[Research progress on the pathogenic mechanisms, diagnosis and treatment of McCune-Albright syndrome].

McCune-Albright syndrome is a rare chimeric disorder due to mutations in the postzygotic GNAS gene. It belongs to the group of guanine nucleotide-binding protein diseases, affecting a wide range of individuals. It is characterized by fibrous dysplasia, café-au-lait skin macules, and precocious puberty with other variable clinical manifestations. At present, there are difficulties in the molecular diagnosis of McCune-Albright syndrome, and there is a lack of effective clinical treatments to halt or reverse the course and regression of the disease. This article summarizes the clinical manifestations, diagnosis, pathogenic molecular mechanisms, treatment and relevant fertility guidelines of McCune-Albright syndrome, with a view to further research and therapy of McCune-Albright syndrome.

[A preliminary study on the efficacy and safety of a new type of trabeculotome tunnelling trabeculoplasty for open-angle glaucoma].

Objective: To compare the efficacy and safety of trabeculotome tunnelling trabeculoplasty and gonioscopy-assisted transluminal trabeculotomy (GATT) in the treatment of open-angle glaucoma. Methods: A prospective randomized controlled study. The patients with open-angle glaucoma diagnosed in the ophthalmology center of Beijing Tongren Hospital affiliated to Capital Medical University from January to July 2022 were collected and divided into GATT group (undergoing GATT) and 3T group (undergoing 3T operation) using a random number table. Intraocular pressure (IOP) was recorded for both groups at 1 day, 1 week, 1 month, and 3 months after the operation, and the types and quantities of anti-glaucoma drugs used, postoperative complications, and surgical success rate were compared. Normal distribution measurement data were analyzed using independent sample t-tests, non-normal distribution measurement data were analyzed using non-parametric tests, and counting data were analyzed using chi-square tests. Results: This study included 35 patients (43 eyes), consisting of 27 males and 8 females, with an average age of (43.0±14.3) years. There were 21 patients (23 eyes) in the GATT group and 19 patients (20 eyes) in the 3T group. The maximum IOP without anti-glaucoma drugs before surgery, the highest IOP with the maximum number of anti-glaucoma drugs, and the IOP at 3 months after surgery in the GATT group were (33.5±9.1), (22.2±6.1), and (16.0±3.1) mmHg (1 mmHg=0.133 kPa), respectively. The corresponding values for the 3T group were (35.2±7.8), (21.5±6.8), and (16.1±2.0) mmHg. After surgery, the IOP in both groups was lower than before surgery, with a statistically significant difference (P<0.05) and no significant difference between the two groups (P>0.05). In the 3 months following surgery, 13 eyes in the GATT group and 11 eyes in the 3T group received more than two types of anti-glaucoma drugs, with no significant difference between the two groups (P>0.05). Three months after surgery, the complete and conditional success rates of the GATT group were 14/18 and 16/18, respectively, and those of the 3T group were 12/15 and 13/15, respectively, with no significant difference between the two groups (P>0.05). The incidence of hyphema, ciliary detachment, and shallow anterior chamber 1 day after surgery was 91%(21/23), 35%(8/23), and 30%(7/23), respectively, in the GATT group and 55%(11/20), 5%(1/20), and 0 in the 3T group, with a statistically significant difference between the two groups (P<0.05). Conclusion: 3T and GATT have similar success rates in the treatment of open-angle glaucoma. However, compared with GATT, 3T has fewer complications and is considered to be safer. (This article was published ahead of print on the Online-First Publishing Platform for Excellent Scientific Researches of Chinese Medical Association Publishing House on February 28, 2023).

Simple and rapid detection Aspergillus fumigatus by loop-mediated isothermal amplification coupled with lateral flow biosensor assay.

AIMS: We have developed a new diagnostic technique, termed loop-mediated isothermal amplification coupled with lateral flow biosensor (LAMP-LFB), which has been successfully applied to the detection of Aspergillus fumigatus. MATERIAL AND METHODS: A set of six LAMP primers was designed according to the A. fumigatus-specific anxC4 gene, which specifically recognized eight different regions of the target sequence. The LFB was employed for reporting the A. fumigatus-LAMP results, and the visual readouts were obtained within 2 min. The strains of A. fumigatus species and non-A. fumigatus species were used to test the assay's sensitivity and examine the analytical specificity of the target assay. Optimal LAMP conditions were 66°C for 50 min. The limit of detection is 100 fg. No cross-reactions were obtained, and the specificity of LAMP-LFB assay was 100%. The whole process of the assay, including 20 min of DNA preparation, 50 min of constant temperature amplification, and 2 min of detection by the sensor strip, took a total of 72 min (less than 75 min). Among 89 sputum specimens for clinical evaluation, 10 (11·23%) samples were A. fumigatus-positive by LAMP-LFB and traditional culture method, 9 (10·11%) samples were A. fumigatus-positive by PCR method. Compared with culture method, the diagnostic accuracy of LAMP-LFB method was 100%. CONCLUSIONS: The novel LAMP-LFB detection technology established in the current research is a rapid and reliable detection tool for A. fumigatus. SIGNIFICANCE AND IMPACT OF THE STUDY: This novel LAMP-LFB assay can quickly, specifically and sensitively detect A. fumigatus, thereby speeding up the detection process and increasing the detection rate. In addition, it can also be used as a new molecular method for detection of A. fumigatus in clinical and laboratory areas.

