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Platelets promote tumor growth and metastasis in several tumor types. Recent research has found platelets can extravasate and infiltrate into the tumor stroma and interact with the tumor microenvironment. The prognostic role of platelet infiltration in colorectal cancer (CRC) remains controversial. A pan-cancer survival analysis was performed to find the potential prognostic value of platelet infiltration in patients with cancer. A survival analysis and a nomogram prognostic model were established to further confirm the results with data from our center. The correlations between patient outcomes and tumor-infiltrating platelets (TIPs) were identified by immunohistochemical staining for CD42b. The prognostic accuracy and discriminative ability of the nomogram were determined by the concordance index (C-index) and a calibration curve. The pan-cancer survival analysis showed platelet infiltration can lead to a poor prognosis in patients with several types of cancers, including CRC. Platelet infiltration was associated with overall survival (OS) and disease-free survival (DFS) in both primary and validation cohorts. The C-index values of the nomogram for predicting OS and DFS were 0.774 and 0.769, respectively, which were higher than that of the TNM staging system alone. Our study found platelet infiltration has a potential prognostic value regarding postsurgical survival in CRC patients. The proposed nomogram resulted in a more accurate prognostic prediction for postsurgical CRC patients.

Purpose Epidural analgesia in the latent phase of the first stage of labor has been recognized and accepted by anesthesiologists worldwide. However, there is no unified consensus on the exact dosage of sufentanil with the combination of ropivacaine in the induction of epidural analgesia in the early first stage of labor. In this sequential dose-finding study, the 90% effective dose (ED90) of sufentanil for epidural administration in the early first stage of labor was estimated to minimize the adverse effects of using higher doses. Methods Forty parturients with cervical dilatation of 2 to 4 cm who requested epidural analgesia were enrolled in this study. Parturients received 15 mL of a combination of ropivacaine 13 mg and the test dose of sufentanil. The initial dose of sufentanil in epidural administration was 1 μg, and the dose of sufentanil for the next parturient was based on the response of the preceding participant as per a biased coin up-and-down design. The primary outcome was the dose of sufentanil that resulted in successful epidural administration by maintaining the parturients’ visual analog scale scores at ≤30 mm in the first 15, 30, and 45 minutes of induction. The ED90 and 95% CIs were estimated using isotonic regression methods and bootstrapping. Findings The estimated ED90 of sufentanil in epidural administration in the early first stage of labor was 1.91 μg (95% CI, 1.82–2.35 μg) in this sequential dose-finding study. Implications Sufentanil at a dosage of 2 μg is recommended for the administration of epidural analgesia in parturients in the early first stage of labor. ChiCTR.org.cn identifier: 1900021683.

BACKGROUND Neoadjuvant therapy (NAT) is becoming increasingly important in locally advanced rectal cancer. Hence, such research has become a problem. AIM To evaluate the downstaging effect of NAT, its impact on postoperative complications and its prognosis with different medical regimens. METHODS Seventy-seven cases from Shanghai Ruijin Hospital affiliated with Shanghai Jiaotong University School of Medicine were retrospectively collected and divided into the neoadjuvant radiochemotherapy (NRCT) group and the neoadjuvant chemotherapy (NCT) group. The differences between the two groups in tumor regression, postoperative complications, rectal function, disease-free survival, and overall survival were compared using the χ2 test and Kaplan-Meier analysis. RESULTS Baseline data showed no statistical differences between the two groups, whereas the NRCT group had a higher rate of T4 (30/55 vs 5/22, P < 0.05) than the NCT groups. Twelve cases were evaluated as complete responders, and 15 cases were evaluated as tumor regression grade 0. Except for the reduction rate of T stage (NRCT 37/55 vs NCT 9/22, P < 0.05), there was no difference in effectiveness between the two groups. Preoperative radiation was not a risk factor for poor reaction or anastomotic leakage. No significant difference in postoperative complications and disease-free survival between the two groups was observed, although the NRCT group might have better long-term overall survival. CONCLUSION NAT can cause tumor downstaging preoperatively or even complete remission of the primary tumor. Radiochemotherapy could lead to better T downstaging and promising overall survival without more complications.

