Objective:To evaluate the effective dose, efficacy and safety of remimazolam for induction of general anesthesia in super-elderly patients.Methods:Trial Ⅰ American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ patients of either sex, aged ≥80 yr, with body mass index of 18-25 kg/m 2, undergoing elective surgery with general anesthesia in the Zhejiang Provincial People′s Hospital from January to March 2022, were selected. Remimazolam 0.12 mg/kg or propofol 0.8 mg/kg was intravenously injected in the first patient, and the dose of remimazolam or propofol in the next patient was determined by using the modified Dixon′s up-and-down method. The difference between the two successive doses was 0.01 mg/kg for remimazolam and 0.05 mg/kg for propofol. A positive response was defined as achieving an anesthesia depth (BIS value ≤ 65) within 5 min of administration. If the response was positive, the next patient received a lower dose, or conversely if negative, a higher dose was given in the next patient. The 50% effective dose (ED 50) and 90% effective dose (ED 90) of remifentanil and propofol and their 95% confidence intervals ( CIs) were calculated by Probit method. Trial Ⅱ One hundred and forty-six American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅲ elderly patients of either sex, aged ≥80 yr, with a body mass index of 18-25 mg/kg, scheduled for elective surgery with general anesthesia from April to October 2023 in Zhejiang Provincial People′s Hospital, were selected and divided into 2 groups ( n=73 each) by using a random number table method: remimazolam group (R group) and propofol group (P group). R group was induced with intravenous remimazolam ED 90 and P group was induced with intravenous propofol ED 90, and the injection time was both 30 s. If the BIS value was still greater than 65 at 5 min after administration, remimazolam 0.05 mg/kg was intravenously added each time in R group and propofol 0.5 mg/kg was intravenously added each time in P group until the patient′s BIS value ≤65. The success of anesthesia induction, time for successful induction of anesthesia and rescue sedation were recorded. The occurrence of intraoperative injection pain, hypertension, hypotension, bradycardia, hypoxemia, intraoperative awareness and postoperative delirium, nausea and vomiting was also recorded. Results:Trial Ⅰ The ED 50 (95% CI) of remimazolam was 0.148 (0.139-0.157) mg/kg, and the ED 90 (95% CI) was 0.160 (0.153-0.202) mg/kg; the ED 50 (95% CI) of propofol was 0.824 (0.726-0.983) mg/kg, and the ED 90 (95% CI) was 0.916 (0.860-2.472) mg/kg. Trial Ⅱ Compared with group P, the time for successful induction of anesthesia was significantly prolonged, the incidence of intraoperative injection pain and hypotension was decreased ( P<0.05), and no significant change was found in the success rate of anesthesia induction, rate of rescue sedation, intraoperative hypertension, bradycardia, hypoxemia, postoperative delirium, and nausea and vomiting in group R ( P>0.05). Conclusions:The ED 50 and ED 90 of remimazolam for induction of general anesthesia are 0.148 and 0.160 mg/kg, respectively, in super-elderly patients. Compared to propofol, remimazolam has a slightly longer onset time, but it is safer when used for induction of general anesthesia in super-elderly patients.

Extracellular polymeric substances(EPS)constitutes crucial elements within bacterial biofilms,facili-tating accelerated antimicrobial resistance and conferring defense against the host's immune cells.Developing precise and effective antibiofilm approaches and strategies,tailored to the specific charac-teristics of EPS composition,can offer valuable insights for the creation of novel antimicrobial drugs.This,in turn,holds the potential to mitigate the alarming issue of bacterial drug resistance.Current analysis of EPS compositions relies heavily on colorimetric approaches with a significant bias,which is likely due to the selection of a standard compound and the cross-interference of various EPS compounds.Considering the pivotal role of EPS in biofilm functionality,it is imperative for EPS research to delve deeper into the analysis of intricate compositions,moving beyond the current focus on polymeric materials.This ne-cessitates a shift from heavy reliance on colorimetric analytic methods to more comprehensive and nuanced analytical approaches.In this study,we have provided a comprehensive summary of existing analytical methods utilized in the characterization of EPS compositions.Additionally,novel strategies aimed at targeting EPS to enhance biofilm penetration were explored,with a specific focus on high-lighting the limitations associated with colorimetric methods.Furthermore,we have outlined the challenges faced in identifying additional components of EPS and propose a prospective research plan to address these challenges.This review has the potential to guide future researchers in the search for novel compounds capable of suppressing EPS,thereby inhibiting biofilm formation.This insight opens up a new avenue for exploration within this research domain.

