Individual variability in functional connectivity of human auditory cortex.

Individual variability in functional connectivity underlies individual differences in cognition and behaviors, yet its association with functional specialization in the auditory cortex remains elusive. Using resting-state functional magnetic resonance imaging data from the Human Connectome Project, this study was designed to investigate the spatial distribution of auditory cortex individual variability in its whole-brain functional network architecture. An inherent hierarchical axis of the variability was discerned, which radiates from the medial to lateral orientation, with the left auditory cortex demonstrating more pronounced variations than the right. This variability exhibited a significant correlation with the variations in structural and functional metrics in the auditory cortex. Four auditory cortex subregions, which were identified from a clustering analysis based on this variability, exhibited unique connectional fingerprints and cognitive maps, with certain subregions showing specificity to speech perception functional activation. Moreover, the lateralization of the connectional fingerprint exhibited a U-shaped trajectory across the subregions. These findings emphasize the role of individual variability in functional connectivity in understanding cortical functional organization, as well as in revealing its association with functional specialization from the activation, connectome, and cognition perspectives.

Behavioral and brain morphological changes before and after hemispherotomy.

Hemispherotomy is an effective surgery for treating refractory epilepsy from diffuse unihemispheric lesions. To date, postsurgery neuroplastic changes supporting behavioral recovery after left or right hemispherotomy remain unclear. In the present study, we systematically investigated changes in gray matter volume (GMV) before and after surgery and further analyzed their relationships with behavioral scores in two large groups of pediatric patients with left and right hemispherotomy (29 left and 28 right). To control for the dramatic developmental effect during this stage, age-adjusted GMV within unaffected brain regions was derived voxel by voxel using a normative modeling approach with an age-matched reference cohort of 2115 healthy children. Widespread GMV increases in the contralateral cerebrum and ipsilateral cerebellum and GMV decreases in the contralateral cerebellum were consistently observed in both patient groups, but only the left hemispherotomy patients showed GMV decreases in the contralateral cingulate gyrus. Intriguingly, the GMV decrease in the contralateral cerebellum was significantly correlated with improvement in behavioral scores in the right but not the left hemispherotomy patients. Importantly, the preoperative voxelwise GMV features can be used to significantly predict postoperative behavioral scores in both patient groups. These findings indicate an important role of the contralateral cerebellum in the behavioral recovery following right hemispherotomy and highlight the predictive potential of preoperative imaging features in postoperative behavioral performance.

Predicting Postoperative Complications in Patients Undergoing Colorectal Surgery with an Enhanced Recovery Pathway.

BACKGROUND: Reducing postoperative complications is the essential requirement of the enhanced recovery after surgery (ERAS) program. This study aimed to identify the key perioperative components affecting postoperative complications in patients undergoing colorectal surgery with ERAS. METHODS: This retrospective cohort study included all patients who underwent major colorectal surgery with ERAS program between February 2019 and June 2020, all perioperative information was retrieved from a database. Univariate and multivariate logistic regression analyses were used to identify predictors for complications within 30 days postoperatively, and a nomogram model was drawn to visualize the model. Receiver operating characteristic curve (ROC) and calibration curve were used to evaluate the model performance. RESULTS: We enrolled 649 patients and 72 patients (11.1%) had at least 1 complication within 30 days postoperatively. Multivariate analyses showed that minimally invasive surgery [odds ratio (OR) 0.323; 95% confidence interval (CI) 0.168-0.620] was associated with a decreased of the complications. However, preoperative anemia (OR 2.052; 95%CI 1.073-3.928) and old age (OR 1.927; 95%CI 1.022-3.632) were independent risk factors for complications within 30 days postoperatively. The C-index of the nomogram was 0.735 (95%CI 0.694-0.776). Calibration curve showed a relatively good agreement between predicted value and observed outcome. In the validation set, the nomogram showed an area under the ROC curve of 0.729 (95%CI 0.680-0.778). CONCLUSIONS: This study suggests that preoperative anemia, old age and minimally invasive surgery may individually influence the prognosis of patients undergoing major colorectal surgery with an enhanced recovery pathway. Trial registration Clinical Trial Registry (number: ChiCTR2000037513).

The Effect of Preoperative Oral Carbohydrate on the Incidence of Complications in PACU After General Anesthesia: A Prospective Cohort Study.