[Epidural block associated with improved long-term survival after surgery for colorectal cancer: A retrospective cohort study with propensity score matching].

OBJECTIVE: To investigate the effect of epidural anesthesia on the long-term prognosis of patients after selective colorectal cancer resection surgery. METHODS: This was a retrospective cohort study and approved by local institution review board. Patients who underwent selective colorectal cancer resection surgery from August 2011 to December 2012 in Peking University First Hospital were enrolled. The patients were divided into general anesthesia (GA) group and combined epidural-general anesthesia (EGA) group according to anesthesia type. Primary outcome was patient's long-term survival status. Secondary outcome included the overall incidence of in-hospital complications and length of postoperative in-hospital stay. Propensity score was used to match cases between the two groups based on the probability of receiving EGA. Survival was analyzed by Kaplan-Meier analysis and compared by Log-rank test between the two groups. Multivariate Cox regression analysis was used to investigate the relationship between epidural anesthesia and other variables with long-term survival status. RESULTS: A total of 264 patients were entered into final analysis, including 166 cases in GA group and 98 cases in EGA group. Mean age of the patients was (63.3±12.1) years and mean survival time was 47.2 (95%CI 45.7-48.7) months. Before the propensity score match, the mortality in EGA group was 16.9% (28/166) and 9.2% (9/98) in GA group. But comparison between the two groups had no statistical significance (P=0.091). After the propensity score match, 87 paired cases were matched and analyzed. The risk of long-term mortality in EGA group was lower than that of GA group by Kaplan-Meier analysis (5.7% vs.16.1%, HR=0.344, 95%CI 0.124-0.955, P=0.041). Mean survival time of EGA group was longer than that of GA group (50.3 months vs. 42.9 months, P=0.032). Multivariate Cox regression ana-lysis showed that EGA, in comparison with GA, was related with lower risk of long-term mortality (HR=0.326, 95%CI 0.117-0.909, P=0.032). Age (HR=1.042, 95%CI 1.001-1.085, P=0.046) and preoperative lymph node metastasis (HR=2.924, 95%CI 1.162-7.356, P=0.023) were also related with increased risk of long-term mortality. CONCLUSION: Present study found that perioperative use of epidural anesthesia and analgesia was associated with improvement of the patient's long-term survival. Well-designed studies are needed to verify this hypothesis.

Randomized clinical trial of intraoperative dexmedetomidine to prevent delirium in the elderly undergoing major non-cardiac surgery.

BACKGROUND: Delirium is common in elderly patients after surgery and is associated with poor outcomes. This study aimed to investigate the impact of intraoperative dexmedetomidine on the incidence of delirium in elderly patients undergoing major surgery. METHODS: This was a randomized double-blind placebo-controlled trial. Elderly patients (aged 60 years or more) scheduled to undergo major non-cardiac surgery were randomized into two groups. Patients in the intervention group received a loading dose of dexmedetomidine 0·6 µg/kg 10 min before induction of anaesthesia followed by a continuous infusion (0·5 µg per kg per h) until 1 h before the end of surgery. Patients in the control group received volume-matched normal saline in the same schedule. The primary outcome was the incidence of delirium during the first 5 days after surgery. Delirium was assessed with the Confusion Assessment Method (CAM) for non-ventilated patients and CAM for the Intensive Care Unit for ventilated patients. RESULTS: In total, 309 patients who received dexmedetomidine and 310 control patients were included in the intention-to-treat analysis. The incidence of delirium within 5 days of surgery was lower with dexmedetomidine treatment: 5·5 per cent (17 of 309) versus 10·3 per cent (32 of 310) in the control group (relative risk (RR) 0·53, 95 per cent c.i. 0·30 to 0·94; P = 0·026). The overall incidence of complications at 30 days was also lower after dexmedetomidine (19·4 per cent (60 of 309) versus 26·1 per cent (81 of 310) for controls; RR 0·74, 0·55 to 0·99, P = 0·047). CONCLUSION: Intraoperative dexmedetomidine halved the risk of delirium in the elderly after major non-cardiac surgery. Registration number: ChiCTR-IPR-15007654 ( www.chictr.org.cn).