Gynecologic malignant tumors are among the leading diseases threatening women's lives and health,with the highest morbidity and mortality rates among all female diseases.These tumors originate from female reproductive organs and are typically classified based on the affected site.Ovarian cancer(OC),endometrial cancer(EC)and cervical cancer(CCA)are the most common types.Currently,gynecologic malignant tumors are primarily treated with a combination of surgery,chemotherapy and radiotherapy,where drugs play a critical role in the treatment process.However,the actual clinical effectiveness is often influenced by various factors,such as adverse reactions due to drug toxicity and the drug resistance and insensitivity observed in some patients,which limit improvements in patient survival rates.Recent studies have shown that the same type of tumor exhibits significant biological characteristics and drug response heterogeneity among different individuals,which is a key factor contributing to the varied clinical outcomes when using the same drug treatment for the same type of gynecologic malignant tumor.To achieve individualized and precise treatment for gynecologic malignant tumors,there is an urgent need to develop in vitro models that closely resemble human tumors for clinical research.Drug screening is a technique used to identify and evaluate compounds with pharmacological activity and potential therapeutic effects,providing doctors with scientific guidance on drug use,thereby avoiding blind drug testing and reducing patients'therapeutic pain and economic burden by assessing the effects of different drugs under specific conditions.Organoid models have been extensively studied as an innovative drug screening tool and personalized medicine for treating gynecologic malignancies.Organoids are tissue-like structures with a specific spatial arrangement formed in vitro through three-dimensional cell culture,capable of highly simulating the structure and function of tissues in vivo and displaying histological and genotypic characteristics very similar to human organs.This approach has largely overcome the limitations of traditional tumor models,such as patient-derived cancer cell models and patient-derived tumor xenograft models,becoming an essential research tool in oncology.It provides a more physiologically relevant experimental platform for drug screening studies of gynecologic malignancies.This paper compared the advantages and disadvantages of several preclinical cancer models,reviewed the development process of organoids,and described the establishment of gynecologic oncology organoids and their application in drug screening for ovarian,endometrial,and cervical cancers.Additionally,we discussed the current limitations of organoid technology in its application and envisioned its future development,aiming to provide insights for future medical research,particularly in new drug discovery and personalized medicine.

Objective:To compare iodine nutritional status of different populations consuming iodized salt and non-iodized salt in iodine adequate areas, and to provide a basis for formulating iodine supplementation strategies.Methods:In October 2021, Luyi County in Henan Province was selected as an iodine adequate area consuming iodized salt, while Ningling County was selected as an iodine adequate area consuming non-iodized salt. Stratified by water iodine (50 - 59, 60 - 69, 70 - 79, 80 - 89, 90 - 100 μg/L), one village was selected from each layer. One hundred children aged 8 - 10, one hundred adults, and 20 pregnant women were selected from each village to collect their urine and salt samples for testing salt and urinary iodine, and their thyroid gland was measured by ultrasound.Results:A total of 600 salt samples in Luyi County were collected, with the coverage rate of iodized salt (99.8%, 599/600) and the consuming rate of qualified iodized salt (95.5%, 573/600). A total of 1 008 salt samples in Ningling County were collected, with the rate of non-iodized salt (93.8%, 946/1 008). The median urinary iodine of children in Luyi County ( n = 240) was higher than that in Ningling County ( n = 468, 305.0 vs 232.0 μg/L, Z = - 8.10, P < 0.001). There was no statistically significant difference in median urinary iodine between pregnant women in Luyi County ( n = 120) and Ningling County ( n = 53, 240.0 vs 236.0 μg/L, Z = - 1.02, P = 0.306). The median urinary iodine of adults in Luyi County ( n = 238) was higher than