Application of PDX model in the evaluation of nano-delivery systems / 药学学报

Malignant tumor is a major disease affecting human health. The nano-delivery system itself has a unique size effect and it can achieve tumor-targeted distribution of drug molecules, improve the therapeutic effect, and reduce the toxic and side effects on normal tissues and cells after functional modification. Patient-derived xenografts (PDX) models can be established by transplanting patient-derived cancer cells or small tumor tissue into immunodeficient mice directly. Compared with the tumor cell line model, this model can preserve the key features of the primary tumor such as histomorphology, heterogeneity, and genetic abnormalities, and keep them stable between generations. PDX models are widely used in drug evaluation, target discovery and biomarker development, especially providing a reliable research platform for the diagnosis and treatment evaluation of nano-delivery systems. This review summarizes the application of several common cancer PDX models in the evaluation of nano-delivery systems, in order to provide references for researchers to perform related research.

Diagnosis and treatment of the short-arm type posterior semicircular canal BPPV / Diagnóstico e tratamento da VPPB de braço curto do canal semicircular posterior

Abstract Introduction The Epley maneuver is useful for the otoconia to return from the long arm of the posterior semicircular canal into the utricle. To move otoconia out of the posterior semicircular canal short arm and into the utricle, we need different maneuvers. Objective To diagnose the short-arm type BPPV of the posterior semicircular canal and treat them with bow-and-yaw maneuver. Methods 171 cases were diagnosed as BPPV of the posterior semicircular canal based on a positive Dix-Hallpike maneuver. We first attempted to treat patients with the bow-and-yaw maneuver and then performed the Dix-Hallpike maneuver again. If the repeated Dix-Hallpike maneuver gave negative results, we diagnosed the patient with the short-arm type of BPPV of the posterior semicircular canal and considered the patient to have been cured by the bow-and-yaw maneuver; otherwise, probably the long-arm type BPPV of the posterior semicircular canal existed and we treated the patient with the Epley maneuver. Results Approximately 40% of the cases were cured by the bow-and-yaw maneuver, giving negative results on repeated Dix-Hallpike maneuvers, and were diagnosed with short-arm lithiasis. Conclusion The short-arm type posterior semicircular canal BPPV can be diagnosed and treated in a convenient and comfortable manner.

Resumo Introdução A manobra de Epley é útil para o retorno da otocônia do braço longo do canal semicircular posterior para o utrículo. Diferentes manobras são necessárias para mover a otocônia para fora do braço curto do canal semicircular posterior e para dentro do utrículo. Objetivo Diagnosticar a VPPB do tipo braço curto do canal semicircular posterior e tratá-la com a manobra de incline and balance. Método Foram diagnosticados 171 casos como VPPB de canal semicircular posterior com base na manobra de Dix-Hallpike positiva. Primeiro tentamos tratar os pacientes com a manobra de incline and balance e, em seguida, executamos a manobra de Dix-Hallpike novamente. Se a repetição da manobra de Dix-Hallpike desse resultados negativos, diagnosticávamos o paciente como VPPB do canal semicircular posterior do tipo braço curto e considerávamos que ele ou ela havia sido curado pela manobra de incline and balance; caso contrário, provavelmente o paciente apresentava VPPB do canal semicircular posterior do tipo braço longo e tratávamos o paciente com a manobra de Epley. Resultados Aproximadamente 40% dos casos foram curados pela manobra de incline and balance, com resultados negativos nas manobras de Dix-Hallpike repetidas, e foram diagnosticados com litíase de braço curto. Conclusão A VPPB de canal semicircular posterior do tipo braço curto pode ser diagnosticada e tratada de maneira conveniente e confortável.

Treatment of chronic fatigue syndrome from yangming meridian / 中国针灸

Based on the theory of "brain-gut communication" and "heart-stomach disease simultaneously", the thinking and method of treating chronic fatigue syndrome (CFS) from yangming meridian were discussed. CFS is related to brain and heart. Based on the analysis of meridian circulation, zang-fu function and the indication characteristics of yangming meridian, the indications of yangming meridian are closely related to brain and heart, so it is proposed to start from yangming meridian and use Chinese herbs combined with acupuncture to treat CFS, including the four methods of clearing away heat and moisturizing dryness, cooling blood and removing blood stasis, promoting qi to clear the organs, and strengthening and replenishing deficiency. It has certain guiding and reference significance for clinical treatment of CFS.