PURPOSE: This study aimed to investigate the effect of preoperative oral carbohydrate (POC) loading on the occurrence of complications in the postanesthesia care unit (PACU) after general anesthesia. DESIGN: Prospective observational cohort study METHODS: Patients who were scheduled for abdominal surgery under general anesthesia at our institution were divided into the POC group and control group based on whether they drank carbohydrate solution 2 hours before surgery. POC loading of the patients was decided by the responsible surgeon. In PACU, the occurrence of postoperative complications including delayed emergence, emergence agitation, hypoxemia, hypertension, hypotension, moderate to severe postoperative pain, nausea and vomiting, hypothermia, shivering, and time to awakening, time to extubation, length of PACU stay were recorded. FINDINGS: Data from 307 patients (n = 154 in POC group and n = 153 in control group) were included in the final analysis. Compared to the control group, POC led to a near-significant reduction in the overall incidence of complications in PACU after surgery (37.0% vs 47.7%, P = .058). The POC group had a lower incidence of hypothermia and shorter mean time to awakening when compared to control group (6.5% vs 16.3%, P = .007 and 19 min vs 21 min, P = .007, respectively). No statistical differences were detected in other outcome measurements between the POC group and the control group. CONCLUSIONS: POC is associated with a trend to decrease the overall incidence of complications during recovery period after general anesthesia in patients who underwent abdominal surgery. Moreover, POC could reduce the risk of hypothermia in PACU and shorten the time to awakening.

Switching the Activity of CRISPR/Cas12a Using an Allosteric Inhibitory Aptamer for Biosensing.

The current CRISPR/Cas12a-based diagnostic techniques focus on designing the crRNA or substrate DNA elements to indirectly switch the trans-cleavage activity of Cas12a responsive to target information. Here, we propose the use of an allosteric DNA probe to directly regulate the trans-cleavage activity of Cas12a and present a method for sensing different types of analytes. An allosteric inhibitor probe is rationally designed to couple the target recognition sequence with the inhibitory aptamer of the CRISPR/Cas12a system and enables binding to a specific target to induce the change of conformation, which leads to the loss of its inhibitory function on Cas12a. As a result, the structure-switchable probe can regulate the degree of activity of Cas12a depending on the dose of target. Scalability of our strategy can be achieved by simply replacing the loop domain with different target recognition sequences. The proposed method was validated by detecting adenosine triphosphate and let-7a, giving the detection limits of 490 nM and 26 pM, respectively, and showing an excellent specificity. We believe that this work exploits a viable approach to use the inhibitory aptamer of Cas12a as a regulatory element for biosensing purposes, enriching the arsenal of CRISPR/Cas12a-based methods for molecular diagnostics and spurring further development and application of aptamers of the CRISPR/Cas system.

Association Between Health Literacy and Enhanced Recovery After Surgery Protocol Adherence and Postoperative Outcomes Among Patients Undergoing Colorectal Cancer Surgery: A Prospective Cohort Study.

BACKGROUND: Low health literacy (HL) adversely affects medical adherence and health outcomes in patients with chronic diseases. However, the association between HL and enhanced recovery after surgery (ERAS) adherence and postoperative outcomes has not been investigated in patients undergoing colorectal surgery. METHODS: The data of all patients from a single academic institution who underwent colorectal surgery on an ERAS pathway from January 2019 to July 2020 were prospectively collected. HL levels were assessed using the Brief Health Literacy Screen (BHLS), a proven tool that was used by surgeons after recruitment. According to the HL score, the participants were categorized into low HL (≤9 points) and high HL (10-15 points) groups. The primary outcome was ERAS adherence. Adherence was measured in 22 perioperative elements, and high adherence was defined as adherence to 17 to 22 elements. Secondary outcomes included postoperative complications, hospital length of stay (LOS), hospital charges, mortality, and readmissions. RESULTS: Of the 865 eligible patients, the high HL group consisted of 329 patients (38.0%), and the low HL group contained 536 patients (62.0%). After propensity score matching (1:1), 240 unique pairs of patients with similar characteristics were selected. Patients with high HL levels had a significantly higher rate of high adherence to ERAS standards than those with low HL levels (55% vs 25.8%; adjusted P < .001). In terms of adherence to each item, high HL levels were significantly associated with higher adherence to preoperative optimization (90.8% vs 71.7%; adjusted P < .001), postoperative gum chewing (59.2% vs 44.6%; adjusted P = .01), early feeding (59.2% vs 31.3%; adjusted P < .001), and early mobilization (56.7% vs 30.4%; adjusted P < .001). In the overall study population, adjusted logistic regression analyses also showed that high HL levels were associated with a significantly increased rate of high adherence when compared with low HL levels (adjusted odds ratio [OR], 3.57; 95% confidence interval (CI), 2.50-5.09; P < .001). In addition, low HL levels were associated with a significantly higher incidence of postoperative complications (32.1% vs 20.8%; P < .01), longer hospital LOS (9 [interquartile range {IQR}, 7-11] vs 7 [IQR, 6-9] d; P < .001), and higher hospital charges (10,489 [IQR, 8995-11942] vs 8466 [IQR, 7733-9384] dollar; P < .001) among propensity-matched patients. However, there were no differences in the mortality and readmission rates between the HL groups. CONCLUSIONS: Low HL levels were associated with lower adherence to ERAS elements among propensity-matched patients undergoing colorectal surgery.

