Objective To explore the clinical effect of carbon nanoparticle in the axillary sentinel lymph node tracer of breast cancer.Methods Fifty-seven patients with breast cancer underwent lymphatic tracing with carbon nanoparticle.The carbon nanoparticle suspension was subcutaneously injected around the areola (points at 4 o'clock) and tumor surface skin at 30 min before operation.The first lymph nodes blacked were named sentinel lymph node.Then performed modified radical mastectomy,observing the application value of carbon nanoparticle.Results The detection rate of sentinel lymph node was 98.2％ (56/57).The correct,sensitive and false negative rates were 98.2％(55/56),95.2％(20/21) and 4.8％(1/21),respectively.The false positive rate was 0.Conclusions The carbon nanoparticle suspension injection subcutaneously around areola in sentinel lymph node biopsy is helpful for accurately evaluating the axillary lymph node condition.Being simple to operate,accurate positioning,dyeing time and is worth popularizing.

Objective To investigate the clinical significance of the antenatal detection of four indices of coagulation(PT,APTT, TT,FIB),D-dimer(DD)and platelet(PLT)in the judgment of parturient coagulation function and bleeding risk.Methods 795 pregnant women and childbearing age non-pregnant women with physical examination in this hospital from June 2012 to September 2013 were collected and divided into the normal pregnancy group(early pregnancy,middle pregnancy,late pregnancy,parturient pe-riod),obstetric accident group,pregnancy complicating other disease group and healthy control group.At the same time,PT, APTT,TT,FIB,DD and PLT were detected and the related statistical analysis was conducted.Results DD and FIB in the normal pregnancy group were significantly higher than those in the healthy control group(P<0.05),PT and APTT were significantly low-er than those in the healthy control group(P <0.05),TT had no statistically significant difference between these two groups(P >0.05 );DD and FIB in the obstetric accident group and the pregnancy complicating other disease group were significantly higher than those in the normal pregnancy group(P <0.05),while PT was significantly lower than that in the normal pregnancy group(P <0.05).PLT in the obstetric accident group and the pregnancy complicating other disease group was significantly lower than that in the normal pregnancy group(P <0.05).The sensitivity and specificity of the combined detection of 3 indices in diagnosing the ob-stetrical accidents were greatly superior to those of the single index detection or the combined detection of two indices.Conclusion The prenatal combination detection of four coagulation indices,DD and PLT can preliminarily judge the coagulation status of preg-nancy period in pregnant women,help to treat abnormal bleeding of pregnant women an possess the important guidance significance in formulating the labor scheme and preventing the occurrence of obstetric accidents.

Objective: To evaluate the role of extracellular signal-regulated kinase (ERK) signaling pathway in intrathecal dexmedetomidine-induced reduction of spinal cord ischemia-reperfusion (I/R) injury in rats. Methods: Eighty clean-grade male Sprague-Dawley rats, aged 9-10 weeks, weighing 300-350 g, were divided into 4 groups (n=20 each) using a random number table method: sham operation group (group S), spinal cord I/R group (group I/R), dexmedetomidine group (group D), and dexmedetomidine plus ERK signaling pathway blocker PD98059 group (group P). Spinal cord ischemia was produced by cross-clamping of the abdominal aorta distal to the left renal artery for 25 min followed by reperfusion to establish the model of spinal cord I/R injury.Dexmedetomidine 1 μg/kg was intrathecally injected at 20 min before establishing the model in D and P groups, PD98059 2 mg/kg was given via the tail vein at the same time in group P, and the equal volume of normal saline was given instead in S and I/R groups.Five rats were selected at 6, 8, 10 and 12 h of reperfusion, and the modified Basso, Beattie, Bresnahan (BBB) scale was used to assess the hindlimb locomotor function.Five rats were sacrificed after assessing the locomotor function at 6 h of reperfusion, and the L_3-5 segments of the spinal cord were taken for determination of cell apoptosis (by TUNEL) and expression of phosphorylated ERK (p-ERK) (by Western blot). The apoptosis index was calculated. Results: Compared with group S, the BBB scores were significantly decreased at each time point of reperfusion, the apoptosis index was increased, and the expression of p-ERK was up-regulated in the other three groups (P<0.05). Compared with I/R group, the BBB scores were significantly increased at each time point of reperfusion, the apoptosis index was increased, and the expression of p-ERK was up-regulated in group D, and no significant change was found in the apoptosis index or p-ERK expression in group P (P>0.05). Compared with group D, the BBB scores were significantly decreased at each time point of reperfusion, the apoptosis index was increased, and the expression of p-ERK was down-regulated in group P (P<0.05). Conclusion The mechanism by which intrathecal dexmedetomidine reduces spinal cord I/R injury is related to activating ERK signaling pathway in rats.