ANTECEDENTES: El delirio después de la cirugía es frecuente en los pacientes de edad avanzada y se asocia con malos resultados. El objetivo de este estudio fue investigar el impacto de la administración intraoperatoria de dexmedetomidina en la incidencia de delirio en pacientes mayores sometidos a operaciones de cirugía mayor. MÉTODOS: Se trataba de un ensayo aleatorizado, doble ciego y controlado con placebo. Un total de 620 pacientes mayores (60 años o más) fueron programados para ser sometidos a intervenciones (no cardiacas) de cirugía mayor y se aleatorizaron a dos grupos. Los pacientes en el grupo de intervención recibieron una dosis de carga de dexmedetomidina (0,6 µg/kg, 10 minutos antes de la inducción anestésica) seguida de una infusión continua (0,5 µg/kg/h) hasta 1 h antes de la finalización de la cirugía. Los pacientes del grupo control recibieron el mismo volumen de suero salino siguiendo la misma pauta. El resultado principal era la incidencia de delirio durante los primeros 5 días postoperatorios. Para la valoración del delirio se utilizó el método para la evaluación de la confusión (Confusion Assessment Method, CAM) en pacientes no intubados y el CAM-UCI para los pacientes intubados. RESULTADOS: En total, 309 pacientes que recibieron dexmedetomidina y 310 del grupo control se incluyeron en el análisis por intención de tratar. La incidencia de delirio durante los primeros 5 días tras la cirugía fue inferior en presencia de tratamiento con dexmedetomidina que en ausencia del mismo: 5,5% (17/309) versus 10,3% (32/310); riesgo relativo (RR) 0,53, i.c. del 95% 0,30-0,94, P = 0,026. La incidencia global de complicaciones a los 30 días excluyendo el delirio también fue inferior en presencia que en ausencia de tratamiento con dexmedetomidina (19,4% (60/309) versus 26,1% (81/301), RR 0,74, i.c. del 95% 0,55-0,99, P = 0,047). CONCLUSIÓN: La administración intraoperatoria de dexmedetomidina reduce la presencia de delirio en los pacientes mayores tras cirugía mayor no cardiaca.

Profiling the effects of physicochemical indexes on the microbial diversity and its aroma substances in pit mud.

Microbial diversity of pit mud (PM) plays a significant role in Baijiu's flavour. Here we explored the microbial community structures and aroma substances of Wenwang Winery with high-throughput sequencing coupling with headspace solid-phase microextraction-gas chromatography-mass spectrometry. We discovered that the odorant was mainly derived from 14 aroma compounds because of their OAVs ≥ 1 (OAV, the ratio of substance concentration to aroma threshold; s, on behalf of the plural), such as ethyl hexanoate (2438), ethyl octanoate (975), caproic acid (52) and etc. Moreover we also revealed that Lactobacillaceae (97·08%) was the mainly bacterial microbial community in 2-year-old PM, companied by the primarily fungi including Aspergillaceae (55·45%), Unclassified Ascomycota (11·13%) and Dipodascaceae (5·72%). Compared with the 2-year-old PM, bacterial floras in 20-year-old PM and 30-year-old PM were more abundant (i.e. Dysgonomonadaceae, Clostridium and Synerggstaceas), while no fungi were detected. Besides, the physicochemical analysis showed that the content of Lactobacillaceae was inversely associated with moisture, pH and ammonia nitrogen. By further Spearman's correlation coefficient analysis, we verified that the content of Lactobacillaceae was positively correlated with ethyl hexanoate, while negatively correlated with ethyl octanoate and caproic acid. Meanwhile, ethyl octanoate and caproic acid were positively correlated with most flora including Ruminococcaceae, Dysgonomonadaceae and Clostridiacea, which were related to physicochemical indexes. This work demonstrates promise for adjusting the physicochemical indexes of PM to affect the micro-organisms and aroma, which may provide a reference for the production of high-quality Baijiu.

[Impact of oliguria during lung surgery on postoperative acute kidney injury].