Prevalence and predictors of chronic postsurgical pain after colorectal surgery: A prospective study.

AIM: The aim was to investigate the incidence, characteristics and the potential predictors of chronic postsurgical pain (CPSP) after colorectal surgery. METHOD: Patients who underwent colorectal surgery at our institution from July 2014 to December 2016 were prospectively enrolled in this study. Perioperative potential demographic, clinical and psychological predictors for CPSP were collected. The follow-up visits were conducted through telephone interviews at 3 and 6 months postoperatively. The interview questionnaire comprised items regarding pain intensity, frequency, site, analgesic administration and impact on activities of daily living. RESULTS: A total of 624 patients completed the 6-month follow-up and were included in the analysis. CPSP was reported by 32.1% of these patients at 3 months and 21.8% at 6 months after colorectal surgery. The pain interfered with several activities of daily living in a considerable proportion of CPSP cases. At 3 months, the identified predictors of CPSP were young age, preoperative abdominal pain and pain elsewhere, preoperative anxiety and depression, longer duration of surgery, and high pain intensity on movement within 24 h after surgery. Predictors of CPSP at 6 months were young age, preoperative abdominal pain, preoperative anxiety, longer duration of surgery, and high pain intensity on movement within 24 h after surgery. CONCLUSION: Chronic pain after colorectal surgery is a common complication associated with young age, preoperative abdominal pain and pain elsewhere, preoperative anxiety and depression, longer duration of surgery, and high pain intensity on movement within 24 h after surgery.

Perioperative breathing training to prevent postoperative pulmonary complications in patients undergoing laparoscopic colorectal surgery: A randomized controlled trial.

OBJECTIVE: The aim of this study was to determine whether perioperative breathing training reduces the incidence of postoperative pulmonary complications in patients undergoing laparoscopic colorectal surgery. DESIGN: A randomized controlled trial. SETTING: University hospital. SUBJECTS: A total of 240 patients undergoing laparoscopic colorectal surgery participated in this study. INTERVENTION: The enrolled patients were randomized into an intervention or control group. Patients in the intervention group received perioperative breathing training, including deep breathing and coughing exercise, balloon-blowing exercise, and pursed lip breathing exercise. The control group received standard perioperative care without any breathing training. MAIN MEASURES: The primary endpoint was the incidence of postoperative pulmonary complications. The secondary objectives were to evaluate the effect of perioperative breathing training on arterial oxygenation, incidence of other postoperative complications, patient satisfaction, length of stay, and hospital charges. RESULTS: The incidence of postoperative pulmonary complications in the breathing training group was lower than that in the control group (5/120 [4%] vs 14/120 [12%]; RR 0.357, 95%CI 0.133-0.960; P = 0.031). In addition, PaO2 and arterial oxygenation index on the first and fourth days after surgery were significantly higher in the breathing training group than in the control group (P < 0.001). In addition, patients with breathing training had shorter length of stay (6d [IQR 5-7] vs 8d [IQR 7-9]), lower hospital charges (7761 ± 1679 vs 8212 ± 1326), and higher patient satisfaction (9.46 ± 0.65 vs 9.21 ± 0.47) than those without. CONCLUSION: Perioperative breathing training may reduce the incidence of postoperative pulmonary complications and preserve of arterial oxygenation after laparoscopic colorectal surgery.

Impact of enhanced recovery after surgery protocol compliance on patients' outcome in benign hysterectomy and establishment of a predictive nomogram model.