Objective To evaluate the effect of hydrogen on blood brain barrier of mice with sepsisassociated encephalopathy (SAE).Methods A total of 100 adult male ICR mice,aged 6-8 weeks,weighing 20-25 g,were divided into 4 groups (n =25 each) using a random number table method:sham operation group (group Sham),sham operation plus hydrogen group (group Sham+H),group SAE and SAE plus hydrogen group (group SAE+ H).Sepsis was induced by cecal ligation and puncture (CLP).Sham+H and SAE+H groups inhaled 2％ hydrogen for 1 h starting from 1 and 6 h after CLP,respectively.At 24 h after CLP,Evans blue (EB) was injected via the caudal vein,and then the mice were sacrificed and brain tissues were removed for measuring the EB and water contents,for examining the pathological changes of hippocampi (with a light microscope) and for detecting the expression of occludin and VE-cadherin (by Western blot).Morris water maze test was performed at days 10-16 after CLP.Results Compared with group Sham,the contents of EB and water in brain tissues were significantly increased,the expression of occludin and VE-cadherin was down-regulated,the escape latency was prolonged,and the number of crossing the original platform was reduced in SAE and SAE+H groups (P＜0.05).Compared with group SAE,the contents of EB and water in brain tissues were significantly decreased,the expression of occludin and VE-cadherin was up-regulated,the escape latency was shortened,the number of crossing the original platform was increased (P＜0.05),and the pathological changes of hippocampi were significantly attenuated in group SAE+H.Conclusion The mechanism by which hydrogen mitigates SAE may be related to reducing the damage to blood brain barrier of mice.

Objective To investigate the changes in FUNDC1/microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ) signaling pathway during sepsis-induced liver injury in mice.Methods Tbirtytwo clean-grade healthy male C57BL/6 mice,aged 6 weeks,weighing 20-25 g,were divided into sham operation group (n =8) and sepsis group (n =24) using a random number table method.Sepsis was induced by cecal ligation and puncture.Blood samples were obtained at 24 h after operation in sham operation group and at 6,12 and 24 h after establishing the model in sepsis group for determination of concentrations of alanine aminotransferase and aspartate aminotransferase in serum.Mice were then sacrificed,and the right lobe of livers was removed for examination of the pathological changes and for determination of the expression of FUNDC1 and LC3 Ⅱ by Western blot.The mitochondria in the right lobe of livers were isolated to measure the respiratory function,and respiratory control rate was calculated.Results Compared with sham operation group,the concentrations of alanine aminotransferase and aspartate aminotransferase in serum and pathological scores were significantly increased,the respiratory control rate of mitochondria was decreased,the expression of FUNDC1 was down-regulated,and the expression of LC3 Ⅱ was up-regulated at each time point after establishing the model in sepsis group (P＜0.05).Conclusion The mechanism by which sepsis induces liver injury may be related to inhibiting activation of FUNDC1/LC3 Ⅱ signaling pathway in mice.

Objective To evaluate the effect of dexmedetomidine on expression of hypoxia-inducible factor-1α (HIF-1α) during endotoxin-caused apoptosis in macrophages of mice.Methods Mouse macrophage cell line RAW264.7 cultured in vitro were seeded in 6-well or 96-well plates and divided into 4 groups (n=16 each) when cell confluence reached 60％-70％ using a random number table method:control group (group Con),dexmedetomidine group (group Dex),lipopolysaccharide (LPS) group,and LPS plus dexmedetomidine group (group LPS+Dex).Phosphate buffer solution was added in group Con.Dexmedetomidine 1 μmol/L was added in group Dex.LPS 1 μg/ml was added in LPS and LPS+Dex groups.Dexmedetomidine 1 μmol/L was added immediately after adding LPS in group LPS+Dex.Cells were then cultured for 24 h in each group.Cell apoptosis was measured using TUNEL,mitochondrial membrane potential using JC-1,reactive oxygen species (ROS) content by ROS kit,and ATP content by ATP kit.The apoptosis rate was calculated.The expression of HIF-1α,cytochrome C (Cyt-c),caspase-9 and cleaved caspase-3 was detected by Western blot.Results Compared with group Con,the apoptosis rate and ROS content were significantly increased,ATP content and mitochondrial membrane potential were decreased,the expression of HIF-1α,Cyt-c,caspase-9 and cleaved caspase-3 was up-regulated in group LPS (P＜ 0.05),and no significant change was found in the parameters mentioned above in group Dex (P＞0.05).Compared with group LPS,the apoptosis rate and ROS content were significantly decreased,ATP content and mitochondrial membrane potential were increased,the expression of HIF-1α was up-regulated,and the expression of Cyt-c,caspase-9 and cleaved caspase-3 was down-regulated in group LPS + Dex (P＜0.05).Conclusion Dexmedetomidine can reduce endotoxin-caused oxidative stress injury to macrophages,improve mitochondrial function and inhibit mitochondrial apoptosis,and the mechanism may be related to upregulating the expression of HIF-1α in mice.