OBJECTIVE: To explore the influence of intraoperative urine volume on postoperative acute kidney injury (AKI) and the independent risk factors of AKI. METHODS: This was a retrospective cohort study recruiting patients who received selective pulmonary resection under general anesthesia in Peking University First Hospital from July, 2017 to June, 2019. The patients were divided into the AKI group and the control group according to whether they developed postoperative AKI or not. Firstly, univariate analysis was used to analyze the relationship between perioperative variables and postoperative AKI. Secondly, receiver operating characteristic (ROC) curve was used to explore the predictive value of intraoperative urine output for postoperative AKI. The nearest four cutoff values [with the interval of 0.1 mL/(kg·h)] at maximum Youden index were used as cutoff values of oliguria. Then univariate analysis was used to explore the relationship between oliguria defined by these four cutoff values and the risk of AKI. And the cutoff value with maximum OR was chosen as the threshold of oliguria in this study. Lastly, the variables with P < 0.10 in the univariate analysis were selected for inclusion in a multivariate Logistic model to analyze the independent predictors of postoperative AKI. RESULTS: A total of 1 393 patients were enrolled in the study. The incidence of postoperative AKI was 2.2%. ROC curve analysis showed that the area under curve (AUC) of intraoperative urine volume used for predicting postoperative AKI was 0.636 (P=0.009), and the cutoff value of oliguria was 0.785 mL/(kg·h) when Youden index was maximum (Youden index =0.234, sensitivity =48.4%, specificity =75.0%). Furthermore, 0.7, 0.8, 0.9, 1.0 mL/(kg·h) and the traditional cutoff value of 0.5 mL/(kg·h) were used to analyze the influence of oliguria on postoperative AKI. Univariate analysis showed that, when 0.8 mL/(kg·h) was selected as the threshold of oliguria, the patients with oliguria had the most significantly increased risk of AKI (AKI group 48.4% vs. control group 25.3%, OR=2.774, 95%CI 1.357－5.671, P=0.004). Multivariate regression analysis showed that intraoperative urine output < 0.8 mL/(kg·h) was one of the independent risk factors of postoperative AKI (OR=2.698, 95%CI 1.260－5.778, P=0.011). The other two were preoperative hemoglobin ≤120.0 g/L (OR=3.605, 95%CI 1.545－8.412, P=0.003) and preoperative estimated glomerular filtration rate < 30 mL/(min·1.73 m2) (OR=11.009, 95%CI 1.813－66.843, P=0.009). CONCLUSION: Oliguria is an independent risk fact or of postoperative AKI after pulmonary resection, and urine volume < 0.8 mL/(kg·h) is a possible screening criterium.

[The correlation between tissue oxygen saturation and postoperative cognitive dysfunction in elderly patients with one lung ventilation].

Objective: To investigate the correlation between tissue oxygen saturation during one lung ventilation and postoperative neuro cognitive dysfunction (PND) in elderly patients in thoracic surgery. Methods: One hundred and twenty-eight elderly patients who underwent selective lobectomy from August 2017 to September 2018 in the Forth Hospital of Hebei Medical University were enrolled. The patients were divided into PND group (n=34) and non-PND group (n=94) according to whether PND occurred 3 days after surgery. Tissue oxygenation was monitored at bilateral forebrain, brachioradialis muscle and quadriceps. Cognitive function was assessed by the Montreal Cognitive Assessment (MoCA) at baseline and the third day after the operation. Postoperative cognitive dysfunction was diagnosed if postoperative MoCA decreased at least 2 scores compared with preoperative baseline value. Outcomes included the incidence of PND, the incidence of tissue oxygen desaturation during one lung ventilation, postoperative complications within 30 days and length of postoperative in-hospital stay. Logistic regression was used to screen independent risk factors of PND. Results: The incidence of postoperative cognitive dysfunction was 26.6% (34/128). The two groups had no significant difference in the incidence of non-neurogenic complications (new occurred arrhythmia, pulmonary infection, pulmonary embolism, acute renal insufficiency, sepsis, deep vein thrombosis, all P>0.05). However, the length of postoperative in-hospital stay of PND group was 7.0 (6.0, 8.5) d, which was longer than that of non-PND group [6.0 (5.0, 8.0) d]. There was significant difference (U=2.394, P=0.017) . There was no correlation between the two groups within the minimum of SmtO(2) in upper limbs (OR=0.988, 95%CI: 0.954-1.024, P=0.519) and the range of desaturation (OR=1.010, 95%CI: 0.979-1.042, P=0.514) , as well as the minimum of SmtO(2) in legs (OR=0.996, 95%CI: 0.961-1.032, P=0.832) and the range of desaturation (OR=0.997, 95%CI: 0.971-1.025, P=0.851) . Multivariate logistic regression analysis showed that the high ASA grade (OR=2.617, 95%CI: 1.112-6.157, P=0.029) and the minimum of cerebral oxygen saturation during one lung ventilation (OR=0.931, 95%CI: 0.880-0.986, P=0.014) were independent risk factors of PND. There was no statistical correlation between muscle oxygen saturation and PND. Conclusion: Cerebral desaturation during one lung ventilation increased the risk of PND in elderly patients, while the muscle desaturation has no statistical correlation with PND.

[Predictive value of umbilical arterial cord pH on complications during hospitalization in neonates after cesarean section].