Inhibition of Toll-like receptor 4 pathway by TAK242 protects the liver in sepsis / 中华危重病急救医学

Objective:To investigate the protective mechanism of TAK242, a specific inhibitor of Toll-like receptor 4 (TLR4), on the liver of septic rats.Methods:Eighteen male Sprague-Dawley (SD) rats were randomly divided into three groups ( n = 6 in each group). The septic model was established by intraperitoneal injection of lipopolysaccharide (LPS) 15 mg/kg. The rats in the TAK242 intervention group received intraperitoneal injection of TAK242 (5 mg/kg) before modeling, while the rats in the septic model group and the control group were injected with the same amount of solvent [10% dimethyl sulfoxide (DMSO) + 90% corn oil]. Six hours later, the blood of abdominal aorta was collected and the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by enzyme linked immunosorbent assay (ELISA). The rats were sacrificed to obtain liver, the expression levels of TLR4, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cysteinyl aspartate-specific proteinase-3 (caspase-3), nuclear factor-κB p65 (NF-κB p65) and phosphorylated NF-κB p65 (p-NF-κB p65) were detected by Western blotting. Immunohistochemical staining was used to observe NF-κB p65 protein expression in liver, and hepatocyte injury was assessed by hematoxylin-eosin (HE) staining. Results:Serum ALT and AST levels in the septic model group were significantly higher than those in the control group [ALT (μg/L): 26.639±7.814 vs. 2.847±2.150, AST (μg/L): 28.442±8.417 vs. 5.779±3.019, both P < 0.01]. The ALT and AST levels in the TAK242 intervention group were significantly lower than those in septic model group [ALT (μg/L): 7.269±3.398 vs. 26.639±7.814, AST (μg/L): 3.580±3.115 vs. 28.442±8.417, both P < 0.01]. Light microscopy showed that the hepatocytes in the septic model group were disordered, with obvious cell edema and increased inflammatory cells infiltration; the hepatocytes in the TAK242 intervention group were more neatly arranged, with significantly reduced hepatocyte edema and reduced inflammatory cells infiltration. Western blotting results showed that caspase-3 protein expression in hepatic tissue of septic model group was significantly higher than that in the control group (caspase-3/GAPDH: 0.794±0.164 vs. 0.482±0.055, P < 0.05), and caspase-3 protein expression in the TAK242 intervention group significantly decreased than that in the septic model group (caspase-3/GAPDH: 0.482±0.056 vs. 0.794±0.164, P < 0.05), which indicated that TAK242 could attenuate hepatocytes apoptosis of septic rats. The expression of IL-6, TNF-α and TLR4 protein and the ratio of p-NF-κB p65/NF-κB p65 in hepatic tissue of septic model group were significantly higher than those in control group (IL-6/GAPDH: 1.442±0.204 vs. 1.019±0.024, TNF-α/GAPDH: 1.089±0.098 vs. 0.806±0.005, TLR4/GAPDH: 1.292±0.085 vs. 0.941±0.087, p-NF-κB p65/NF-κB p65 ratio: 1.936±0.081 vs. 1.579±0.183, all P < 0.05), IL-6, TNF-α and TLR4 protein expression and p-NF-κB p65/NF-κB p65 ratio in the TAK242 intervention group were significantly lower than those in septic model group (IL-6/GAPDH: 1.035±0.042 vs. 1.442±0.204, TNF-α/GAPDH: 0.572±0.096 vs. 1.089±0.098, TLR4/GAPDH: 0.984±0.078 vs. 1.292±0.085, p-NF-κB p65/NF-κB p65 ratio: 1.484±0.255 vs. 1.936±0.081, all P < 0.05), it is suggested that LPS-induced sepsis could activate the inflammatory response mediated by TLR4/NF-κB pathway in liver, and the activation of TLR4/NF-κB pathway was inhibited by TAK242 through the TLR4 pathway, therefore, the inflammation of liver in septic rats was reduced. Immunohistochemical staining showed that the positive expression of NF-κB p65 in liver was significantly increased in the septic model group compared with the control group; the positive expression of NF-κB p65 was significantly reduced in the TAK242 intervention group compared with the septic model group, and there was almost no positive expression in the nucleus. Conclusion:TAK242 could reduce liver function injury and protect the liver by inhibition TLR4/NF-κB pathway in septic rats.

Changes in the structure of intestinal mucosal flora in colorectal cancer patients / 南方医科大学学报

OBJECTIVE@#To investigate the changes in bacterial flora in fecal samples, at the tumor loci and in adjacent mucosa in patients with colorectal cancer (CRC).@*METHODS@#We collected fecal samples from 13 patients with CRC and 20 healthy individuals and tumor and adjacent mucosa samples from 6 CRC patients. The differences in bacterial composition between the fecal and mucosa samples were analyzed with 16S rDNA sequencing and bioinformatics methods. We also detected the total number of bacteria in the feces using flow cytometry, isolated and identified the microorganisms in the fecal and mucosa samples using common bacterial culture media. We further tested the effects of 7 isolated bacterial strains on apoptosis of 3 CRC cell lines using lactate dehydrogenase detection kit.@*RESULTS@#The bacterial α-diversity in the feces of healthy individuals and in adjacent mucosa of CRC patients was significantly higher than that in the feces and tumor mucosa in CRC patients (P < 0.05). Lactobacillaceae is a specific bacteria in the feces, while Escherichia, Enterococcus, and Fusobacterium are specific bacteria in tumor mucosa of CRC patients as compared with healthy individuals. Cell experiment with3 CRC cell lines showed that Bacteroides fragilis isolated from the tumor mucosa of CRC patients produced significant inhibitory effects on cell proliferation (P < 0.0001), while the isolated strain Fusobacterium nucleatum obviously promoted the proliferation of the cell lines (P < 0.001).@*CONCLUSION@#The bacterial flora in the feces, tumor mucosa and adjacent mucosa of CRC patients is significantly different from that in the feces of healthy individuals, and the fecal flora of CRC patients can not represent the specific flora of the tumor mucosa. Inhibition of F. nucleatum colonization in the tumor mucosa and promoting B. fragilis colonization may prove beneficial for CRC treatment.