BACKGROUND: Enhanced recovery after surgery (ERAS) pathways have been shown to improve clinical outcomes after surgery. Considering the importance of patient experience for patients with benign surgery, this study evaluated whether improved compliance with ERAS protocol modified for gynecological surgery which recommended by the ERAS Society is associated with better clinical outcomes and patient experience, and to determine the influence of compliance with each ERAS element on patients' outcome after benign hysterectomy. METHODS: A prospective observational study was performed on the women who underwent hysterectomy between 2019 and 2020. A total of 475 women greater 18 years old were classified into three groups according to their per cent compliance with ERAS protocols: Group I: < 60% (148 cases); Group II:≥60 and < 80% (160 cases); Group III: ≥80% (167 cases). Primary outcome was the 30-day postoperative complications. Second outcomes included QoR-15 questionnaire scores, patient satisfaction on a scale from 1 to 7, and length of stay after operation. After multivariable binary logistic regression analyse, a nomogram model was established to predict the incidence of having a postoperative complication with individual ERAS element compliance. RESULTS: The study enrolled 585 patients, and 475 completed the follow-up assessment. Patients with compliance over 80% had a significant reduction in postoperative complications (20.4% vs 41.2% vs 38.1%, P < 0.001) and length of stay after surgery (4 vs 5 vs 4, P < 0.001). Increased compliance was also associated with higher patient satisfaction and QoR-15 scores (P < 0.001),. Among the five dimensions of the QoR-15, physical comfort (P < 0.05), physical independence (P < 0.05), and pain dimension (P < 0.05) were better in the higher compliance groups. Minimally invasive surgery (MIS) (P < 0.001), postoperative nausea and vomiting (PONV) prophylaxis (P < 0.001), early mobilization (P = 0.031), early oral nutrition (P = 0.012), and early removal of urinary drainage (P < 0.001) were significantly associated with less complications. Having a postoperative complication was better predicted by the proposed nomogram model with high AUC value (0.906) and sensitivity (0.948) in the cohort. CONCLUSIONS: Improved compliance with the ERAS protocol was associated with improved recovery and better patient experience undergoing hysterectomy. MIS, PONV prophylaxis, early mobilization, early oral intake, and early removal of urinary drainage were of concern in reducing postoperative complications. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800019178 . Registered on 30/10/2018.

Prevalence and risk factors for chronic pain following cesarean section: a prospective study.

BACKGROUND: Chronic post-surgical pain (CPSP) remains a major clinical problem which may be associated with impaired activities of daily life and decreased health-related quality of life. Although cesarean section is one of the most commonly performed operations, chronic pain after cesarean delivery has not been well-studied. The purpose of this prospective study was to assess the incidence and risk factors of chronic pain at 3, 6 and 12 months after cesarean delivery. METHODS: We prospectively investigated preoperative demographic and psychological factors, intraoperative clinical factors, and acute postoperative pain in a cohort of 527 women undergoing cesarean section. The women were interviewed and completed pain questionnaires after 3, 6 and 12 months. Questions were about pain intensity, frequency, and location, as well as medical treatment and impact on daily living. RESULTS: The incidence of CPSP at 3, 6 and 12 months after cesarean section was 18.3 %, 11.3 % and 6.8 %, respectively. Most of the women with CPSP experienced mild pain at rest. The incidence of moderate and severe pain on movement was high at 3 month, and then has a significant decrease at 6 and 12 months. CPSP had a negative influence on the activities of daily living. Independent predictors of CPSP at 3 months included higher average pain intensity on movement within 24 h postoperatively, preoperative depression, and longer duration of surgery. At 6 months, more severe pain during movement within 24 h of surgery and preoperative depression were predictive of pain persistence. And 12 months after surgery, only higher average pain score on movement within 24 h following cesarean section was found to be significant associated with CPSP. The three models all showed moderate discrimination and good calibration for the prediction of CPSP at 3, 6 and 12 months postoperatively. CONCLUSIONS: CPSP was not rare in women undergoing cesarean section. Patients with more intense of acute postoperative pain on movement, preoperative depression, and longer surgical time had greater risk for CPSP following surgery.

[Effects of two analgesic regimens on the postoperative analgesia and knee functional recovery after unilateral total knee arthroplasty-a randomized controlled trial].

