Targeted Lipidomics Reveals Lipid Modulation of Kaixuan Bushen Method on Psoriasis Vulgaris / 中国实验方剂学杂志

ObjectiveThrough the targeted lipidomics， we explored the intervention mechanism of Kaixuan Bushen method on psoriasis vulgaris （PV） from the perspective of lipid metabolism， providing reference for the diagnosis and treatment of PV. MethodTwenty-six patients with PV admitting the outpatient clinic of the Department of Dermatology， Guang'anmen Hospital， China Academy of Chinese Medical Sciences from September 2019 to November 2020 were selected as the research object （observation group）， and 26 sex- and age-matched healthy volunteers in the same period were recruited as control group. Venous blood was collected for lipid index and targeted lipidomics detection in the control and observation groups at inclusion. After 12 weeks of continuous treatment of Kaixuan Bushen method， the psoriasis area and severity index （PASI） was measured and compared before and after treatment to assess the clinical efficacy， while venous blood was collected again in the observation group to compare the blood lipid level and lipid metabolism of patients before and after treatment. Targeted lipidomics analysis was performed by ultra performance liquid chromatography tandem mass spectrometry （UPLC-MS/MS） on an ACQUITY UPLC BEH C8 column （2.1 mm×100 mm， 1.7 μm） with mobile phase of 5 mmol∙L-1 ammonium formate in acetonitrile-water （6∶4， A）-5 mmol∙L-1 ammonium formate in acetonitrile-isopropanol （1∶9， B） for gradient elution and flow rate of 0.26 mL∙min-1. Conditions of MS were electrospray ionization （ESI）， positive and negative ion modes， and scanning range of m/z 50-1 200. Then principal component analysis （PCA） and partial least squares-discriminant analysis （PLS-DA） models were developed to screen differential metabolites， and the differential metabolites were identified and the pathways were enriched. ResultAfter 12 weeks of treatment with Kaixuan Bushen method， PASI score decreased by more than 50% in a total of 22 out of 26 patients with PV， suggesting the total effective rate was 84.62%. The serum triglyceride level of patients with PV was significantly higher than that of healthy individuals （P<0.05）， and the triglyceride level was significantly reduced after treatment （P<0.05）. Targeted lipidomics analysis screened a total of 43 potential biomarkers for PV， of which 42 were up-regulated and 1 was down-regulated， involving 7 signaling pathways such as linoleic acid metabolism， glycerophospholipid metabolism and unsaturated fatty acid biosynthesis. Moreover， there were 14 response makers for clinical efficacy of Kaixuan Bushen method on PV， of which 6 were up-regulated and 8 were down-regulated， involving five signaling pathways such as linoleic acid metabolism， glycerophospholipid metabolism and sphingolipids metabolism. In a comparison between healthy individuals and patients with PV and PV before and after treatment， the common differential metabolites were screened as phosphatidylcholine （PC） 38∶0 and ceramide （Cer） 42∶1， and the common pathways were linoleic acid and glycerophospholipid metabolic pathways. ConclusionThe disorder of lipid metabolism in PV are largely due to abnormal sphingolipid， glycerophospholipid and linoleic acid metabolic pathways， of which Kaixuan Bushen method can regulate the glycerophospholipid and linoleic acid metabolism， thereby improving psoriatic lesions.

Clinicopathological characteristics and prognostic analysis of patients with female genital tract diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To investigate the clinicopathological characteristics, gene mutation profile, and prognostic factors of diffuse large B-cell lymphoma (DLBCL) in female genital tract.Methods:A retrospective analysis was performed on the clinicopathological data of 30 patients with female genital tract DLBCL who were admitted to Rui Jin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from October 2003 to October 2021. Targeted sequencing was used to detect 55 lymphoma-related genes, and the gene mutation status of patients was evaluated. Kaplan-Meier method was used for survival analysis, and prognostic factors were analyzed by Cox proportional hazards model.Results:The median age of 30 female genital tract DLBCL patients at diagnosis was 58 years old (23-77 years old). The initial symptoms mainly included abdominal pain, distension, and masses (8 cases, 32%). Tumors most commonly located in the adnexal region (including ovaries and fallopian tubes) (13 cases, 45%), of which 9 cases were unilateral. Twenty-one cases (70%) had multiple extra-nodal involvements, 22 cases (73%) had Ann Arbor stage Ⅲ-Ⅳ, 8 cases (27%) had Eastern Cooperative Oncology Group (ECOG) score of ≥2, and 22 cases (73%) had elevated lactate dehydrogenase (LDH), 21 cases (70%) had International Prognostic Index (IPI) score of 3-5. Within 30 patients, 11 patients (37%) received surgery, and all patients received R-CHOP regimen-based chemotherapy. All 30 cases were evaluated for efficacy, the complete remission rate was 83% (25/30), the 5-year progression-free survival (PFS) rate was 69.7%, and the 5-year overall survival (OS) rate was 79.6%. Univariate analysis showed that ECOG score ≥2 was associated with worse OS ( P = 0.048). Among the 30 patients, 7 patients (23%) were primary and 23 patients (77%) were secondary. The proportions of patients with Ann Arbor stage Ⅲ-Ⅳ, IPI score 3-5 and elevated LDH in secondary patients were higher than those in primary patients (all P < 0.001), but there were no significant differences in PFS and OS between the two ( P values were 0.261 and 0.671). The targeted sequencing results of 16 patients showed that the mutation rates of PIM1, MYD88, KMT2D, TP53, CARD11, CCND3 and GNA13 were all > 20%, and TP53 mutation was associated with poorer PFS and OS ( P values 0.012 and 0.002). Conclusions:Female genital tract DLBCL is a rare invasive extranodal DLBCL with similar survival prognosis in primary and secondary patients. High-frequency mutations of PIM1, MYD88 and TP53 genes may provide new directions for treatment.

