Objective:To investigate the effect of dexmedetomidine (DEX) on intestinal barrier function impairment in gynecologic neoplasms patients undergoing laparoscopic surgery and the possible role of silent information regulator 1 (SIRT1) in this process.Methods:A prospective randomized controlled study was conducted. Forty patients who were to undergo laparoscopic surgery of gynecologic neoplasms under general anesthesia in the Second Hospital of Shanxi Medical University from May 2022 to May 2023 were prospectively selected. All patients were divided into the experimental group and the control group using the method of randomized numerical table, with 20 cases in each group. The experimental group was given a loading dose of DEX 0.5 μg/kg (intravenously pumped in 10 min) before induction of general anesthesia, and then maintained with DEX 0.2 μg·kg -1·h -1 until 30 min before the end of surgery. In the control group, the same dose of 0.9% sodium chloride injection was pumped intravenously. Taking 5 ml of peripheral venous blood from the upper extremities 10 min before induction of anesthesia (T 1), 1 h after the release of pneumoperitoneum (T 2) and 24 h after the release of pneumoperitoneum (T 3), respectively, the serum levels of SIRT1 and Claudin-1 proteins were measured by enzyme-linked immunosorbent assay. Then the concentrations of SIRT1 and Claudin-1 proteins and the time of first postoperative exhaust in the two groups of patients were compared. Results:The differences in age, body mass index, pneumoperitoneum time, operation time and anesthesia time between the two groups were not statistically significant (all P >0.05). At T 1, there was no statistically significant difference in concentrations of SIRT1 [(10.2±1.5) ng/ml vs. (10.0±1.3) ng/ml, t = 0.46, P = 0.468] and Claudin-1 [(405±45) pg/ml vs. (404±40) pg/ml, t = 0.13, P = 0.901] proteins between the control group and the experimental group. At T 2, the concentrations of SIRT1 [(8.4±1.3) ng/ml vs. (6.1±1.3) ng/ml, t=-5.55, P<0.001] and Claudin-1 [(383±39) pg/ml vs. (331±44) pg/ml, t=-4.02, P<0.001] proteins in the experimental group were higher than those in the control group, the differences were statistically significant. At T 3, the concentrations of SIRT1 [(8.4±1.2) ng/ml vs. (6.7±1.1) ng/ml, t=-4.56, P<0.001] and Claudin-1 [(388±40) pg/ml vs. (341±43) pg/ml, t=-3.63, P<0.001] proteins in the experimental group were higher than those in the control group, the differences were statistically significant. The time of first postoperative exhaust in the experimental group was shorter than that in the control group [(21.7±2.2) h vs. (27.9±3.4) h], and the difference was statistically significant ( t =6.78, P < 0.001). Conclusions:Dexmedetomidine may reduce the intestinal epithelial cell injury induced by laparoscopic surgery in patients with gynecologic neoplasms via activating SIRT1, and exert a protective effect on intestinal barrier function.

Objective:To explore the effects of different doses of dexmedetomidine (DEX) on inflammatory factors and immune function in patients with gynecological malignant tumors who underwent laparoscopic surgery.Methods:A total of 60 patients with gynecological malignant tumors who underwent laparoscopic surgery from January 2021 to December 2021 in the Second Hospital of Shanxi Medical University were selected as the research objects. All patients were divided into the control group, low-dose DEX group (group D1) and high-dose DEX group (group D2) by using random number table method, 20 cases in each group. Patients in D1 and D2 groups were intravenously pumped DEX 0.5 μg/kg and 1.0 μg/kg 10 minutes before induction of anesthesia, and then maintained with DEX 0.5 μg·kg -1·h -1 and 1.0 μg·kg -1·h -1 until 30 minutes before the end of operation; and patients in the control group were given the same amount of Nacl solution. The 10 ml peripheral venous blood were collected at 10 minutes before induction of anesthesia (T 1), 1 h after pneumoperitoneum relief (T 2) and 24 h after pneumoperitoneum relief (T 3). The changes of interleukin-6 (IL-6), interleukin-10 (IL-10), the proportion of CD4 +, the proportion of CD8 + and CD4 +/CD8 + ratio of the three groups were compared, and the cases of bradycardia and hypotension in perioperative period and the time of first exhaust after operation were recorded. Results:At T 1,T 2 and T 3, the expression level of IL-6 in the control group was (7.95±0.26) pg/ml, (8.30±0.24) pg/ml and (8.35±0.28) pg/ml, respectively, and the difference was statistically significant ( F = 14.14, P < 0.001); the expression level of IL-10 in the control group was (38.9±2.6) pg/ml, (44.5±6.6) pg/ml and (46.3±4.6) pg/ml, respectively, and the difference was statistically significant ( F = 12.45, P < 0.001); the proportion of CD4 + in the control group was (38.5±2.1)%, (29.5±4.6)% and (29.6±3.5)%, respectively, and the difference was statistically significant ( F = 40.82, P < 0.001); the ratio of CD8 + in the control group was (30.1±3.7)%, (35.1±6.3)% and (40.3±8.2)%, respectively, and the difference was statistically significant ( F = 13.02, P < 0.001); the CD4 +/CD8 + ratio in the control group was 1.29±0.14, 0.84±0.09 and 0.75±0.14, respectively, and the difference was statistically significant ( F = 99.94, P < 0.001). The expression level of IL-6 in group D1 and group D2 was (8.10±0.32) pg/ml and (8.01±0.30) pg/ml at T 2, and (8.12±0.35) pg/ml and (8.05±0.34) pg/ml at T 3,which were lower than those in the control group, and the differences were statistically significant (all P < 0.05). The expression level of IL-10 in group D2 was (40.6±3.5) pg/ml at T 2, which was lower than that in the control group, and the difference was statistically significant ( P < 0.05). At T 3, the expression level of IL-10 in group D1 and group D2 was (43.7±3.5) pg/ml and (42.4±3.9) pg/ml, which were lower than those in the control group, and the differences were statistically significant (all P < 0.05). At T 2, the proportion of CD4 + in group D2 was (34.5±4.3)%, which was higher than that in the control group, and the difference was statistically significant ( P < 0.05). At T 3, the proportion of CD4 + in group D1 and group D2 was (32.1±4.2)% and (33.7±2.8)%, which were higher than those in the control group, and the differences were statistically significant (all P < 0.05). At T 2, the proportion of CD8 + in group D2 was (30.7±5.5)%, which was lower than that in the control group, and the difference was statistically significant ( P < 0.05). At T 3, the proportion of CD8 + in group D1 and group D2 was (35.4±5.8)% and (32.5±5.1)%, which were lower than those in the control group, and the differences were statistically significant (all P < 0.05). The CD4 +/CD8 + ratio in group D1 and D2 was 0.99±0.17 and 1.14±0.16 at T 2, 0.93±0.19 and 1.05±0.16 at T 3, which were higher than those in the control group, and the differences were statistically significant (all P < 0.05). Meanwhile, 1 case of hypotension occurred in the the control group and group D1, respectively; 3 cases of bradycardia and 2 cases of hypotension occurred in the group D2. The time of exhaust in the control group was later than that in group D1 and D2, and the difference was statistically significant ( P < 0.05). Conclusions:DEX can inhibit the inflammatory reaction during laparoscopic surgery in patients with gynecological malignant tumors, reduce immune damage. The anti-inflammatory action and immune protection of high-dose of DEX is more significant compared with low-dose of DEX, while high dose of DEX is more likely to cause hemodynamic fluctuations in perioperative period.

Objective:To explore the effects of dexmedetomidine (DEX) on intestinal stress response and cellular immune function in patients with gynecologic malignancies undergoing laparoscopic surgery.Methods:A total of 60 patients with gynecologic malignancies who scheduled to undergo laparoscopic surgery under general anesthesia in the Second Hospital of Shanxi Medical University from March 2021 to March 2022 were selected. All patients were divided into the DEX group and the control group according to the random number table method, with 30 cases in each group. The DEX group included 12 cases of cervical cancer, 10 cases of endometrial cancer and 8 cases of ovarian cancer; the control group included 14 cases of cervical cancer, 9 cases of endometrial cancer and 7 cases of ovarian cancer. The DEX group: intravenous anesthesia was induced with a dose of DEX 0.5 μg/kg (infusion was completed within 10 min), general anesthesia was maintained with DEX 0.2 μg·kg -1·h -1 pumped intravenously, and the drug was stopped 30 min before surgery. The control group: equal amount of 0.9% sodium chloride solution was pumped intravenously. The venous blood was drawn at the time points of 10 min before general anesthesia (T 0), at the end of operation (T 1) and 1 d after the operation (T 2) to detect the stress response indicators such as cortisol (COR), epinephrine (E), norepinephrine (NE) levels, and immune indicators such as CD4 +, CD8 + proportions and CD4 +/CD8 + at T 0, T 1,and T 2. In addition, the pneumoperitoneum time, general anesthesia time, operation time and intestinal function recovery time were recorded. Results:At T 0, there