Objective To investigate the causal relationship between gut microbiota and pigmented villonodular synovitis using Mendelian randomization analysis.Methods We conducted a two-sample Mendelian randomization analysis to investigate the causal relationship between 211 gut microbiome taxa and pigmented villonodular synovitis based on GWAS summary data,with inverse variance weighted(IVW)analysis as the primary result and the other methods as supplementary analyses.The reliability of the results was tested using Cochran's Q test,MR-Egger regression,MR-PRESSO method and conditional Mendelian randomization analysis(cML-MA).Results The increased abundance of Barnesiella(OR=3.12,95%CI:1.15-8.41,P=0.025)and Rumatococcaceae UCG010(OR=4.03,95%CI:1.19-13.68,P=0.025)may increase the risk of pigmented villous nodular synovitis,and elevated abundance of Lachnospiraceae(OR=0.33,95%CI:0.12-0.91,P=0.032),Alistipes(OR=0.16,95%CI:0.05-0.53,P=0.003),Blautia(OR=0.20,95%CI:0.06-0.61,P=0.005),and Lachnospiraceae FCS020 group(OR=0.38,95%CI:0.15-0.94,P=0.036)and Ruminococcaceae UCG014(OR=0.36,95%CI:0.14-0.94,P=0.037)were all associated with a reduced risk of pigmented villonodular synovitis,which were supported by the results of sensitivity analyses.Reverse Mendelian randomization analysis did not reveal any inverse causal association.Conclusion Increased abundance of specific intestinal microorganisms is associated with increased or decreased risks of developing hyperpigmented villonodular synovitis,and gut microbiota plays an important role in the pathogenesis of this disease.

Objective To investigate the causal relationship between gut microbiota and pigmented villonodular synovitis using Mendelian randomization analysis.Methods We conducted a two-sample Mendelian randomization analysis to investigate the causal relationship between 211 gut microbiome taxa and pigmented villonodular synovitis based on GWAS summary data,with inverse variance weighted(IVW)analysis as the primary result and the other methods as supplementary analyses.The reliability of the results was tested using Cochran's Q test,MR-Egger regression,MR-PRESSO method and conditional Mendelian randomization analysis(cML-MA).Results The increased abundance of Barnesiella(OR=3.12,95%CI:1.15-8.41,P=0.025)and Rumatococcaceae UCG010(OR=4.03,95%CI:1.19-13.68,P=0.025)may increase the risk of pigmented villous nodular synovitis,and elevated abundance of Lachnospiraceae(OR=0.33,95%CI:0.12-0.91,P=0.032),Alistipes(OR=0.16,95%CI:0.05-0.53,P=0.003),Blautia(OR=0.20,95%CI:0.06-0.61,P=0.005),and Lachnospiraceae FCS020 group(OR=0.38,95%CI:0.15-0.94,P=0.036)and Ruminococcaceae UCG014(OR=0.36,95%CI:0.14-0.94,P=0.037)were all associated with a reduced risk of pigmented villonodular synovitis,which were supported by the results of sensitivity analyses.Reverse Mendelian randomization analysis did not reveal any inverse causal association.Conclusion Increased abundance of specific intestinal microorganisms is associated with increased or decreased risks of developing hyperpigmented villonodular synovitis,and gut microbiota plays an important role in the pathogenesis of this disease.

Objective To delve into the causal relationship between 211 gut microbiota and sepsis employing bidirectional Mendelian randomization(MR).Methods The gut microbiota genome-wide association study(GWAS)data from the Microbiome Genetics Consortium(MiBioGen,n = 18 340)and sepsis GWAS data from the FinnGen(n = 286 146)were harnessed for this study.Initially,single nucleotide polymorphisms(SNP)significantly associated with the relative abundance of 211 gut microbiota taxa were identified as instrumental variables using predefined selection criteria.The primary analytical approach was characterized by the application of inverse variance weighting(IVW),with the effect measure represented by the odds ratio(OR)to assess the results of MR.To ensure precision and reliability,analyses were conducted,including leave-one-out analysis,heterogeneity testing,and tests for pleiotropy at both coherent and incoherent levels.Results The increased risk of sepsis was associated with the elevated abundance of Collinsella[OR = 1.28,95%confidence interval(95%CI)was 1.06-1.56,P = 0.01]and Ruminococcus(OR = 1.19,95%CI was 1.05-1.35,P = 0.005).Furthermore,a protective effect against the development of sepsis was observed in association with the increased abundance of Prevotella(OR = 0.88,95%CI was 0.79-0.97,P = 0.01)and Firmicutes(OR = 0.86,95%CI was 0.75-0.996,P = 0.04).No obvious heterogeneity and irrelevant level pleiotropy were detected.Conclusion Collinsella and Ruminococcus increase the risk of sepsis,while Prevotella and Firmicutes have protective effects against sepsis.

