Clinicopathological and prognostic features of subungual melanoma in situ / 中华病理学杂志

Objective: To investigate the clinicopathological characteristics, immunohistochemical profiles, molecular features, and prognosis of subungual melanoma in situ (SMIS). Methods: Thirty cases of SMIS were collected in Fudan University Shanghai Cancer Center, Shanghai, China from 2018 to 2022. The clinicopathological characteristics and follow-up data were retrospectively analyzed. Histopathologic evaluation and immunohistochemical studies were carried out. By using Vysis melanoma fluorescence in situ hybridization (FISH) probe kit, combined with 9p21(CDKN2A) and 8q24(MYC) assays were performed. Results: There were 8 males and 22 females. The patients' ages ranged from 22 to 65 years (median 48 years). All patients presented with longitudinal melanonychia involving a single digit. Thumb was the most commonly affected digit (16/30, 53.3%). 56.7% (17/30) of the cases presented with Hutchinson's sign. Microscopically, melanocytes proliferated along the dermo-epithelial junction. Hyperchromatism and nuclear pleomorphism were two of the most common histological features. The melanocyte count ranged from 30 to 185. Most cases showed small to medium nuclear enlargement (29/30, 96.7%). Pagetoid spread was seen in all cases. Intra-epithelial mitoses were identified in 56.7% (17/30) of the cases. Involvement of nailfold was found in 19 cases, 4 of which were accompanied by cutaneous adnexal extension. The positive rates of SOX10, PNL2, Melan A, HMB45, S-100, and PRAME were 100.0%, 100.0%, 96.0%, 95.0%, 76.9%, and 83.3%, respectively. FISH analysis was positive in 6/9 of the cases. Follow-up data were available in 28 patients, and all of them were alive without disease. Conclusions: SMIS mainly shows small to medium-sized cells. High melanocyte count, hyperchromatism, nuclear pleomorphism, Pagetoid spreading, intra-epithelial mitosis, nailfold involvement, and cutaneous adnexal extension are important diagnostic hallmarks. Immunohistochemistry including SOX10 and PRAME, combined with FISH analysis, is valuable for the diagnosis of SMIS.

Heixiaoyao Powder interferes with microglia polarization in AD model mice by regulating NOX2/ROS/NF-κB signaling pathway / 中国中药杂志

The effect and mechanism of Heixiaoyao Powder on the polarization of microglia(MG) in APP/PS1 double transgenic mice were explored based on NADPH oxidase 2(NOX2)/reactive oxygen species(ROS)/nuclear factor kappaB(NF-κB) signaling pathway. Fifty 4-month-old male APP/PS1 mice were randomly divided into a model group, an MCC950 group(10 mg·kg~(-1)), and low-, medium-, and high-dose Heixiaoyao Powder groups(6.45, 12.89, and 25.78 g·kg~(-1)). Thirty male C57BL/6J mice of the same age and strain were randomly divided into a blank group, a blank + intragastric intervention group, and a blank + intraperitoneal injection group. Drug intervention lasted 90 days. Morris water maze test was used to detect learning and cognitive ability. Nissl staining and transmission electron microscopy were used to observe the pathological morphology and ultrastructure of hippocampal neurons. Immunofluorescence was used to detect the positive expression of M1-type marker CD16/32~+/Iba-1~+, M2-type marker CD206~+/Iba-1~+ of MG and the expression of hippocampal ROS. The colorimetric method was used to detect the content of malondialdehyde(MDA) and superoxide dismutase(SOD) in the hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory factors, including interleukin-6(IL-6), interleukin-8(IL-8), and tumor necrosis factor-α(TNF-α), in the hippocampus. Western blot was used to detect the protein expression of β-amyloid protein(Aβ), Iba-1, CD16/32, CD206, NOX2, NF-κB, p-NF-κB, NF-κB inhibitor alpha(IκBα), and p-IKBα in the hippocampus. The results showed that as compared with the blank group, the model group showed prolonged target quadrant movement distance and escape latency(P<0.01), shortened target quadrant retention time and percentage(P<0.01), disorganized neuronal cells with swelling, nuclear disappearance or bias, reduced number of cells, dissolved or absent Nissl bodies, and a clear area in the cytoplasm, damaged and shrunk cell membrane with abnormal cell morphology, few organelles in the cytoplasm, reduced and swollen mitochondria, increased MG M1-type marker CD16/32~+/Iba-1~+(P<0.01), decreased M2-type marker CD206~+/Iba-1~+(P<0.01), increased ROS activity and MDA content(P<0.01), decreased SOD level(P<0.01), elevated inflammatory factors IL-6, IL-8, and TNF-α(P<0.01), up-regulated protein expression and phosphorylation of Aβ, CD16/32, Iba-1, NOX2, NF-κB, and IKBα(P<0.01), and down-regulated CD206(P<0.01). There was no statistically significant difference between the blank group, the blank + intragastric intervention group, and the blank + intraperitoneal injection group. After the intervention of Heixiaoyao Powder, the Heixiaoyao Powder groups showed shortened target quadrant movement distance and escape latency(P<0.01), prolonged target quadrant retention time and percentage(P<0.01), increased and neatly arranged cells with relieved swelling, increased Nissl bodies, regular cell morphology, and intact cell membrane, relieved swelling of mitochondria, slightly expanded endoplasmic reticulum, decreased CD16/32~+/Iba-1~+(P<0.05 or P<0.01), increased CD206~+/Iba-1~+(P<0.01), decreased ROS activity and MDA content(P<0.01), increased SOD level(P<0.01), decreased content of inflammatory factors IL-6, IL-8, and TNF-α(P<0.01), down-regulated protein expression and phosphorylation of Aβ, CD16/32, Iba-1, NOX2, NF-κB, and IKBα(P<0.01), and up-regulated CD206(P<0.01). In conclusion, Heixiaoyao Powder can alleviate neuronal damage and improve the learning and memory abilities of APP/PS1 mice. The mechanism of action may be related to the inhibition of NOX2/ROS/NF-κB signaling pathway, regulating the polarization of MG, increasing the expression of M2 type, inhibiting the expression of M1 type, and reducing the release of inflammatory factor.