Activation-induced markers for evaluation of specific CD4 + T cell immune response in HIV-1-infected patients / 中华微生物学和免疫学杂志

Objective:To establish a method using activation-induced markers (AIM) to detect the function of HIV-1-specific CD4 + T cell subsets for evaluating the immune response of HIV-1-specific CD4 + T cells more effectively. Methods:Twelve chronically HIV-1-infected patients without antiviral therapy and six healthy people without HIV-1 infection were enrolled in this study. The function of HIV-1-specific T lymphocytes was detected by AIM and ICS based on polychromatic flow cytometry. The performance of the two methods in assessing HIV-1-specific CD4 + T cell immune response in HIV-1-infected patients was evaluated. Results:The positive rates of HIV-1-specific PD-1 + CD25 + CD4 + T, CD69 + CD200 + CD4 + T, CD69 + ICOS + CD4 + T, CD69 + ICOS + CD8 + T、CD137 + CD69 + CD8 + T、PD-1 + CD25 + CD8 + T and OX40 + PD-1 + CD8 + T cells in all of the HIV-1 patients were 11/12, 8/12, 7/12, 8/12, 8/12, 7/12 and 7/12 using AIM method. ICS results showed that the positive rates of HIV-1-specific IL-2 + CD4 + T, IFN-γ + CD4 + T, TNF-α + CD4 + T, IFN-γ + CD8 + T, TNF-α + CD8 + T and IL-2 + CD8 + T cells were 2/12, 2/12, 0, 12/12, 10/12 and 5/12, respectively. Conclusions:AIM method was more sensitive in antigen-specific CD4 + T cell detection, and could be used as a complementary method to ICS in assessing antigen-specific T cell response.

Inhibitory Effect of Hederasaponin B on Gastric Cancer HGC-27 Cells and Its Mechanism Based on Bioinformatics / 中国实验方剂学杂志

ObjectiveTo investigate the inhibitory effect of hederasaponin B on gastric cancer HGC-27 cell and the mechanism. MethodMethyl thiazolyl tetrazolium （MTT） assay， hematoxylin-eosin （HE） staining， 4'，6-diamidino-2-phenylindote （DAPI） staining， colony formation assay， scratch assay， and flow cytometry were employed for the analysis of apoptosis and cell cycle. Thereby， the inhibitory effect of hederasaponin B on gastric cancer HGC-27 cell was investigated. Then the Pharm Mapper， UniProt， Swissdock， STRING， and Metascape were used for target screening， gene annotation， molecular docking， protein-protein interaction （PPI） network construction， Gene Ontology （GO） term and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis to explore the mechanism. ResultHederasaponin B （15， 30， 60， 120 μmol·L-1） can significantly reduce the survival rate of HGC-27 cell （P<0.01） in a time-dependent and dose-dependent manner compared with the blank group. It had no significant toxicity to normal GES-1 cell at concentration below 120 μmol·L-1. Compared with the blank group， hederasaponin B （30， 60， 120 μmol·L-1） induced cytoplasmic vacuolization， and nuclear deformation and karyopyknosis， inhibited the migration of HGC-27 cell （P<0.01）， and brought about the apoptosis （P<0.05， P<0.01） and cell cycle arrest of HGC-27 cell （P<0.05， P<0.01）. Hederasaponin B （10， 20， 30 μmol·L-1） also suppressed the independent survival ability and proliferation ability of HGC-27 cell （P<0.01）. The possible action targets were kinesin-like protein KIF11， cGMP-specific 3，5 cyclic phosphodiesterase， caspase-3， serine/threonine protein kinase Chk1， proto-oncogene tyrosine protein kinase， epidermal growth factor receptor， and mitogen-activated protein kinase （MAPK） 8. The mechanism may be related to MAPK signaling pathway （pathways in cancer）， adhesion connection， focal adhesion and proteoglycans in cancer （epithelial cell signaling pathways in Helicobacter pylori infection）. ConclusionHederasaponin B exerts significant inhibitory effect on gastric cancer HGC-27 cell through multiple targets and multiple pathways.

Expert Consensus on Sepsis Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

To give full play to the therapeutic advantages of traditional Chinese medicine （TCM） in sepsis， clarify the entry point of integrated TCM and western medicine， further standardize the clinical treatment of TCM， develop a recognized and integrated treatment protocol of TCM and western medicine， and improve the clinical efficacy on sepsis，the Chinese Association of Chinese Medicine organized TCM and western medicine experts specialized in sepsis treatment to conduct in-depth discussions on the advantages of TCM and integrated TCM and western medicine in the treatment of sepsis based on the TCM etiology and pathogenesis of sepsis， a representative acute and critical disease. They emphasized the pathogenesis characteristics of asthenia of healthy Qi and sthenia of pathogenic factors and summarized the roles of Chinese medicine in correcting the imbalance of inflammatory response， improving blood coagulation dysfunction， and relieving organ damage. Furthermore， they proposed the treatment protocol with integrated TCM and western medicine， which is expected to provide references for actual clinical treatment and scientific research.

In Vitro Pharmacokinetics and Pharmacodynamic Evaluation of Jiaojiang Cataplasms / 中国实验方剂学杂志