Clinical and cardiac MR characteristics of heart involvement in patients with Fabry disease / 中华放射学杂志

Objective:To investigate the clinical and cardiac magnetic resonance (CMR) characteristics of heart involvement in patients with Fabry disease (AFD).Methods:From January 2018 to March 2021, eight AFD patients [3 males and 5 females, mean age (50±11) years old, range 26-60 years old] confirmed by genetic testing or pathology in Fuwai Hospital were retrospectively included in this study. At the same time, sixteen patients with hypertrophic cardiomyopathy (HCM) [6 males and 10 females, mean age (46±15) years old] and 16 healthy individuals [6 males and 10 females, mean age (51±11) years old] were included as controls. The clinical baseline data and CMR data of the patients were collected and analyzed. The CMR data were analyzed using the software CVI42, with the corresponding parameters automatically generated. One-way ANOVA or Kruskal-Wallis test was used to compare the differences in the parameters among the three groups. Independent-samples t test, Fisher precise test or Mann-Whitney U test were used for the comparison between each two groups. Results:Statistically significant difference was found in renal insufficiency between the HCM group and the AFD group; No other significant difference was found in other clinical factors and ECG results (all P>0.05). CMR results showed that in the AFD group, there were 5 cases with symmetric or roughly symmetric hypertrophy, and 3 with asymmetric hypertrophy. The late gadolinium enhancement (LGE) showed myocardial enhancement in 5 patients, mainly presenting as multiple intermural enhancement, and partially as local subendocardial enhancement. In the HCM group, fourteen cases suffered mainly asymmetric ventricular septal thickening, with or without thickening of other parts of left ventricular wall; and 2 cases had thickening of middle and distal part of the left ventricle. The LGE showed myocardial enhancement in 14 patients, which manifested as focal or patchy enhancement in hypertrophic myocardium, including focal enhancement in the right ventricular insertion of ventricular septum (more common) and subendocardial enhancement in the middle and far segments of left ventricle. Statistically significant difference was found in the differences between the left atrial anterior posterior diameter, the maximum wall thickness of left ventricular, the left ventricular myocardial mass index (LVMI) and the native T 1 value among the three groups (all P<0.001). However, there was no statistically significant difference in the left atrial anterior posterior diameter and the maximum wall thickness of left ventricular between AFD group and HCM group ( P>0.05). The LVMI in AFD group was higher than that in healthy group and HCM group (all P<0.05). Significant difference was found in the native T 1 value among the three groups, with the native T 1 value of the AFD group [(1 177.4±46.0) ms] was significantly lower than that of the healthy group [(1 244.5±34.3) ms] and the HCM group [(1 278.8±41.6) ms], with ( F=13.10, P<0.001). Conclusions:The clinical characteristics of AFD and HCM are quite similar. When AFD is suspected, CMR imaging should be the first choice for imaging examination. Especially, T 1 mapping imaging can provide important information for the diagnosis of AFD.

Recent progress of nanoparticle-enabled modulation of macrophages for cancer immunotherapy / 药学学报

Macrophages play an important role in maintaining homeostasis of the body, and they are also one of the most abundant immune cells in the tumor microenvironment (TME). These macrophages are often called tumor-associated macrophages (TAMs), which play an important role in the development of tumor and are an important target for tumor therapy. Studies have shown that tumor growth and metastasis can be inhibited by regulating the function of macrophages, but the therapeutic efficacy was often hampered by the poor performance of the drugs such as lack of targeting, poor solubility, low bioavailability, and severe side effects. After introduction of the background of macrophage and tumor therapy, this review focuses on the research progress of nano-drug delivery systems in the modulation of the function of macrophages to enhance tumor immunotherapy. Nano-drug delivery systems are diverse in structures and functions, and can regulate macrophage functions through a variety of mechanisms. Four important aspects of macrophage modulation, which included TAMs depletion, repolarization of TAMs, promoted phagocytosis of TAMs, and combinational modulation of TAMs were summarized. Each strategy together with typical examples was reviewed and future directions in this field were also prospected.