Complete genome analysis of a Chikungunya virus imported into Tianjin, China / 中华检验医学杂志

Objective:To study the characteristics and evolution of the whole genome sequence of an imported Chikungunya virus (CHIKV) case in Tianjin, China, and to provide a scientific basis for the surveillance and control of CHIKV.Methods:The serum specimen of CHIKV was collected at Tianjin Second People's Hospital, on November 4th, 2019, and the viral RNA was extracted. Eleven overlapping primers were used to amplify the complete genome of CHIKV by RT-PCR. The amplification products were then subjected to next generation sequencing (NGS) using Illumina Miniseq platform.Results:The complete genome sequence of the Tianjin CHIKV obtained had similarities ranging from 92.72% to 99.86% with other Chinese isolates. Phylogenetic analysis indicated that the Tianjin CHIKV belonged to the Indian Ocean Lineage (IOL), East/Central/South African (ECSA) cluster, consistent with most strains from China. The Tianjin CHIKV is most similar (99.74%) to a Pakistan strain. Compared with the reference strain S27, 37 non-structural and 28 structural protein amino acid substitutions had been detected in Tianjin CHIKV genome, including two key site mutations, E1-D284E and E2-I211T, in accordance with other strains in the ECSA cluster. Besides, Tianjin CHIKV possessed two point virulent residues at position 12 and 82 in E2, and also a nsP3-R524Opal nonsense mutation.Conclusions:Tianjin CHIKV showed stronger virulence and greater transmissibility in Aedes albopictus. Therefore, the surveillance and monitoring of CHIKV in China should be strengthened.

DHM improves cognitive dysfunction in T2DM rats by inhibiting hippocampal endoplasmic reticulum stress / 中国药理学通报

Aim To investigate the effeet of dihydro- myricetin ( DHM ) on cognitive dysfunction in type 2 diabetes mellitus ( T2DM) rats and its mechanism.Methods SD rats were randomly divided into the normal control group ( n = 56) : normal diet and citrate buffer solution (30 mg • kg 1 ) ; T2DM model group (n =60) : high glucose, fat and low dose STZ ( 30 mg • kg 1 ) ( Four unsuccessful rats were eliminated ).Then rats in the above two groups were treated with or without DHM (250 mg • kg 1 • d intragastric).After 12 weeks, eight rats in each group were randomly selected to perform Morris water maze and Y maze test to observe the effect of DHM on cognitive function of rats.The remaining rats in each group were injected ERS antagonist tauroursodeoxycholic acid ( TUDCA ) 10 jxg • d 1 or ERS activator tunicamycin (TUN) 10 jxL, respectively.After the behavioral analysis, the hippocampal tissues of rats were taken out.The expressions of EH stress related proteins GRP78 and P- PERK were detected by Western blot.Results Both DHM and TUDCA could improve cognitive dysfunction in T2DM rats.On the contrary, TIJN reduced the effect of DHM on cognitive dysfunction in T2DM rats.TUDCA decreased the expression of GRP78 and p- PERK proteins in T2DM rats, while TUN increased the expression of GRP78 and p-PERK proteins in T2DM rats treated by DHM.Conclusion DHM improves cognitive dysfunction in T2DM rats, and the mechanism may be related to the inhibition of endoplasmic reticulum stress.