Objective:To evaluate the efficacy of esketamine for patient-controlled intravenous analgesia (PCIA) in elderly patients undergoing modified radical mastectomy for breast cancer.Methods:Ninety elderly female patients, aged 65-78 yr, weighing 46-75 kg, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, undergoing elective modified radical surgery for breast cancer under general anesthesia, were divided into 2 groups ( n=45 each) using a random number table method: esketamine PCIA group (group E) and sufentanil PCIA group (group S). Anesthesia was induced with target-controlled infusion of propofol, intravenous atracurium besylate and sufentanil and maintained with target-controlled infusion of propofol and remifentanil and intermittent intravenous boluses of cis-benzenesulfonic acid atracurium.The patients were connected to an analgesic pump for PCIA at 10 min before completion of operation.The PCIA solution in group E contained esketamine 2 mg/kg, ketorolac tromethamine 90 mg and tropisetron 5 mg in 100 ml of normal saline.The PCIA solution in group S contained sufentanil 1 μg/kg, ketorolac tromethamine 90 mg and tropisetron 5 mg in 100 ml of normal saline.The PCA pump was set up with a 1.5 ml bolus dose, a 15 min lockout interval and background infusion at a rate of 1.5 ml/h, and the analgesia was performed until 48 h after operation.When numeric rating scale score ≥ 4 points and the efficacy of patient-controlled analgesia was not good, tramadol 100 mg was intravenously injected for rescue analgesia.Steward recovery scores were recorded at 4, 8, 24 and 48 h after operation.The requirement for rescue analgesia, effective pressing times of analgesic pump and time to first flatus were recorded within 48 h after operation.The nausea and vomiting, respiratory depression, dizziness and pruritus within 48 h after operation and delirium within 7 days after operation were recorded.The 40-item Quality of-Recovery scale was used to evaluate the early postoperative recovery of patients at 24 and 48 h after operation. Results:Compared with group S, the 40-item Quality of Recovery scale score was significantly increased at each time point, postoperative time to first flatus was shortened, the incidence of postoperative nausea and vomiting and pruritus was decreased ( P<0.05), and no significant change was found in the Steward recovery score at each time point after operation, effective pressing times of PCA and requirement for rescue analgesia in group E ( P>0.05). Conclusions:Esketamine provides better efficacy than sufentanil when used for PCIA in elderly patients undergoing modified radical mastectomy for breast cancer.

Iron (Fe) is an important trace element involved in many important plant physiological and metabolic processes such as photosynthesis, respiration and nitrogen metabolism. Plants maintain iron homeostasis through absorption, transporting, storage and redistribution of iron. Iron metabolism is strictly regulated in plants. Iron regulatory transcription factors and iron transporters constitute the regulatory network of plant iron absorption and transport in plants. Ferritin and iron transporter jointly regulate the response to excess iron in plants. In recent years, important progress has been made in understanding how abscisic acid (ABA) regulates iron metabolism in plants. ABA may be used as a signal to regulate the absorption, transportation and reuse of Fe, or to relieve the symptoms of iron stress by regulating the oxidative stress responses in plants. In order to gain deeper insights into the crosstalk of ABA and iron metabolism in plants, this review summarized the mechanisms of iron absorption and transport and metabolic regulatory network in plants, as well as the mechanisms of ABA in regulating iron metabolism. The relationship between ABA and FER-like iron deficiency-induced transcription factor (FIT), iron-regulated transporter 1 (IRT1), and oxidative stress of iron deficiency were highlighted, and future research directions were prospected.
Abscisic Acid/metabolism* ; Gene Expression Regulation, Plant ; Homeostasis ; Iron/metabolism* ; Plants/metabolism* ; Transcription Factors/metabolism*