ObjectiveTo study the in vitro kinetics of Jiaojiang cataplasms and evaluate its pharmacodynamics， so as to provide a feasible basis for the development of this preparation. MethodThe improved Franz diffusion cell was used for the in vitro release in semipermeable membrane and transdermal absorption in in vitro mouse skins. The contents of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb1 were determined by high performance liquid chromatography （HPLC）， to evaluate the in vitro release and transdermal absorption of Jiaojiang cataplasms. The mobile phase of 6-gingerol and hydroxy-α-sanshool was water-acetonitrile-methanol （2∶1∶1） with the detection wavelength of 280 nm. The mobile phase of ginsenoside Rb1 was acetonitrile-0.1% phosphoric acid aqueous solution （31∶69） with the detection wavelength of 203 nm. A mouse intestinal paralysis model was established， and mice were randomly divided into five groups， namely sham operation group， model group， domperidone group （3.9 mg·kg-1） and high- and low-dose groups of Jiaojiang cataplasms （6.2， 3.1 g·kg-1， measured by crude drug dosage）， to observe the effect of this preparation on gastrointestinal propulsion function. ResultAverage release rates of hydroxy-α-sanshool， 6-gingerol and ginsenoside Rb1 at 24 h were 16.41， 4.23， 4.15 μg∙cm-2∙h-1， the average transdermal rates of them at 24 h were 2.31， 0.64， 0.29 μg∙cm-2∙h-1， their skin retention values were 19.56， 3.59， 1.61 μg， respectively. According to the Ritger-Peppas equation， the release of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb1 was non-Fick diffusion. The high-dose group of Jiaojiang cataplasms could improve intestinal function of model mice after small intestinal friction injury， and promote intestinal peristalsis and small intestinal propulsion rate （P<0.05）. ConclusionJiaojiang cataplasms has in vitro release and transdermal properties， the in vitro release conforms to Higuchi equation， and transdermal absorption behavior conforms to zero-order kinetic equation， which can improve the postoperative function of the small intestine and the propulsion function of small intestine. It preliminarily indicates that the preparation has certain clinical development value.

Engineering prodrug nanomicelles as pyroptosis inducer for codelivery of PI3K/mTOR and CDK inhibitors to enhance antitumor immunity

Aberrant activation of oncogenic signaling pathways in tumors can promote resistance to the antitumor immune response. However, single blockade of these pathways is usually ineffective because of the complex crosstalk and feedback among oncogenic signaling pathways. The enhanced toxicity of free small molecule inhibitor combinations is considered an insurmountable barrier to their clinical applications. To circumvent this issue, we rationally designed an effective tumor microenvironment-activatable prodrug nanomicelle (PNM) for cancer therapy. PNM was engineered by integrating the PI3K/mTOR inhibitor PF-04691502 (PF) and the broad spectrum CDK inhibitor flavopiridol (Flav) into a single nanoplatform, which showed tumor-specific accumulation, activation and deep penetration in response to the high glutathione (GSH) tumoral microenvironment. The codelivery of PF and Flav could trigger gasdermin E (GSDME)-based immunogenic pyroptosis of tumor cells to elicit a robust antitumor immune response. Furthermore, the combination of PNM-induced immunogenic pyroptosis with anti-programmed cell death-1 (αPD-1) immunotherapy further boosted the antitumor effect and prolonged the survival time of mice. Collectively, these results indicated that the pyroptosis-induced nanoplatform codelivery of PI3K/mTOR and CDK inhibitors can reprogram the immunosuppressive tumor microenvironment and efficiently improve checkpoint blockade cancer immunotherapy.

Preliminary evaluation of immune checkpoint inhibitors as a salvage treatment of tumor recurrence after liver transplantation for hepatocellular carcinoma / 中华器官移植杂志

Objective:To explore the safety and efficacy of immune checkpoint inhibitors(ICI)for patients with tumor recurrence after liver transplantation(LT).Methods:A single-center retrospective study was conducted for 6 recipients of tumor recurrence after LT on a therapy of ICI admitted into Shulan(Hang Zhou)Hospital from September 2015 to June 2018.The authors examined the occurrences of graft rejection and clinical outcomes of overall response rate, progression-free survival and overall survival after dosing of PD-1/PD-L1 inhibitors.Results:Six patients enrolled with tumor recurrence on a therapy of ICI undergoing LT due to hepatocellular carcinoma (HCC). Nivolumab (n=4) and duvalizumab (n=2) were administrated.The median session of treatment was 8.3(2-31) cycles.The disease outcomes were stable (3/6, 50%) and progressive (3/6, 50%), The progression-free survival time of 3 disease-controlled patients was 1.5, 16.2 and 18 months and the median survival time after recurrence was 19.75(10.8-37.8) months.Rejection occurred in 1 patients (1/6, 16.7%) and the occurring time of rejection was 28 days after PD-1 inhibitor dosing.After acute rejection, high-dose corticosteroids and immunoglobulin were ineffective and the patient died from acute rejection related liver failure.Conclusions:ICI may be employed as a salvage treatment for tumor recurrence after LT for HCC.Due to a possibility of severe acute rejection, usage should be cautious under close monitoring of liver function.

Safety and efficacy of domestic single-port robotic surgery system for extraperitoneal urological surgery / 中华泌尿外科杂志

