Genetic, Clinical, and Pathologic Backgrounds of Children With X-Linked Alport Syndrome in China: A Monocenter Study.

Background. Characteristics of X-linked Alport syndrome (XLAS) in a cohort of Chinese children. Methods. This work is a retrospective study covering the clinical information, pathological data, and gene sequencing results of 32 cases with XLAS from 2011 to 2022. Results. Among these 32 patients, the youngest age of onset was 3 months. Renal biopsy was performed on 29 children. The lamellated glomerular basement membrane was observed in 19 children using electron microscopy (65.5%). Of the 26 samples tested, 73.1% were found to be negative for collagen-a5 under immunohistochemical staining, showing clinical significance. Next-generation sequencing (NGS) detected 27 pathogenic gene mutations. A total of 15.4% of patients carried de novo mutations. Conclusions. The boys with XLAS showed more typical pathological performance than the girls. Patients with severe mutation were more likely to have proteinuria and hearing impairment. Renal pathology combined with NSG is an important means of diagnosis of AS.

Effect of Qiwei Baizhusan on Cognitive Dysfunction in Rats with Diabetic Encephalopathy Based on PI3K/Akt/GSK-3β Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the therapeutic effect of Qiwei Baizhusan（QWBZS） on diabetic encephalopathy（DE） rat model， and to explore the possible mechanism of QWBZS in the treatment of DE based on phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β） signaling pathway. MethodForty-eight SPF male Wistar rats were randomly divided into blank group（8 rats） and high-fat diet group（40 rats）. After 12 weeks of feeding， rats in the high-fat diet group were intraperitoneally injected with 35 mg·kg-1 of 1% streptozotocin（STZ） for 2 consecutive days to construct a DE model， and rats in the blank group were injected with the same amount of sodium citrate buffer. After successful modeling， according to blood glucose and body weight， model rats were randomly divided into model group， low， medium and high dose groups of QWBZS（3.15， 6.3， 12.6 g·kg-1）， combined western medicine group（metformin+rosiglitazone， 0.21 g·kg-1）， with 6 rats in each group. The administration group was given the corresponding dose of drug by gavage， and the blank group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage， 1 time/day for 6 weeks. Morris water maze was used to detect the spatial memory ability of DE rats. Fasting insulin （FINS） level was detected by enzyme-linked immunosorbent assay（ELISA） and insulin resistance index（HOMA-IR） was calculated. Hematoxylin-eosin（HE） staining was used to observe the morphological changes of hippocampus in rats， ELISA was used to detect the indexes of oxidative stress in hippocampal tissues， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to detect mRNA expression levels of PI3K， Akt， nuclear transcription factor-κB（NF-κB）， tumor necrosis factor-α（TNF-α） and interleukin-1β（IL-1β） in hippocampus， and Western blot was used to detect the protein expression of PI3K， Akt， phosphorylated（p）-Akt， GSK-3β and p-GSK-3β in hippocampus of rats. ResultCompared with the blank group， FINS and HOMA-IR values of the model group were significantly increased（P<0.01）， the path of finding the original position of the platform was significantly increased， and the escape latency was significantly prolonged（P<0.01）， the morphology of neuronal cells in hippocampal tissues was disrupted， the levels of reactive oxygen species（ROS） and malondialdehyde（MDA） in hippocampus of rats were increased， and the activity of superoxide dismutase（SOD） was decreased（P<0.05， P<0.01）， mRNA expression levels of PI3K and Akt were decreased（P<0.01）， mRNA expression levels of NF-κB， TNF-α and IL-1β were increased（P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly decreased， and the protein expression of GSK-3β was significantly increased（P<0.01）. Compared with the model group， the FINS and HOMA-IR values of the medium dose group of QWBZS and the combined western medicine group were significantly decreased（P<0.01）， the path of finding the original position of the platform and the escape latency were significantly shortened（P<0.01）， the hippocampal tissue structure of rats was gradually recovered， and the morphological damage of nerve cells was significantly improved， the contents of ROS and MDA in hippocampus of rats decreased and the level of SOD increased（P<0.01）， the mRNA expression levels of PI3K and Akt were increased（P<0.01）， and the mRNA expression levels of NF-κB， TNF-α and IL-1β were decreased （P<0.05， P<0.01）， the protein expression levels of PI3K， p-Akt and p-GSK-3β were significantly increased（P<0.01）， and the expression of GSK-3β was significantly decreased（P<0.01）. ConclusionQWBZS can alleviate insulin resistance in DE rats， it may repair hippocampal neuronal damage and improve learning and cognitive ability of DE rats by activating PI3K/Akt/GSK-3β signaling pathway.

