Objective:To evaluate the diagnostic value of 1, 3-β-D glucan (BDG), mannan IgM antibody (Mn-IgM) and mannan IgG antibody (Mn-IgG) in invasive candidiasis and to compare the differences in the diagnostic capability of serological markers used alone or in combination.Methods:Serum samples of 126 patients with invasive candidiasis and 104 healthy people who took physical examination during the same period were collected. BDG was detected by dynamic chromogenic method, and Mn-IgM and Mn-IgG were detected by ELISA. The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, coincidence rate and Kappa value of the three serological markers used alone or in combination in the diagnosis of invasive candidiasis were analyzed and compared. The receiver operating characteristic (ROC) curves were drawn and the areas under the curves (AUCs) were calculated.Results:The levels of BDG, Mn-IgM and Mn-IgG in patients with invasive candidiasis were significantly higher than those in healthy people ( P<0.01). The sensitivity, specificity, Kappa value and AUC of BDG were 48.41%, 92.31%, 0.389 and 0.842. The sensitivity, specificity, Kappa value and AUC of Mn-IgM were 64.29%, 91.35%, 0.540 and 0.829. The sensitivity, specificity, Kappa value and AUC of Mn-IgG were 27.78%, 95.19%, 0.214 and 0.737. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgM were 76.19%, 88.46%, 0.637 and 0.921. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgG were 59.52%, 91.35%, 0.491 and 0.856. The sensitivity, specificity, Kappa value and AUC of Mn-IgM+ Mn-IgG were 69.84%, 90.38%, 0.588 and 0.891. The sensitivity, specificity, Kappa value and AUC of BDG+ Mn-IgM+ Mn-IgG were 80.16%, 88.46%, 0.679 and 0.922. Conclusions:The sensitivity of Mn-IgM was higher than that of BDG and Mn-IgG in the diagnosis of invasive candidiasis. When the serological biomarkers were used in combination, BDG+ Mn-IgM and BDG+ Mn-IgM+ Mn-IgG had relatively high Kappa value and AUC, showing high accuracy. The clinical diagnostic value of multiple serological biomarkers used in combination was significantly higher than that of any serological biomarkers used alone. Early combined detection and continuous monitoring of multiple serological biomarkers in patients with high risk of invasive candidiasis could be used clinically to adjust antifungal treatment strategies timely.

Neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) are a heterogeneous group of disorders characterized by progressive degeneration of neurons. NDDs threaten the lives of millions of people worldwide and regretfully remain incurable. It is well accepted that dysfunction of mitochondria underlies the pathogenesis of NDDs. Dysfunction of mitochondria results in energy depletion, oxidative stress, calcium overloading, caspases activation, which dominates the neuronal death of NDDs. Therefore, mitochondria are the preferred target for intervention of NDDs. So far various mitochondria-targeting drugs have been developed and delightfully some of them demonstrate promising outcome, though there are still some obstacles such as targeting specificity, delivery capacity hindering the drugs development. In present review, we will elaborately address 1) the strategy to design mitochondria targeting drugs, 2) the rescue mechanism of respective mitochondria targeting drugs, 3) how to evaluate the therapeutic effect. Hopefully this review will provide comprehensive knowledge for understanding how to develop more effective drugs for the treatment of NDDs.

Objective:To explore the efficacy and safety of robot assisted laparoscopic sacrocolpopexy in the treatment of pelvic organ prolapse.Methods:The data of 16 patients who underwent robot assisted laparoscopic sacrocolpopexy in Beijing Hospital from September 2019 to May 2022 were collected. The average age was (73.5±9.3) years, the preoperative course was 4-240 months, the body mass index was (24.2±1.7) kg/m 2, the number of births was (1.7±0.8), and the quantitative index of pelvic organ prolapse (POP-Q) was grade Ⅲ -Ⅳ. The maximum urine flow rate before operation was (9.6±3.4) ml/s, the maximum detrusor pressure during urination was 26 (20, 32) cmH 2O, the first sense urine volume of the bladder was (119.1±39.4) ml, the first sense urine urgency volume of the bladder was (253.6±75.7) ml, the maximum bladder pressure capacity was (406.0±79.8) ml, and the residual urine volume was 10 (10, 28) ml. The preoperative PFDI-20 score was 100 (70, 122) and the PFIQ-7 score was 107 (90, 160). During the robot assisted laparoscopic sacrocolpopexy, the right area of the sacral promontory was exposed, the anterior and posterior walls of the uterus were separated, and the 2 cm small hole was separated from the right broad ligament of the uterus. The mesh was cut into a "Y" shape and passed through the small hole. The anterior and posterior leaves of the Y-shaped mesh were sutured to fix the cervix, and the other end was fixed to the anterior longitudinal ligament of the sacrum. The operation time and intraoperative bleeding were observed. The effect of surgery was evaluated by preoperative and postoperative urodynamic imaging, POP-Q stage, PFDI-20 score and PFIQ -7 score. Results:All the 16 operations were successfully completed. No injury of urethra, bladder, rectum, important blood vessels and nerves occurred during the operation. The average operation time was (255.6±56.0) min, and the average amount of bleeding was (28.8±18.2) ml. There was no inhibitory contraction wave in 7 patients (44%) before operation, suggesting that there was detrusor overactivity. After operation, the detrusor overactivity disappeared or significantly decreased in 7 patients. The postoperative follow-up period was 3-36 months. During the follow-up period, one patient had recurrence, and the rest had no prolapse and urination problems. The POP-Q stage was reduced to grade 0-Ⅰ after the operation. The subjective satisfaction rate of patients was 94%. The PFDI-20 score [13(8, 24)] and PFIQ -7 score [11(6, 15)] after operation were significantly reduced ( P<0.001), the initial urgent volume of bladder (272.5±88.5) ml was significantly increased compared with that before operation ( P=0.038), and the maximum volume of bladder (427.2±79.2) ml was significantly increased compared with that before operation ( P=0.006). Image urodynamics showed that the patient basically recovered the pelvic floor anatomy and achieved functional reduction. Conclusions:Robot assisted laparoscopic sacrocolpopexy has good subjective and objective effects in POP, low recurrence rate and less complications. It needs a larger sample size study for confirming the improvement of bladder function.