Objective:To investigate the safety and efficacy of the novel single-port surgical robotic surgical system in extraperitoneal urological surgery.Methods:From February to April 2022, patients was prospectively enrolled who required laparoscopic radical prostatectomy, partial nephrectomy and adrenal tumor resection in urology department. Inclusion criteria were: age ≥ 18 years old; BMI 18.5-30 kg/m 2; American Society of Anesthesiologists (ASA) physical status classification system grades 1 to 3; can cooperate with the completion of the visits and related examinations stipulated in the plan, and participate voluntarily clinical trials, and consent or the guardian agrees to sign the informed consent form; tumor indicators meet one of the following surgical treatment indications: kidney tumor T 1 stage, single, maximum tumor diameter ≤ 4 cm; prostate cancer, stage ≤ T 2b, preoperative PSA ≤ 20 ng /ml; Gleason score ≤ 7; adrenal tumor diameter ≤ 7 cm, for non-functioning adrenal adenoma, tumor diameter ≥ 3 cm. Exclusion criteria were: patients with other malignancies or a history of other malignancies and the investigators believe that they are not suitable for inclusion in this researcher; patients who have received the same type of urological surgery in the past and are not suitable for participating in this study as assessed by the investigators; included Those who have undergone other major surgery within the first 3 months and during the trial period, or who cannot recover from the side effects of any such surgery; syphilis, hepatitis B, HIV infection and carriers; long-term use of anticoagulants or blood system diseases; Unable to use effective contraception during the trial period and other conditions that the investigators deem inappropriate to participate in this trial. All operations were performed by a novel single-port robotic surgical operating system, and all surgical procedures were performed through an extraperitoneal approach. Surgical method: the surgical system is mainly composed of a remote console including a high-definition display, a surgical equipment trolley, a surgical execution system that accommodates a serpentine robotic arm, and a bendable serpentine robotic arm. In this study, the extraperitoneal approach was used. For radical prostatectomy, the patient was placed in a supine position, a longitudinal incision of about 3 cm was made below the umbilicus, the anterior rectus sheath was incised, the extraperitoneal space was separated, and an operating sheath was placed. A 12 mm trocar is placed between the right McBurney point and the umbilicus as an auxiliary hole. For partial nephrectomy and adrenal tumor resection, the patient is placed in the lateral position, and an 3cm incision is made 2 cm above the iliac crest on the midaxillary line as the main operating hole. The skin, subcutaneous tissue, and muscle were incised to the retroperitoneal cavity, and a 12mm trocar was placed at the level of the anterior superior iliac spine on the anterior axillary line as an auxiliary hole. The operation was performed after connecting each robotic arm. After the operation, the specimen was placed in the specimen bag, and a drainage tube is placed in the auxiliary hole, the specimen was taken out, and the incision was closed in turn. Preoperative basic information, operation time, blood loss, incision size, postoperative complications, preoperative and postoperative PSA score, eGFR index, postoperative pathological information and other perioperative information were collected. Results:A total of 17 patients were included in this study, including 6 with prostate cancer, 8 with renal tumor, and 3 with adrenal tumor. There were 9 males and 8 females, with an average age of (56.7±14.6) years and a BMI of (23.3±3.4) kg/m 2. The mean operation time of radical prostatectomy was (244.6±35.1) min, the mean operating time of the chief surgeon was (184.0±39.0) min, and the mean blood loss was (36.6±23.8) ml. Postoperative positive margin was found in 2 cases. The average operation time of partial nephrectomy was (189.6±49.4) minutes, the average operating time of the chief surgeon was (115±39.7) minutes, the average blood loss was (12.7±8.3) ml, and the average warm ischemia time was (23.1±10.8) minutes. There was no significant difference in the eGFR index before and after the operation ( P>0.05). The average operation time of adrenalectomy was (177.6±26.9) min, the average operating time of the chief surgeon was (99±20.4) min, and the average blood loss was (11.6±6.2) ml. The overall average operation time of the three surgical methods was (206.9±50.1) min, the overall average operating time of the chief surgeon was (136.5±51.1) min, the overall average blood loss was (21.0±9.2) ml, and the overall average incision size was (3.5±0.5) cm, all added a 12 mm auxiliary channel, and the overall average hospital stay was (8.1±2.7) days. All operations were successfully completed, and there was no conversion to open surgery during the operation, and no operation holes were added. There was no Clavien-Dindo≥grade 3 complication after operation. Conclusions:The novel single-port robot could safely and effectively perform radical prostatectomy, partial nephrectomy and adrenalectomy which are common in urology through extraperitoneal approach.

Clinicopathologic features and prognosis of Xp11.2/TFE3 gene fusion associated renal cell carcinoma in adults / 中华泌尿外科杂志

Objective:To investigate the clinicopathological features and prognosis of adult Xp11.2/TFE3 gene fusion-associated renal cell carcinoma (TFE3 RCC).Methods:The clinical data of 55 patients with TFE3 RCC admitted to the First Affiliated Hospital of Zhejiang University Medical College from January 2013 to February 2021 were retrospectively analyzed, including 26 males and 29 females. The patients’ mean age was (40.6 ± 14.7) years. The median tumor size was 4.0 (1.9-20.0) cm. Tumors were located in the left kidney in 30 cases (54.5%) and the right kidney in 25 cases (45.5%). Preoperative imaging assessment was well-circumscribed in 41 patients (74.5%) and ill-defined in 14 patients (25.5%). There were 2 cases of regional lymph node metastasis and 2 cases of distant metastasis, including 1 case of lung metastasis and 1 case of bone metastasis. Preoperative staging included stage I in 38 patients (69.1%), stageⅡ in 5 patients (9.1%), stage Ⅲ in 9 patients (16.4%), and stageⅣin 3 patients (5.5%). Nephron-sparing surgery was performed in 31 patients (56.4%) and radical nephrectomy in 24 patients (43.6%). Progression-free survival curves were plotted by the Kaplan-Meier method and analyzed by the log-rank test. Cox proportional hazards regression model was applied for multivariate analysis of factors influencing progression-free survival.Results:Postoperative pathological stage included pT 1 in 41 patients (74.5%), pT 2 in 5 patients (9.1%), pT 3 in 8 patients (14.5%), and pT 4 in 1 patient (1.8%). Four patients (7.3%) had N 1 stage and 2 (3.6%) had M 1 stage. After immunohistochemical analysis, TFE3 showed diffuse strong positive reaction in 55 patients, cathepsin K positive in 36 patients (65.5%), CD10 positive in 48 patients (87.3%), CK7 positive in 7 patients (12.7%), CA-IX positive in 2 patients (3.6%), and PAX8 positive in 35 patients (63.6%). Two cases were tested by fluorescent in situ hybridization (FISH), and the results were positive. The proportion of nuclei with mitotic signals was 40% and 30%, respectively. The median follow-up time was 27 (3-96) months. The results of survival analysis showed that the 3-year and 5-year progression-free survival rates were 80.0% and 64.0%, respectively. The results of univariate analysis showed that tumor size ( P = 0.009), pT stage ( P<0.001), regional lymph node invasion ( P = 0.003), and surgical approach ( P = 0.006) were associated with the prognosis of TFE3 RCC patients. Multivariate analysis of the Cox model was performed on significant univariate factors, and its results showed that pT stage ( HR=4.824, 95% CI 1.129-20.604, P=0.034) and regional lymph node invasion ( HR=5.522, 95% CI 1.066-28.611, P = 0.042) were independent prognostic factors for progression-free survival in TFE3 RCC patients. The results of stratified analysis showed that for patients with pT 1 disease, the effect of surgical approach on the prognosis of patients was not statistically significant ( P=0.091). The 3-year progression-free survival rates for nephron-sparing surgery and radical nephrectomy were 94.7% and 81.5%, respectively. Conclusions:Given that TFE3 RCC imaging studies often lack characteristic features, diagnosis mainly relies on immunohistochemical analysis and FISH tests. Most of the patients with TFE3 RCC have a better prognosis after surgical treatment. However, pT stage and regional lymph node invasion were prognostic factors in patients with TFE3 RCC.