Objective To evaluate the role of autophagy in dexmedetomidine-induced reduction of lipopolysaccharide ( LPS)-caused inflammatory responses in macrophages of mice. Methods Mouse mac-rophage cell line RAW264. 7 cultured in vitro were seeded in 6-well or 96-well plates and divided into 4 groups ( n=20 each ) when cell confluence reached 60％ using a random number table method: control group (group Con), LPS group, LPS plus dexmedetomidine group (group LPS+DEX), and LPS plus dexmedetomidine plus autophagy inhibitor 3-MA group (group LPS+DEX+3-MA). PBS was added and cells were cultured for 12 h in group Con. LPS at the final concentration of 1000 ng∕ml was added and cells were incubated for 12 h in group LPS. LPS at the final concentration of 1000 ng∕ml was added, and then dexmedetomidine at the final concentration of 1 μmol∕L was immediately added, and cells were incubated for 12 h in group LPS+Dex. In group LPS+Dex+3-MA, 3-MA at the final concentration of 2 mmol∕L was added and cells were incubated for 1 h, LPS at the final concentration of 1000 ng∕ml was added, and then dexmedetomidine at the final concentration of 1 μmol∕L was immediately added, and cells were incubated for 12 h. Cell viability was detected by CCK-8 assay, and the concentrations of nitrous oxide ( NO) , tumor necrosis factor-alpha ( TNF-α) and interleukin-1beta ( IL-1β) in the supernatant were determined by en-zyme-linked immunosorbent assay, and the expression of microtubule-associated protein 1 light chain 3 Ⅰ( LC3 Ⅰ) , LC3Ⅱ, P62 and Bcelin-1 was detected by Western blot. LC3Ⅱ∕LC3Ⅰ ratio was calculated. Results Compared with group Con, the cell viability was significantly decreased, the concentrations of TNF-α, IL-1β and NO and LC3Ⅱ∕LC3Ⅰratio were increased, and the expression of P62 and Beclin1 was up-regulated in group LPS (P<0. 05). Compared with group LPS, the cell viability was significantly in-creased, the concentrations of TNF-α, IL-1βand NO were decreased, LC3Ⅱ∕LC3Ⅰratio was increased, the expression of P62 was down-regulated, and the expression of Beclin1 was up-regulated in group LPS+DEX ( P<0. 05) . Compared with group LPS+Dex, the cell viability was significantly decreased, the con-centrations of TNF-α, IL-1β and NO were increased, LC3Ⅱ∕LC3Ⅰ ratio was decreased, the expression of P62 was up-regulated, and the expression of Beclin1 was down-regulated in group LPS+Dex+3-MA ( P<0. 05) . Conclusion Enhanced autophagy is involved in dexmedetomidine-induced reduction of LPS-caused inflammatory responses in macrophages of mice.

Objective:To investigate the clinical manifestations, laboratory tests, diagnosis and treatment of discordant lymphoma (DL).Methods:The clinical data of a patient with EB virus-positive DL admitted to Taizhou People's Hospital in November 2019 were retrospectively analyzed and the related literature was reviewed.Results:The patient underwent a cervical lymph node biopsy pathology examination at onset, and then results suggested angioimmunoblastic T-cell lymphoma (AITL). The patient subsequently developed gastrointestinal bleeding and underwent resection of small bowel lesions, and postoperative pathology suggested diffuse large B-cell lymphoma (DLBCL). The patient was finally diagnosed as DL. The R2-CHOP chemotherapy regimen was given to the patient, but the patient still had recurrent gastrointestinal bleeding and poor general condition. The patient refused chemotherapy and was changed to lenalidomide monotherapy. Finally, the patient died due to multiorgan failure, with an overall survival of 13 months.Conclusions:DL is rarely seen in lymphoma, whereas the combination of AITL and DLBCL is extremely rare. The clinicians need to improve the understanding of this disease to avoid misdiagnosis and missed diagnosis.