OBJECTIVE: To analyze the predictive value of umbilical arterial cord pH on complications of hospitalized neonates after cesarean section. METHODS: This was a retrospective cohort study and carried out in Peking University First Hospital from January 1, 2017 to June 30, 2017. Neonates who were delivered by cesarean section were enrolled. The primary endpoint was the incidence of complications during in-hospital stay (including infection, aspiration pneumonia, myocardial damage, etc.). The subjects were divided into two groups:with or without complication. The umbilical arterial cord pH values were compared between the two groups. Perinatal baseline characteristics of maternal and neonatal data were recorded. The ROC curve was used to analyze the value of umbilical arterial cord pH in predicting neonatal complications during hospitalization. Multivariate Logistic regression was employed to analyze the potential risk factors of neonatal complications. RESULTS: In the study, 872 neonates were included in the final analysis (541 in elective surgery and 331 in emergency surgery). The overall incidence of neonatal complications during hospitalization was 14.1%. The first three higher incidences were infection, aspiration pneumonia and myocardial damage. The average pH value in neonates without complication was 7.31 while 7.29 in neonates with complication. There was statistical significance between the two groups (P<0.001). The overall incidence of pH≤7.20 was 3.1% (27/872). The patients in neonates without complication had higher incidence of pH≤7.20 than those in neonates with complication (1.6% vs. 12.2%, P<0.001). Multivariate Logistic regression showed 6 risk factors of neonatal hospitalized complications including preterm delivery (OR=8.224, 95%CI: 4.910-13.777, P<0.001), pregnancy-induced hypertension (OR=1.886, 95%CI: 1.004-3.546, P=0.049), intrauterine growth restriction (OR=4.429, 95%CI: 1.280-15.330, P=0.019), emergency cesarean section (OR=2.711, 95%CI: 1.682-4.369, P<0.001), umbilical arterial blood gas pH≤7.20 (OR=7.420, 95%CI: 2.951-18.655, P<0.001) and 5-minute Apgar score <10 scores (OR=11.849, 95%CI: 3.977-35.128, P<0.001). The areas under the ROC curve of umbilical arterial blood gas pH in all neonatal, elective and emergency cesarean section were 0.570 (95%CI: 0.508-0.633, P=0.012), 0.559 (95%CI: 0.465-0.652, P=0.189) and 0.617 (95%CI: 0.538-0.697, P=0.002), respectively. CONCLUSION: Umbilical arterial cord pH≤7.20 was related with increased incidence of neonatal complications after cesarean section,but ROC curve analysis showed a lower predictive value.

Maternal infection during pregnancy and type 1 diabetes mellitus in offspring: a systematic review and meta-analysis.

Previous studies have demonstrated that type 1 diabetes mellitus (T1DM) could be triggered by an early childhood infection. Whether maternal infection during pregnancy is associated with T1DM in offspring is unknown. Therefore, we aimed to study the association using a systematic review and meta-analysis. Eighteen studies including 4304 cases and 25 846 participants were enrolled in this meta-analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were synthesised using random-effects models. Subgroup analyses and sensitivity analyses were conducted to assess the robustness of associations. Overall, the pooled analysis yielded a statistically significant association between maternal infection during pregnancy and childhood T1DM (OR 1.31, 95% CI 1.07-1.62). Furthermore, six studies that tested maternal enterovirus infection showed a pooled OR of 1.54 (95% CI 1.05-2.27). Heterogeneity from different studies was evident (I2 = 70.1%, P < 0.001) and was mainly attributable to the different study designs, ascertaining methods and sample size among different studies. This study provides evidence for an association between maternal infection during pregnancy and childhood T1DM.

[Prevalance of peri-anesthesia allergy and its related risk factor: a retrospective survey from 2012-2017].

OBJECTIVE: To investigate the incidence of peri-anesthesia allergy in a tertiary teaching hospital. METHODS: This was a retrospective cohort study. Patients who received anesthesia in operation rooms at Peking University First Hospital from January 2012 to April 2017 were enrolled. Researchers reviewed all the patients' electronic records and screened suspect allergy cases. Allergy was diagnosed according to the definition in Consensus on Management of Perioperative Allergy (China) and Scandinavian Clinical Practice Guidelines on the Diagnosis, Management and Follow-up of Anaphylaxis during Anesthesia. After obtaining the electronic records, two researchers began to screen and supplement missing data according medical records independently, then they checked out each other's data. The final data were reviewed by another two researchers. We collected the patients' basic characteristics, surgery type, anesthesia type, peri-anesthesia use of drugs, prognosis and other data. Univariate logistic regression was employed to screen potential factors of allergy. Factors with statistical significance (P<0.05) in univariate Logistic regression were entered into multivariate Logistic regression to identify independent risk factors of allergy. RESULTS: In the study, 106 074 patients entered final statistic analysis. The incidence of peri-anesthesia allergy was about 1.5/1 000 (156/106 074). The incidence of Grades I, II and III allergy was 64.1% (100/156), 30.1% (47/156), and 5.8% (9/156) respectively. Multivariate logistic regression showed 5 independent risk factors of allergy including history of allergy (OR=6.836, 95%CI: 4.461-10.474, P<0.001), intraoperative use of sufentanil (OR=1.993, 95%CI: 1.228-3.232, P=0.005), intraoperative use of cis-atracuronium (OR=2.495, 95%CI: 1.599-3.893, P<0.001), intraoperative infusion of antibiotics (OR=2.005, 95%CI: 1.375-2.924, P<0.001) and frozen fresh plasma (OR=3.055, 95%CI: 1.842-5.068, P<0.001). CONCLUSION: The incidence of peri-anesthesia allergy is high and further attempt is needed to establish standard operation process of diagnosis and treatment of allergy.