Study on the correlationship between hearing loss and cognitive decline among older adults in Beijing / 中华健康管理学杂志

Objective:To study the correlation between hearing loss and cognitive decline in community-dwelling older adults and to analyze the influencing factors.Methods:Using Pure-tone audiometry, the Hearing Handicap Inventory for the Elderly (HHIE), Mini-Mental State Examination (MMSE), Patient Health Questionnaire-9 (PHQ-9), and Generalized Anxiety Disorder, a survey was conducted with 492 community-dwelling older adults aged 60 years and above in Beijing. Age, gender, education level, hearing loss, levels of anxiety and depression, and other factors were used as independent variables, and the MMSE scores were used as dependent variables. Analysis of variance and multiple linear regression were performed.Results:Among the 492 subjects, based on the better ears, 418 (85.0%) had hearing loss and 160 (32.5%) had disabled hearing loss. Factors such as age (β=-0.33, P<0.01), gender (β=0.09, P=0.04), education level (β=0.31, P<0.01), hearing loss (β=-0.11, P=0.02) and marital status (β=0.56, P=0.02) were significantly related to cognitive decline. Gender (β=-0.17, P<0.01) and hearing loss (β=0.08, P=0.02) correlated with anxiety indicators; gender (β=-0.84, P=0.02) and hearing loss (β=0.04, P=0.01) also correlated with depression indicators. Conclusion:Results indicated a correlation between hearing loss and cognitive decline, and between hearing loss and anxiety and depression among community-dwelling older adults in Beijing.

Effect of salvianolic acid on behaviors and brain inflammatory factors in depression model rats / 中华行为医学与脑科学杂志

Objective:To investigate the effect of salvianolic acid on depressive behavior in depression model rats induced by chronic mild stress (CMS) and its mechanism.Methods:Fifty healthy male clean grade Sprague-Dawley(SD) rats were divided into five groups according to a random number table with 10 in each group: control group (nCMS+ Nal group), CMS+ normal saline group (CMS+ Nal group), CMS+ fluoxetine group (CMS+ Flu group), CMS+ salvia acid group (CMS+ Sal group), CMS+ fluoxetine+ Salvia acid group (CMS+ Flu+ Sal group). Except the control group, the rats in the other four groups were all received CMS modeling for 21 days. Twenty-one days after CMS modeling, rats were intraperitoneally injected with 0.9% normal saline (10 mg·kg -1·d -1), fluoxetine (20 mg·kg -1·d -1), salvia acid(40 mg·kg -1·d -1), fluoxetine(20 mg·kg -1·d -1)+ salvia acid(40 mg·kg -1·d -1)for 21 days. During the administration period, rats in the other four groups continued to receive CMS intervention for 21 days. Forced swimming test and sucrose preference test were conducted at baseline (day 0), after modeling (day 21) and after intervention (day 42) so as to evaluate depression like behavior. Then the rats were sacrificed and the hippocampus and prefrontal cortex were taken. The mRNA levels of Toll like receptor 4 (TLR4) and myeloid differentiation primary response 88 (MyD88) were detected by RT-qPCR. The cytokines including interleukin-1β(IL-1β), interleukin-2(IL-2), interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were detected by Luminex technique.SPSS 21.0 was used for statistical analysis.Repeated measurement ANOVA was used for behavioral data analysis, one-way ANOVA was used for molecular index data analysis, and Spearman was used for correlation analysis. Results:The results of repeated measurement ANOVA showed that the interaction effects between group and time of body mass, sucrose preference, forced swimming immobility time were significant at baseline, after modeling and after intervention ( F=18.238, 6.921, 7.591, all P<0.05). After modeling, compared with nCMS+ Nal group, the rats in CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and CMS+ Nal group had lower body weight, lower sucrose preference rate and longer forced swimming immobility time (all P<0.05). After intervention, compared with CMS+ Nal group(body weight (350.15±41.65)g, sucrose preference(52.95±11.13)%, static time(91.40±15.22)s), the body weight((378.21±30.78)g, (385.12±43.19)g, (391.41±31.21)g, (402.33±18.67)g, all P<0.05) and sucrose preference((69.30±15.56)%, (68.12±10.99)%, (71.18±9.51)%, (75.47±11.55)%, all P<0.05) of CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and nCMS+ Nal group were all increased, while the forced swimming immobility time ((68.81±21.74)s, (66.10±25.51)s, (63.53±22.32)s, (71.21±21.41)s, all P<0.05) were shorter (all P<0.05). After intervention, among the body weight, sucrose preference and the immobility time of CMS+ Flu group、CMS+ Sal group and CMS+ Flu+ Sal group, there were no differences between each two groups(all P>0.05). After intervention, the levels of TLR4 mRNA and MyD88 mRNA in prefrontal cortex and hippocampus of CMS+ Flu group, CMS+ Sal group, CMS+ Flu+ Sal group and nCMS+ Nal group were all lower than those in CMS+ Nal group (all P<0.05). In prefrontal cortex, the levels of TLR4 mRNA (0.715±0.358) and MyD88 mRNA (0.739±0.233) in CMS+ Flu+ Sal group were lower than those in CMS+ Sal group (1.943±0.606, 1.815±0.897) (both P<0.05). The level of TLR4 mRNA in prefrontal cortex and hippocampus of rats were positively correlated with the level of MyD88 mRNA and TNF-α level and forced swimming immobility time and negatively correlated with sucrose preference rate (prefrontal cortex r=0.915, 0.041, 0.027, -0.178, all P<0.05; hippocampus r=0.810, 0.070, 0.011, -0.153, all P<0.05). Conclusion:The antidepressant effect of salvianolic acid is presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CMS rats.