Mechanism of Aconiti Kusnezoffii Radix Processed with Chebulae Fructus Against H9c2 Cardiomyocyte Toxicity Based on TRPV1 Channel / 中国实验方剂学杂志

ObjectiveTo explore the role of transient receptor potential vanilloid 1 （TRPV1） channel in reducing cardiomyocyte toxicity of Aconiti Kusnezoffii Radix processed with Chebulae Fructus. MethodH9c2 cardiomyocytes cultured in vitro were used as a model to assess cell viability by methyl thiazolyl tetrazolium （MTT） assay， the expression of TRPV1 mRNA was detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the leakage rate of lactate dehydrogenase （LDH）， the changes of nucleus， reactive oxygen species （ROS）， mitochondrial membrane potential and Ca2+ contents were detected by enzyme linked immunosorbent assay （ELISA）. ResultCompared with the blank group， when the concentration was ≥0.5 g·L-1， the cell viability was significantly decreased （P<0.01）， the leakage rate of LDH， the release of ROS and Ca2+ were increased， the mitochondrial membrane potential was decreased， and the nucleus was pyknosis or even broken in raw Aconiti Kusnezoffii Radix and Aconiti Kusnezoffii Radix processed with Chebulae Fructus groups. When the concentration was ≥0.5 g·L-1， compared with the same mass concentration of raw Aconiti Kusnezoffii Radix group， the cell viability increased significantly （P<0.01）， the leakage rate of LDH， the release of ROS and Ca2+ decreased， the mitochondrial membrane potential increased， and the nuclear morphology improved in Aconiti Kusnezoffii Radix processed with Chebulae Fructus group. Application of the same mass concentration of raw Aconiti Kusnezoffii Radix to H9c2 cardiomyocytes pretreated with the TRPV1 inhibitor BCTC significantly increased cell viability， decreased leakage rate of LDH， ROS and Ca2+ release， increased mitochondrial membrane potential and improved nuclear pyknosis compared with untreated H9c2 cardiomyocytes. Application of the same mass concentration of Aconiti Kusnezoffii Radix processed with Chebulae Fructus to H9c2 cardiomyocytes pretreated with BCTC decreased cell viability， increased LDH leakage rate， ROS and Ca2+ release， reduced mitochondrial membrane potential compared with untreated H9c2 cardiomyocytes. Real-time PCR results showed that both raw Aconiti Kusnezoffii Radix and Chebulae Fructus decoction could increase the expression of TRPV1 mRNA in cardiomyocytes in a concentration dependent manner. ConclusionRaw Aconiti Kusnezoffii Radix can induce cardiomyocyte apoptosis and cardiotoxicity by activating TRPV1 channel， while Aconiti Kusnezoffii Radix processed with Chebulae Fructus can attenuate the toxicity through TRPV1 channel， which may be related to the synergistic effect of acid components in Chebulae Fructus and alkaloids in Aconiti Kusnezoffii Radix on TRPV1 channel.

Comparison of vesselplasty and percutanous kyphoplasty in the treatment of Kümmell disease / 中国骨伤

OBJECTIVE@#To compare the efficacy between vesselplasty and percutanous kyphoplasty (PKP) in the treatment of Kümmell disease.@*METHODS@#The clinical data of patients with Kümmell disease from July 2018 to December 2019 were retrospectively analyzed. According to the different therapeutic methods, the patients were divided into vesselplasty group and PKP group. There were 20 patients in vesselplasty group, including 2 males and 18 females, aged from 54 to 83 years with an average of (67.40±7.44)years, 1 case of T10 fracture, 3 cases of T12 fracture, 9 cases of L1 fractures, 5 cases of L2 fractures and 2 cases of L3 fractures. There were 20 patients in PKP group, including 3 males and 17 females, aged from 56 to 81 with an average of(67.20±7.01) years, 2 cases of T10 fracture, 1 case of T11 fracture, 6 cases of T12 fracture, 10 cases of L1 fracture and 1 case of L3 fracture. Visual analogue scale(VAS), Cobb angle, anterior vertebral height were recorded before operation, 1 day after operation and 1 year after operation. Oswestry Disability Index(ODI) was recorded before operation, 1 month after operation and 1 year after operation. And bone cement leakage rate was compared between two groups after operation.@*RESULTS@#All the patient were followed up for more than 1 year. In vesselplasty group, VAS score was 1.20±0.41, ODI was(13.50±3.10)%, Cobb angle was(17.20±3.12)° and anterior vertebral height was(20.20±1.35) mm at 1 year after operation. In PKP group, VAS score was 1.15±0.40, ODI was (13.20±3.00)%, Cobb angle was (17.10±3.19)° and anterior vertebral height was (20.10±1.37) mm at 1 year after operation. These index was significantly better than pre-operation through intra-group comparison(P<0.05), and there was no statistically difference between the two groups(P>0.05). There were 20 cases (20 vertebrae) in vesselplasty group, of which 1 case had bone cement leakage at the upper endplate, with a leakage rate of 5%(1/20). In PKP group, there were 20 cases (20 vertebrae), 3 cases of upward endplate leakage(3/7), 1 case of downward endplate leakage(1/7), 1 case of leakage to the front of the vertebral body(1/7), 2 cases of leakage to the side of the vertebral body(2/7), with a leakage rate of 35% (7/20). The difference between two groups was statistically significant(P<0.05).@*CONCLUSION@#Vesselplasty in the treatment of Kümmell disease can better reduce leakage rate of bone cement and reduce complications.