OBJECTIVE: To evaluate the efficacy of continuous femoral block on the postoperative analgesia and functional recovery after total knee arthroplasty (TKA). METHODS: Two hundreds and eighty patients who underwent TKA were randomized into two groups:the group receiving continuous femoral block (CFNB) and the group receiving patient controlled intravenous analgesia (PCIA), each group included 140 participants. Femoral nerve block with ropivacaine by ultrasonic guidance was performed in group CFNB and group PCIA were administrated with patient controlled intravenous analgesia. Numerical rating scale (NRS) scores at rest and in motion at 24, 48, 72 h, 3, 6 and 12 months postoperatively, also the NRS scores at hospital discharge were recorded. The incidence of moderate-severity pain, as well as the degree of knee flexion and the WOMAC scores at 3, 6 and 12 months after surgery were analyzed. The rescue analgesic administration and analgesia-related adverse effects were also recorded. Data were expressed as mean± standard deviation (SD) for normally distributed continuous variables and total number (percent frequency) for categorical variables. If non-normally distributed, data were expressed median inter-quartile range. Student's t-test, Wilcoxon rank test were used to compare results for continuous variables, when appropriate. Chi-square test was used to compare results for categorical variable, Fisher exact test was used for categorical variables when the number of event was less than 5. RESULTS: NRS scores of group CFNB in motion was 3 (3-4) at discharge time, and 3 (2-4), 3 (2-3) at 3 months and 6 months postoperatively, while the scores of group PCIA was 4 (4-4), 3 (3-4), 3 (3-4), respectively. And at rest, NRS scores of group CFNB was 3 (2-3), 1 (1-2), 1 (1-1) at discharge time, and 3, 6 months postoperatively. Compared with group PCIA, NRS scores in motion of group CFNB at discharge time (Z=-5.174, P<0.05) and 3 months (Z=2.308, P=0.021), as well as 6 months postoperatively (Z=-2.495, P=0.013), were significantly lower,also for the NRS scores at rest (Z=-2.405, P=0.016; Z=-4.360, P<0.05; Z=-9.268, P<0.05). The degree of knee flexion of group CFNB at 3 and 6 months postoperatively was 92 (88-97), 103 (99-106), while the degree of knee flexion of group PCIA was 89 (86-95), 100 (97-105); the WOMAC scores of group CFNB at 3 and 6 months postoperatively was 21 (18-26), 18 (16-22), while the scores of group PCIA was 24 (20-27), 21 (17-24). WOMAC scores of group CFNB was lower compared with group PCIA at 3 (Z=-2.467, P=0.014) and 6 (Z=-2.537, P=0.011) months postoperatively while the degree of knee flexion of group CFNB was higher (Z=-2.175, P=0.030; Z=-2.471, P=0.013). Moreover, the frequency of bolus and frequency of rescue of group CFNB was 2.3 and 0.6, while the frequency of group PCIA was 2.6 and 1.1, the frequency of bolus and frequency of rescue were lower in group CFNB (t=-2.984, P=0.003; t=-3.213, P=0.002). The incidence of adverse events such muscle weakness of low limbs,nausea and vomiting were similar in two groups (P>0.05). CONCLUSION: CFNB can alleviate the postoperative pain after TKA with safety, help improving the short-middle-term functions of knee and quality of patients' lives.

Lateral quadratus lumborum block vs acupuncture for postcesarean analgesia: a randomized clinical trial.

BACKGROUND: Improved pain control after cesarean section remains a challenging objective. Although both the lateral quadratus lumborum block (L-QLB) and acupuncture have been reported to provide superior postoperative analgesia after cesarean section when compared to placebo, the efficacy of these techniques has never been compared head-to-head. OBJECTIVE: This study was conducted to investigate the comparative analgesic efficacy of L-QLB and acupuncture following elective cesarean section. STUDY DESIGN: In this prospective, randomized, controlled clinical trial, a total of 190 patients with singleton-term pregnancies scheduled for cesarean section under spinal-epidural anesthesia were enrolled. Patients were randomized 1:1 to acupuncture group or L-QLB group. L-QLB group received bilateral L-QLB with 0.33% ropivacaine and sham acupuncture, acupuncture group received transcutaneous electrical acupoint stimulation and press needle therapy, and sham L-QLB. All patients received the standard postoperative pain treatment. The primary outcome was pain scores on movement at 24 hours. Secondary endpoints included pain scores in the first 48 hours postoperatively, patient-controlled intravenous analgesia (PCIA) demands, analgesia-related adverse effects, postoperative complications, QoR-15, the time to mobilization, and gastrointestinal function. RESULTS: Median (interquartile range [range]) pain scores at 24 hours on movement were similar in patients receiving acupuncture or L-QLB (3 [2-4] vs 3 [2-4], respectively; P=.40). PCIA consumption and pain scores within 48 hours postoperatively also showed no difference between the two groups. The acupuncture improved QoR-15 scores at 24 and 48 hours postoperatively (P<.001), as well as shortened the time to first flatus (P=.03) and first drinking (P<.001) compared to L-QLB. In addition, the median time to mobilization in the L-QLB group was markedly prolonged compare with acupuncture group (17.0 [15.0-19.0] hours vs 15.3 [13.3-17.0] hours, estimated median difference, 1.5; 95% CI, 1-2; P<.001). CONCLUSION: As a component of multimodal analgesia regimen after cesarean section, acupuncture did not lower postoperative pain scores or reduce analgesic medication consumption compared to L-QLB.