were no statistically significant differences in the levels of COR, E and NE between the DEX group and the control group (all P > 0.05). At T 1, the levels of COR, E and NE were (146±12) μg/L, (158±14) ng/L, (265±12) ng/L, respectively in the control group, and (136±18) μg/L, (149±15) ng/L, (158±12) ng/L, respectively in the DEX group; the levels of COR, E and NE in the DEX group were lower than those in the control group ( t values were -2.51, -2.37, -2.08, all P < 0.05). At T 2, the levels of COR, E and NE were (124±12) μg/L, (131±16) ng/L, (234±8) ng/L, respectively in the control group, and (116±15) μg/L, (123±12) ng/L, (228±10) ng/L, respectively in the DEX group; the levels of COR, E and NE in the DEX group were also lower than those in the control group ( t values were -2.35, -2.23, -2.17, all P < 0.05). At T 0, there were no statistically significant differences in the proportions of CD4 +, CD8 + and CD4 +/CD8 + between the DEX group and the control group (all P > 0.05). At T 1, the proportions of CD4 +, CD8 + and CD4 +/CD8 + were (23±3)%, (20±3)%, 1.12±0.16, respectively in the control group, and (27±4)%, (23±4)%,1.22±0.19, respectively in the DEX group; the proportions of CD4 +, CD8 + and CD4 +/CD8 + in the DEX group were higher than those in the control group ( t values were -3.43, -2.29, 2.13, all P < 0.05). At T 2, the proportions of CD4 +, CD8 + and CD4 +/CD8 + were (26±3)%, (23±4)%, 1.17±0.16, respectively in the control group, and (31±5)%, (25±4)%, 1.26±0.19, respectively in the DEX group; the proportions of CD4 +, CD8 + and CD4 +/CD8 + in the DEX group were higher than those in the control group ( t values were -4.32, -2.02, 2.02, all P < 0.05). In addition, the time of first exhaust in the DEX group was shorter than that in the control group ( P<0.05). Conclusions:DEX can reduce the intestinal stress response of gynecologic malignancies patients undergoing laparoscopic surgery, thereby improving the immunosuppression of patients. It is also of great significance to protect intestinal mucosal barrier and recover the intestinal function, and DEX has a high safety.

Objective:To explore the effect of different doses of dexmedetomidine (Dex) on levels of tight-junction protein claudin-1 and diamine oxidase (DAO) in patients undergoing laparoscopic radical resection of gynecological malignant tumors.Methods:A total of 60 patients with gynecological malignant tumors who were scheduled to undergo laparoscopic radical resection under general anesthesia from January 2019 to January 2020 in the Second Hospital of Shanxi Medical University were selected, including 43 cases of cervical cancer (stageⅠ-Ⅱ A), 9 cases of ovarian cancer (stageⅠ A-Ⅲ C), and 8 cases of endometrial carcinoma (stageⅠ). Accroding to the random number table method, the patients were divided into control group (group C), low-dose Dex group (group D 1) and high-dose Dex group (group D 2), with 20 cases in each group. Patients in group D 1 were given Dex 0.5 μg·kg -1·h -1 by constant rate intravenous infusion pump after induction until 30 min before the end of operation. Patients in group D 2 were given Dex 1.0 μg·kg -1·h -1 by constant rate intravenous infusion pump after induction until 30 min before the end of operation. Group C adopted the same calculation method and received the same amount of 0.9% sodium chloride solution by infusion pump. At 10 min before induction (T 1), 1 hour after pneumoperitoneum (T 2) and 12 hours after pneumoperitoneum (T 3), 5 ml of brachial vein blood was collected from the patients, and the levels of claudin-1 protein, DAO and blood glucose were measured. Results:At T 1, T 2 and T 3, the expression levels of claudin-1 in group C were (77.05±17.61) pg/ml, (66.76±12.97) pg/ml and (55.93±12.71) pg/ml, and the difference was statistically significant ( F = 10.449, P<0.05); the expression levels of DAO in group C were (4.83±0.93) ng/ml, (5.62±1.01) ng/ml and (5.98±1.21) ng/ml, and the difference was statistically significant ( F = 6.139, P < 0.05); the levels of blood glucose in group C were (4.82±0.66) mmol/L, (7.55±0.94) mmol/L and (6.51±0.54) mmol/L, and the difference was statistically significant ( F = 70.197, P < 0.05). At T 2, the expression level of claudin-1 in group D 1 was (69.12±13.02) pg/ml, which was not significantly different from group C ( t = -0.575, P > 0.05); the expression level of claudin-1 in group D 2 was (76.36±14.89) pg/ml, which was higher than that in group C, and the difference was statistically significant ( t = -2.175, P < 0.05). At T 3, the expression levels of claudin-1 in group D 1 and group D 2 were (66.14±14.36) pg/ml and (73.37±16.93) pg/ml, which