that in Ningling County ( n = 486, 289.0 vs 178.5 μg/L, Z = - 11.14, P < 0.001). Children's urinary iodine ( r s = 0.21, P = 0.001) in Luyi County and adults' urinary iodine ( r s = 0.17, P < 0001) in Ningling County were positively correlated with water iodine. There was no statistically significant difference in the incidence of thyroid enlargement in children between Luyi County (0.8%, 2/240) and Ningling County (0.4%, 2/468, χ 2 = 0.80, P = 0.586), but the incidence of thyroid nodules in children in Luyi County (11.2%, 27/240) was higher than that in Ningling County (1.7%, 8/468, χ 2 = 27.36, P < 0.001). The incidence of thyroid nodules in pregnant women in Luyi County (23.3%, 28/120) was lower than that in Ningling County (46.5%, 33/71, χ 2 = 10.99, P = 0.001). There was no statistically significant difference in the incidence of adult thyroid nodules between Luyi County and Ningling County (χ 2 = 0.86, P = 0.354), with a ratio of 29.6% (71/240) to 32.9% (160/486). Conclusions:Providing population with non-iodized salt in iodine adequate areas, the overall iodine nutrition is at an appropriate level. However, children consuming iodized salt in iodine adequate areas have high level of iodine nutrition, and it is necessary to consider supplying non-iodized salt or reducing the concentration of iodized salt. Pregnant women in iodine adequate area should maintain the current policy of supplying iodized salt unchanged.

Objective:To investigate the iodine nutritional status of key populations in iodine adequate areas in Henan Province, and provide a basis for timely adoption of targeted prevention and control measures and scientific formulation of iodine supplementation strategies in iodine adequate areas.Methods:From March to September 2022, a cross-sectional survey was conducted in 60 iodine adequate counties (cities, districts) in 13 provincial-level cities in Henan Province. Administrative villages with a median water iodine level of 40 - 100 μg/L within each county (city, district) were stratified by water iodine value (40 - 49, 50 - 59, 60 - 69, 70 - 79, 80 - 89, 90 - 100 μg/L). One administrative village was selected from each water iodine layer, and 40 non boarding students aged 8 - 10 years old (age balanced, half male and half female) and 20 pregnant women were selected from each administrative village to collect their household edible salt samples and once random urine sample for test salt iodine and urinary iodine contents; and the thyroid volume of children was measured.Results:A total of 12 203 samples of household edible salt were collected from children aged 8 - 10 years old, with a median salt iodine of 24.5 mg/kg, the iodized salt coverage rate was 85.3% (10 414/12 203), and the qualified iodized salt consumption rate was 77.1% (9 406/12 203). A total of 3 999 samples of household edible salt were collected from pregnant women, with a median salt iodine of 24.0 mg/kg, the iodized salt coverage rate was 84.2% (3 366/3 999), and the qualified iodized salt consumption rate was 74.5% (2 981/3 999). A total of 12 241 urine samples from children aged 8 - 10 years old were collected, with a median urinary iodine of 290.4 μg/L. A total of 4 084 urine samples from pregnant women were collectedd, with a median urinary iodine of 233.0 μg/L. The thyroid volume of 11 971 children was examined, and the rate of goiter was 2.1% (257/11 971). Stratified by water iodine content, the median urinary iodine levels of children in 40 - 59, 60 - 79, and 80 - 100 μg/L water iodine groups were 269.7, 298.0 and 308.0 μg/L, respectively, with a statistically significant difference between the groups ( H = 67.32, P < 0.001). The goiter rates of children were 2.2% (100/4 603), 2.1% (80/3 733), 2.1% (77/3 635), respectively, with no statistically significant difference between the groups (χ 2 = 0.03, P = 0.986). The median urinary iodine levels of pregnant women were 225.4, 243.1, 234.4 μg/L, respectively, with a statistically significant difference between the groups ( H = 10.96, P = 0.004). Conclusions:The iodine nutrition level of children in iodine adequate areas in Henan Province is at an excessively suitable level, and pregnant women's iodine nutrition is at an appropriate level. It is recommended to strengthen surveillance on the basis of maintaining current prevention and control measures, and adjust prevention and control measures in a timely manner according to changes in iodine nutrition in the population.