[Dexmedetomidine combined with ropivacaine for continuous femoral nerve block improved postoperative sleep quality in elderly patients after total knee arthroplasty].

Objective: To investigate the effect of dexmedetomidine adding to ropivacaine for continuous femoral nerve block on the improvement of postoperative sleep quality in elderly patients after total knee arthroplasty. Methods: One hundred and sixty patients aged 60 years or older in Jishuitan Hospital scheduled for single total knee arthroplasty between Nov. 2016 and Jun. 2017 were recruited. All patients received spinal anesthesia and were randomized to receive either combined ropivacaine and dexmedetomidine (0.2% ropivacaine 250 ml and 5 µg/kg dexmedetomidine, at a rate of 5 ml/h or 0.1 µg·kg-1·h-1 dexmedetomidine, dexmedetomidine group) or only ropivacaine (0.2% ropivacaine, at a rate of 5 ml/h, controlled group) for continuous femoral nerve block as postoperative analgesia after surgery. The severity of postoperative pain was assessed with numeric rating scale at 4, 24, and 48 hours after surgery both at rest and with movement. Subjective sleep quality and delirium were evaluated daily during the first 3 days postoperatively. Results: The subjective sleep quality scores were 2(1-4), 2(1-4) and 4(2-8), 4(2-7) in dexmedetomidine group and controlled group respectively on the 1st and 2nd days after surgery. The scores of dexmedetomidine group were much better than those of controlled group (Z=-4.597, -4.183, both P<0.05). The difference was statistically significant. The NRS pain scores at rest were 2(1-2), 2(1-4), and 3(2-5), 3(2-6) in dexmedetomidine group and controlled group respectively at 24 and 48 hours after surgery. The scores of dexmedetomidine group were lower than those of controlled group (Z=-6.671, -4.010, both P<0.05). The difference was statistically significant. The NRS pain scores with movement were 1(1-2), 3(2-4), 3(2-3) and 3(2-4), 5(3-6), 5(4-7)in dexmedetomidine group and controlled group respectively at 4, 24 and 48 hours after surgery. The scores of dexmedetomidine group were lower than those of controlled group (Z=-7.167, -6.824, -7.473, all P<0.05). The difference was statistically significant. The incidence of 3-day delirium was lower in dexmedetomidine group (5%) than that in controlled group (15%) (χ2=4.444, P<0.05). The difference was statistically significant. There were no significant differences between groups regarding the incidences of adverse events. Conclusion: Dexmedetomidine combined with ropivacaine for continuous femoral nerve block may improve subjective sleep quality, postoperative analgesia, and reduce delirium in the elderly after total knee arthroplasty.

Exosome-associated AAV vector as a robust and convenient neuroscience tool.

Adeno-associated virus (AAV) vectors are showing promise in gene therapy trials and have proven to be extremely efficient biological tools in basic neuroscience research. One major limitation to their widespread use in the neuroscience laboratory is the cost, labor, skill and time-intense purification process of AAV. We have recently shown that AAV can associate with exosomes (exo-AAV) when the vector is isolated from conditioned media of producer cells, and the exo-AAV is more resistant to neutralizing anti-AAV antibodies compared with standard AAV. Here, we demonstrate that simple pelleting of exo-AAV from media via ultracentrifugation results in high-titer vector preparations capable of efficient transduction of central nervous system (CNS) cells after systemic injection in mice. We observed that exo-AAV is more efficient at gene delivery to the brain at low vector doses relative to conventional AAV, even when derived from a serotype that does not normally efficiently cross the blood-brain barrier. Similar cell types were transduced by exo-AAV and conventionally purified vector. Importantly, no cellular toxicity was noted in exo-AAV-transduced cells. We demonstrated the utility and robustness of exo-AAV-mediated gene delivery by detecting direct GFP fluorescence after systemic injection, allowing three-dimensional reconstruction of transduced Purkinje cells in the cerebellum using ex vivo serial two-photon tomography. The ease of isolation combined with the high efficiency of transgene expression in the CNS, may enable the widespread use of exo-AAV as a neuroscience research tool. Furthermore, the ability of exo-AAV to evade neutralizing antibodies while still transducing CNS after peripheral delivery is clinically relevant.