were higher than that in group C, and the differences were statistically significant ( t values were -2.380 and -3.682, both P < 0.05). The expression levels of DAO in group D 1 and group D 2 were (5.02±0.84) ng/ml and (4.91±0.93) ng/ml at T 2, and (5.29±0.86) ng/ml and (5.20±0.98) ng/ml at T 3, which were lower than those in group C, and the differences were statistically significant ( t values were 2.051, 2.295, 2.079 and 2.285, all P < 0.05). The levels of blood glucose in group D 1 and group D 2 were (7.10±0.66) mmol/L and (6.77±0.97) mmol/L at T 2, and (5.95±0.94) mmol/L and (5.93±0.74) mmol/L at T 3, which were lower than those in group C, and the differences were statistically significant ( t values were 2.565, 5.374, 2.293 and 2.765, all P < 0.05). Conclusion:Continuous infusion of Dex can inhibit the stress response caused by long-term CO 2 pneumoperitoneum in laparoscopic radical resection of gynecological malignant tumors, and adjust the changes of expression levels of claudin-1 protein and DAO, reduce the damage of intestinal mucosal cells, facilitate the recovery of intestinal function, and the effect of high-dose Dex is better than low-dose Dex.

Objective:To explore the effects of dexmedetomidine (Dex) on perioperative intrapulmonary shunt rate (Qs/Qt), inflammatory factors and Claudin-4 in patients with esophageal cancer undergoing radical operation.Methods:Sixty patients with thoraco-laparoscopic combined esophageal cancer radical resection under general anesthesia were selected from the Second Hospital of Shanxi Medical University from March to August 2018. The patients were divided into Dex group (observation group) and 0.9% sodium chloride injection group (control group) according to the random number table method, and both groups were given the same anesthesia. In the observation group, Dex was injected intravenously before the anesthesia induction, the infusion was first performed at the loading dose of 1.0 μg/kg (the infusion was completed in 10 minutes) and then the infusion was performed at the rate of 0.4 μg·kg -1·h -1 until 30 minutes before the end of the operation. The control group was injected with the same dose of 0.9% sodium chloride injection. The radial artery blood and the subclavian venous blood was collected from the two groups at four time points of double lung ventilation for 15 minutes (T 0), 30 minutes (T 1) and 1 hour (T 2) after one-lung ventilation and 30 minutes (T 3) after the restoration of bipulmonary ventilation. The blood gas was analyzed, and Qs/Qt was calculated. The blood samples from subclavian vein were collected, and the serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and Claudin-4 were measured by enzyme-linked immunosorbent assay. Results:The Qs/Qt in the control group at T 0, T 1, T 2 and T 3 were (13.6±3.6)%, (36.1±2.9)%, (31.8±2.4)%, and (15.3±3.2)%, the difference was statistically significant, ( F = 397.273, P < 0.01), and the Qs/Qt in the observation group were (12.5±1.8)%, (27.4±3.0)%, (27.7±4.2)%, and (13.9±3.4)%, the difference was statistically significant, ( F = 205.124, P < 0.01); the Qs/Qt in the observation group at T 1 and T 2 were significantly lower than those in the control group ( t values were 178.011 and 23.791, both P < 0.05). The concentrations of TNF-α in the control group at T 0, T 1, T 2 and T 3 were (12.4±2.4) pg/ml, (20.5±3.0) pg/ml, (24.8±4.1) pg/ml, and (34.3±8.0) pg/ml, the difference was statistically significant, ( F = 109.749, P < 0.01), and the concentrations of TNF-α in the observation group were (11.4±3.0) pg/ml, (17.6±2.8) pg/ml, (17.4±3.2) pg/ml, and (26.2±5.0) pg/ml, the difference was statistically significant, ( F = 87.653, P < 0.01); the concentrations of TNF-α in the observation group at T 1, T 2 and T 3 were significantly lower than those in the control group ( t values were 10.471, 44.730 and 24.132, all P < 0.05). The concentrations of IL-6 in the control group at T 0, T 1, T 2 and T 3 were (18.4±4.0) pg/ml, (28.5±5.4) pg/ml, (40.1±6.0) pg/ml, and (43.1±6.0) pg/ml, the difference was statistically significant, ( F = 200.151, P < 0.01), and the concentrations of IL-6 in the observation group were (17.7±4.8) pg/ml, (21.9±3.9) pg/ml, (24.8±4.6) pg/ml, and (24.0±3.8) pg/ml ( F = 14.655, P < 0.01); the concentrations of IL-6 in the observation group at T 1, T 2 and T 3 were significantly lower than those in the control group ( t values were 38.983, 120.110 and 594.878, all P < 0.01). The concentrations of Claudin-4 in the control group at T 0, T 1, T 2 and T 3 were (5.9±0.8) ng/ml, (13.6±1.8) ng/ml, (14.7±4.5) ng/ml, and (16.8±2.5) ng/ml, the difference was statistically significant, ( F = 89.332, P < 0.01), the concentrations of Claudin-4 in the observation group were (5.5±0.7) ng/ml, (16.8±1.8) ng/ml, (18.0±4.8) ng/ml, and (21.2±4.4) ng/ml, the difference was statistically significant, ( F = 120.367, P < 0.01), the concentrations of Claudin-4 in the observation group at T 1, T 2 and T 3 were significantly higher than those in the control group ( t values were 54.619, 7.112 and 18.766, all P < 0.05). Conclusion:Dex can improve the intrapulmonary shunt to some extent, inhibit the inflammatory response during the operation, and increase the level of Claudin-4, which plays an active role in perioperative lung protection.