Objective:To explore the correlation between preoperative echocardiography indicators and surgical prognosis of children with ventricular septal defect (VSD) and conduct verification based on significant indicators and indicator ratios.Methods:A total of 1 357 children with VSD who were admitted to the Children′s Hospital, Zhejiang University School of Medicine from June 2016 to June 2021 were selected. Various measurements including the size of the VSD, left ventricular ejection fraction (LVEF), left atrial (LA) diameter, the aortic (AO) flow rate, the tricuspid regurgitation velocity and pressure gradient were extracted from preoperative echocardiography reports. This paper explored the correlation between echocardiography reports indicators, indicator ratios and postoperative auxiliary ventilation time, respectively. The patients were divided into two groups according to whether there were complications, and the differences of echocardiography reports indicators between the two groups were compared. A linear regression model was established to predict the postoperative auxiliary ventilation time using these indicators, and the least absolute shrinkage and selection operator (LASSO) regression model was used for variable selection.Results:The VSD size and AO flow velocity were weakly correlated with the postoperative auxiliary ventilation time ( r=0.32, 0.25; all P<0.01). There was no significant correlation between VSD flow velocity and postoperative auxiliary ventilation time. The AO flow velocity/VSD flow velocity and LVEF/VSD flow velocity were strongly correlated with the postoperative auxiliary ventilation time ( r=0.67, 0.51; all P<0.01). In the significance test, there were no significant differences in tricuspid regurgitation flow velocity, tricuspid regurgitation pressure gradient, LA diameter, and LVEF between the complication group and the non-complication group(all P>0.01). However, the ratio of LVEF/tricuspid regurgitation velocity in the complication group was significantly lower than that in the non-complication group, and the ratio of tricuspid regurgitation pressure gradient/LA diameter was significantly higher than that in the non-complication group (all P<0.01). The postoperative auxiliary ventilation time of VSD patients was predicted on an independent test set, with an R2 of 0.51. Conclusions:Echocardiography report indicator ratios of AO flow velocity/VSD flow velocity and LVEF/VSD flow velocity have strong correlations with postoperative auxiliary ventilation time in children with VSD, and the ratios of LVEF/tricuspid regurgitation velocity and tricuspid regurgitation pressure gradient/LA diameter are significantly different between groups with and without postoperative complications. The ratios of indicators can significantly improve this correlation and difference, which can be used to predict the prognosis of VSD operation.

Objective:To evaluate the efficacy and safety of oral anisodine hydrobromide tablets in the treatment of nonarteritic anterior ischemic optic neuropathy (NAION).Methods:A multicenter nonrandomized controlled trial was conducted.A total of 282 acute NAION patients (282 eyes) were recruited from 16 hospitals in China from July 2020 to May 2021.Patients were divided into two groups according to treatment methods, which were control group (124 cases, 124 eyes) receiving regular treatment including citicoline sodium plus Ginkgo biloba leaf liquid extract or Ginkgo biloba leaf extract tablets plus mecobalamin, and experimental group (158 cases, 158 eyes) receiving treatment in control group plus oral anisodine hydrobromide tablets 1 mg, twice daily for 2 to 3 months.Best corrected visual acuity (BCVA), visual field index (VFI), peripapillary retinal nerve fiber layer (pRNFL) and radial peripapillary capillary vessel density (RPC) were assessed at 1, 2, 3, and 6 months after enrollment using the standard decimal visual acuity chart, 750i Humphery visual field analyzer, Cirrus HD-OCT 4000/Cirrus HD-OCT 5000, RTVue-XR optical coherence tomography respectively.The primary outcomes were BCVA and VFI, and the secondary outcomes were pRNFL, RPC, and the side effects during the follow-up.The study adhered to the Declaration of Helsinki.All patients were fully informed about the treatment and purpose of this study and voluntarily signed the informed consent form.The study protocol was approved by Chinese PLA General Hospital (No.S2020-021-01). Results:In all, 242 patients (242 eyes) completed the follow-up of BCVA, and 98 patients (98 eyes) completed the VFI follow-up.In terms of visual function, BCVA and VFI improved significantly over time in the two groups, and BCVA and VFI were better in experimental group than in control group at various follow-up time points (all at P<0.05). In terms of structure, pRNFL gradually decreased in both groups with the extension of treatment, and pRNFL was significanthy thinner in experimental group than in control group at various follow-up time points (all at P<0.05). There was no significant difference in RPC between the two groups at the last follow-up ( P>0.05). There were two cases with side effects and one case was discontinued due to side effects 25 days after enrollment. Conclusions:Oral anisodine hydrobromide can improve visual acuity and visual field in NAION and accelerate the regression of optic disc edema, with good safety.