The clinical application of ultrasonic root canal intermittent irrigation in endodontic vascular reconstruction / 中国医师杂志

Objective:To investigate the clinical effect of ultrasonic root canal intermittent irrigation in endodontic vascular reconstruction.Methods:32 young permanent teeth with pulp and periapical lesions were randomly divided into two groups ( n=32): experimental group was treated with ultrasonic root canal intermittent irrigation and the control group was rinsed with sodium hypochlorite root canal. The changes of periapical lesions and root development were evaluated by preoperative and postoperative clinical symptom observation and radiograph examination, and the clinical effect of endodontic vascular reconstruction was discussed. The time of inflammation control was discussed by analyzing the starting point from the first diagnosis to the date of mineral trioxide aggregate (MTA) coverage. Results:The clinical symptoms of the 16 affected teeth in the experimental group and the control group disappeared, the periapical lesions were eliminated, and the root continued to develop. In the experimental group, root formation was observed in 13 of the affected teeth, with a success rate of 81.25% and a reduction rate of 18.75%. In the control group, root formation was observed in 10 of the affected teeth, with a success rate of 62.5% and a reduction rate of 37.5%. There was no difference in the effective rate between the experimental group and the control group ( P>0.05). The control time of inflammation was (28.44±5.98)days in the experimental group and (34.13±7.17)days in the control group, with statistically significant differences ( P<0.05). Conclusions:Ultrasonic root canal intermittent swabbing applied to pulp revascularization can achieve good clinical effect and shorten the time of inflammation control.

Comparison of femoral tunnel and early curative effect analysis between arthroscopic three approach and traditional anteromedial portal for reconstruction of anterior cruciate ligament / 中国骨伤

OBJECTIVE@#To study the three-approach and traditional anterior medial technique to establish the femoral tunnel of position, length, and coronal angle and the early efficacy of anterior cruciate ligament reconstruction.@*METHODS@#Through retrospective research, from December 2018 to June 2019, a total of 36 patients diagnosed with simple anterior cruciate ligament tear and undergoing surgery were collected. All patients had a clear history of knee sprains and were divided into two groups. A group of 16 patients, including 11 males and 5 females, with an average age of (30.13±6.54) years and an injury time of 7 to 60 (30.19±15.78) days, three-approach technique was used to drill the femoral tunnel to reconstruct the anterior cruciate ligament. Another group of 20patients, including 15 males and 5 females, with an average age of (30.80±8.60) years, and an injury time of 7 to 60 (27.35±15.50) days, the traditional anterior medial approach was used to drill the femoral tunnel to reconstruct anterior cruciate ligament. CT 3D reconstruction technique was used to evaluate the femoral tunnel and the knee joint function was evaluated by Lysholm score of the knee joint.@*RESULTS@#All patients achieved primary healing after the surgical incision. No femoral tunnel fracture, vascular and nerve damage, difficulty in graft passage during the operation, and venous thrombosis occurred. All 36 patients were followed up on an outpatient basis, with a follow up period of 9 to 15 (12.00±2.83) months. Three-dimensional CT reconstruction was used to evaluate the femoral tunnel of the patients. The position of the femoral tunnel was described using the quartile method as the three-approach group:the lower (27.83±1.97) % of the femoral condyle and the posterior (25.57±3.20) %;the traditional approach group:the lower (28.38±3.21) % of the femoral condyle and the posterior (26.23±3.20) %. Bone tunnel length, three-approach group:(35.20±5.52) mm in total length, (23.20±2.07) mm in thick bone tunnel;traditional approach group:(34.60±4.26) mm in total length, (22.56±2.50) mm in thick bone tunnel. Coronal plane angle, three-approach group:(47.93±5.98) °;traditional approach group:(41.78±6.62) °. Knee joint Lysholm score, three-approach group:48.67±4.18 before surgery;97.00±2.48 at last follow up;traditional approach group:49.75±5.33 before surgery, 97.30±2.68 at last follow up, there were significant differences before and after surgery, no significant statistical difference between two groups.@*CONCLUSION@#The positions of the femoral tunnel drilled by the two methods were within the range of the anatomic stop of the anterior cruciate ligament, and there was no statistical difference. Compared with the traditional anterior medial approach, the coronal plane angle of the femoral tunnel drilled by the three-approach approach is relatively large, and there were no statistical differences in the length of the tunnel, the early postoperative effect of the two surgical methods, and the operation time. But the three approach has a wider and clearer vision. In addition, the knee flexion angle required for drilling the femoral tunnel during surgery is significantly smaller than that of traditional approach technology, which reduces the difficulty of surgery.