Exploring the detection of MYD88 mutation in patients with Waldenström macroglobulinemia by different methods and specimens / 中华血液学杂志

Objective: To improve the positivity rate and accuracy of MYD88 mutation detection in patients with Waldenström macroglobulinemia (WM) . Methods: MYD88 mutation status was retrospectively evaluated in 66 patients diagnosed with WM in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from June 2017 to June 2021. The positivity rate and accuracy of the different methods and specimens for MYD88 mutation detection were analyzed. Results: MYD88 mutations were detected in 51 of 66 patients with WM, with an overall positivity rate of 77%. The positivity rate of the next-generation sequencing (NGS) or allele-specific polymerase chain reaction (AS-PCR) was significantly higher than that of the first-generation Sanger sequencing (84% vs 71% vs 46%, P<0.05) . For the different specimens, the positivity rate for the lymph nodes or bone marrow was significantly higher than that of peripheral blood (79% vs 84% vs 52%, P<0.05) . The positivity rate of the MYD88 mutation in the lymph nodes, bone marrow, and peripheral blood determined by NGS was 86%, 90%, and 67%, respectively. The positivity rate in the lymph nodes, bone marrow, and peripheral blood detected by AS-PCR was 78%, 81%, and 53%, respectively. Thirty-nine patients with WM underwent ≥ 2 MYD88 mutation detections. The final MYD88 mutational status for each patient was used as the standard to determine the accuracy of the different methods and in different specimens. The accuracy of MYD88 mutation detection in the lymph nodes (n=18) and bone marrow (n=13) by NGS was significantly higher than that in the peripheral blood (n=4) (100% vs 100% vs 75%, P<0.05) . There was no statistically significant difference in the accuracy of MYD88 mutation detection by AS-PCR in the lymph nodes (n=15) , bone marrow (n=11) , or peripheral blood (n=16) (93% vs 91% vs 88%, P>0.05) . Conclusions: In the detection of the MYD88 mutation in patients diagnosed with WM, NGS or AS-PCR is more sensitive than Sanger sequencing. Lymph nodes and bone marrow specimens are better than peripheral blood specimens.

Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy

The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death (ICD), showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment (ITM). However, the therapeutic effectiveness has been restricted by inferior drug bioavailability. Herein, we reported a universal bioresponsive doxorubicin (DOX)-based nanogel to achieve tumor-specific co-delivery of drugs. DOX-based mannose nanogels (DM NGs) was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy. As expected, the DM NGs exhibited prominent micellar stability, selective drug release and prolonged survival time, benefited from the enhanced tumor permeability and prolonged blood circulation. We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD. Meanwhile, the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo, via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle. Overall, the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy, offering a paradigm for the exploitation of immunomodulatory nanomedicines.

The function of auditory cortex in the elderly using functional near-infrared spectroscopy technology / 中华耳鼻咽喉头颈外科杂志

Objective: Functional near-infrared spectroscopy (fNIRS) was used to study the effect of aging on the neuroimaging characteristics of cerebral cortex in the process of speech perception. Method: Thirty-four adults with normal hearing were recruited from March 2021 to June 2021, including 17 in the young group, with 6 males, 11 females, age (32.1±5.0) years, age range 20-39 years. and 17 in the elderly group, with 6 males, 11 females, age (63.2±2.8) years, age range 60-70 years. The test material was the sentence table of the Mandarin Hearing Test in Noise (MHINT). The task state block experiment design was adopted, and the temporal lobe, Broca's area, Wernicke's area, motor cortex were used as regions of interest. Objective brain imaging technology (fNIRS) combined with subjective psychophysical testing method was used to analyze the activation area and degree of cerebral cortex related to auditory speech perception in the elderly and young people under different listening conditions (quiet, signal-to-noise ratio of 10 dB, 5 dB, 0 dB, -5 dB). SPSS 23 software was used for statistical analysis. Result: The activation area and degree of activation in the elderly group were lower than those in the young group under each task condition; The number of activation channels in the young group were significantly more than those in the old group, and the number of activation channels in the left hemisphere were more than those in the right hemisphere, but there was no difference in the number of activation channels. There were more channels affected by age in the left hemisphere than in the right hemisphere. The activation degree of the young group when the signal-to-noise ratio was 0 dB was significantly higher than that of other signal-to-noise ratio conditions (P<0.05), but there was no significant difference in the old group under the five conditions (P>0.05). The speech recognition score of the young group was higher than that of the old group under all conditions. When the quiet and signal-to-noise ratio was 10 dB, the correct score of the two groups was equal or close to 100%. With the gradual decrease of signal-to-noise ratio, there was a significant difference between the two groups when the signal-to-noise ratio was 5 dB. The speech recognition accuracy of the young group decreased significantly when the signal-to-noise ratio was 0 dB, while that of the old group decreased significantly when the signal-to-noise ratio was 5 dB. Conclusions: With the increase of age, the speech perception in noisy environment and the activity of cerebral cortex gradually deteriorate, and the speech dominance hemisphere (left hemisphere) will be significantly affected by aging. The overall activation area and activation degree of the elderly under different speech tasks are lower than those of the young.

