Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na⁺/Ca²⁺ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)‍-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals ; Reperfusion Injury/drug therapy* ; Hypernatremia/complications* ; Rats ; Liver/metabolism* ; Rats, Inbred Lew ; Male ; Apoptosis ; Sodium-Calcium Exchanger/antagonists & inhibitors* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Epithelial Sodium Channel Blockers/pharmacology* ; Epithelial Sodium Channels ; Cell Line ; Liver Transplantation

Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.

Heart failure is a fatal stage of end-stage cardiovascular disease,which brings a huge medical burden to the society because of its high mortality and re-hospitalisation rates.Intestinal microecology is the largest and most com-plex microecosystem of human body.It is inhabited by tens of thousands of microorganisms in human gastrointestinal tract.In recent years,with the deepening of the study of intestinal flora,more and more studies have found that the im-balance of intestinal microecology can cause changes of metabolites in heart failure patients,which is one of the key triggers for the development of heart failure,therefore,using the intestinal microbial homeostasis as a new entry point for the treat-ment of heart failure will be a hotspot in medical research.However,the theory of Chinese medicine,"the spleen is the guardian",covers the physiological functions of the spleen,such as the spleen's main function of transporting,spleen's main function of ascending and clearing,and its main function of hiding camping,etc.,and the functions of intestinal flora and the"spleen is the guardian"are similar to a certain extent.Therefore,this paper starts from a holistic viewpoint and takes the theory of"spleen as the guardian"in Chinese medicine as an entry point to elaborate on the pathogenesis of intes-tinal microecological imbalance and heart failure,so as to provide a reference for Chinese medicine treatment or drug re-search.

Humans ; Aged ; Acute Kidney Injury ; Risk Factors ; Creatinine

Objective:To compare the clinical effect of Ilizarov frame and unilateral frame in the treatment of tibial segmental bone defect combined with soft tissue defect by open bone transport.Methods:A retrospective case-control study was conducted to analyze the clinical data of 32 patients with tibial segmental bone defect and soft tissue defect-up who underwent open bone transport technique in Tianjin Hospital from August 2008 to August 2016 and obtained complete followed-up. There were 22 males and 10 females, aged 22-64 years (mean, 36.8 years). Nineteen patients in the Ilizarov group showed the mean bone defect length of 7.9 cm and mean soft tissue defect area of 41.4 cm 2. Thirteen patients in the unilateral group showed the mean bone defect length of 7.8 cm and the mean soft tissue defect area of 39.2 cm 2. The results of fracture healing, wound healing time, radiological consolidation index, external fixation index, Association for the Study and Application of the Method of Ilizarov (ASAMI) bone and lower-limb function score and incidence of complications were compared between the groups. Results:All patients were followed up for 24 to 60 months [(32.6±1.3)months]. Bone healing was achieved in all patients. The wound healing time was (2.7±2.3)days in Ilizarov group and (2.4±1.8)days in unilateral group ( P>0.05). The consolidation index was (43.4±8.7)d/cm in Ilizarov group and (45.8±10.3)d/cm in unilateral group ( P>0.05). The external fixation index was (52.6±8.9)d/cm in Ilizarov group and (58.7±12.9)d/cm in unilateral group ( P<0.05). The results of ASAMI bone score was excellent in 10 patients, good in 6, fair in 2 and poor in 1 in Ilizarov group, with the excellent rate of 84%; and excellent in 6 patients, good in 4, fair in 2, and poor in 1 in unilateral group, with the excellent rate of 77%, with insignificant difference between two groups ( P>0.05). The results of ASAMI lower-limb function score was excellent in 8 patients, good in 7, fair in 3, poor in 1 in Ilizarov group, with the excellent rate of 79%; and excellent in 6, good in 3, fair in 3, poor in 1 in unilateral group, with the excellent rate of 69%, with insignificant difference between the two groups ( P>0.05). Incidence of axial deviation was zero in Ilizarov group versus 23% in unilateral group ( P<0.05). After operation, Ilizarov group had refracture in 1 patient and pin site infection in 5, and unilateral group had refracture in 1 patient and pin site infection in 1, showing no significant difference between the two groups ( P>0.05). Conclusions:Tibial segmental bone defect with soft tissue defect can be effectively treated by open bone transport with Ilizarov and unilateral frame. Ilizarov frame has better biomechanical properties and is more convenient for correction of poor postoperative axial alignment.