Efficacy of suspended moxibustion stimulating Shenshu (BL23) and Guanyuan (CV4) on the amygdala-HPA axis in rats with kidney-deficiency symptom pattern induced by hydrocortisone.

OBJECTIVE: To investigated the effects of suspended moxibustion stimulating Shenshu (BL23) and Guanyuan (CV4) acupoints on the amygdala and HPA axis in our rat model and elucidated the possible molecular mechanisms of moxibustion on kidney- deficiency symptom pattern (KYDS). METHODS: Sixty male Sprague Dawley rats were randomly divided into a control group ( 12) and an experimental group ( 48). Rats in the experimental group were given intramuscular injections of hydrocortisone to establish a KYDS model. The 48 rats successfully modeled were then randomly divided into a model group (model, 12), a carbenoxolone intraperitoneal injection group (CBX, 12), a moxibustion group (moxi, 12), and a moxi + CBX group ( 12). In the moxi, the Shenshu (BL23) and Guanyuan (CV 4) acupoints were treated with moxibustion for 14 d. After treatment, measures were taken of serum levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), and corticotropin-releasing hormone (CRH). The expression of mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs), 11beta-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), CRH, and ACTH in the rats' amygdala, hypothalamus, or pituitary (as appropriate) was detected. Data were analyzed using one-way analysis of variance. RESULTS: Compared with those of the control group, the serum levels of CRH, ACTH, and CORT; the mRNA and protein expressions of MR, GR, and 11ß-HSD1 in the amygdala; the mRNA and protein expressions of 11ß-HSD1 in the hypothalamus; the CRH mRNA expression in the amygdala and hypothalamus; and the ACTH mRNA expression in the pituitary of the rats in the model group were all significantly decreased (0.05 or 0.01). After treatment with moxibustion, all the aforementioned observation indices except for 11ß-HSD1 mRNA expression were ameliorated compared with those in the model group (0.05 or 0.01). CONCLUSIONS: Suspended moxibustion can effectively improve the serum levels of ACTH, CRH, and CORT and can up-regulate the mRNA and protein expressions of MR, GR, 11ß-HSD1, CRH, and ACTH in the amygdala and hypothalamus of KYDS rats. This may be one of the molecular mechanisms with which moxibustion alleviates KYDS.

Correlation between changes of swallowing function in oral and pharyngeal phases, and aspiration in stroke patients based on videofluroscopic swallowing study / 中国康复理论与实践