BackgroundThe aim of this prospective randomized controlled study was to evaluate whether pretreatment with a small dose of dezocine could prevent remifentanil-induced cough in general anesthesia induction.Trial designa prospective, randomized, controlled study.MethodsA total of 210 patients receiving elective operative hysteroscopy from December 2018 to April 2019 were enrolled in the present study. They were randomly equally separated into dezocine group (n = 105) and control group (n = 105). Patients were intravenously pre-administrated with dezocine 0.03 mg/kg (diluted to 5 mL) or the same volume of normal saline 1 min prior to remifentanil infusion. One minute later, intravenous injection of propofol 1.5 mg/kg and cisatracurium 0.1 mg/kg were given to all patients for induction of general anesthesia. The counts of coughs occurred during the anesthesia induction period were recorded and the severity of cough was scaled.ResultsThere were 7 cases of mild cough in dezocine group and 18 cases of mild cough, 12 cases of moderate cough and 4 cases of severe cough in control group. The incidence rate of cough was significantly lower and the severity of cough was obviously relieved in dezocine group compared to control group (6.67% vs. 32.38%,P ConclusionThis study recommends the efficacy and safety of a pretreatment with a small dose of dezocine in reducing remifentanil-induced cough during general anesthesia.Trial RegistrationChiCTR2000032035.Date of registration: Retrospectively registered on 2020/04/18.

Survivals after prenatal hypoxia-ischemia (HI) usually suffer long-lasting cognitive defects. Reduced blood-oxygen supplies and the following reperfusion cause mitochondrial injury. Damaged mitochondria could be replaced by mitochondrial biogenesis program and peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) is the specific up-regulator. The objective of this study was to determine whether PGC-1α and mitochondrial biogenesis participate in the resistant responses of an immature brain to prenatal HI. We used a pregnant rat model of transient occlusion of uterine perfusion to induce intrauterine HI associated brain injury. SH-SY5Y cells exposed to oxygen-glucose deprivation was used to investigate the HI induced reactions in vitro. PGC-1α and its downstream signaling pathway (NRF-1 and TFAM) were examined by Western blot and quantitative Real-time PCR. Mitochondrial respiratory enzyme COX-IV was investigated by Western blot and immunohistochemistry. Mitochondrial density and morphology was detected by transmission electron microscopy. The hippocampal injury and cognitive function were examined. We found that the intrauterine HI triggered PGC-1α-NRF-1-TFAM pathway in both protein and mRNA levels. COX-IV expression significantly increased after HI injury. Intrauterine HI induced both mitochondrial impairment and mitochondrial biogenesis. Postnatal administration of pioglitazone further promoted PGC-1α and mitochondrial biogenesis, alleviated hippocampal injury, and improved performance in the behavioral tasks after intrauterine HI. Our investigation implicated activation of PGC-1α, and mitochondrial biogenesis is a neuroprotective mechanism against brain injury caused by systemic prenatal HI. Promotion of PGC-1α by pioglitazone might be a potential treatment for protecting against hippocampal injury and cognitive defects after intrauterine HI.

Background Maternal hypotension after spinal anaesthesia occurs at a high rate during caesarean delivery and can lead to adverse maternal or foetal outcomes. The aim of this study was to determine the optimal dose of spinal ropivacaine for caesarean section with or without intravenous single bolus of S-ketamine and to observe the rates of hypotension associated with both methods. Methods Eighty women undergoing elective caesarean delivery were randomly allocated into either a ropivacaine only or ropivacaine with intravenous S-ketamine group. If the upper sensory level of the patient reached T6 and the visual analogue scale (VAS) scores remained below 3 points before delivery, the next patient had a 1/9th chance of receiving a lower dose or an 8/9th chance of receiving the same dose as the previous patient. If the patient had VAS scores of more than 2 points or needed an extra epidural rescue bolus before delivery, a higher dose was used for the next patient. The primary outcome was the successful use of spinal ropivacaine to maintain patient VAS score of Results The estimated ED90 of ropivacaine was 11.8 mg (95% CI: 11.7–12.7) with and 14.7 mg (95% CI: 14.6–16.0) without intravenous S-ketamine, using biased coin up-down sequential dose-finding method. The rates of hypotension and associated symptoms were significantly lower in S-ketamine group than in the ropivacaine only group. Conclusions A spinal dose of ropivacaine 12 mg with a single intravenous 0.15 mg/kg bolus dose of S-ketamine may significantly reduce the risk of hypotension and induce sedation before delivery. This method may be used with appropriate caution for women undergoing elective caesarean delivery and at a high risk of hypotension or experiencing extreme nervousness. Trial registration http://www.chictr.org.cn (ChiCTR2000040375; 28/11/2020).