Application of spinal surgical robots in minimally invasive surgery for thoracolumbar fracture / 中国骨伤

OBJECTIVE@#To evaluate the safety and accuracy of Renaissance robot navigation system in minimally invasive surgery for thoracolumbar fracture.@*METHODS@#The clinical data of patients with thoracolumbar fracture who underwent posterior minimally invasive pedicle screw internal fixation from July 2016 to July 2019 was retrospectively analyzed. And the patients were divided into robot group and artificial group. Robot navigation assisted screw placement was used in robot group, and traditional unarmed screw placement was used in artificial group. There were 20 patients in robot group, including 13 males and 7 females, aged from 23 to 69 years old with an average of(45.05±11.81)years old, one case was T11 fracture, 2 cases were T12, 10 cases were L1, 6 cases were L2 and 1 case was L3. There were 20 patients in artificial group, including 11 males and 9 females, aged from 26 to 65 years old with an average of(43.40±11.22)years old, 2 cases were T11 fractures, 7 cases were T12, 10 cases were L1, and 1 case was L3. The numbers of fluoroscopy, operation time and intraoperative blood loss were observed. The screw position was evaluated by Neo method.@*RESULTS@#A total of 126 screws were implanted in robot group and 124 screws were implanted in artificial group. The operation time, fluoroscopy times, intraoperative blood loss were(115.75±14.26) min, (7.95±0.89) times and (132.50±29.36) ml in robot group and (129.50±10.50) min, (14.40±2.56) times and(182.50±23.14) ml in artificial group, respectively, there was significant difference between the groups(P<0.05). According to Neo classification method, there were 122 screws at grade 0, 4 screws at grade 1 in robot group, and there were 108 screws at grade 0, 9 screws at grade 1 and 7 screws at grade 2 in artificial group. The accuracy of the robot group was better than that of artificial group(P<0.05).@*CONCLUSION@#Compared with free hand screw placement, Renaissance robot navigation system can effectively improve the accuracy of pedicle screw placement, reduce the number of fluoroscopy times and intraoperative blood loss, thereby improving the safety of operation.

Protective effect of TAK242 blocking Toll-like receptor 4 pathway on septic myocardial injury and cardiac dysfunction / 中华危重病急救医学

Objective:To investigate the role of Toll-like receptor 4 (TLR4) pathway on myocardial injury and cardiac dysfunction in septic rats.Methods:According to the random number table, 18 male Sprague-Dawley (SD) rats were divided into control group, lipopolysaccharide (LPS) group and TLR4 specific inhibitor TAK242 pretreatment group (TAK242+LPS group) with 6 rats in each group. The rat model of septic cardiac dysfunction was induced by intraperitoneal injection of LPS 15 mg/kg, and the control group was given the same amount of normal saline. The TAK242+LPS group was intraperitoneally given injection of TAK242 [it was injected intraperitoneally at a dose of 3 mg/kg and dissolved in 10% dimethyl sulfoxide (DMSO) and 90% corn oil according to the concentration of 0.2 g/L] 3 hours before LPS stimulation. The control group and LPS group were given the same amount of 10% DMSO and 90% corn oil. The cardiac function of rats in each group was examined by Doppler echocardiography 14 hours after injection of LPS. The blood of abdominal aorta was taken and the level of serum troponin (cTn) was measured by enzyme linked immunosorbent assay (ELISA). Myocardial tissue was harvested for hematoxylin-eosin (HE) staining, and the morphological changes of myocardial tissue were observed under light microscope. The mRNA expressions of interleukin-6 (IL-6) and tumor necrosis factor-α(TNF-α) in myocardial tissue were detected by real-time fluorescence quantitative polymerase chain reaction (qPCR). The protein expression of TLR4 in myocardial tissue was observed by immunohistochemical method. Western blotting was used to detect the levels of TLR4, nuclear factor-κB p65 (NF-κB p65) and its phosphorylation (p-NF-κB p65) in myocardial tissue.Results:① The cardiac function and myocardial injury: Doppler echocardiography showed that the levels of left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) in the LPS group were significantly higher than those in the control group, while left ventricular ejection fraction (LVEF) and left ventricular shortened fraction (LVFS) were significantly lower than those in the control group. The degeneration, necrosis and inflammatory cell infiltration of cardiomyocytes were found with light microscope in the LPS group, and the levels of serum cTn were significantly higher than those in the control group, indicating that LPS-induced sepsis could cause cardiac dysfunction and myocardial injury. TAK242 blocking TLR4 pathway had a protective effect on cardiac function and myocardium during sepsis. LVEDV and LVESV in the TAK242+LPS group were significantly lower than those in the LPS group [LVEDV (μL): 71.25±21.16 vs. 118.01±11.89, LVESV (μL): 9.57±5.75 vs. 32.70±9.22, both P < 0.01]. LVEF and LVFS were significantly higher than those in the LPS group [LVEF: 0.868±0.075 vs. 0.722±0.095, LVFS: (59.88±8.46)% vs. (42.37±8.71)%, both P < 0.05]. Myocardial tissue injury was significantly reduced, and the serum cTn level was significantly lower than that in the LPS group (μg/L: 107.85±21.38 vs. 152.25±27.46, P < 0.05). ② Inflammatory parameters: the results of qPCR, Western blotting and immunohistochemistry showed that the mRNA expressions of IL-6 and TNF-α, the expression of TLR4 protein and the p-NF-κB p65/NF-κB p65 ratio in the LPS group were significantly higher than those in the control group, indicating that LPS-induced sepsis could activate the inflammatory response mediated by TLR4/NF-κB pathway in the heart. However, blocking the TLR4 pathway by TAK242 could inhibit the TLR4/NF-κB pathway and reduce the myocardial inflammation in septic rats. The mRNA expressions of IL-6 and TNF-α, the expression of TLR4 protein and the p-NF-κB p65/NF-κB p65 ratio in the TAK242+LPS group were significantly lower than those in the LPS group [IL-6 mRNA (2 -ΔΔCT): 10.44±3.30 vs. 107.50±29.48, TNF-α mRNA (2 -ΔΔCT): 2.38±0.68 vs. 3.77±0.56, TLR4 protein (TLR4/GAPDH): 0.39±0.01 vs. 0.58±0.04, p-NF-κB p65/NF-κB p65 ratio: 1.21±0.11 vs. 2.10±0.18, all P < 0.05]. Conclusion:TAK242 can protect LPS-induced cardiac dysfunction and myocardial injury by blocking the TLR4 mediated inflammatory response.