Dihydromyricin inhibited hepatic lipid deposition induced by high-fat diet in obese mice by activating SIRT1-AMPK pathway / 中国药理学通报

Aim To investigate the effect of dihydromyricetin (DHM) on lipid accumulation in liver of obese mice induced by high fat diet and its mechanism. Methods Sixty C57BL/6J mices were randomly divided into six groups (n = 10); (1)ND group; normal diet, (2)ND + L-DHM group; normal diet and treatment with low-dose DHM (125 mg • kg

Ultrasound-guided closed reduction and kirschner wires internal fixation for the treatment of KilfoyleⅡand Ⅲ medial condylar fracture of humerus in children / 中国骨伤

OBJECTIVE@#To explore clinical effectiveness and safety of ultrasound-guided closed reduction and K-wires internal fixation in treating of Kilfoyle Ⅱand Ⅲ medial condylar fracture of humerus in children.@*METHODS@#Clinical data of 32 children with medial condylar fracture of humerus treated with closed reduction and internal fixation with K-wires under the guidance of ultrasound were retrospectively analyzed from January 2014 to August 2019, including 23 males and 9 females, age ranged from 3.2 to 12.8 years old with an average of (8.3±2.1) years old;According to classification of Kilfoyle, 12 patients classified to typeⅡ and 20 patients were type Ⅲ;5 patients combined with elbow dislocation;the time from injury to operation ranged from 1 to 5 days with an average of (3.1±1.3) days. Radiological evaluation of treatment results and complications were observed. At the final follow up, Mayo elbow performance score(MEPS) was used to evaluate elbow function. And humerus-ulna angle on the affect side and healthy side were measured and compared.@*RESULTS@#All patients were followed up from 8 to 26 months with an average of(19.3±5.5) months. All fractures were healed well, the healing time ranged from 4 to 6 weeks with an average of (4.5±0.5) weeks. No infection, vascular and nerve injury, bone nonunion, trochlear necrosis, cubitus varus or valgus deformity were occurred. According to Mayo scoring, all patients were assessed as excellent. There was no significant difference in angle of humerus-ulna between affectedside (9.5±3.6)° and healthy side (9.1±3.5)°, and no difference in MEPS scores between affected side(95.3±2.5) and healthy side(96.3±2.2)(@*CONCLUSION@#For Kilfoyle typeⅡand Ⅲ medial condylar fracture of humerus in children, closed reduction and internal fixation with K-wire under ultrasound guidance is a safe and effective method, and could promote in further.

Progress on femorotibial mechanical axis of total knee arthroplasty / 中国骨伤

Femorotibial mechanical axis (FTMA) is one of important factors influencing clinical effect after total knee arthroplasty (TKA). It is generally believed that the range of lower limb alignment after TKA is controlled within neutral FTMA ± 3 °, which has more advantages in improving joint function, prolonging prosthesis survival rate and reducing revision rate, and obtain better clinical results. Therefore, neutral FTMA is also considered to be the gold standard for TKA. However, with the application of computer-assisted surgery and other technologies, the alignment of FTMA is more accurate than before, but the clinical effect after surgery has not significantly improved. Some scholars have begun to question the necessity of neutral alignment of FTMA, and proposed alignment methods such as kinematics and retained residual deformity, which could achieve better clinical effects. In recent years, it has been reported that FTMA might not be the most important factor influencing postoperative clinical effects, and it is suggested that the arrangement and measurement of lower limbs and the effects on adjacent joint functions could affect clinical effect after TKA. The paper reviews neutral FTMA alignment is still an important factor for success of TKA. After a thorough evaluation according to the patient's condition, it should be appropriately applied in the case of neutral FTMA alignment; the operator should explore other factors which affect clinical outcome after TKA, and improve it to achieve the best therapeutic effect.

Effect of a disintegrin and metalloproteinase 17 short hairpin RNA transfection of bone marrow mesenchymal stem cells on proliferation of human breast cancer MCF-7 cells / 中国综合临床

Objective:To investigate the effect of a disintegrin and metalloproteinase 17 (ADAM17) - short hairpin RNA (shRNA) transfection on the proliferation of human breast cancer MCF-7 cells.Methods:Four shRNA sequences (adam17-hsa-297, adam17-hsa-1508, adam17-hsa-1658) targeting ADAM17 were designed, Adam17-hsa-1864) and a negative control (LV10-NC) were used to screen the best inhibition rate of ADAM17 shRNA by qPCR.The experiment was divided into three groups: transfection group, meaningless sequence group and control group.RNA was extracted according to routine steps, and then reverse transcripted and amplified.The expression of ADAM17 mRNA was detected by qPCR and the proliferation of MCF-7 cells was measured by MMT method.Results:The results of MTT assay showed that the absorbance values of control group, nonsense sequence group and transfection group were 0.270±0.040, 0.250±0.035 and 0.185±0.080, respectively.There was significant difference between the two groups ( F=3.854, P=0.045). There was no significant difference between the control group and the nonsignificant sequence group ( P>0.05), and the difference between the control group and the transfection group was statistically significant ( P<0.05). There was no significant difference between the nonsignificant sequence group and the transfection group ( P>0.05); the absorbance values of the control group, the meaningless sequence group and the transfection group at 48 h were 0.500±0.057, 0.494±0.086 and 0.311±0.007, respectively, and the differences between the two groups were statistically significant( F=19.42, P<0.001). There were significant differences between transfection group and control group and no significant sequence group (all P<0.05), but there was no significant difference between control group and non significant sequence group ( P>0.05). The absorbance values of control group, nonsense sequence group and transfection group at 72 h were 0.720±0.150, 0.713±0.174 and 0.558±0.071, respectively.There was no Conclusion:BMSC transfected with ADAM17 shRNA could inhibit the proliferation of MCF-7 cells at 24 h and 48 h, while the proliferation of MCF-7 cells decreased at 72 h.