[Shrinkage mode of the primary breast tumor after neoadjuvant chemotherapy analyzed with part-mount sub-serial sectioning and three-dimensional reconstruction technique].

OBJECTIVE: The aim of this study is to evaluate the shrinkage mode of the primary tumor in women with breast cancer after neoadjuvant chemotherapy (NAC) determined by part-mount sub-serial section (PMSS) and three-dimensional (3D) reconstruction technique. METHODS: Eighty-six women with pathologically proven solitary invasive ductal carcinoma (ⅡA-ⅢC) were recruited. They were divided into two groups. Group A (n=25) received half cycles of NAC and Group B (n=61) received whole cycles of NAC. Breast specimen was prepared with PMSS, and residual tumors were microscopically outlined, scanned and registered by Photoshop software. The 3D model of residual tumors was reconstructed with 3D-Doctor software to evaluate the shrinkage mode. Further, the clinicpathologic shrinkage modes were divided into 2 categories: concentric shrinkage mode (CSM, the longest diameter of the pathological residual tumors was less than 50% and ≤2 cm in comparison with the primary tumor before NAC), and non-concentric shrinkage mode (NCSM, the longest diameter of the pathological residual tumors was more than 50% and/or >2 cm in comparison with the primary tumor before NAC). RESULTS: Pathological shrinkage modes: Group A: modes Ⅰ, Ⅱ, and Ⅴ were observed in 1, 1, and 23 cases, respectively; Group B: modesⅠ, Ⅱ, Ⅲ, Ⅳ, and Ⅴwere observed in 18, 3, 12, 21, and 7 cases, respectively (P<0.001). The multivariate analysis showed that patients with lower primary tumor stage, PR(-) or mammographic malignant calcification before NAC(-) and lymph nodes down-staging after NAC were more likely to present with CSM after NAC (P<0.05 for all). CONCLUSIONS: The pathologic reconstruction of breast residual tumors can fully and three-dimensionally reveal the shrinkage mode of the primary breast tumor in women with breast cancer after NAC. PMSS and 3D reconstruction of pathology provide a new platform in this area. Primary tumor stage, PR expression and mammographic malignant calcification before NAC and lymph node down-staging after NAC are independent predictors of the clinicopathologic shrinkage mode.

Neurodevelopmental delay with critical congenital heart disease is mainly from prenatal injury not infant cardiac surgery: current evidence based on a meta-analysis of functional magnetic resonance imaging.

OBJECTIVE: No consensus has been reached regarding whether brain injury related to congenital heart disease (CHD) is caused by infant cardiac surgery and/or prenatal injury resulting from the CHD. We performed this meta-analysis to identify the likely cause of neurodevelopmental delay in CHD patients. METHODS: We carried out a literature search without language restriction in December 2013, retrieving records from PubMed, EMBASE, the Cochrane Library and the World Health Organization trials center, to identify studies applying functional magnetic resonance imaging (fMRI) evaluation of brain function before surgery and, in some cases, after surgery (both immediate term and short term postoperatively). The preoperative and postoperative fMRI results were extracted, and meta-analysis was performed using Revman 5.1.1 and STATA 11.0, according to the guidelines from the Cochrane review and MOOSE groups. RESULTS: The electronic search yielded 937 citations. Full text was retrieved for 15 articles and eight articles (nine studies) were eligible for inclusion: six studies (n = 312 cases) with fMRI analysis before surgery and three (n = 36 cases) with complete perioperative fMRI analysis. The overall average diffusivity of CHD cases was significantly higher than that of controls, with a summarized standard (std) mean difference of 1.39 (95% CI, 0.70-2.08), and the fractional anisotropy was lower in CHD cases, with a summarized mean difference of -1.43 (95% CI, -1.95 to -0.91). N-acetylaspartate (NAA)/choline (Cho) for the whole brain was significantly lower in CHD cases compared with healthy ones, while lactate/Cho was significantly higher in CHD cases. Immediate term postoperatively, significant changes in NAA/creatine and NAA/Cho, relative to preoperative values, were found. However, the difference did not persist at the short-term follow-up. CONCLUSION: This meta-analysis suggests that the delay in neurological development in newborns with CHD is due mainly to prenatal injury, and cardiac surgery might lead to mild brain injuries postoperatively, but fMRI shows recovery within a short period.

Correlation between p53 and epidermal growth factor receptor expression in breast cancer classification.