Risk Factors for Surgical Site Infection after Conversion from Laparoscopic to Open Cholecystectomy / 中国医学科学院学报

Objective To investigate the incidence of surgical site infection(SSI)following conversion from laparoscopic to open cholecystectomy and to analyze the related risk factors. Methods The clinical data of 179 patients who had experienced conversion from laparoscopic to open cholecystectomy in Peking Union Medical College Hospital from January 2014 to August 2019 were analyzed retrospectively.Univariate and multivariate logistic regression analyses were performed to evaluate the associations between clinical variables and SSI. Results The incidence of SSI was 19.0%(34/179)after conversion from laparoscopic to open cholecystectomy.The multivariable analysis demonstrated that preoperative endoscopic retrograde cholangiopancreatography(ERCP)(

Study on iodine nutrition and related influencing factors of children aged 8-10 in Wuhan / 中国学校卫生

Objective@#To understand the status of iodine nutrition and its related influencing factors of school-age children in Wuhan, so as to provide the basis for adjusting the strategies of IDD prevention and control.@*Methods@#In 5 districts of Wuhan (Hongshan, Hanyang, Hannan, Jiangxia, Dongxihu), non-boarding students aged 8-10 years old were selected from each of the five sample areas in the east, west, south, north and middle. Samples of urine and the cooking salt from their home were randornly colleted among children. Height, weight measurement and a self-administered questionnaire were conducted at the same time. A total of 942 valid questionnaires were collected, including 484 boys and 458 girls.@*Results@#The median of iodine content of children s household salt was 23.20 mg/kg, the median of urinary iodine of children in the city was 251.00 μg/L. Children s random urine iodine concentration was related to gender, whether kelp was consumed the day before the survey, the frequency of consuming milk, and whether they received radiological examinations(P<0.05). Male (OR=1.38, 95%CI=1.04-1.82), consumption of kelp the day before the survey (OR=1.67,95%CI=1.13-2.47) and radiological examination (OR=1.26,95%CI=1.05-1.52) were risk factors for children with urinary iodine concentration higher than the upper limit of the appropriate value(P<0.05). The awareness rate of children s iodine deficiency disease prevention knowledge in Wuhan was 69.64%.@*Conclusion@#The iodine nutritional status of children aged 8-10 years in Wuhan was higher than the appropriate level recommended by international organizations. The random urine iodine concentration of children was affected by many factors and the awareness rate of children s iodine deficiency disease knowledge in Wuhan was low. Therefore, health education for children and residents on iodine deficiency disorders should be strengthened, and they should be properly guided and intervened to ensure that iodine deficiency is prevented while iodine excess is avoided.

Hair Growth Promoting Effects of 650 nm Red Light Stimulation on Human Hair Follicles and Study of Its Mechanisms via RNA Sequencing Transcriptome Analysis

Background@#Androgenetic alopecia (AGA) leads to thinning of scalp hair and affects 60%~70% of the adult population worldwide. Developing more effective treatments and studying its mechanism are of great significance. Previous clinical studies have revealed that hair growth is stimulated by 650-nm red light. @*Objective@#This study aimed to explore the effect and mechanism of 650-nm red light on the treatment of AGA by using ex vivo hair follicle culture. @*Methods@#Human hair follicles were obtained from hair transplant patients with AGA. Hair follicles were cultured in Williams E medium and treated with or without 650-nm red light.Real-time RT-PCR and immunofluorescence staining were used to detect the expression level of genes and proteins in hair follicles, respectively. RNA-sequencing analysis was carried out to reveal the distinct gene signatures upon 650 nm treatment. @*Results@#Low-level 650 nm red light promoted the proliferation of human hair follicles in the experimental cultured-tissue model. Consistently, 650 nm red light significantly delayed the transition of hair cycle from anagen to catagen in vitro. RNA-seq analysis and gene clustering for the differentially expressed genes suggests that leukocyte transendothelial migration, metabolism, adherens junction and other biological process maybe involved in stimulation of hair follicles by 650-nm red light treatment. @*Conclusion@#The effect of 650-nm red light on ex vivo hair follicles and the transcriptome set which implicates the role of red light in promoting hair growth and reversing of miniaturization process of AGA were identified.