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Pre-testing preparation is the basis and starting point of genetic testing.The process includes collection of clinical information,formulation of testing scheme,genetic counseling before testing,and completion of informed consent and testing authorization.To effectively identify genetic diseases in clinics can greatly improve the diagnostic rate of next generation sequencing (NGS),thereby reducing medical cost and improving clinical efficacy.The analysis of NGS results relies,to a large extent,on the understanding of genotype-phenotype correlations,therefore it is particularly important to collect and evaluate clinical phenotypes and describe them in uniform standard terms.Different types of genetic diseases or mutations may require specific testing techniques,which can yield twice the result with half the effort.Pre-testing genetic counseling can help patients and their families to understand the significance of relevant genetic testing,formulate individualized testing strategies,and lay a foundation for follow-up.

With high accuracy and precision,next generation sequencing (NGS) has provided a powerful tool for clinical testing of genetic diseases.To follow a standardized experimental procedure is the prerequisite to obtain stable,reliable,and effective NGS data for the assistance of diagnosis and/or screening of genetic diseases.At a conference of genetic testing industry held in Shanghai,May 2019,physicians engaged in the diagnosis and treatment of genetic diseases,experts engaged in clinical laboratory testing of genetic diseases and experts from third-party genetic testing companies have fully discussed the standardization of NGS procedures for the testing of genetic diseases.Experts from different backgrounds have provided opinions for the operation and implementation of NGS testing procedures including sample collection,reception,preservation,library construction,sequencing and data quality control.Based on the discussion,a consensus on the standardization of the testing procedures in NGS laboratories is developed with the aim to standardize NGS testing and accelerate implementation of NGS in clinical settings across China.

Bioinformatic analysis and variant classification are the key components of high-throughput sequencing-based genetic diagnostic approach.This consensus is part of the effort to develop a standardized process for next generation sequencing (NGS)-based test for germline mutations underlying Mendelian disorders in China.The flow-chart,common software,key parameters of bioinformatics pipeline for data processing,annotation,storage and variant classification are reviewed,which is aimed to help improving and maintaining a high-quality process and obtaining consistent outcomes for NGS-based molecular diagnosis.

Clinical genetic testing results are compiled into a standardized report by genetic specialists and provided to clinicians and patients (Should the patient be intellectually disabled or under 18,the report will be provided to his/her parents or legal guardians).The content of genetic testing report should conform to relevant guidelines,industry standards and consensus.The decisions of clinicians will be made based on the report and clinical indications.Genetic counselors should provide post-test counseling to clinicians and patients or their authorized family members.A mechanism of follow-up visit after the genetic testing should be established with informed consent.Data should be shared by clinical institutions and genome sequencing institutions.As findings upon follow-up visit can help with further evaluation of the results,genome sequencing institutions should regularly re-analyze historical and follow-up data,and the updated results should be shared with clinical institutions.All activities involving reporting,genetic counselling,follow-up visiting,and re-analyzing should follow the relevant guidelines and regulations.