Importance Quantification of potential consequences associated with the use of epidural analgesia during labor could help to improve the safety and quality of labor and delivery care for parturient women. Objective To evaluate the association between epidural analgesia use during labor and neonatal infection in a large cohort of parturient women. Design, Setting, and Participants This propensity score-matched cohort study was conducted at a university-affiliated hospital in Shanghai, China. Women at full-term pregnancy undergoing vaginal delivery between January 2013 and October 2018 were included in the study. Parturient women who were parous, experiencing premature delivery (gestational age

BACKGROUND Pressure recording analytical method (PRAM) of MOSTCARE is a minimally invasive system based on mathematical analysis of arterial pressure profile changes and allows continuous recording of hemodynamic measurements. Herein, we aimed to use the MostCare system to investigate the hemodynamics of patients receiving spinal anesthesia during elective cesarean section. METHODS In this observational study, we recruited 17 patients scheduled for elective cesarean section. For each patient, we acquired continuous recordings of hemodynamic parameters at 14 key timepoints: surgical admission (two baseline parameters), immediately after the administration of spinal anesthesia, six subsequent time points (2, 4, 6, 8, 10, and 12 min after anesthesia), during peritoneum and uterine incision, during delivery, following the administration of oxytocin, and after surgery had been completed. Statistical analysis was carried out by repeated measures analysis of variance (ANOVA). RESULTS During a twelve min period after spinal anesthesia, we observed significant reductions in mean arterial pressure (MAP), dicrotic pressure (Pdic), cardiac index (CI), stroke volume index (SVI), dP/dtmax, and cardiac cycle efficiency (CCE) (P

Background: Oxaliplatin resistance is a major challenge for treatment of metastatic colorectal cancer (mCRC). Many molecular targeted drugs for refractory CRC have been developed to solve colorectal cancer drug resistance, but their effectiveness and roles in the progression of CRC and oxaliplatin- resistance still not clear.Methods: PDOs derived from CRC patients were constructed to conduct the sensitivity assays of oxaliplatin in vitro. Oxaliplatin resistant PDOs were selected and treated under the combined treatment of ML264(a KLF5 inhibitor) and oxaliplatin to determine the effects of KLF5 inhibition on apoptosis. Using CRC cell lines to investigate downstream mechanisms and xenograft models to confirm whether ML264 can restore oxaliplatin sensitivity of CRC cells in vivo.Results: We successfully constructed CRC PDOs and conducted the sensitivity test of oxaliplatin in PDOs from different patients. We found that ML264 restores oxaliplatin sensitivity in CRC PDOs by restoring the apoptotic response, and this effect was achieved by inhibiting the KLF5/Bcl-2/caspase3 signal pathway. Chromatin immunoprecipitation (ChIP) and luciferase reporter assay verified that KLF5 promoted the transcription of Bcl-2 in CRC cells. KLF5 inhibition also overcomed oxaliplatin resistance in xenograft tumors.Conclusions: Our study demonstrated that ML264 can restores oxaliplatin sensitivity in CRC PDOs by restoring the apoptotic response. KLF5 might be a potential therapeutic target for CRC resistant to oxaliplatin. PDOs have strong potential in evaluating inhibitors and drug combinations therapy in a preclinical environment.