Topoisomerase II alpha promotes gallbladder cancer proliferation and metastasis through activating phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway / 中华医学杂志(英文版)

BACKGROUND@#Topoisomerase II alpha (TOP2A) has been reported to play a crucial role in the tumorigenesis of various cancer types. However, the biological role of TOP2A in gallbladder cancer (GBC) remains unknown. The current study aimed to explore the function and potential mechanism of TOP2A in GBC.@*METHODS@#Based on Gene Expression Profiling Interactive Analysis data, we found TOP2A was significantly up-regulated in GBC tissues and resulting in shorter overall survival. Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expression of TOP2A in 45 pairs of GBC tissues and adjacent non-tumor tissues. In vitro, cell proliferation, migration, and invasion ability were examined by cell counting kit-8 and transwell assay, respectively. Epithelial-mesenchymal transition (EMT) related and phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway-related markers were measured by Western blotting. Xenograft model assay was performed to evaluate the effect of TOP2A in vivo.@*RESULTS@#TOP2A was found up-regulated in GBC (tumor vs. normal, 12.62 vs. 0.34) and correlated with the late tumor node metastasis stage (P = 0.0032), present of lymph node metastasis (P = 0.0273), and poor prognosis in GBC patients (log-rank P = 0.028). In vitro and in vivo assays showed that knockdown of TOP2A notably inhibited cell proliferation, migration, invasion, EMT process, and tumor growth in GBC. In addition, TOP2A down-regulation significantly decreased the protein levels of phosphor (p)-PI3K, p-Akt, and p-mTOR.@*CONCLUSION@#Our study demonstrates that TOP2A was overexpressed in GBC and associated with poor prognosis in GBC patients. TOP2A promotes GBC cell proliferation, migration, invasion, EMT process, and tumor growth through activating PI3K/Akt/mTOR signaling pathway, and may serve as a novel prognostic biomarker and therapeutic target for GBC.

Comparison of clinical efficacy of femoral calcar prosthesis replacement and intramedullary nail in the treatment of elderly patients with intertrochanteric fracture / 中国骨伤

OBJECTIVE@#To analyze the clinical efficacy of hip arthroplasty with femoral calcar prosthesis and proximal femoral nail fixation(PFNA) in the treatment of elderly patients(≥80 years old) with unstable intertrochanteric fractures(Evans Ⅲ, Ⅳ).@*METHODS@#From June 2016 to March 2018, 60 elderly patients with unstable intertrochanteric fractures treated with prosthetic replacement and PFNA were retrospectively analyzed. According to the surgical methods, they were divided into PFNA group and prosthesis group. In PFNA group there were including 21 males and 15 females, with an average age of(84.3± 2.9) years old;in the prosthetic group, there were 10 males and 14 females with an average age of (82.9±2.4) years old. The operation time, hemoglobin difference between preoperative and postoperative 1 day, postoperative ambulation time, hospitalization time and complications were observed and compared between the two groups. Harris hip score was performed 3 and 12 months after operation.@*RESULTS@#All patients were followed up for 12 to 24 months (19.3±4.8) months. One patient in the prosthesis group died of lung cancer one year later and the follow-up was terminated. The operation time of prosthetic group was longer than that of PFNA group(@*CONCLUSION@#The elderly patients with intertrochanteric arthroplasty can reduce the burden of intertrochanteric arthroplasty and improve the quality of life.

Comparison between daptomycin plasma concentration in left ventricle and that in right ventricle of rats / 中国中西医结合急救杂志

Objective To detect the plasma concentrations of daptomycin in the left ventricle and right ventricle of rats by high-performance liquid chromatography-mass spectrometry(LC-MS/MS), and evaluate the therapeutic effect of daptomycin on left ventricular endocarditis. Methods Thirty-five healthy Sprague-Dawley (SD) rats were divided into a normal saline group (5 rats) and a daptomycin group (30 rats) according to the random number table method. The daptomycin group was subdivided into 6 subgroups according to the times of blood collection (0.25, 0.5, 1, 2, 4, 8 hours), with 5 rats in each subgroup. The normal saline group was given 4 mL/kg normal saline; the daptomycin group was injected with 50 mg/kg daptomycin into the tail vein. The blood samples from left ventricle and right ventricle were extracted at the corresponding time points, the plasma concentrations of daptomycin group were determined by high performance liquid chromatography-mass spectrometry (HPLC-MS) and the differences of left ventricular and right ventricular plasma concentrations were compared at different time points. The plasma in normal saline group was the blank plasma that was used for HPLC-MS methodological evaluation. Results There were no statistical significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin at 0.25, 0.5, 1, 2, 4, and 8 hours after administration (g/L: 2.67±0.30 vs. 2.77±0.31, 1.77±1.27 vs. 1.64±0.55, 1.35±0.40 vs. 1.36±0.41, 0.97±0.07 vs. 0.92±0.09, 0.73±0.16 vs. 0.65±0.18, 0.07±0.06 vs. 0.06±0.05, respectively all P > 0.05). Conclusion There are no significant differences between the left ventricle and right ventricle in plasma concentrations of daptomycin. It is speculated that daptomycin may have the same therapeutic effect on left endocarditis.