Effect of lidocaine or dexmedetomidine on postoperative recovery in elder patients undergoing colorectal surgery.

BACKGROUND: Opioid sparing techniques have been shown to promote gastrointestinal recovery, shorten length of stay (LOS), and reduce opioid-related complications. We investigated whether intraoperative intravenous lidocaine or dexmedetomidine infusion could improve gastrointestinal recovery in elderly patients undergoing laparoscopic colorectal surgery. METHODS: Ninety-six patients aged 65 years or older who underwent elective laparoscopic colorectal resection were randomly allocated into the following three groups: the control group (N.=32) received an equal volume of saline, the lidocaine group (N.=32) received intraoperative intravenous lidocaine infusion, and the dexmedetomidine group (N.=32) received intraoperative intravenous dexmedetomidine infusion. The primary outcome was time to first feces. Secondary outcomes were time to first flatus, postoperative pain intensity, patient-controlled intravenous analgesia (PCIA) consumption, postoperative inflammatory response, postoperative complications, anesthetic adverse events, and LOS. RESULTS: The lidocaine group had a significantly shorter time to first flatus (24.6 [IQR, 14.4-48.8] hours vs. 48.1 [IQR, 30.0-67.1] hours; adjusted P=0.022) and time to first feces (48.0 [IQR, 19.0-67.8] hours vs. 74.8 [IQR, 40.3-113.3] hours; adjusted P=0.032) than the control group. However, no significant differences were found between dexmedetomidine and control group for first flatus or first feces. Intraoperative sufentanil consumption and postoperative plasma concentrations of IL-6 were significantly lower in lidocaine group and dexmedetomidine group compared with control group. No difference could be observed in postoperative PCIA consumption, pain scores, postoperative complications, anesthetic adverse events, and LOS among the groups. CONCLUSIONS: Intraoperative intravenous lidocaine infusion accelerated return of the bowel function in elderly patients undergoing elective colorectal surgery.

Transversus Abdominis Plane Block Versus Local Wound Infiltration for Postoperative Pain After Laparoscopic Colorectal Cancer Resection: a Randomized, Double-Blinded Study.

BACKGROUND: Despite the extensive administration of the enhanced recovery after surgery (ERAS) program, postoperative pain remains a major concern for patients. Transversus abdominis plane (TAP) block and local wound infiltration (LWI) are two techniques that have been widely applied in abdominal surgery. However, these two techniques have rarely been compared in terms of their analgesic effects on patients that undergo laparoscopic colorectal surgery with the ERAS program. METHODS: A randomized, double-blinded study was conducted in this study. Briefly, 174 patients that underwent colorectal surgery with the ERAS program were randomly allocated to TAP block treatment (TAP group) or local wound infiltration (LWI group). All patients were assessed for their pain scores at rest and in motion at 6, 24, 48, and 72 h after surgery. The administration frequency of bolus for PCIA and the use amount of rescue analgesics (parecoxib) were recorded. Finally, the patients were monitored with follow-up surveys on their postoperative function recovery, complications, lengths of stay, treatment cost, and satisfaction. RESULTS: In terms of the pain scores at rest and in motion, the two groups revealed no significant difference throughout the study sessions, and no difference was found in the administration frequency of bolus and the use amount of parecoxib. Moreover, the two groups demonstrated similar results in their postoperative recovery, and no significant differences were found in terms of postoperative complications. CONCLUSIONS: Compared with local wound infiltration, transversus abdominis plane block is not significantly advantageous for postoperative pain control and recovery in patients undergoing laparoscopic colorectal surgery with the ERAS program. However, local wound infiltration might be preferred since it is available with less technical difficulties.

An RNA-based catalytic hairpin assembly circuit coupled with CRISPR-Cas12a for one-step detection of microRNAs.

CRISPR-Cas nuclease-based nucleic acid detection has exhibited extraordinary value in the field of molecular diagnostics, but it usually involves two separate reaction steps of nucleic acid amplification and Cas-based endpoint detection, resulting in the use of multiple enzymes, inconvenient operation, and potential carry-over contamination. Here, we propose an RNA-based catalytic hairpin assembly (CHA) circuit coupled with CRISPR-Cas12a for one-step detection of microRNAs (miRNAs) at an isothermal condition. This method relies on the rational design of a spacer-blocking crRNA as a bridge between the two systems. The target miRNA can specifically trigger RNA-based CHA and induce a configurational change of the blocked crRNAs into precursor crRNAs (pre-crRNAs), which can be processed into mature crRNAs to function by leveraging the inherent RNase activities of Cas12a. In this way, the developed circuit achieves a femtomolar detection limit and shows an accurate detection of miRNA levels in different cell lines. Therefore, our method would provide a new paradigm to develop miRNA detection methods based on the CRISPR/Cas system.