Myocardial remodeling assessed by MR feature tracking in hypertrophic obstructive cardiomyopathy after surgical myectomy / 中华放射学杂志

Objective:To investigate the changes of strains based on feature tracking in patients with hypertrophic obstructive cardiomyopathy (HOCM) after surgical myectomy and the potential factors that influenced post-myectomy global strains.Methods:A total of 27 patients with HOCM who underwent septal myectomy in Fuwai Hospital from June 2014 to July 2017 were retrospectively collected. They all received cardiac MR (CMR) cine acquisitions before and after surgery. Their preoperative and postoperative strain parameters, including radial strain (RS), circumferential strain (CS), and longitudinal strain (LS) of the global left ventricle, septum, and lateral wall, were assessed by feature tracking. Comparisons of pre-myectomy and post-myectomy imaging parameters were performed using paired-samples t-test or Wilcoxon matched-pairs signed-ranks test. Pearson or Spearman correlation analysis and linear regression analysis were utilized to find the correlated factors of postoperative global strains. Results:Compared with preoperative strains, postoperative global LS, septal LS, lateral RS, lateral CS, and lateral LS increased statistically (all P<0.05); postoperative global RS, global CS, and septal CS decreased (all P<0.05); no statistically significant difference was observed in septal RS ( P=0.165). Age at surgery ( r=0.428, P=0.026) and preoperative myocardial maximum ventricular wall thickness ( r=-0.587, P=0.001) were both linearly related to postoperative global RS; the further multivariate stepwise linear regressions showed that only preoperative myocardial maximum ventricular wall thickness might be correlated with postoperative global RS (adjusted R 2=0.287, P=0.002). Only myocardial maximum ventricular wall thickness was linearly related to global CS ( r=0.679, P<0.001) and global LS ( r=0.588, P=0.001), respectively; univariate linear regression revealed that preoperative myocardial maximum ventricular wall thickness might be correlated postoperative global CS (adjusted R 2=0.337, P=0.001) and postoperative global LS (adjusted R 2=0.281, P=0.003), respectively. Conclusions:Cardiac surgery definitely relieves left ventricular outflow tract obstruction and generally improves longitudinal and lateral strains, but a negative impact may occur in global and septal CS and RS. Preoperative maximum ventricular wall thickness may affect postoperative global strains.

Advances in clinical assessment of bone healing / 中华创伤骨科杂志

The process of bone healing is absolutely complicated and affected by a wide variety of factors. The quality of bone healing directly determines management approaches. Therefore, it is crucial to evaluate accurately outcomes of bone healing. The assessments of bone healing mostly used in current clinical practice are a combination of clinical manifestations and X-ray examination while computed tomography (CT) and ultrasound may be applied alternatively for particular parts and populations. As understanding of bone healing process and bone biomechanical structure is deepening in recent years, both traditional and novel assessments of bone healing have been well refined. This review will expound on the advantages, disadvantages and clinical indications of various assessments, as well as their future development trends, to provide useful information for clinicians.

Reconstuctive strategy of the defect of anterior rectus fascia and rectus abdominus muscle / 中华医学美学美容杂志

Objective:To discuss the reconstuctive strategy of the defect of anterior rectus fascia and rectus abdominus muscle in the clinical practice.Methods:Between November 2009 and Janurary 2020, clinical data of 24 female patients that underwent 29 anterior rectus fascia and rectus abdominus muscle reconstructions of defect were reviewed retrospectively. The median age was 42.5 years (range, 35-60 years), including 20 breast reconstructions, 2 pelvic reconstructions, 1 thoracic defect after tumor resection and 1 abdominal defect after tumor resection. According to the location and size of the anterior rectus fascia and rectus abdominus muscle defect, three reconstructive methods were applied: 6 direct clousres were applied if the width of defect was less than half of the anterior rectus fascia, 21 polypropylene mesh onlay reconstructions were applied for which the width of defect was or more than half of the anterior rectus fascia, and 2 direct suture closure were applied for the simple rectus abdominus muscle defect.Results:All the patients healed eventfully without abdominal wound complications, such as infection, hematoma, dehiscence. The patients were followed up for a median period of 30 months (range, 5-126 months). 1 patient died of breast cancer recurrence and matastasis at 36 months postoperatively. No patient developed a mesh infection or required mesh removal secondary to infection or foreign body reaction. There was no abdominal wall hernia, 1 patient developed abdominal bulge without further treatment because of no abdominal wall discomfort.Conclusions:The key of successful operation is different reconstructive methods applied to reconstruct the integrity and stability of abdominal wall, based on the location and size of the anterior rectus fascia and rectus abdominus muscle defect.