OBJECTIVE：To investigate the effects of d exmedetomidine on postoperative delirium （POD） in liver tumor resection elderly patients with sleep disorder （SD）. METHODS ：Totally 80 patients undergoing liver tumor resection with preoperative Pittsburgh sleep quality index （PSQI）score ≥7 were selected from the Affiliated Cancer Hospital of Zhengzhou University from Jan. 1st，2020 to Oct. 31st，2020. They were randomly divided into group SD and group Dex according random number table ，with 40 cases in each group. At the same time ，40 patients with preoperative PSQI score ＜7 were selected as group C. Thirty min before anesthesia induction ，Dexmedetomidine hydrochloride injection 0.4 μg/kg was injected intravenously in group Dex. Etomidate emulsion injection ，Sufentanil citrate injection and Rocuronium bromide injection were used for anesthesia induction in 3 groups，and Ropofol medium/long chain fat emulsion injection + Remifentanil hydrochloride for injection was used to maintain anesthesia. The drug use ，operation time ，PACU stay time and postoperative hospital stay were recorded in 3 groups. The cognitive function was evaluated 2 h before operation and 1，3，5，7 days after operation. The occurrence of POD was observed. The plasma levels of IL- 6 and S 100β were measured 2 h before operation ，2 h after operation ，1，3，5 days after operation. The occurrence of ADR was recorded. RESULTS ：There was no statisti cal significance in intraoperativ e drug use and operation time among 3 groups （P＞0.05）. The PACU stay time ， the incidence of POD and the duration of POD in group SD an d lixxi18@126.com group Dex were significantly higher or longer than group C ， while the Dex group was significantly lower or shorter thangroup SD （P＜0.05）. The postoperative hospitalization stay ofgroup SD was significantly longer than group C and group Dex （P＜0.05），and there was no statistical significance between group Dex and group C （P＞0.05）. Before operation ，there was no statistical significance in MMSE scores or plasma levels of IL- 6 and S100β among 3 groups（P＞0.05）. MMSE scores of group C 1，3 days after operation ，those of group SD and group Dex 1，3，5 and 7 days after operation were significantly lower than those before operation. MMSE scores of group SD and group Dex 1，3，5 and 7 days after operation were significantly lower than group C at corresponding period ；the group Dex was significantly higher than the group SD at corresponding period （P＜0.05）. The plasma levels of IL- 6 and S 100 β at different time points were significantly higher than before operation ，and the group SD and group Dex were significantly higher than the group C ，and the group Dex was significantly lower than group SD at corresponding period （P＜0.05）. There was no statistical significance in the total incidence of ADR among 3 groups（P＞0.05）. CONCLUSIONS ：SD can promote the occurrence of POD in liver tumor resection elderly patients. Dexmetomidine can reduce the incidence of POD in elderly patients with preoperative SD ，the mechanism of which may be associated with the inhibition of IL- 6 and S 100β expression and the alleviation of brain injury with good safety.