Objective:To explore the potential relationship of urethral pressure profilometry and the complications of artificial urethral sphincter (AUS) implantation.Methods:The clinical data of patients who underwent AUS implantation in Beijing Hospital from March 2019 to March 2022 were retrospectively analyzed. All the patients were male. The average course of disease was 43.1 months(ranging 11-120 months). The average age was (68.6±13.2) years. The median number of pads used was 4.5 (3.0, 6.0). The preoperative maximum urethral pressure (MUP) was (84.6±25.5) cmH 2O, and the maximum urethral closure pressure (MUCP) was 51.0 (41.0, 74.0) cmH 2O. AUS implantation was performed through a single perineal incision in all patients. The sleeve size was mainly determined by the measured urethral circumference of the patient. After installation of all components, the urethral pressure profilometry was performed under the state of device inactivation and activation. The pump was activated 6 weeks after the operation, and telephone follow-up was performed 3 months after the activation of the device. The urinary control and complications were recorded. The results of follow-up were compared with the results of urethral pressure profilometry, and the preliminary conclusions were drawn. Results:In this study, 3 patients (20%) received 4.0cm cuffs, 10 patients (66.7%) received 4.5cm cuffs, and 2 patients (13.3%) received 5.0cm cuffs. The MUP and MUCP of AUS device in inactivated state were (82.5±30.2) cmH 2O and 51.0(48.0, 77.0) cmH 2O. In the activated state, MUP was (138.9±21.7) cmH 2O and MUCP was 109.0(94.0, 133.0) cmH 2O. Compared with that before operation, the urethral pressure in the inactivated state did not increase significantly (all P > 0.05), while the urethral pressure in the activated state increased significantly (all P < 0.001). The patients were followed-up for 3-33 months. Thirteen patients (86.7%) used the initial installation device, and all of them met the standard of social continence. One patient died of cerebrovascular accident. One patient took out the device due to urethral erosion. The incidence of complications was 26.7% (4/15), including painless hematuria in 2 cases, scrotum and penis infection in 1 case, and urethral erosion in 1 case. The MUP and MUCP of these patients were (100.0 ± 40.7) cmH 2O and (80.8 ± 39.7) cmH 2O respectively. In the intraoperative active state, the MUP was (151.5 ± 15.3) cmH 2O and the MUCP was (123.0 ± 17.2) cmH 2O. The MUP of the other 3 patients in the device activation state was significantly higher than the average value, and all of them were above 150 cm H 2O, except one patient who was infected due to cognitive problems and chronic urinary retention. In 11 patients without complications, the MUP and MUCP were (76.1±24.7) cmH 2O and (55.1±20.0) cmH 2O respectively. In the intraoperative active state, the MUP was (134.4±22.5) cmH 2O and the MUCP was (108.5±29.8) cmH 2O. Conclusions:AUS implantation has a definite curative effect. Poor comprehension, and MUP higher than 150 cmH 2O in the activated state of the device may be risk factors for complications.