Characteristics and failure risk factors of sequential high-flow nasal cannula oxygen therapy after weaning from invasive ventilation in patients of surgical intensive care unit / 中华危重病急救医学

Objective To investigate the characteristics and failure risk factors of sequential high-flow nasal cannula oxygen therapy (HFNC) after weaning from invasive ventilation. Methods The patients who received sequential HFNC after weaning from invasive ventilation admitted to surgical intensive care unit (ICU) of Peking University People's Hospital from June 1st 2016 to May 31st 2018 were retrospectively analyzed. Clinical variables, respiratory therapy parameters, respiratory variables, cardiac variables and outcomes were reviewed and analyzed. Treatment characteristics of HFNC after weaning was analyzed. Patients were divided into HFNC success group and HFNC failure group according to the failure of HFNC, and the differences between the two groups were compared. The independent risk factors of HFNC treatment failure were analyzed by Logistic regression analysis. The value of predictive treatment failure of risk factors and regression models were analyzed by receiver operating characteristic (ROC) curve. Results A total of 99 patients were included, 61 men, and the median age was 67.0 (57.0, 76.0) years old. The medianinitial HFNC flow was 50 (50, 60) L/min, and inspired oxygen concentration (FiO2) was 0.50 (0.40, 0.60). Eighteen patients experienced HFNC failure (18.2%). Compared with the HFNC success group, the sequential organ failure assessment (SOFA) score in the HFNC failure group was higher [4 (3, 5) vs. 2 (1, 3), P < 0.01], B type natriuretic peptide (BNP) before HFNC therapy were significant higher [ng/L: 647.2 (399.2, 1 331.3) vs. 127.2 (55.2, 369.5), P < 0.01], and respiratory frequency (RR) and heart rate (HR) were significant faster, mean arterial pressure (MAP) was significant higher, oxygen index (PaO2/FiO2) was significant lower after 30 minutes HFNC treatment [RR (times/min): 26 (22, 28) vs. 19 (17, 21), HR (bpm): 105 (97, 107) vs. 85 (77, 90), MAP (mmHg, 1 mmHg = 0.133 kPa): 104.3 (101.7, 110.7) vs. 92.3 (88.3, 97.7), PaO2/FiO2 (mmHg): 207.3 (185.8, 402.8) vs. 320.2 (226.2, 361.5), all P < 0.05]. It was shown by multiple Logistic regression analysis that the SOFA score [odds ratio (OR) = 2.818, P = 0.022, β = 1.036], BNP before HFNC treatment (OR = 1.002, P = 0.033, β = 0.002) and HR after HFNC treatment 30 minutes (OR = 1.140, P = 0.032, β = 0.131) were independent risk factors for HFNC treatment failure. It was shown by ROC curve that the area under the ROC curve (AUC) for the prediction of HFNC failure was 0.840, 0.859, 0.860 and 0.962 for SOFA, BNP before HFNC treatment, HR after HFNC treatment 30 minutes, and regression model, all had good forecast values (all P < 0.01). Conclusions HFNC is one of the commonly used oxygen therapy methods in the ICU, but not all patients who are treated as a sequential therapy after invasive mechanical ventilation weaning can benefit from it. SOFA score, BNP before HFNC treatment and HR after 30 minutes HFNC treatment were independent risk factors of HFNC failure. Each independent risk factor and regression model can predict the success of HFNC treatment.

Dihydromyricetin promoted browning of subscapular adipose tissues in obese mice fed with high-fat diet via activating AMPK-PGC1 a-Sirtl signaling pathway / 中国药理学通报

Aim To observe the effect of dihydromyricetin (DHM) on the browning of subscapular adipose tissues in the high-fat diet fed obese mice, and clarify the mechanism. Methods C57BL/6J mice were fed with normal and high-fat diet, and were treated with or without low dose (125 mg • kg"1 • d"1) or high dose (250 mg • kg"1 • d"1) DHM for 16W. The body mass of mice was measured every four weeks during the experiment. After 16 weeks, the mice were fasted overnight. Blood samples were taken for fasting blood glucose. The mice were then sacrificed and the body length measured. The Lee' s index was calculated. The size of the subscapular adipocytes was observed by HE staining. The mRNA and protein expression of uncoupling protein 1 (UCP1) , PR domain containing 16 (Prdml6) , adenylate-activated protein kinase (AMPK) , peroxisome proliferator-activated receptor gamma-assisted activator alpha (PGCla) and silencing signal regulator 1 (Sirtl) were assessed by real time quantitative PCR and Western blot assay. Results Compared with normal control group (ND group) , the body mass of mice in high-fat diet group (HFD group) significantly increased, suggesting that the obese mice model was successfully replicated. In addition , blood glucose, Lee' s index and the fat cell diameter of the subscapular adipose tissues in HFD group all significantly increased, while the mRNA and pro-tein expression of UCP1, Prdml6, AMPK, PGCla and Sirtl significantly decreased. DHM markedly re-versed the changes of the above indexes of HFD mice, but DHM did not significantly affect the above indexes of normal mice. Conclusions Dihydromyricetin promotes the browning of subscapular adipose tissues in mice fed with high-fat diet, which might be via activating AMPK-PGC1 a-Sirtl signaling pathway.

