced the biomass and relative dominance index of S.canadensis.Moreover,high propagule pressure only decreased the total and aboveground biomass of the legumes.However,the competitive effect between S.canadensis and the native community and biomass of the whole native community varied according to different frequencies.Conclusion:Overall,high propagule pressure encouraged invasion by S.canadensis,while alow nitrogen frequency was advantageous for the native community to resist invasion in this experiment.The results provide a scientific basis to manage and control the invasion of S.canadensis.

Effects of clonal integration and nitrogen supply on responses of a clonal plant to short-term herbivory

Aims Clonal integration,i.e.resource sharing between interconnected ramets,can help clonal plants tolerate abiotic stress.However,few studies have directly examined the ecological significance of clonal integration in the ability of clonal plants to tolerate biotic stress such as herbivory.Methods We grew clonal fragments of an invasive clonal plant Alternanthera philoxeroides,each consisting of an apical part(relatively young)and a basal part(relatively old),at two levels(low and high)of soil nitrogen(N).For each fragment,the apical part was subjected to either no herbivory or herbivory for 2 weeks by a specialist insect,Agasicles hygrophila,and was either connected with or discon-nected from the basal part not subjected to herbivory.Important Findings Herbivory in the apical part severely reduced leaf growth(leaf mass,leaf number or leaf area)and ramet production of both apical and basal parts,and increased root to shoot ratio of the apical part.Irrespective of herbivory and soil N,stem connection between the apical and the basal part decreased root to shoot ratio of the ap-ical part,but did not change its growth measures.Meanwhile,con-nection increased stem N concentration of the apical part growing under high-N supply and decreased stem carbon(C)concentration of the apical part under low-N supply.By contrast,connection in-creased root to shoot ratio of the basal part,but reduced its leaf and ramet production.Connection also increased leaf and stem C concentrations of the basal part under low-N supply.Thus,clonal integration can be beneficial for the early development of young A.philoxeroides ramets,but not for their local adaptation to herbivory damage by A.hygrophila.

Does hydrological fluctuation alter impacts of species richness on biomass in wetland plant communities?

Aims The diversity-productivity relationship is one of the most critical questions in ecology and can be altered by environmental factors.Hydrological fluctuation affects growth of wetland plants,and such effects vary with plant species.Therefore,we hypothesized that hydrological fluctuation changes effects of species richness on productivity of wetland plant communities.Methods We constructed wetland plant communities consisting of three or six wetland plant species and subjected them to hydrological fluctuation(i.e.gradually changing water level)of two frequencies and two ranges,with unchanged water level as the control.We measured height,root and shoot dry mass of each plant at harvest.Important Findings Hydrological fluctuation significantly decreased biomass of wetland plant communities,which was due to impacts of fluctuation range,but not those of fluctuation frequency.Community biomass was significantly higher when species richness was higher,and such an effect did not depend on hydrological fluctuation.Therefore,hydrological fluctuation can decrease the productivity of wetland plant communities but may not alter the diversity-productivity relationship.

入侵植物的相对多度比群落系统发育均匀度更能解释湿地群落对不同入侵程度的响应

本地植物群落普遍受到入侵植物不同程度的入侵。然而,入侵植物相对多度与群落系统发育均匀度对不同入侵程度下湿地植物群落响应入侵的相对贡献尚不明确。此外,这种贡献是否随淹水等环境条件的变化而变化也不清楚。为了探讨这些问题,我们选择空心莲子草(Alternanthera philoxeroides)作为入侵植物,通过改变植物群落物种组成,构建了4个不同的入侵程度,并且设置了水淹和无水淹两种处理。改变群落入侵程度的同时改变了空心莲子草的相对多度和群落的系统发育均匀度。研究结果表明,不同的入侵程度显著影响了空心莲子草和一些本地物种的单株生物量。变异分割结果表明,无论淹水情况结果如何,空心莲子草相对多度对植物群落指标变异的贡献都大于系统发育均匀度。斯皮尔曼等级相关检验结果表明,空心莲子草的相对多度与空心莲子草和部分本地物种的单株生物量显著负相关;群落系统发育均匀度仅与少数本地种性状显著正相关。其相关强度和显著性均受特定的物种和水淹环境的影响。总之,这些研究结果表明:无论淹水情况如何,入侵植物(空心莲子草)的相对多度都比群落的系统发育均匀度更能有效地解释湿地植物群落对不同入侵程度的响应。

克隆植物蛇莓对光照强度和养分条件的适应性可塑性

表型可塑性可帮助植物缓冲环境压力并使其表型与当地环境相匹配,但目前仅少数性状的可塑性被广泛认为是适应性的。为充分理解可塑性的适应性意义,仍需进一步研究更多的植物功能性状及其环境因子。本研究将匍匐茎克隆植物蛇莓(Duchesnea indica)的21个基因型种植于不同的光照和养分条件下,并利用选择梯度分析检测了形态和生理可塑性对光照强度和养分有效性变化的适应性值。在遮荫条件下,蛇莓适合度(果实数、分株数和生物量)降低,节间缩短变细,成熟叶叶绿素含量降低,但叶柄长度、比叶面积、老叶叶绿素含量均增加。在低养分条件下,植株叶柄缩短,叶面积缩小变厚,叶绿素含量降低,但果实数量和根冠比增加。选择梯度分析表明,叶柄长度和老叶叶绿素含量对光照变化的可塑性是适应性的,老叶和成熟叶叶绿素含量对养分变化的可塑性也是适应性的。因此,不同性状的可塑性适应值取决于特定的生态背景。该研究的发现有助于理解克隆植物表型可塑性响应环境变化的适应性意义。