Objective:To evaluate the efficacy and safety of robotic arm assisted laparoscopic hysterosacral fixation in patients with pelvic organ prolapse(POP), and its impact on lower urinary tract function.Methods:This study retrospectively analyzed the clinical data of POP patients who had undergone robotic arm assisted laparoscopic hysterosacral fixation at our center from June 2019 to October 2020, and conducted exploratory research.Results:A total of 6 patients were included in the study, with POP quantitative staging above stage Ⅲ.The ages ranged from 70 to 82 years.The number of births each patient had given ranged from 1 to 3, & all were via vaginal deliveries.There were no significant changes in urodynamic parameter scores in any patients before and after surgery, but half of the patients had detrusor overactivity before surgery, which all disappeared after surgery.In addition, synchronous X-ray images showed that the postoperative pelvic organs were closer to the normal anatomical position.At the same time, quantitative staging of POP had achieved clear improvement, and related scale scores also significantly improved.One patient complained of occasional lumbar and back discomfort with postoperative over-stretching during outpatient review, which improved after symptomatic treatment.Conclusions:robotic arm assisted Laparoscopic hysterosacral fixation is satisfactory in efficacy and safety for POP patients, with good postoperative restoration of the uterus to the anatomical position and has insignificant influence on the function of the lower urinary tract.It is worth further assessment for wide application.

Human epidermal growth factor receptor 2 (HER2) proteins are overexpressed in a high proportion of gastric cancer (GC) cases and affect the maintenance of cancer stem cell (CSC) subpopulations, which are used as targets for the clinical treatment of patients with HER2-positive GC. Despite improvements in survival, numerous HER2-positive patients fail treatment with trastuzumab, highlighting the need for more effective therapies. In this study, we generated a novel type of genetically modified human T cells, expressing a chimeric antigen receptor (CAR), and targeting the GC cell antigen HER2, which harbors the CD137 and CD3ζ moieties. Our findings show that the expanded CAR-T cells, expressing an increased central memory phenotype, were activated by the specific recognition of HER2 antigens in an MHC-independent manner, and effectively killed patient-derived HER2-positive GC cells. In HER2-positive xenograft tumors, CAR-T cells exhibited considerably enhanced tumor inhibition ability, long-term survival, and homing to targets, compared with those of non-transduced T cells. The sphere-forming ability and in vivo tumorigenicity of patient-derived gastric cancer stem-like cells, expressing HER2 and the CD44 protein, were also inhibited. Our results support the future development and clinical application of this adoptive immunotherapy in patients with HER2-positive advanced GC.
Animals ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasms, Experimental ; immunology ; pathology ; therapy ; Receptor, ErbB-2 ; immunology ; Receptors, Antigen, T-Cell ; immunology ; Stomach Neoplasms ; immunology ; pathology ; therapy ; Tumor Cells, Cultured

Objective:To observe and compare the clinical effect of single-incision and two-incision posterior chamber phakic intraocularlens implantation in the correction of extreme myopia.Methods:40 cases(80 eyes) of patients with extreme myopia underwent conventional two-incision posterior chamber phakic intraocularlens implantation in our hospital from January 2011 to June 2013 were selected as the control group and 40 cases(80 eyes) underwent single-incision posterior chamber phakic intraocularlens implantation from July 2013 to January 2016 were selected as observation group.The open hole before and after operation,best corrected visual acuity of vision,operation safety,effectiveness index,diopter (column mirror,equivalent ball for eyeglasses),intraocular pressure,ECD,anterior chamber depth and occurrence of complications were compared between two groups.Results:The uncorrected visual acuity (UCVA) of both groups at 6 months after operation were significantly higher than those before operation (P＜0.05),which was significantly higher in the observation group than that of the control group (P＜0.05);The operation safety and effectiveness index of observation group were significantly higher than those of the control group (P＜0.05);The cylinder and spherical equivalent degree of both groups at 6 months after operation were significantly better than those before operation(P＜0.05),which was significantly better in the observation group than that of the control group(P＜0.05).The corneal endothelial cell counts(ECL) of control group after operation was significantly lower than that before operation (P＜0.05),and no significant difference was found in the ECL of observation group before and after operation (P＞0.05).The ECL of observation group after operation was significantly higher than that of the control group (P＜0.05);The incidence rate of complication in observation group was significantly lower than that of the control group (P＜0.05).Conclusion:Compared with two-incision operation,the single-incision posterior chamber phakic intraocularlens implantation had remarkable clinical effect in the correction of extreme myopia with higher security.