Quantitative study of cardiac MR T 1 mapping/iECV in patients with aortic insufficiency / 中华放射学杂志

Objective:To explore the clinical value of T 1 mapping/indexed extracellular volume fraction (iECV) quantified with cardiac MR (CMR) parameters, and its correlation with traditional indicators of myocardial dysfunction in aortic insufficiency (AI) patients. Methods:A total of 36 patients clinically and radiologically diagnosed with chronic AI in our hospital between May 2012 and February 2016 were retrospectively selected. All AI patients underwent conventional CMR protocol, native and post T 1 mapping. CMR parameters, such as aortic regurgitant fraction (RF), late gadolinium enhancement (LGE) mass fraction, myocardial extracellular volume fraction (ECV) and iECV. Based on the values of aortic RF, AI patients were divided into mild AI group (9 cases), moderate AI group (14 cases) and severe AI group (13 cases). The clinical characteristics were teased from the patients′ electronic medical records. Univariate analysis of variance was used to compare the measurement data of native T 1 mapping, post-contrast T 1 mapping, ECV, and iECV. LSD test was used for pair wise comparison between the mild AI, moderate AI and severe AI groups. Data about cardiovascular history, New York Heart Association (NYHA) heart function classification, and LGE were compared by chi-square test or Fisher exact test. The correlation between left ventricle ejection fraction (LVEF) and iECV was evaluated by Spearman correlation analysis. Results:There was no difference in age, sex, cardiovascular history among the three groups. Comparison of patients with different severity of AI in the three groups: (1) There was statistically significant difference in the LGE positive rate among the three groups ( P=0.023), while the myocardial replacement of fibrosis increased with the grade of aortic regurgitation. (2) There was no statistically significant difference in the measurement data of native T 1 mapping, post-contrast T 1 mapping, ECV among the three groups ( H=1.815, 0.929, 2.496, all P values>0.05), while the diffuse myocardial fibrosis tended to increase with the degree of aortic regurgitation. There was statistically significant difference in iECV among the three groups ( H=16.725, P<0.001). The measurement data of iECV in the severe AI group was significantly higher than those in the other two groups ( P<0.05). LVEF value was inversely correlated with iECV ( r=-0.649, P<0.001). Conclusions:Quantitative T 1 mapping/iECV can serve as a parameter to noninvasively identify diffuse myocardial fibrosis in AI patients of different severities. It changes with LVEF and can manifest the reversible stage of left ventricular decompensation.

Antimicrobial activity and mode of action of terpene linalyl anthranilate against carbapenemase-producing Klebsiella pneumoniae / 药物分析学报

Mining of plant-derived antimicrobials is the major focus at current to counter antibiotic resistance.This study was conducted to characterize the antimicrobial activity and mode of action of linalyl anthranilate(LNA)against carbapenemase-producing Klebsiella pneumoniae(KPC-KP).LNA alone exhibited bacteri-cidal activity at 2.5％(V/V),and in combination with meropenem(MPM)at 1.25％(V/V).Comparative proteomic analysis showed a significant reduction in the number of cytoplasmic and membrane proteins,indicating membrane damage in LNA-treated KPC-KP cells.Up-regulation of oxidative stress regulator proteins and down-regulation of oxidative stress-sensitive proteins indicated oxidative stress.Zeta po-tential measurement and outer membrane permeability assay revealed that LNA increases both bacterial surface charge and membrane permeability.Ethidium bromide influx/efflux assay showed increased uptake of ethidium bromide in LNA-treated cells,inferring membrane damage.Furthermore,intracel-lular leakage of nucleic acid and proteins was detected upon LNA treatment.Scanning and transmission electron microscopies again revealed the breakage of bacterial membrane and loss of intracellular ma-terials.LNA was found to induce oxidative stress by generating reactive oxygen species(ROS)that initiate lipid peroxidation and damage the bacterial membrane.In conclusion,LNA generates ROS,initiates lipid peroxidation,and damages the bacterial membrane,resulting in intracellular leakage and eventually killing the KPC-KP cells.

Impact of aesthetic suture techniques training in improving the suture quality of non-plastic surgeons / 中华医学美学美容杂志

Objective:To investigate the effect and necessity of aesthetic suture techniques training in improving the suture quality of non-plastic surgeons.Methods:The well-planned aesthetic suture techniques training programs were run in non-plastic surgery senior residents and attending surgeons at Peking University People＇s Hospital from January 2017 to January 2019. There were 120 senior residents and attending surgeons included (aged from 25-32 years, average 28.9 years, with 66 males and 54 females). Mixed teaching methods were used such as video shows, lectures, surgery live show and scenario simulation. Baseline tests were taken before the training. Suture quality tests were taken when the trainings came to the end. Self-assessments were carried out both before and after the trainings.Results:Eight rounds of aesthetic suture techniques training were accomplished and 120 trainees were included in all. One hundred and two trainees passed the test while eight failed, while 10 trainees were absent in some courses or the final test. The passing rate was 85.0%. The scales of suture tools and material selection, incision design, subcutaneous tissue suture quality, tension relaxation, aesthetic suture appearance, and flexibility of different suture techniques were sharply improved after the training in both subjective and objective assessments.Conclusions:The aesthetic suture techniques training is effective in improving the suture quality of non-plastic surgeons, which is worthy to generalize in resident training.