ObjectiveTo analyze the correlation between the changes of swallowing function and aspiration in stroke patients using videofluroscopic swallowing study. MethodsFrom January, 2014 to December, 2021, 240 stroke patients who underwent videofluroscopic swallowing study in the radiology department of Xuzhou Central Hospital were retrospectively analyzed. They were divided into aspiration group (n = 108, ≥ grade 5) and non-aspiration group (n = 132, < grade 5) according to Rosenbek Penetration/Aspiration Scale (PAS). The swallowing function changes in the oral and pharyngeal phases were compared between two groups according to Videofluoroscopic Dysphagia Scale, the risk factors of aspiration were analyzed using Logistic multivariate regression. ResultsThere were significant differences in incomplete lip closure, impaired bolus formation, apraxia, incomplete tongue-to-palate contact, premature bolus loss, prolonged oral transit time, delayed triggering of pharyngeal swallow, epiglottis folding dysfunction, pyriform sinus residue, and coating of pharyngeal wall (χ2 > 5.802, P < 0.05). Prolonged oral transit time (OR = 3.964, P = 0.036), delayed triggering of pharyngeal swallow (OR = 5.684, P < 0.001), epiglottis folding dysfunction (OR = 11.571, P < 0.001) and pyriform sinus residue (OR = 4.524, P = 0.002) were correlated with aspiration. ConclusionProlonged oral transit time, delayed triggering of pharyngeal swallow, epiglottis folding dysfunction and pyriform sinus residue are risk factors of aspiration after stroke.

Safety and efficacy of Rezūm water vapor thermal therapy system in the treatment of benign prostatic hyperplasia / 中华泌尿外科杂志

Objective:To evaluate the efficacy and safety of Rezūm Water Vapor Thermal Therapy system in the treatment of patients with benign prostatic hyperplasia (BPH).Methods:The clinical data of 22 patients with benign prostatic hyperplasia treated with Rezūm Water Vapor Thermal Therapy system in Boao Yiling Life Care Center in Hainan from December 2020 to January 2021 were retrospectively analyzed, with age of (61.0±5.9) years, prostate volume of (43.7±8.4) ml. international prostate symptom score (IPSS) of (19.3±3.7), quality of life (QOL) score of (4.2±0.8), maximum urinary flow rate (Q max) of (11.9±3.4) ml ml/s, and residual urine volume (PVR) of (14.0±19.0). For 19 patients with sexual life, the International Index of Erectile Function Questionnaire-5 (IIEF-5) were 17.0±5.5, the Men's Sexual Health Questionnaire-Ejaculatory Dysfunction Score (MSHQ-EjD) ejaculatory function score were 10.0±3.2, and the ejaculatory satisfaction score were 1.5±1.0. Twenty-two patients underwent Rezūm Water Vapor Thermal Therapy under intravenous anesthesia (general anesthesia without intubation) in the dorsal lithotomy position. The Rezūm system consisted of reusable thermal steam treatment device and disposable prostate thermal steam treatment instrument. The thermal steam treatment device used radiofrequency energy to heat sterile distilled water, generating high-temperature steam at 103℃. In a 9-second timeframe, the tissue temperature within each treatment area was raised approximately 70℃, causing cell death and resulting in a shrink in prostate tissue volume. The disposable prostate thermal steam treatment instrument could be inserted through a cystoscope and had a retractable needle tip that extends to a length of 10.25 mm. The needle tip had 12 evenly distributed holes arranged in three rows of four holes each, with a spacing of 120° between rows, allowing for even diffusion of thermal steam along the circumference. The patient was placed in a lithotomy position, and the disposable prostate thermal steam treatment instrument was used to examine the prostate, urethra, and bladder via cystoscopy, assessing the lateral lobes and median lobe of the prostate. The tissue spacing within each field of view of the treatment instrument is 0.5 cm, and the distance from the bladder neck to the verumontanum is calculated. The first needle was injected at 3 o’clock along the left lobe, withdrawing 2 fields of view each time. During the release of thermal steam, the needle tip was positioned perpendicular to the prostate urethral mucosa, and each needle injection delivered 0.42 ml of sterile distilled water-formed thermal steam into the prostate tissue. The thermal steam injection lasted for 9 seconds, followed by a 2-3 seconds waiting period before retracting the needle tip. One needle was injected per 2 fields of view, progressing towards the proximal urethra of the verumontanum. The same method was used to treat the right lobe. For cases with significant median lobe enlargement, two fields of view were retracted at the bladder neck, and the needle was inserted at a 45° angle. The second needle was injected at intervals determined by the extent of median lobe enlargement. Each puncture point was observed for no significant bleeding, and the instrument was then removed, with an F16/F18 silicone catheter left in place. The operative time as well as indwelling catheter time were recorded. The clinical parameters such as IPSS, QOL, prostate volume, Qmax, PVR, QOL, IIEF-5 and MSHQ-EjD at preoperative and 12 to 22 weeks post operation were compared. Adverse events from the Rezūm procedure to 12-22 weeks postoperatively were recorded. Results:All the operations were successfully completed. The operation time of Rezūm system was 3.9±1.6 min, and the indwelling catheter time after operation was 4.8±1.1 days. The IPSS scores of 22 patients at 12-22 weeks after operation were 4.4±3.3, whose reduction was 14.9±4.4 compared with these at baseline( P<0.01). The PV was (37.7±8.4)ml, Qmax was (25.5±9.6)ml/s, PVR was (6.2±8.1)ml, and QOL was 1.6±0.9, all demonstrating statistically significant differences compared to preoperative values ( P<0.05). Among the 19 cases with sexual activity, the IIEF-5 score was 20.4±3.2, and the ejaculatory function score of MSHQ-EjD was 13.1±3.1, both showing statistically significant differences compared to preoperative scores ( P<0.05). The ejaculatory satisfaction score of MSHQ-EjD was 1.1±0.5, and there was no statistically significant difference compared to preoperative scores ( P>0.05). None of the 22 cases required medication or further surgical treatment for BPH after surgery. There were no urethral injuries, rectal or bladder perforations during the surgeries, and no severe complications such as rectal fistula or bladder neck contracture occurred postoperatively. There were no deaths reported. Postoperative discomfort in the urethra occurred in 19 cases, urethral pain in 8 cases, hematuria in 15 cases, poor sleep quality in 2 cases, and constipation in 1 case, all of which resolved within 7 to 10 days after surgery. Erectile dysfunction and retrograde ejaculation occurred in one case each at 4 to 5 weeks postoperatively but did not reoccur thereafter. Prostatitis and nodular hyperplasia of the middle lobe of the prostate occurred in one case each at 21 weeks and 25 weeks postoperatively, respectively, and no treatment was administered. Conclusions:In the real world, the short-term overall effect of Rezūm Water Vapor Thermal Therapy system in the treatment of benign prostatic hyperplasia is satisfactory, which shows good efficacy and safety.