Background Post-spinal anesthesia hypotension during cesarean delivery is caused by decreased systemic vascular resistance due to the blockage of the autonomic nerves, which is further worsened by inferior vena cava (IVC) compression by the gravid uterus. This study aimed to assess whether peak velocity and diameter of the IVC below the xiphoid or right common femoral vein (RCFV) in the inguinal region, as measured on ultrasound, could reflect the degree of IVC compression and further identify parturients at risk of post-spinal hypotension. Methods Fifty-six parturients who underwent elective cesarean section with spinal anesthesia were included in this study; peak velocities and anteroposterior diameters of the IVC and peak velocities and transverse diameters of the RCFV were measured using ultrasound before anesthesia. The primary outcome was the ultrasound measurements of IVC and RCFV acquired before spinal anesthesia and their association with post-spinal hypotension. Hypotension was defined as a drop in systolic arterial pressure by > 20% from the baseline. Multinomial logistic regression analysis was used to identify the association between the measurements of IVC, RCFV, and post-spinal hypotension during cesarean delivery. Receiver operating characteristic curves were used to test the abilities of the identified parameters to predict post-spinal hypotension; the areas under the curve and optimum cut-off values for the predictive parameters were calculated. Results A longer transverse diameter of the RCFV was associated with the occurrence of post-spinal hypotension (odds ratio = 2.022, 95% confidence interval [CI] 1.261–3.243). The area under the receiver operating characteristics curve for the prediction of post-spinal hypotension was 0.759 (95% CI 0.628–0.890, P = 0.001). A transverse diameter of > 12.2 mm of the RCFV could predict post-spinal hypotension during cesarean delivery. Conclusions A longer transverse diameter of RCFV was associated with hypotension and could predict parturients at a major risk of hypotension before anesthesia. Trial registration This study was registered at http://www.chictr.org.cn on 16, May, 2018. No. ChiCTR1800016163.

Background: The pain control effect of ketamine versus control in women during cesarean operation is not well determined. Objectives: The present meta-analysis aimed to evaluate the clinical efficacy of ketamine versus control in cesarean section anesthesia for reducing the postoperative pain and analgesia. Study Design: We used meta-analysis to address this concern. Setting: Meta-analysis-based study. Methods: The databases PubMed, Embase, and the Cochrane Library were systematically searched to identify the relevant randomized controlled trials (RCTs) of ketamine versus control in controlling pain after cesarean section from inception to August 2018. Based on the Cochrane Handbook, the combined analysis was performed using Revman 5.3 software. Results: A total of 20 RCTs with 1,737 patients who underwent cesarean section were included. Meta-analysis showed that the pain score in the ketamine group was less than that of the control group (mean difference [MD], –1.10; 95% confidence interval [CI], –1.61, –0.59; P < 0.0001). Application of ketamine during cesarean section also resulted in decreased consumption of morphine when compared with the control group (MD, –6.11 mg; 95% CI, –9.93, –2.29; P = 0.002). In addition, the first time required for analgesia was significantly longer in the ketamine group than that of the control group (MD, 72.48 minutes; 95% CI, 50.85, 94.11; P < 0.00001). Limitations: Limited patients were included with moderate strength. Conclusions: Ketamine supplementation during cesarean section reduces pain and morphine consumption and prolongs the postoperative analgesia. Key words: Ketamine, cesarean section, randomized controlled trials, meta-analysis