Objective To observe the echocardiographic manifestations of infective endocarditis(IE)complicated with valve damage in children.Methods Totally 104 children with IE were retrospectively enrolled and divided into non-damage group(n=34),mild damage group(n=39)and dysfunction group(n=31)according to whether complicated with valve damage and damage's degree.The general and echocardiographic data were compared among groups,and the echocardiographic characteristics of IE complicated with valve damage in children were analyzed.Results Significant difference of the proportion of combining with other congenital heart diseases(excluding bicuspid aortic malformations),the incidence of embolization events during hospital stay,also of endocarditis of left cardiac system were found among groups(all P＜0.05).Pairwise comparison showed that in non-damage group,the proportion of combining with other congenital heart diseases was higher,while the incidence of endocarditis of left cardiac system was lower than those in both mild damage group and dysfunction group(all P＜0.05).The incidence of embolization events during hospital stay in non-damage group was lower than that in dysfunction group(P＜0.05).Among 70 cases of IE complicated with valve damage,mitral valve(30/70,42.86％)was the most common involved valve,mostly presented as valve stenosis(63/70,90.00％).No significant difference of valve involvement site,valve structural lesions nor the incidence of valve stenosis was found between mild damage group and dysfunction group(all P＞0.05).Conclusion IE complicated with valve damage in children mostly involved left cardiac system,and the risk of embolization events was higher than that of IE children without valve damage.Echocardiography could be used as an important method for evaluating the site of valve involvement and the degree of damage.

OBJECTIVE To investigate the effect and mechanism of Panax notoginseng saponins （PNS） on wound healing after anal fistula surgery in rats by regulating the hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor （VEGF）/ vascular endothelial growth factor receptor-2 （VEGFR2） signaling pathway. METHODS SD rats were selected to establish a postoperative rat model of anal fistula by infecting wound with Escherichia coli. The model rats were randomly grouped into model group， PNS low-dose and high-dose groups （15， 30 mg/cm2）， high-dose of PNS+2-methoxyestradiol （2ME2） group （PNS 30 mg/cm2+HIF-1α inhibitor 2ME2 4 mg/kg）， with 10 rats in each group. Another 10 normal rats were selected for back hair removal treatment as the control group. Each drug group was injected with the corresponding drug solution intramuscularly or （and） intraperitoneally， once a day， for 3 weeks. After the last administration， the wound healing rate （excluding the control group）， microvascular density （MVD）， the expression of collagen Ⅰ and fibronectin （FN） in the wound tissue were detected in each group； the levels of angiogenic factors [VEGF， E-mail：842710813@qq.com angiopoietin-Ⅰ （Ang-Ⅰ）， Ang-Ⅱ] in serum， the levels of inflammatory factors [interleukin-6 （IL-6） and IL-2] in serum binggui7183@163.com and wound tissue as well as the expressions of the related proteins of HIF-1α/VEGF/VEGFR2 signaling pathway in the wound tissue of rats were also detected in each group. RESULTS The MVD， the expression of collagen Ⅰ and FN in the wound tissue， and the levels of IL-6 and IL-2 in serum and wound tissue of rats increased significantly in the model group， compared to the control group （P＜0.05）， while the serum levels of VEGF， Ang- Ⅰ and Ang-Ⅱ decreased significantly （P＜0.05）. The wound healing rate， the MVD in wound tissue， the serum levels of VEGF， Ang-Ⅰ and Ang-Ⅱ， the expressions of collagen Ⅰ and FN in the wound tissue， and protein expressions of HIF-1α， VEGF and VEGFR2 in the PNS low-dose and high-dose groups increased significantly， compared to the model group （P＜0.05）， while the levels of IL-6 and IL-2 in serum and wound tissue decreased significantly （P＜0.05）； the high-dose PNS had a stronger effect （P＜ 0.05）. 2ME2 could weaken the effect of PNS on above indicators of rats after anal fistula surgery （P＜0.05）. CONCLUSIONS PNS can promote the production of angiogenic factors and inhibit the production of pro-inflammatory factors， thereby promoting wound healing in rats after anal fistula surgery. The above effects are related to the activation of HIF-1α/VEGF/VEGFR2 signaling pathway.