Management of periprosthetic femur fracture after total knee arthroplasty / 中华骨科杂志

Periprosthetic fracture of femur is the most common postoperative complication after total knee arthroplasty (TKA). Risk factors for periprosthetic fractures include female sex, osteoporosis/osteopenia, rheumatoid arthritis, osteoarthritis, neuromuscular disease, cognitive disorder, chronic use of corticosteroids, obesity, advanced age, infection, osteolysis around the prosthesis, knee joint ankyloses, notching of the anterior femoral cortex, etc. According to epidemiological research, the incidence of femoral periprosthetic fractures following TKA ranges from 0.3% to 2.5%. Lewis and Rorabeck classifications, the most commonly used classification of periprosthetic fractures of the femur, introduce the concept of prosthesis loosening and emphasize the ecessity of revision surgery. Other classifications include Su typing, Universal Typing System, and Rhee typing, the latest of which is the Kim typing proposed in 2022. Treatment strategies for periprosthetic femoral fractures after TKA include nonsurgical treatment, external fixation techniques, single-plate fixation, double-plate fixation, intramedullary nail fixation, and revision TKA and distal femur replacement. The purpose of this paper is to better guide the prevention and treatment of periprosthetic fractures after TKA by searching and analyzing relevant literature on periprosthetic fractures after TKA.