OBJECTIVE：To c ompare the effects o f intravenous anesthesia with remimazolam and propofol on perioperative cellular immune function in patients underwent radical mastectomy. METHODS ：Eighty patients underwent selective radical mastectomy were collected ，and then randomly divided into remimazolam group （group R ）and propofol group （group P ）. During anesthesia induction ，group R was intravenously injected with remimazolam 0.2 mg/kg+sufentanil 0.3 μg/kg+cisatracurium 0.2 mg/kg；group R was intravenously injected with propofol 2 mg/kg+sufentanil 0.3 μg/kg+cisatracurium 0.2 mg/kg. During anesthesia maintenance，group R was intravenously pumped with remimazolam 0.4-1.2 mg/（kg·h）+remifentanil 0.1-0.2 μg（/ kg·min）；group P was intravenously pumped with propofol 4-10 mg/（kg·h）+remifentanil 0.1-0.2 μg（/ kg·min）. Both groups were given intravenous injection of cisatracurium intermittently. The anesthesia depth was monitored during the operation and the pumping speed of remimazolam，propofol and remifentanil was adjusted accordingly. The intraoperative infusion volume ，blood loss ，operation time ， opioid dosage ，and visual analogue scale （VAS）scores at 24 and 72 hours after operation were recorded in 2 groups；at the same time，the levels of T lymphocyte CD 3+，CD4+，CD8+ and NK cells were measured 30 min before anesthesia induction ，24 h and 72 h after operation ；CD4+/CD8+ was also calculated. The incidence of ADR was recorded in 2 groups. RESULTS ：There was no statistical significance in intraoperative infusion volume ，blood loss ，operation time ，opioid dosage ，VAS score at 24，72 hours after operation and the incidence of ADR between 2 groups（P＞0.05）. Compared with 30 min before anesthesia induction ，the levels of CD 3+，CD4+，NK cells and CD 4+/CD8+ ratio in 2 groups at 24 hours after operation were significantly decreased （P＜ 0.05）；compared with group P ，the levels of CD 3+，CD4+ and NK cells as well as CD 4+/CD8+ ratio in group R increased significantly in group R （P＜0.05）. CONCLUSIONS ：For anesthesia maintenance ，the inhibitory effects of remimazolam on perioperative cellular immunity in patients underwent radical mastectomy are poorer than propofol.

Objective:To evaluate the efficacy of sugammadex for the reversal of residual neuromuscular blockade after laparoscopic radical gastrectomy in elderly patients.Methods:Sixty patients of both sexes, aged 65-85 yr, with body mass index of 20-26 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, undergoing elective laparoscopic radical gastrectomy under general anesthesia, were divided into 2 groups ( n=30 each) by a random number table method: sugammadex group (S group) and neostigmine group (N group). Rocuronium 0.3-0.6 mg·kg -1·h -1 was intravenously infused during operation, and the muscle relaxation was monitored by a Veryark-TOF monitor, maintaining TOF ratio=0 and counting 1 or 2 after tonic stimulation.Rocuronium was discontinued when the peritoneum was closed.The patients were admitted to the PACU after operation.When the muscle relaxation monitoring T 2 appeared, sugammadex 2 mg/kg was intravenously injected in S group, and neostigmine 0.03 mg/kg plus atropine 0.015 mg/kg was intravenously injected in N group.The tracheal tube was removed after the patient′s consciousness and spontaneous breathing recovered.Before anesthesia (T 1) and 5 and 30 min after tracheal extubation (T 2, 3), arterial blood samples were collected for blood gas analysis, PaO 2 and PaCO 2 were recorded, and ultrasound was used to measure the diaphragm end-inspiratory thickness, end-expiratory thickness and mobility of diaphragm muscle at the above time points.The diaphragm thickening fraction was calculated.The time of T 2 appeared, time of extubation, time of postanesthesia care unit (PACU) stay, postoperative hospital stay, and residual neuromuscular blockade (TOF ratio <0.9) and hypoxemia occurred within 30 min after extubation were recorded.The pulmonary complications within 7 days after operation were recorded. Results:Compared with group N, PaO 2 was significantly increased and PaCO 2 was decreased at T 2, 3, the mobility of diaphragm muscle and diaphragm thickening fraction were increased at T 2, the tracheal extubation time, time of PACU stay and postoperative hospital stay were shortened, the residual neuromuscular blockade and hypoxemia occurred after extubation and incidence of pulmonary complications after operation were decreased ( P<0.05), and no significant change was found in the time of T 2 appeared in group S ( P>0.05). Conclusion:Sugammadex can quickly and effectively reverse the residual neuromuscular blockade after laparoscopic radical gastrectomy, which is helpful for early postoperative recovery in elderly patients.