ObjectiveTo explore the prevalence difference between northwest dryness syndrome and blood stasis syndrome of coronary heart disease （CAD） and their correlations with major adverse cardiovascular events （MACE）. MethodsThe medical records including general information and risk factors for vascular diseases （gender， age， smoking history， diabetes history， hypertension history， chronic kidney disease history and body mass index）， laboratory indicators （fasting blood glucose， triglyceride， high density lipoprotein cholesterol， etc.） of 499 CAD patients in the Department of Cardiology of the Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University from November 1st， 2015 to September 30th，2020 were collected， and whether they suffered from northwest dryness syndrome or blood stasis syndrome was judged. The incidence of MACE was followed up for one year. The differences of cardiovascular risk factors between the northwest dryness syndrome and blood stasis syndrome of CAD were compared， and the correlation with MACE was analyzed. ResultsAmong the 499 CAD patients， there were 128 cases （25.65%） of simple blood stasis syndrome， 33 cases （6.61%） of simple northwest dryness syndrome， 209 cases （41.88%） of northwest dryness syndrome plus blood stasis syndrome， and 129 （25.85%） cases of not blood statis syndrom either northwest dryness syndrome. Univariate regression analysis showed that smoking history， diabetes history， fasting blood glucose abnormality， triglyceride abnormality， and high density lipoprotein cholesterol abnormality were positively correlated with northwest dryness syndrome in CAD patients （OR＞1， P＜0.05）， while smoking history， abnormal triglyceride and abnormal high density lipoprotein cholesterol were positively correlated with blood stasis syndrome in CAD patients （OR＞1， P＜0.05）. Multivariate regression analysis showed that the history of diabetes， abnormal triglyceride and abnormal high density lipoprotein cholesterol were positively correlated with northwest dryness syndrome of CAD （P＜0.05）. Smoking history， abnormal triglycerides and abnormal high density lipoprotein cholesterol were positively correlated with blood stasis syndrome （P＜0.05）. Association rule analysis showed that the confidence of CAD patients with northwest dryness syndrome complicated with blood stasis syndrome was 86.36%， and that of patients with blood stasis syndrome complicated with northwest dryness syndrome was 62.02%. Among the 499 patients， 96 had MACE in one year， accounting for 19.24% of the total. Logistics regression analysis showed that the correlation with incidence of MACE in CAD patients within one year from strong to weak was northwest dryness syndrome plus blood stasis syndrome ［OR = 5.113， 95%CI （3.118， 8.387）， P＜0.001）］， blood stasis syndrome［OR = 4.630， 95%CI （2.394， 8.955）， P＜0.001］， northwest dryness syndrome ［OR = 4.395， 95%CI （2.642， 7.309）， P＜0.001］. ConclusionBlood stasis syndrome is the main syndrome type of CAD in Xinjiang Uygur Autonomous Region. CAD patients with northwest dryness syndrome are more likely to have blood stasis syndrome， and most suffer from both northwest dryness syndrome and blood stasis syndrome simultaneously. There is the strongest correlation between northwest dryness syndrome plus blood stasis syndrome and 1-year occurrence of MACE in CAD.