This study aimed to explore new opportunities for developing targeted therapy for triple-negative breast cancer (TNBC) by analyzing the significance and association between p53 and epidermal growth factor receptor (EGFR) expression in different molecular subtypes of breast cancer. The clinical and pathological data of 264 patients with breast cancer receiving surgery in our hospital from January 2012 to August 2013 were retrospectively analyzed. According to the expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), Ki-67, CK5/6, p53, and EGFR detected by immunohistochemical methods, breast cancer was divided into four molecular subtypes. Then, the expression of p53 and EGFR as well as their correlation in the different subtypes were determined. Among the four subtypes, luminal B breast cancer was the most common type. TNBC and HER2-enriched breast cancer had larger tumor sizes with higher expression of Ki-67 as compared with the luminal types. TNBC had a lower lymph node metastasis rate but higher CK5/6 and EGFR expression than the other three types. The expression of p53 was higher in luminal B, HER2-enriched, and triple-negative breast cancers, and this was positively correlated with the expression of EGFR in TNBC but not in the other subtypes. p53 and EGFR expression was positively correlated in TNBC, which enables us to explore the molecular biological characteristics of TNBC, so as to provide new ideas for the treatment of TNBC.

Correlation analysis of hormone receptors and the expressions of HER-2 and Ki-67 in breast cancer.

OBJECTIVE: This study aims to investigate the correlation and clinical significance of hormone receptors and the expressions of HER-2 and Ki-67 in breast cancer primary lesions and lymph node metastatic tissues. METHODS: 83 cases were studied, who were performed breast cancer surgeries and confirmed the ipsilateral axillary lymph node metastasis by the postoperative pathological diagnosis. Immunohistochemical method was used to simultaneously detect the expressions of ER, PR, HER-2 and Ki-67 in the primary lesions and lymph node metastases. RESULTS: ER exhibited the expression concordance rate as 85.5% in primary lesions and metastases, with significant difference (P = 0.039); the expression concordance rates of PR and HER-2 in primary lesions and metastases were 90.4% and 89.2%, respectively, without significant difference (P = 0.289, 0.180); between the Ki-67-highly-expressed primary lesions and Ki-67-lowly-expressed metastases, the expressions of ER in primary lesions and metastases exhibited statistical significance, with P as 0.031. CONCLUSIONS: The primary lesions and lymph node metastases had higher consistency, while there was still about 10% patients showed differentiated expression. The simultaneous detection of breast cancer primary lesions and lymph node metastases was still very necessary.

Pathological analysis of extracapsular extension of metastatic lymph node and its potential impact on nodal clinical target volume in the radiotherapy of esophageal squamous cell carcinoma.

There is no consensus regarding the clinical target volume (CTV) margins which surround the gross tumor volume of metastatic lymph nodes (LN) in radiotherapy of esophageal squamous cell carcinoma (ESCC). This study retrospectively assessed the distance of extracapsular extension (ECE) of metastatic LN in thoracic ESCC and defined nodal CTV margins. Histological sections of metastatic LNs from 217 patients with thoracic ESCC were re-examined. The incidence and maximal distance of ECE of metastatic LNs were assessed. The relationships between ECE and clinicopathologic features were also investigated. The ECE was found in 37.3% of patients (81/217) and 23.1% of metastatic LN (159/689), and the incidences had a significant relationship with N stage and LN size. The median distance of ECE was 1.0 mm (range, 0.2-9.7 mm). The distance of ECE showed a positive correlation with LN size (Spearman's correlation coefficient = 0.419; p<0.001). The ECE distances of LN with <10 mm diameter were significantly smaller than LN with 10-30 mm diameter (p<0.001). The 95th percentiles of ECE distances for these two groups were 3 mm and 5 mm, respectively. For pathologic LN <10 mm in diameter, a 3-mm CTV margin appears to be adequate to encompass 95% of the microscopic ECE, and for LN 10-30 mm, a 5-mm CTV margin is recommended.

Etiological factors, prognostic assessment, and outcomes of patients with acute kidney injury and multiple organ dysfunction syndrome.

This clinical study assessed the etiological factors implicated in acute kidney injury (AKI). AKI has a complicated etiology with many serious complications. Understanding the interactions among these factors will help physicians treat patients with AKI. This retrospective study analyzed the etiological factors and assessed the incidence and outcome of 123 patients with AKI and multiple organ dysfunction syndrome. The general conditions, original disease, number of organ dysfunctions, type of organ dysfunction, complications, score, time, dose of renal replacement therapy, and outcomes were recorded. The etiologies of the manifested diseases were complicated. The number of injured organs was directly associated with prognosis. Cardiovascular dysfunction and cataphora were independently associated with a risk of mortality (P < 0.05; odds ratios: 12.44 and 2.16, respectively). Meanwhile, cardiovascular dysfunction and choloplania were independently associated with a risk of irreparable renal function (P < 0.05; odds ratios: 23.64 and 11.59, respectively). In summary, the etiologies of the manifested diseases are complex. In addition, cardiovascular dysfunction is significantly associated with prognosis including survival and the recovery rate of renal function.