Objective:To evaluate the effect of operation duration on the pharmacokinetics of desflurane in the patients undergoing tumor resection.Methods:One hundred and fifty patients of both sexes, aged 18-75 yr, with body mass index of 19-25 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, in whom abnormal preoperative lung function was not found, undergoing elective surgery with general anesthesia from November 2019 to March 2020, were enrolled in this study.Anesthesia was induced with intravenous injection of sufentanil 0.3 μg/kg, cisatracurium besylate 0.2 mg/kg and propofol 2 mg/kg.The patients were tracheally intubated after mechanical ventilation.Anesthesia was maintained with inhalation of desflurane, the vaporizer dial was adjusted to 6% with fresh gas flow rate of 2 L/min, and sufentanil and cisatracurium besylate were intermittently injected intravenously according to the changes in hemodynamics and degree of muscle relaxation during operation.The duration required for the end-tidal concentration of desflurane reaching 0.5 minimum alveolar concentration (MAC), time when the ratio of the end-tidal concentration of desflurane to the pre-set concentration of the vaporizer reached 1/2, time when the ratio of the end-tidal concentration of desflurane to the inhaled concentration reached 1/2, time for the end-tidal concentration of desflurane to decrease to 0.5 MAC and time for the end-tidal concentration to decrease from 0.5 MAC to 0.2 MAC immediately after closing the volatile tank were recorded.The patients were divided into 3 groups according to the operation time: operation time <2 h group (group S), operation time 2-4 h group (group M), and operation time >4 h group (group L). Results:There were no significant differences among the 3 groups in the duration required for the end-tidal concentration of desflurane reaching 0.5 MAC, time when the ratio of the end-tidal concentration of desflurane to the pre-set concentration of the vaporizer reached 1/2, time when the ratio of the end-tidal concentration of desflurane to the inhaled concentration reached 1/2, time for the end-tidal concentration of desflurane to decrease to 0.5 MAC and time for the end-tidal concentration to decrease from 0.5 MAC to 0.2 MAC immediately after closing the vaporizer ( P>0.05). Conclusion:Operation duration does not affect the pharmacokinetics of desflurane in the patients undergoing tumor resection.

Objective:To evaluate the effect of remimazolam pretreatment on brain injury following thalamic hemorrhage in mice.Methods:Sixty clean-grade healthy adult CD1 male mice, weighing 25-30 g, aged 7-8 weeks, were divided into 3 groups ( n=20 each) by using a random number table method: sham operation group (Sham group), brain injury group (BI group) and remimazolam pretreatment group (Rem group). Remimazolam 25 mg/kg was intravenously injected via the tail vein in group Rem.and the equal volume of normal saline was given instead in Sham group and BI group.Ten min later, type Ⅳ collagenase 0.01 U/10 nl was microinjected into unilateral ventroposterolateral nucleus and ventromedial nucleus to develop a mouse model of brain jury induced by thalamic hemorrhage.The rats were sacrificed at 6 h after developing the model, brain tissues were taken for measurement of the wet/dry weight (W/D) ratio, and hippocampal tissues were taken and stained with haematoxylin and eosin for determination of the count of the viable neurons in the hippocampal dentategyrus area, count of apoptotic neurons in the hippocampal CA1 region (by TUNEL), expression of CCAAT/enhancer-binding protein homologous protein (CHOP), activating transcription factor 4 (ATF4) and X-box binding protein-1 (XBP1) mRNA (by real-time polymerase chain reaction) and expression of CHOP, Bcl-2, Bax and caspase-3 (by Western blot) and for microscopic examination of ultrastructure of hippocampal tissues (with a transmission electron microscope). Results:Compared with group Sham, the W/D ratio of brain tissues and count of apoptotic neurons in the hippocampal CA1 area were significantly increased, the count of viable neurons in the hippocampal dentate gyrus was decreased, the expression of CHOP, ATF4 and XBP1 mRNA in hippocampal tissues was up-regulated, the expression of CHOP, caspase-3 and Bcl-2 was up-regulated, and the expression of Bax was down-regulated in BI and Rem groups ( P<0.05). Compared with group BI, the W/D ratio of brain tissues and count of apoptotic neurons in the hippocampal CA1 area were significantly decreased, the number of viable neurons in the hippocampal dentate gyrus was increased, the expression of CHOP, ATF4 and XBP1 mRNA in hippocampal tissues was down-regulated, the expression of CHOP, caspase-3 and Bcl-2 was down-regulated, and the expression of Bax was up-regulated in group Rem ( P<0.05). Conclusion:Remimazolam pretreatment can reduce the brain injury following thalamic hemorrhage in mice, and the mechanism may be related to inhibition of cell apoptosis induced by endoplasmic reticulum stress in hippocampus.