Value of semi-quantitative indices of 68Ga-PSMA-11 PET/CT in differential diagnosis of malignant and benign prostate lesions / 中华核医学与分子影像杂志

Objective To evaluate the value of semi-quantitative indices of 68Ga-prostate specific membrane antigen (PSMA)-11 PET/CT in differentiating malignant and benign prostate lesions.Methods From November 2017 to June 2018,30 patients (age:52-86 years) who underwent 68Ga-PSMA-11 PET/CT imaging in the Third Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed,and the serum total prostate specific antigen (tPSA) and free prostate specific antigen (fPSA) were examined within 1 week before PET/CT imaging.Semi-quantitative indices of 68Ga-PSMA-11 PET/CT on prostate lesions were measured by automatic segmentation algorithm method,including PSMA-related lesion volume (VPSMA),maximum standardized uptake value (SUVmax),mean standardized uptake value (SUVmean),peak standardized uptake value (SUVpeak) and total lesion uptake value of PSMA (TLUPSMA).The indices were compared between malignant and benign prostate lesions,and the optimal cut-off values for differentiating malignant and benign prostate lesions were obtained by receiver operating characteristic (ROC) curve analysis.Results According to the pathological results,19 patients had malignant lesions and 11 were with benign diseases.The differences of tPSA,SUVmax,SUVmean SUVpeak and TLUPSMA between malignant and benign prostate lesions were statistically significant (u values:17.00-48.00,all P＜0.05),but there were no significant differences of fPSA,fPSA/tPSA and VPSMA between 2 groups (u values:64.00-99.00,all P＞0.05).The optimal cut-off value of tPSA was 18.30 μg/L for differentiating malignant and benign prostate lesions,with sensitivity of 13/17 (PSA of 2 patients were missing),specificity of 9/11 and area under curve (AUC) of 0.743.The optimal cut-off values of SUVmax,SUVmean and SUVpeak were 5.50,3.09 and 3.56,respectively,with all corresponding sensitivity of 18/19,all specificity of 9/11,and AUC of 0.902,0.907 and 0.919,respectively.The optimal cut-off value of TLUPSMA was 54.81 cm3,with sensitivity of 14/19,specificity of 9/11 and AUC of 0.804.Conclusion The semi-quantitative indices of 68Ga-PSMA-11 PET/CT are valuable for differentiating malignant and benign prostate lesions,in which SUVpeak is superior to other indices.

Correlation betw een serum 25-hydroxyvitamin D level and enlarged perivascular spaces in patients w ith lacunar infarction / 国际脑血管病杂志

Objective To investigate the correlation betw een serum 25-hydroxyvitamin D (25(OH) D) level and enlarged perivascular spaces (EPVS) in patients w ith lacunar infarction. Methods Consecutive inpatients w ith acute lacunar infarction w ere enrolled. Chemiluminescence immunoassay w as used to measure the serum 25(OH)D. Head MRI w as used to assess the severity of EPVS in the centrum ovale and the basal ganglia region (grade 1, 0-10; grade 2, 11-25; grade 3, >25). Univariate analysis w as used to analyze the differences in baseline data among the three groups. Multivariate ordinal logistic regression analysis w as used to investigate the independent correlation betw een the 25(OH)D levels and the severity of EPVS. Results A total of 194 patients w ere enrolled,96 w ere males.Their mean age w as 63.4 ±9.3 years. The mean baseline National Institutes of Health Stroke Scale (NIHSS) score w as 2.0 ±1.7. The mean 25(OH)D level w as(50.25 ±15.50)nmol/L. There w ere 112 patients (57.7%), 45 (23.2%) and 37 (19.1%) w ith EPVS grade 1,grade 2 and grade 3 in the centrum ovale,and 109 (56.2%),53(27.3%) and 32 (16.5%) w ith EPVS grade 1, grade 2 and grade 3 in basal ganglia region, respectively. Multivariate ordinal logistic regression analysis show ed that serum 25(OH)D levels w ere independently associated w ith the severity of EPVS in the centrum ovale (odds ratio 2.898,95% confidence interval 1.345-9.612; P=0.028) and basal ganglia region (odds ratio 2.688, 95% confidence interval 1.182-10.281; P=0.039). Conclusion The low serum 25 (OH) D levels are independently associated w ith the severity of EPVS in patients w ith lacunar infarction.