A novel missense mutation in obscurin gene in a Chinese consanguineous family with left ventricular noncompaction.

BACKGROUND: Left ventricular noncompaction (LVNC) is an increasingly recognised cardiomyopathy of which a significant percentage are genetic in origin. The purpose of the present study was to identify potential pathogenic mutation leading to disease in a Chinese LVNC family. METHODS: A 3-generation family affected by LVNC was recruited. Clinical assessments were performed on available family members, with clinical examination, ECG, echocardiography and cardiac MRI. The proband (I-2), the proband's daughter (II-1, affected) and mother (III-1, unaffected) were selected for WGS. Sanger sequencing were performed in all of the 4 surviving family members. RESULTS: Combined whole genome sequencing with linkage analysis identified a novel missense mutation in the giant protein obscurin (OBSCN NM_001098623, c.C19063T), as the only plausible disease-causing variant that segregates with disease among the four surviving individuals, with interrogation of the entire genome excluding other potential causes. This c.C19063T missense mutation resulted in p.R6355W in the encoded OBSCN protein. It affected a highly conserved residue in the C terminus of the obscurin-B-like isoform between the PH and STKc domains, which was predicted to affect the function of the protein by different bioinformatics tools. CONCLUSIONS: Here we present clinical and genetic evidence implicating the novel R6355W missense mutation in obscurin as the cause of familial LVNC. This expands the spectrum of obscurin's roles in cardiomyopathies. It furthermore highlights that rare obscurin missense variants, currently often ignored or left uninterpreted, should be considered to be relevant for cardiomyopathies and can be identified by the approach presented here. This study also provided new insights into the molecular basis of OBSCN mutation positive LVNC.

Implementation of the pre-operative rehabilitation recovery protocol and its effect on the quality of recovery after colorectal surgeries.

BACKGROUND: Patients' recovery after surgery is the major concern for all perioperative clinicians. This study aims to minimize the side effects of peri-operative surgical stress and accelerate patients' recovery of gastrointestinal (GI) function and quality of life after colorectal surgeries, an enhanced recovery protocol based on pre-operative rehabilitation was implemented and its effect was explored. METHODS: A prospective randomized controlled clinical trial was conducted, patients were recruited from January 2018 to September 2019 in this study. Patients scheduled for elective colorectal surgeries were randomly allocated to receive either standardized enhanced recovery after surgery (S-ERAS) group or enhanced recovery after surgery based on pre-operative rehabilitation (group PR-ERAS). In the group PR-ERAS, on top of recommended peri-operative strategies for enhanced recovery, formatted rehabilitation exercises pre-operatively were carried out. The primary outcome was the quality of GI recovery measured with I-FEED scoring. Secondary outcomes were quality of life scores and strength of handgrip; the incidence of adverse events till 30 days post-operatively was also analyzed. RESULTS: A total of 240 patients were scrutinized and 213 eligible patients were enrolled, who were randomly allocated to the group S-ERAS (n = 104) and group PR-ERAS (n = 109). The percentage of normal recovery graded by I-FEED scoring was higher in group PR-ERAS (79.0% vs. 64.3%, P < 0.050). The subscores of life ability and physical well-being at post-operative 72 h were significantly improved in the group PR-ERAS using quality of recovery score (QOR-40) questionnaire (P < 0.050). The strength of hand grip post-operatively was also improved in the group PR-ERAS (P < 0.050). The incidence of bowel-related and other adverse events was similar in both groups till 30 days post-operatively (P > 0.050). CONCLUSIONS: Peri-operative rehabilitation exercise might be another benevolent factor for early recovery of GI function and life of quality after colorectal surgery. Newer, more surgery-specific rehabilitation recovery protocol merits further exploration for these patients. TRIAL REGISTRATION: ChiCTR.org.cn, ChiCTR-ONRC-14005096.

Integrated Proteomic and Transcriptomic Analyses Reveal the Roles of Brucella Homolog of BAX Inhibitor 1 in Cell Division and Membrane Homeostasis of Brucella suis S2.