Screening of active components of Euchresta japonica against nasopharyngeal carcinoma / 中国药房

OBJECTIVE To screen t he active component s of Euchresta japonica against nasopharyngeal carcinoma. METHODS Main chemical components of E. japonica were selected ，and their target proteins were predicted in Swiss Target Prediction database. The target proteins of nasopharyngeal cancer were obtained with GeneCards database. Protein-protein interaction（PPI）network was established after the target of chemical components of E. japonica was intersected with the target of nasopharyngeal carcinoma ；PPI network was analyzed by using Cytoscape 3.6.1 software，and the potential active components and key targets of E. japonica against nasopharyngeal carcinoma were screened. The molecular docking technology was used to evaluate binding ability of active component-key target ；active components of E. japonica against nasopharyngeal carcinoma were screened. The anti-nasopharyngeal cancer effect of potential active components of E. japonica was verified by cell proliferation experiment. RESULTS Seven potential active components （tonkinensisol，quercetin，sophoranone，matrine，genistein，coumarin，maackiain） and 10 core targets （SRC，PIK3CA，MAPK1，MAPK3，AKT1，MAPK8，MAP2K1，PTK2，EGFR，JAK3）of E. japonica against nasopharyngeal carcinoma were screened. The molecular docking results showed that above potential active components all possessed certain anti-nasopharyngeal cancer effect. Cell proliferation activity test showed that tonkinensisol ，sophoranone and maackiain had a very significant inhibitory activity on nasopharyngeal carcinoma cells CNE- 1. CONCLUSIONS Tonkinensisol， sophoranone and maackiain might be the main active components of E. japonica against nasopharyngeal carcinoma.

The risk factors associated with apex or basal positive surgical margins after radical prostatectomy / 中华泌尿外科杂志

Objective:To analyze the risk factors associate with apex or basal positive surgical margins in patients after radical prostatectomy.Methods:During the period from January 2013 to December 2017, data was collected in 180 patients undergoing radical prostatectomy in Urological department of Peking University Cancer Hospital. Surgical margins were stated negative, positive, apex positive, basal positive. Dichotomous logistic regression analysis was used to evaluate the age, total prostate volume, biopsy positive cores, D’Amico risk classification, tumor pathology stage, Gleason score, tPSA, f/tPSA and pelvic lymph nodes metastasis with the PSMs.Results:PSMs were detected in 97 cases, including 78 cases with positive apex, 51 cases with positive basal, and 83 cases with negative margin, the PSMs proportion was 53.9%. In univariable analysis, pT 3b( OR=6.871, P=0.010), pT 4( OR=12.13, P<0.05), Gleason≥8( OR=4.989, P=0.005), pelvic lymph nodes metastasis( OR=9.516, P=0.043) associated with higher proportion of PSMs. In multivariable analysis, pT 3b( OR=5.782, P=0.030), pT 4( OR=10.15, P<0.05), Gleason≥8( OR=11.13, P=0.012) were the independent factors positively associated with higher proportion of PSMs. In univariable analysis, pT 3b( OR=4.040, P=0.026), Gleason≥8( OR=2.390, P=0.010) associated with higher proportion of apex positive. In multivariable analysis, Gleason≥8 ( OR=1.980, P=0.030) was the only independent factor associated with higher proportion of apex positive. In univariable analysis, D’Amico high risk ( OR=1.847, P=0.035), pT 4 ( OR=1.780, P=0.001) associated with higher proportion of basal positive. In multivariable analysis, D’Amico high risk ( OR=1.540, P=0.041) was the only independent factor associated with higher proportion of basal positive. Conclusions:In patients radical prostatectomy, pathology staging and Gleason score were associated with positive surgical margins.Gleason score was associated with positive apex margins, and D’Amico risk classification was associated with positive basal margins.

Prediction of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage based on permeability parameters of CT perfusion imaging / 中华放射学杂志

Objective:To explore the value of blood-brain barrier permeability (BBBP) parameters based on CT perfusion (CTP) in predicting delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) within 24 hours of admission.Methods:Totally 69 patients underwent whole-brain CTP within 24 h after aneurysm rupture from July to November 2020 in Yijishan Hospital of Wannan Medical College. The volume transfer constant (K trans) reflecting BBBP, the time to drain (TTD) and transit time to the center of the impulse response function (TMax) reflecting cerebral perfusion were obtained. Patients were divided into DCI and non-DCI groups. Quantitative and qualitative CTP parameters, clinical data were compared between the two groups. On the basis of univariate analysis, the multivariate logistic regression analysis was used to determine the independent risk factors of DCI using the stepwise regression method. The predictive efficiency of clinical data and CTP parameters were evaluated by ROC analysis. Results:Twenty-one of 69 aSAH patients developed DCI. Whole brain average values of K trans (mK trans) in the DCI group [(0.67±0.16)ml/(100 ml·min)] were significantly higher than those in the non-DCI group [(0.41±0.15)ml/(100 ml·min), t=-6.454, P<0.001]. mK trans in the diffused hypoperfusion patients [(0.61±0.18)ml/(100 ml·min)] was significantly higher than that in the normal perfusion group [(0.36±0.15)ml/(100 ml·min), P<0.001] and localized hypoperfusion group [(0.43±0.16)ml/(100 ml·min), P<0.001]. Multivariate logistic regression analysis showed mK trans (OR=1.13, 95%CI 1.05-1.21, P=0.001), World Federation of Neurosurgery Scale (OR=5.35, 95%CI 1.12-25.65, P=0.036) and modified Fisher Score (OR=5.32, 95%CI 1.02-27.80, P=0.048) were significantly independent predictors of DCI. ROC curve analysis revealed that mK trans produced the highest AUC of 0.875 (95%CI 0.78-0.97), with a threshold of 0.545 ml/(100 ml·min) had sensitivity of 85.7%, specificity of 79.2% and Youden index of 64.9% for prediction of developing DCI. Conclusion:It is feasible to evaluate cerebral perfusion and BBBP status and predict the risk of developing DCI in aASH patients who admitted within 24 h after aneurysm rupture using whole-brain CTP.