ObjectiveThe glycosidic linkage structural characteristics of polysaccharides from Pinelliae Rhizoma（PR） and its processed products were analyzed by sugar spectrum， high performance thin layer chromatography（HPTLC）， fluorescence-assisted carbohydrate gel electrophoresis（PACE） based on partial acid hydrolysis and specific glycosidase hydrolysis， and the antioxidant activities of polysaccharides before and after hydrolysis（enzymolysis） were compared. MethodPolysaccharides from PR and its processed products were extracted by ultrasound extraction， starch was hydrolyzed by α-amylase， and small molecules below 3 kDa were removed by ultrafiltration. The purified polysaccharides were prepared by hydrolysis of acid and five different specific glycosidases， and the hydrolysates were analyzed by HPTLC and PACE. The antioxidant capacity of polysaccharides was analyzed by 2，2′-azino-bis（3-ethylbenzthiazoline-6-sulfonic acid）（ABTS） and 2，2-diphenyl-1-picrylhydrazyl（DPPH） free radical scavenging experiment before and after different hydrolysis. ResultThrough HPTLC and PACE analysis， it was found that polysaccharides from PR and its processed products could be hydrolyzed by β-galactosidase， β-mannase， cellulase and pectinase， but hardly hydrolyzed by glucanase， indicating that the polysaccharides contained β-galactopyranoside bond， β-1，4-mannoside bond， β-1，4-glucoside bond and α-1，4-galacturonic acid glycosidic bond. In vitro antioxidant experiments showed that the ABTS radical scavenging capacity of the polysaccharides from PR and its processed products was weakened after acid hydrolysis and pectinase enzymatic hydrolysis， while the ABTS radical scavenging capacity was enhanced after enzymatic hydrolysis with cellulase， β-galactosidase， and β-mannase. And after different hydrolysis， the DPPH free radical scavenging capacity of polysaccharides from PR and its processed products was all significantly enhanced. ConclusionThe glycosidic linkage structural characteristics of polysaccharides from PR and its processed products was analyzed by sugar spectrum in this paper， and the relationship between glycosidic bond types and their antioxidant activity was clarified through in vitro antioxidant experiments， which is beneficial for further elucidating the material basis of the related efficacy of PR and its processed products， and providing new ideas and methods for analyzing the structural characteristics of polysaccharides in Chinese medicines.

Purpose To explore the pathological features of angioimmunoblastic T-cell lymphoma(AITL)with bone marrow involvement and to improve awareness of bone marrow infiltration in AITL.Methods The tissue morphology of 32 cases of AITL with bone marrow involvement was retrospectively analyzed.Im-munohistochemistry using the EnVision method and ten-color flow cytometry were conducted to detect AITL-related immune markers.T cell clonality was analyzed through T cell receptor(TCR)gene rearrangement.Results The predominant pat-terns of tumor cell infiltration were nodular(20/32,62.5％)and interstitial or small clusters(10/32,31.3％).The nodules showed a mixture of cellular components.In some cases,the fo-ci contained a mixture of cells with characteristic"granuloma-toid"changes.The tumor cells were mainly small to medium-sized lymphocytes with inconspicuous atypia.Some cases showed plasma cell proliferation.19 cases were subject to immunohisto-chemical staining,which revealed a low count of CD4-positive T cells,with an average of 8.4％.The positive rates of T follic-ular helper cells(TFH)markers were as follows:CD10(7/14,50.0％),BCL6(6/19,31.6％),PD-1(13/19,68.4％),and CXCL13(13/19,68.4％).In most cases,tumor cells showed co-expression of PD-1 and CXCL13,but the number of positive cells was less than 1％.Flow cytometry analysis was performed in 24 cases,among which 22 cases all consistently expressed cytoplasmic CD3(cCD3),CD5,CD4,and CD2,with varying degrees of CD10 expression.In some cases,there was a lack of expression of surface CD3(sCD3)(12/22,54.5％),while there was a lack of expression of CD7(8/22,36.4％).and no abnormal T cells were found in 2 cases.TCR gene rearrangement analysis was performed in 7 cases,with 3 cases showing TCR clonality.Conclusion AITL with bone marrow involvement exhibits a lower proportion of tumor cells and less atypia,making it prone to misdiagnosis.The presence of lymphocytic foci with mixed cellular components in the bone marrow can indicate bone marrow involvement in AITL.Flow cy-tometry detection of abnormal T cells(double positive for CD4 and CD10)strongly suggests bone marrow infiltration in AITL.A comprehensive diagnosis of bone marrow involvement in AITL re-quires consideration of bone marrow biopsy,flow cytometry,and TCR gene rearrangement analysis.