BAX inhibitor 1 (BI-1) is an evolutionarily conserved transmembrane protein first identified in a screening process for human proteins that suppress BAX-induced apoptosis in yeast cells. Eukaryotic BI-1 is a cytoprotective protein that suppresses cell death induced by multiple stimuli in eukaryotes. Brucella, the causative agent of brucellosis that threatens public health and animal husbandry, contains a conserved gene that encodes BI-1-like protein. To explore the role of the Brucella homolog of BI-1, BrBI, in Brucella suis S2, we constructed the brbI deletion mutant strain and its complemented strain. brbI deletion altered the membrane properties of Brucella suis S2 and decreased its resistance to acidic pH, H2O2, polymyxin B, and lincomycin. Additionally, deleting brbI led to defective growth, cell division, and viability in Brucella suis S2. We then revealed the effect of brbI deletion on the physiological characteristics of Brucella suis S2 via integrated transcriptomic and proteomic analyses. The integrated analysis showed that brbI deletion significantly affected the expression of multiple genes at the mRNA and/or protein levels. Specifically, the affected divisome proteins, FtsB, FtsI, FtsL, and FtsQ, may be the molecular basis of the impaired cell division of the brbI mutant strain, and the extensively affected membrane proteins and transporter-associated proteins were consistent with the phenotype of the membrane properties' alterations of the brbI mutant strain. In conclusion, our results revealed that BrBI is a bacterial cytoprotective protein involved in membrane homeostasis, cell division, and stress resistance in Brucella suis S2.

The impact of patient-controlled analgesia on prognosis of patients receiving major abdominal surgery.

BACKGROUND: Postoperative pain is a major disease burden after surgery. Patient-controlled analgesia has been wide used for pain management in surgical patients, yet, large-scaled studies are lacking to assess its impact on the prognosis of patients. METHODS: We prospectively enrolled patients who underwent major abdominal surgeries receiving patient-controlled analgesia (PCA) and who received non-PCA for assessment of 60-day mortality, major postoperative complications using electronic medical chart system. Pain intensity was also assessed with visual analogue scale from postoperative day 1 to day 7, chronic post-surgical pain was assessed by telephone follow-up using numerical rating scale. RESULTS: In total, 12,015 patients were included in the primary analysis. At the end of the follow-up, 1185 patients were lost to follow-up. Patients in the non-PCA group reported increased incidence of moderate-to-severe pain on postoperative day 3 (6.5% versus 9.6%, P<0.001). Patients receiving non-PCA had increased mortalities on postoperative 60-day (1.02% versus 0.47%, P<0.001). The survival probability of patients in PCA group was statistically higher than those in non-PCA group (99.52% [95% CI: 99.34-99.70%] versus 98.97% [95% CI: 98.73-99.92%]). Patient receiving non-PCA reported increased in-hospital major complications compared with (2.7% versus 1.9 %, P=0.003). Pain intensity was also assessed with visual analogue scale from postoperative day 1 to day 7, chronic post-surgical pain was assessed by telephone follow-up using numerical rating scale. CONCLUSIONS: Intravenous patient-controlled analgesia was related to improved survival, less complications and chronic post-surgical pain after major abdominal surgery, reiterating the important role of pain management for the prognosis of patients who underwent surgery.

Propofol ameliorates electroconvulsive shock-induced learning and memory impairment by regulation of synaptic metaplasticity via autophosphorylation of CaMKIIa at Thr 305 in stressed rats.

Electroconvulsive therapy (ECT) is an effective treatment for depression, but it can induce learning and memory impairment. Our previous study found propofol (γ-aminobutyric acid (GABA) receptor agonist) could ameliorate electroconvulsive shock (ECS, an analog of ECT to animals)-induced cognitive impairment, however, the underlying molecular mechanisms remain unclear. This study aimed to investigate the effects of propofol on metaplasticity and autophosphorylation of CaMKIIa in stressed rats receiving ECS. Depressive-like behavior and learning and memory function were assessed by sucrose preference test and Morris water test respectively. LTP were tested by electrophysiological experiment, the expression of CaMKIIa, p-T305-CaMKII in hippocampus and CaMKIIα in hippocampal PSD fraction were evaluated by western blot. Results suggested ECS raised the baseline fEPSP and impaired the subsequent LTP, increased the expression of p-T305-CaMKII and decreased the expression of CaMKIIα in hippocampal PSD fraction, leading to cognitive dysfunction in stressed rats. Propofol could down-regulate the baseline fEPSP and reversed the impairment of LTP partly, decreased the expression of p-T305-CaMKII and increased the expression of CaMKIIα in hippocampal PSD fraction and alleviated ECS-induced learning and memory impairment. In conclusion, propofol ameliorates ECS-induced learning and memory impairment, possibly by regulation of synaptic metaplasticity via p-T305-CaMKII.