CT features and diagnosis and treatment of emphysema pancreatitis / 中华消化外科杂志

Objective:To investigate the computed tomography (CT) features and diagnosis and treatment of emphysema pancreatitis (EP).Methods:The retrospective and descriptive study was conducted. The clinical and imaging data of 12 patients with EP who were admitted to Xuanwu Hospital of Capital Medical University from January 2017 to June 2020 were collected. There were 10 males and 2 females, aged from 25 to 71 years, with a median age of 42 years. All patients received CT examination. Step-up treatment or one-step surgical treatment was performed on patients according to their conditions. Observation indicators: (1) CT features; (2) bacteriological characteristics; (3) treatment and follow-up. Follow-up using outpatient examination was conducted at postoperative 1, 3, 6 months to detect survival of patients up to January 2021. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M (range). Count data were described as absolute numbers. Results:(1) CT features: 1 of the 12 patients underwent abdominal+pelvic CT plain scan, and 11 cases underwent abdominal+pelvic CT plain scan and enhanced scan of arterial and portal venous phase. CT examination of 12 patients showed diffuse enlargement of the pancreas, unclear borders and a large amount of exudation around the pancreas. Pancreatic necrotic tissues accounted for >30% of the total pancreatic volume; the Balthazar CT score was 10 (range, 8-10). Of the 12 patients, 5 cases showed that the exudation or necrosis involved bilateral prerenal fascia, 7 cases only involved the left prerenal fascia; the necrotic infection area of 11 patients formed obvious wraps. The distribution of pancreatic, peripancreatic infection and gas in 12 patients: 6 cases had pancreatic, peripancreatic infection and gas located in Ⅰ+Ⅱa area, 3 cases located in Ⅰ+Ⅱa+Ⅲ area, 2 cases located in Ⅰ+Ⅲ area, and 1 case located in Ⅰ area. There was gas in the pancreatic parenchyma in 12 patients, with fluid in the abdominal cavity and pelvic cavity. (2) Bacteriological characteristics: the culture results of peripancreatic necrotic issues in 12 patients were all positive for the pathogenic specimens, and 27 strains were cultured. Klebsiella pneumoniae was the most common in the culture of necrosis from 12 patients, followed by Escherichia coli and Enterococcus bacteria. Fungus was found in the culture of necrosis from 1 patient. Of the 12 patients, 5 had negative blood cultures and 7 had positive blood cultures. A total of 14 strains were cultured, with Klebsiella pneumoniae being the most common; fungus was found in the blood culture from 4 patients. (3) Treatment and follow-up: 1 patient underwent percutaneous catheter drainage, 7 underwent step-up surgical treatment, 4 underwent one-step surgical treatment; 11 patients undergoing surgical treatment received laparoscopic-assisted removal of pancreatic necrotic tissue, including 1 case with exploratory laparotomy due to abdominal hemorrhage. Of the 11 patients undergoing surgical treatment, 7 cases received the left retroperitoneal approach surgery (including 1 case combined with the upper abdominal median approach), 2 cases received the upper abdominal median transomental sac approach surgery, 1 case received the right retroperitoneal approach surgery, and 1 case received the left rectus abdominis approach surgery. The number of operations of all the 11 patients were (3.1±0.9)times, the number of step-up treatments was (3.6±0.8)times, and the number of one-step surgery was (2.3±0.5)times. Nine of 12 patients had organ dysfunction that lasted for more than 48 hours during the treatment, which received surgical treatment after organ support and anti-infection therapy. All the 12 patients were followed up for 6 months after operation, of which 9 cases were cured after treatment and 3 cases died including 1 case dying of bleeding and 2 cases dying of septic shock combined with multiple organ failure.Conclusions:Emphysema pancreatitis is complicated by pancreatic necrosis, which is characterized by pancreatic and peripancreatic gas accumulation on CT. Most patients with EP have organ failure. Surgery is an important treatment for EP.

Clinical study on treatment of senile hypertension with Bushen-Yijing-Tiansui Decoction combined with levoclodipine besylate tablets / 国际中医中药杂志

Objective:To observe the therapeutic effect of Bushen-Yijing-Tiansui Decoction combined with levoclodipine besylate in the treatment of senile hypertension. Methods:A total of 150 elderly hypertensive patients admitted in our hospital from January 2019 to February 2020 were randomly divided into 2 groups by a random number table method, with 75 in each. Both groups were given basic symptomatic treatment of other comorbidities and concurrent health education. The control group received oral amlodipine besylate tablets, and the observation group received Bushen-Yijing-Tiansui Decoction on the basis of the control group. Both groups were treated for 4 weeks. The TCM syndromes were scored before and after treatment, manometer was used to measure blood pressure and heart rate, the serum ET-1 level was detected by Enzyme-Linked Immunosorbent Assay (ELISA), and the nitrate reductase method was used to detect serum NO levels, and adverse events occurred during treatment in the two groups were recorded. Results:The total effective rate of the observation group was 88.0% (66/75), and the control group was 73.3% (55/75), and the comparison difference in 2 groups was statistically significant ( χ2 =5.172, P=0.022). After treatment, the symptom scores of pain, palpitations, constipation, insomina, sore feeling on back and legs of the observation group were signigicantly lower than those in the control group ( t value were 5.814, 10.397, 12.094, 7.019, 6.121, all Ps<0.001). After treatment, heart rate [(79.60 ± 4.80) times/min vs. (84.30 ± 5.40) times/min, t=5.634], SBP [(144.8 ± 7.90) mmHg vs. (150.60 ± 7.90) mmHg, t=4.729], DBP [(78.80 ± 8.20) mmHg vs. (85.20 ± 9.10) mmHg, t=4.525] of the observation group were signigicantly lower than those of the control group ( P<0.01). After treatment, the serum ET-1 [(179.25 ± 30.45) μmol/L vs. (190.83 ± 30.89) μmol/L, t=2.312] of the observation group was signigicantly lower than that of the control group ( P<0.05), NO [(58.51 ± 8.78) μmol/L vs. (54.12 ± 9.03) μmol/L, t=3.019] of the observation group was signigicantly higher than that of the control group ( P<0.05). During treatment, the incidence of adverse events in the control group was 4.0% (3/75), and the observation group was 1.3% (1/75), and the two groups had no significant difference ( χ2 =1.027, P=0.311). Conclusion:Bushen-Yijing-Tiansui Decoction combined with levoclodipine besylate in the treatment of senile hypertension can relieve the clinical symptoms and blood pressure of patients, improve the function of vascular endothelial cells.