BACKGROUND The processes of mechanical ventilation-induced lung injury (VILI) triggers the release of high-mobility group box 1 (HMGB1), a prominent damage-associated molecular pattern (DAMP) family member, which can cause damage to pulmonary vascular endothelial cells. We aimed to determine whether propofol protected against endothelial cell injury induced by HMGB1 in vitro and in vivo. MATERIAL AND METHODS ICR mice (male) were mechanically ventilated for 4 h after anesthetization at both low tidal volume (LVT, 6 ml/kg) and high tidal volume (HVT, 30 ml/kg). A propofol bolus (10 mg/kg) was administered to the animals prior to the onset of ventilation, followed by infusion at 5 mg/(kg·h). We obtained confluent cultures of mouse lung vascular endothelial cells (MLVECs) and then performed cyclic stretching at 20% stretch for 4 h with or without propofol. RESULTS HMGB1 reduced the expression of tight junctions between endothelial cells, including VE-cadherin and ZO-1, and increased endothelial permeability, and both were blocked by propofol. We found that MLVECs exhibited mitochondrial oxidative damage by HMGB1, which was successfully suppressed through administration of MnTBAP as well as propofol. Propofol ameliorated HVT-associated lung vascular hyperpermeability and HMGB1 production in vivo. Propofol also inhibited HMBG1 release caused by cyclic stretching in MLVECs in vitro. CONCLUSIONS Our results prove that the cyto-protective function of propofol protects against lung ventilation-induced dysfunction of the lung endothelial barrier. This function of propofol is mediated through inhibition of HMGB1 release caused by mechanical stretching and mitochondrial oxidative damage triggered by HMGB1.

BACKGROUND: Evidence showed that the use of epidural analgesia increased the risk of maternal fever during labor, and the potential mechanisms involved inflammation. Lymphocyte played a role in the inflammatory responses, and lymphopenia predicted adverse outcomes for patients. The aim of this study was to investigate whether lymphocyte count was associated with the incidence of intrapartum fever in nulliparous women undergoing vaginal delivery. METHODS: In this retrospective cohort study, electronic medical record data at the International Peace Maternity and Child Health Hospital (IPMCH, Shanghai, China) between 2012 and 2017 were extracted. The primary outcome of this study was baseline lymphocyte count in febrile and afebrile parturients who received labor epidural analgesia. Other confounding factors associated with the development of intrapartum fever were analyzed using multivariable logistic regression. RESULTS: The final study population consisted of 36,562 parturients, of whom 18,952 (51.8%) received labor epidural analgesia. Labor epidural analgesia was associated with an increased risk of maternal fever [relative risk: 4.55; 95% confidence interval (CI): 4.16–4.98; P

CRC (colorectal cancer) is one of the most malignant tumours in both developing and developed countries. It is estimated that 60% of CRC patients have liver metastasis. In the present study, we show that miR-30b is an important regulator in human CRC migration and invasion, which are vital steps in CRC liver metastasis. miR-30b was significantly down-regulated in primary CRC specimens compared with normal tissues. Furthermore, miR-30b was much lower in liver metastasis tissues than in CRCs. We validated SIX1 (SIX homeobox 1), a member of the SIX homeodomain family of transcription factors and an EMT (epithelial–mesenchymal transition)-promoting gene, as the direct target of miR-30b . Forced expression of miR-30b inhibited CRC cell migration and invasion in vitro via its target gene SIX1 . Furthermore, an inverse correlation between expression of SIX1 and miR-30b has been observed both in primary CRC specimens and liver metastasis. Taken together, miR-30b plays an important role in mediating metastatic related behaviour in CRC . miR-30b may serve as a potential diagnostic marker and therapeutic target for patients with CRC in the future. Abbreviations: CRC, colorectal cancer; EGF, epidermal growth factor; EMT, epithelial–mesenchymal transition; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HEK, human embryonic kidney; IHC, immunohistochemistry; LM, liver metastasis; qPCR, quantitative real-time PCR; SIX1, SIX homeobox 1; ZEB1, zinc finger E-box-binding homeobox 1

Background The pleth variability index (PVI) has been demonstrated to be a useful, noninvasive indicator of continuous fluid responsiveness. Whether PVI can be used to assess the changes of intravascular volume status remains to be elucidated. Material/Methods Using correlation analysis and receiver operating characteristic (ROC) curves, we sought a correlation between PVI and the initial distribution volume of glucose (IDVG), evaluating PVI as an indicator of the central extracellular fluid volume after anesthesia induction in patients undergoing elective abdominal surgery. Results Strong negative correlations existed between IDVG and PVI (r=−0.72), IDVG, and pulse pressure variation (PPV) (r=−0.73), and between IDVG and systolic pressure variation (SPV) (r=−0.53), P