Objective:To investigate the accuracy and postoperative efficacy of fluoroscopy and CT in measuring the mounting parameters of Taylor Spatial Frame.Methods:Data of patients with peripheral knee deformities who were treated by Taylor Spatial Frame from June 2006 to December 2017 were retrospectively analyzed. According to different measurement methods of mounting parameters, they were divided into fluoroscopy group (mounting parameters were obtained by intraoperative fluoroscopy) and CT group (mounting parameters were obtained by postoperative CT). There were 33 patients (35 segments) in the fluoroscopy group, 23 males (23 segments) and 10 females (12 segments), with an average age of 36.4±11.6 years old. In CT group, there were 30 patients, 19 males and 11 females, with an average age of 36.9±13.8 years. There were 22 cases (24 segments) of high tibial osteotomy, 5 cases (5 segments) of distal femur osteotomy, and 6 cases (6 segments) of both distal femur and high tibial osteotomy. Operation time, external fixation time, the number of electronic prescription and deformity correction time, mechanical axis deviation (MAD), medial proximal tibia angle (MPTA), mechanical lateral distal femoral angle (mLDFA), range of motion (ROM) andhospital for special surgery (HSS) knee functional scores were compared between the two groups.Results:All the 63 patients were followed up for 21.9 months (range, 12-60 months). In fluoroscopy group, operating time was 100.9±9.1 min, electronic prescription number 1.4±0.6, and deformity correction time was 19.4±3.6 days. In CT group, operating time was 79.2±10.8 min, electronic prescription number 1.2±0.4, and deformity correction time was 16.0±4.4 days. The difference of the above indexes between the two groups was statistically significant ( t=8.803, 2.042, 3.440, all P < 0.05). In the fluoroscopy group, the external fixation time was 4.8±0.9 months; MAD was 4.3±2.1 mm; MPTA was 88.5°±1.9°; mLDFA was knee 89.2°; ROM was 122.4°±3.9° and HSS score was 90.0±3.6. In CT group, the external fixation time was 4.6±0.9 months; MAD was 4.0±1.9 mm; MPTA was 87.8°±1.7°; mLDFA was knee 88.6°; ROM was 122.7°±3.4° and HSS score was 91.1±2.9. There was no statistically significant difference in the above indexes between the two groups (all P >0.05). In the fluoroscopy group, 22 segmental deformities were corrected by one electronic prescription, and 13 segmental deformities were corrected by two or more electronic prescriptions. In CT group, 25 segmental deformities were corrected by one electronic prescription, and 5 segmental deformities were corrected by two electronic prescriptions. There was no incision infection and no neurovascular injury in the two groups. Conclusion:Both fluoroscopy and CT scan can obtain the mounting parameters of the Taylor Spatial Frame, and the results of correction of the peripheral deformities of the knee joint are satisfactory. However, CT measurement of the mounting parameters is more accurate which could achieve shorter operation time, and less times of electronic prescriptions.

Objective To evaluate the clinical outcomes and correction accuracy of deformities around the knee joint using external fixator-assisted internal fixation (FAIF).Methods From January 2014 to March 2018,data of 15 patients (17 bone segments) with deformities around the knee joint who had been corrected with external fixator-assisted internal fixation were retrospectively analyzed.There were 6 males and 9 females,with an average age of 39 years (range,21-60 years).There were 9 patients with genu varus and 6 with genu valgus.All the 15 patients had shortening ranging from 5 to 22 mm,with an average of 12 mm.Unilateral external fixator was used to stabilize the osteotomy site intraoperatively until the satisfied mechanical axis was acquired.Then the plate or Intramedullary nail was inserted and fixed,the external fixator was removed after internal fixation.Results Femur osteotomy was done in 7 patients and tibia osteotomy was done in 6 patients,while 2 patients had osteotomy in both tibia and femur.Intramedullary nailing was used in 2 bone segments,and plate was used in 15 bone segments.The correction of angle ranged from 7° to 22°,with an average of 12.5°.The correction of the 9 cases of genua varus ranged from 10° to 22°,with an average of 17.6°.The correction of the 6 cases of genu valgum ranged from 7° to 13°,with an average of 10.4°.The mean time to achieve union of the osteotomy sites was 3.5 months (range,2.5-5.0 months).All the 15 patients were followed up for 8-48 months (average,23 months).The mechanical axis deviation (MAD) was 5.93 mm (range,0-15 mm) after operation which was 34.8 mm (range,8-55 mm) before operation.The mean post-operative mechanical lateral distal femoral angle (mLDFA) was 87.5° (range,84°-90°) which was 76.1° (range,66°-82°) before operation.The mean medial proximal tibia angle (MPTA) was 87.8° (range,86°-89°) which was 76.8° (range,68°-80°) before operation.There were no deep infection and neurovascular injury.Conclusion The FAIF not only has the advantage of minimal invasiveness and easy adjustment,but also can avoid uncomfortableness and complications of long-term of wearing the external fixator.It is an accurate and safe method to correct the deformities around the knee joint.