Research progress on clinical diagnosis and treatment for external snapping hip / 中国骨伤

External snapping hip(ESH) is a vague term used to describe palpable or auditory snapping with hip movements with or without pain. The pathogenesis of ESH is related to the specific anatomical structure and friction factor. The clinical symptom is auditory snapping during activities, physical examination, X-ray, magnetic resonance imaging(MRI), dynamic ultrasound and other imaging techniques can be used to diagnose. Conservative medical management includes rest, avoidance of aggravating activities, and antiinflammatory medications. Treatment Patients with mild symptoms can achieve good results by medication, rest and physiotherapy. Surgical treatment for patients with ineffective conservative treatment was performed. All kinds of open surgery method can achieve good clinical curative effect, arthroscopic surgery is gradually been promoted due to small trauma, less complications. Besides, there are some reports that traditional treatments such as massage, acupuncture and acupotomology have achieved good clinical results, which deserve further study and promotion.

Pharmacokinetic and Pharmacodynamic Efficacies of Continuous versus Intermittent Administration of Meropenem in Patients with Severe Sepsis and Septic Shock: A Prospective Randomized Pilot Study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The antibiotic meropenem is commonly administered in patients with severe sepsis and septic shock. We compared the pharmacokinetic, clinical, and bacteriological efficacies of continuous infusion of meropenem versus intermittent administration in such patients.</p><p><b>METHODS</b>Patients admitted to the Intensive Care Unit (ICU) with severe sepsis or septic shock who received meropenem were randomly assigned to either the continuous (n = 25) or intermittent groups (n = 25). The continuous group received a loading dose of 0.5 g of meropenem followed by a continuous infusion of 3 g/day; the intermittent group received an initial dose of 1.5 g followed by 1 g for every 8 h. Clinical success, microbiological eradication, superinfection, ICU mortality, length of ICU stay, and duration of meropenem treatment were assessed. Serial plasma meropenem concentrations for the first and third dosing periods (steady state) were also measured.</p><p><b>RESULTS</b>Clinical success was similar in both the continuous (64%) and intermittent (56%) groups (P = 0.564); the rates of microbiological eradication and superinfection (81.8% vs. 66.7% [ P = 0.255] and 4% vs. 16% [ P = 0.157], respectively) showed improvement in the continuous group. The duration of meropenem treatment was significantly shorter in the continuous group (7.6 vs. 9.4 days; P= 0.035), where a better steady-state concentration was also achieved. Peak and trough concentrations were significantly different between the continuous and intermittent groups both in the first (Cmax: 19.8 mg/L vs. 51.8 mg/L, P= 0.000; Cmin: 11.2 mg/L vs. 0.5 mg/L, P= 0.000) and third dosing periods (Cmax: 12.5 mg/L vs. 46.4 mg/L, P= 0.000; Cmin: 11.4 mg/L vs. 0.6 mg/L, P= 0.000). For medium-susceptibility pathogens, continuous infusion concentrations above the minimal inhibitory concentration were 100%, which was better than that in the intermittent group.</p><p><b>CONCLUSIONS</b>Continuous infusion of meropenem provides significantly shorter treatment duration and a tendency for superior bacteriological efficacy than intermittent administration. Continuous infusion may be more optimal against intermediate-susceptibility pathogens.</p>

Effects of different target plasma concentrations of propofol on ventricular repolarization in elderly patients / 中华麻醉学杂志

Objective To evaluate the effects of different target plasma concentrations of propofol on ventricular repolarization in elderly patients.Methods Forty-five patients,aged 65-80 yr,weighing 43-85 kg,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,scheduled for elective surgery under general anesthesia,were divided into 3 groups (n=15 each) using a random number table:propofol at target plasma concentration of 2 μg/ml group (group P1),propofol at target plasma concentration of 3 μg/ml group (group P2) and propofol at target plasma concentration of 4 μg/ml group (group P3).Before induction of anesthesia (T1) and at 5 min after propofol reached the target plasma concentration (T2),12-lead electrocardiogram was recorded,the QT and Tp-e intervals were measured,and the corrected QT (QTc) interval and Tp-e/QT ratio were calculated.Results There were no significant differences in QTc interval,Tp-e interval or Tp-e/QT ratio at T1,2 between the three groups (P＞0.05).Compared with those at T1,the QTc and Tp-e intervals were significantly shortened and the Tp-e/QT ratio was decreased at T2 in P1 and P2 groups,and the Tp-e interval was shorten and the Tp-e/QT ratio was decreased at T2 (P＜ 0.05),and no significant change was found in the QTc interval at T2 in group P3 (P＞0.05).Conclusion Propofol at clinically relevant concentrations can shorten the ventricular repolarization in elderly patients.