Background: As a relatively new drug in obstetrical anesthesia, norepinephrine is less likely to induce bradycardia and decrease cardiac output, which makes it a potential alternative to phenylephrine. The purpose of this study was to determine the optimal norepinephrine bolus dose needed to either prevent or reverse hypotension after the use of combined spinal and epidural (CSE) anesthesia in 90% of women during elective cesarean delivery (CD). Methods: Eighty women undergoing elective CD were randomly allocated into either a prophylactic group or a rescue group in this dose finding study. If the women’s systolic blood pressure (SBP) was maintained above 80% of their baseline, the next patient had an 8/9 th chance of receiving the same dose or a 1/9 th chance of receiving a lower dose. If the patient’s SBP was not maintained, a higher dose was used for next patient. The primary outcome was the successful use of the norepinephrine bolus dose to maintain SBP above 80% of the baseline until after delivery. Secondary outcomes included nausea, vomiting, breathlessness, dizziness, hypertension, bradycardia due to hypotension and supplemental use of atropine and norepinephrine, upper sensory level of anesthesia, umbilical vein (UV) blood gases, and 1- and 5-minute Apgar scores. The 90% effective dose (ED 90 ) and 95% confidence interval (95% CI) were estimated using isotonic regression methods. Results: The estimated ED90 of the norepinephrine prophylactic bolus was 10.85 µg (95% CI, 9.20– 11.67 µg) and that of the norepinephrine rescue bolus was 12.3 µg (95% CI, 10.0–12.8 µg) using isotonic regression methods. Conclusions: For norepinephrine, either a prophylactic bolus dose of 11 µg or a rescue bolus dose of 12 µg was recommended for clinical practices.

Whether pulse oximeter perfusion index (PI) may be applied to detect the onset of caudal block in pediatric patients under ketamine intravenous basal anesthesia is investigated. 40 ASA I, 2–8-year-old boys scheduled for elective circumcision surgery were randomized into two groups. Group I: 20 patients were anesthetized by 2 mg·kg−1 ketamine intravenous injection (IV) followed by caudal block using 1 mL·kg−1 lidocaine (1%); Group II: 20 patients were anesthetized by 2 mg·kg−1 ketamine IV only. PI on the toe in Group II decreased by 33 ± 12%, 71 ± 9% and 65 ± 8% at 1 min, 15 min, and 30 min after ketamine injection. The maximum increase in MAP and HR after ketamine IV was 11 ± 6% at 3 min and 10 ± 6% at 2 min. Compared to the PI value before caudal injection of lidocaine, PI in Group I increased by 363 ± 318% and 778 ± 578% at 5 min and 20 min after caudal block, while no significant changes in MAP and HR were found compared to the baseline before caudal block. Thus, PI provides an earlier, more objective, and more sensitive indicator to assess the early onset of caudal block under basal ketamine anesthesia.

Recent studies have found that propofol may protect brain from cerebral ischemic-reperfusion injury. However, the underlying mechanism remains unclear. The effects of propofol were evaluated in HBVSMC after hypoxia/reoxygenation (H/R). Cell viability and levels of SOD, LDH, and MDA were measured. Apoptosis was detected by flow cytometry. The levels of Bax, Bcl-2, Caspase3, Sur2b, Kir6.1, JNK, p-JNK, mTOR, and p-mTOR proteins were measured by western blotting. H/R decreased cell viability and SOD activity and increased LDH leakage and MDA content in HBVSMC, all of which were significantly reversed by propofol. Propofol suppressed the levels of H/R-induced apoptosis. The expression of Bcl-2 and p-mTOR was significantly downregulated and the expression levels of Bax, Caspase3, Kir6.1, and p-JNK were upregulated following H/R injury. The ratio of p-JNK/JNK was increased; however, that of p-mTOR/mTOR decreased correspondingly. The effects on the expression of these proteins were reversed by propofol treatment. SP600125 enhanced and Everolimus attenuated the effect of propofol. These findings suggested that the protective effect of propofol against H/R injury in the HBVSMC was through the inhibition of apoptosis by inducing the expression of Bcl-2 and p-mTOR as well as inhibiting the expression levels of Bax, Caspase3, Kir6.1, and p-JNK.