Objective:To detect the expressions of ovarian function-related proteins in the ovarian follicles in different development stages,and to explore their roles and significances in the regulation of follicular development and ovarian function. Methods:The ovarian tissue containing primordial,primary,secondary follicles,mature follicles, atretic follicles and corpus albicans of the woman in the childbearing age was selected. Immunohisto chemical analysis was used to detect the expressions of Glyoxal enzyme I (glyoxalase I),ubiquitin carboxy-terminal hydrolase L1 (UCH-L1),heat shock protein 27 (HSP27),serum amyloid P (SAP)proteins in the ovarian follicles in different stages.The expression intensities of these proteins were compared.Results:The expression intensities of Glyoxalase I and UCH-L1 in the granulosa cells and theca cells of secondary follicles and marure follicles were strong,which were higher than those in the cytoplasm of primordial and primary follicles.The expression intensities of HSP27 in the cytoplasm of primordial and primary follicles were strong,which were higher than those in the granulosa cells and theca cells of secondary follicles and marure follicles.The expression intensities of Glyoxalase I and HSP27 in the atretic follicles were strong,which were higher than that in the growth follicles. The expressions of SAP were positive in the primordial,primary follicles,secondary and mature follicles and the expression intensities were not different.The expressions of four proteins in the corpus albicans did not express. Conclusion:The high expression of UCH-L1 and low expression of HSP27 are associated with the mature and development of follicles;the high expressions of Glyoxalase I and HSP27 are associated with the follicular atresia and ovarian failure.

BACKGROUND: BALB/c and C57BL/6 mice are two inbred strains, but after voluntary movement, there is no report on how to scientifical y reasonably select behavioral experiment methods and indicators and to evaluate the learning and memory abilities of mice.
OBJECTIVE: To analyze and compare the behavioral indicators between BALB/c and C57BL/6 mice fol owing voluntary wheel running, to explore the effect of exercise on learning and memory, and to provide a reference for selecting reasonable behavioral indicators.
METHODS: 2.5-month-old BALB/c and C57BL/6 mice were randomly divided into control and voluntary wheel running groups. Independent running wheel movement of mice was recorded with VitalView system. 4 weeks later, newborn neurons were labeled via DCX immunofluorescence. Spatial learning, memory and exploration abilities were compared through new arm test, new object recognition test and Morris water maze test.
RESULTS AND CONCLUSION: (1) The mean spontaneous activity of BALB/c mice daily was 2.56 fold of that of C57BL/6 mice during wheel running (P < 0.001). (2) Hippocampal DCX-positive cel s in exercised BALB/c and C57BL/6 mice were more than those in control group. (3) Meantime, exhibited by higher frequencies to explore new arm or object, and longer time and distance of moving around them, the learning and exploring capability was improved after exercising (P < 0.001), especial y in BALB/c mice. (4) Wheel running C57BL/6 mice exhibited progressed spatial learning and memory abilities compared with control mice in Morris water maze test, characterized by decreased latency to target, elevated target crossings and longer time or distance in quadrant zone (P < 0.05). However, there was no significant difference between wheel running and control BALB/c mice. Taken these data together, voluntary wheel running contributed to hippocampal neurogenesis of BALB/c and C57BL/6 mice, accompanied by the change of learning and memory capability, which could be detected properly via both new arm test and new object recognition test, but for Morris water maze test, C57BL/6 mice might be superior to BALB/c mice.

BACKGROUND:It is not fuly understood that whetherp53 inhibitor can directly intervene in the viability of bone marrow mesenchymal stem cels and the possible mechanism. OBJECTIVE:To investigate the effect of p53 inhibitor, PFT-α, on the aging process of bone marrow mesenchymal stem cels in late-phase amplification and to discover the key target to delay the replicative senescence of human bone marrow mesenchymal stem cels. METHODS:The expression levels ofp53,p21, andp15 mRNA in human bone marrow mesenchymal stem cels in both early and late-phase amplification were detected by quantitative PCR assay. Then, human bone marrow mesenchymal stem cels in late-phase amplification were respectively treated with 20 μmol/L PFT-α or an equivalent amount of dimethyl sulfoxide for 2 weeks. The positive rate of aging cels was determined by SA-β-Gal staining. The apoptosis was detected by TUNEL staining. Human bone marrow mesenchymal stem cels were treated with 300 μmol/L H2O2 for 30 minutes, and then celular anti-oxidative stress capacity was detected by cel counting kit-8 assay. RESULTS AND CONCLUSION:The quantitative PCR assay showed that the mRNA expression level ofp15, p21 andp53 in human bone marrow mesenchymal stem cels in late-phase amplification was significantly increased (1.45±0.23), (1.51±0.14) and (1.78±0.14) times as much as that in early phase amplification (P < 0.05). The positive rate of aging cels in PFT-α group was significantly lower than that in the dimethyl sulfoxide group[(41±5)%vs. (63±7)%,P < 0.05)]. However, there was no significant difference in apoptosis rate between PFT-α group and dimethyl sulfoxide group. After treatment with H2O2, the absorbance value in the PFT-α group was(1.27±0.13) times as much as that in the dimethyl sulfoxide group (P < 0.001). The above results demonstrate that the activation ofp53 signaling pathway may be an important factor of causing aging of human bone marrow mesenchymal stem cels. Application ofp53 inhibitor PFT-αcan enhance the anti-oxidative stress capacity of human bone marrow mesenchymal stem cels in late phrase amplification.