Objective To analyze the relationship between preoperative serum sodium concentration and preoperative status of liver transplantation recipients and it's effect on early prognosis. Methods Retrospectively collected the clinical data of 281 patients underwent liver transplantation in First Affiliated Hospital of Zhengzhou University from January 2016 to September 2017. According to the preoperative serum sodium concentration, they were divided into hyponatremia group (< 130 mmol/L) 18 patients, normonatremia group (130-145 mmol/L)232 patients and hypernatremia group(> 145 mmol/L) 31 patients. The SPSS 21.0 statistical software was used to analyze the difference of preoperative MELD score, Child-Pugh score, postoperative survival rate and the incidence of graft dysfunction among three groups. Multivariate comparisons of measurement data were performed using analysis of variance. Pairwise comparisons between groups were performed using the LSD-t test. Chi-square tests were used to compare the count data sets. Results The preoperative MELD score was(19.27 ±7.35) scores, Child-Pugh score was(10.39±2.28) scores, serum creatinine concentration was(95.89 ± 49.40) μmol/L in hyponatremia group, the preoperative MELD score was(12.17土8.79) scores(P=0.001), Child-Pugh score was(8.50±2.68) scores (P =0.004) and serum creatinine was(66.07 ±24.13) μmol/L(P <0.05) in normonatremia group, the difference between two groups were statistically significant. There were no significant difference in the length of postoperative ICU stay and postoperative hospital stay among the three groups, there were no significant difference between the 30th and 90th postoperative survival rates and the incidence of graft dysfunction. Conclusions Hyponatremia is an indicator of poor preoperative status in liver transplantation recipients. Preoperative serum sodium concentration has no significant effect on early prognosis of liver transplantation.

Objective To determine the difference of macular ganglion cell-inner plexiform layer (mGCIPL) thickness and peripapillary retinal nerve fiber layer (pRNFL) thickness using Cirrus HD-OCT between older and young people in order to provide information for glaucomatous progressive analysis.Methods A prospective case series study was adopted.Sixty-seven old persons (114 eyes) aged 60-80 years old were selected from retired staff of an institution who underwent routine physical examinations between June and July 2016 in Beijing Tongren Hospital as older group and 24 young persons(42 eyes) aged (20-40 years old) who underwent routine physical examination at the same period were selected as young group.The total superior,superonasal,inperonasal,inferior,inferotemporal and superotemporal mGCIPL thickness and PRNFL thickness were measured by Cirrus HD-OCT.The research followed the Declaration of Helsinki.The ethics committee of the Tongren Eye Center approved the study and all participants provided an informed consent.Results There were statistical differences in all measurement parameters (mGCIPL and pRNFL) between older and young people (all at P＜0.05) except nasal pRNFL thickness.Minimum mGCIPL thickness was significantly different between older and young group [(74.02±11.01) pm vs.(82.74 ±3.94) μm;t =-7.290,P＜0.001],while in the pRNFL parameters,temporal pRNFL thickness was siginicantly changed between older and young group [(70.83 ± 12.30) μm vs.(82.10 ± 17.02) μm;t =-3.930,P ＜ 0.001].The nasal pRNFL thickness showed no significant difference between the two groups.Conclusions All mGCIPL and most pRNFL parameters in older people were obviously thinner than young people except nasal pRNFL,age factor should be considered seriously in the progression analysis of glaucomatous neuropathy.