Correlation analysis for the lateral condylar tibial plateau fracture and complete medial collateral ligament rupture / 中华骨科杂志

Objective:To investigate the relationship between the CT images of a lateral condylar tibial plateau fractures and complete medial collateral ligament (MCL) injury.Methods:Data of 59 patients with lateral condylar fracture of tibial plateau complicated with MCL injury admitted to Tianjin Hospital from January 2020 to November 2021 were collected, including 32 males and 27 females, aged 42.4±12.3 years (range, 19-65 years), there were 26 cases of extension injury and 33 cases of flexion injury. The patients were separated into two groups: those with partial MCL injury and those with total rupture based on preoperative MR examination and intraoperative valgus stress test following fracture fixation. According to the ABC fracture classification of lateral condyle tibial plateau proposed by Sun et al., the fracture locations were determined on CT images, and the lateral plateau collapse depth (LPD) was measured. The relationship between LPD and MCL complete rupture was analyzed by receiver operating characteristic (ROC) curve.Results:Among 59 patients with lateral condylar tibial plateau fracture and MCL injury, 42 had partial injuries and 17 had complete ruptures. According to the ABC fracture classification, there were 26 cases of extension injury (involving area A), 21 cases of AB type, and 5 cases of ABC type; and 33 cases of flexion type injury, 19 cases of B type, 12 cases of BC type, and 2 cases of C type. All the 17 cases of MCL complete fracture occurred in extension injury, including type AB (14 cases) and type ABC (3 cases). The difference between the mean LPDs of the MCL full rupture group and the partial injury group was not statistically significant ( t=0.11, P=0.567), and the mean LPDs of both groups were 11.7±5.3 mm (range, 4.3-28.1 mm) and 11.5±4.8 mm (range, 3.8-23.6 mm), respectively. The area under the curve (AUC) of the ROC curve analysis was 0.504, and there was no statistical correlation between lateral platform collapse depth and MCL injury. Among the 26 patients with extensional injury area, MCL was completely ruptures in 17 cases and partially injury in 9 cases, LPD was 11.7±5.3 mm (range, 4.3-28.1 mm) and 6.6±1.8 mm (range, 3.8-9.4 mm), respectively, and the difference was statistically significant ( t=3.57, P=0.009). The best predictive cut-off value of LPD was 7.25 mm, the sensitivity was 88.2%, the specificity was 77.8%, and the AUC was 0.868. Conclusion:When the lateral condyle fracture of the tibial plateau is located in the extensional injury area (involving the A area in the ABC fracture classification) and the LPD measured on the CT image is greater than 7.25 mm, the complete rupture of the MCL should be considered. Clinical MCL repair is required after the fracture fixation surgery for improved surgical outcomes.

Correlation between hypertriglyceridemia with repeatedly hospitalization in patients with acute pancreatitis / 中华肝胆外科杂志

Objective:To study the factors influencing repeatedly hospitalization in patients with acute pancreatitis (AP), and to analyse the predictive value of triglyceride for repeated hospitalization.Methods:The clinical data of 1 958 patients with AP treated at the First Affiliated Hospital of Anhui University of Science and Technology from January 2012 to April 2022 were analyzed. Of 1 733 AP patients who were enrolled, there were 1 000 males and 733 females, with mean ± s. d age being (49.4±16.4) years. Patients were grouped based on their ID numbers to determine their number(s) of hospitalization. Those who were admitted only once were included in the initial hospitalization group ( n=1 030), and those who were admitted twice or more were included in the repeated hospitalization group ( n=703). The factors influencing repeated hospitalization were analyzed by univariate analysis and multivariate logistic regression analysis. The predictive value of triglyceride for repeated hospitalization was evaluated by receiver operating characteristic (ROC) curve. Results:Multivariate logistic regression analysis showed that hypertriglyceridemia ( OR=1.445, 95% CI: 1.144-1.825, P=0.002) and biliary causes ( OR=3.184, 95% CI: 1.978-5.125, P<0.001) were independent risk factors for repeated hospitalization. When triglyceride <10.9 mmol/L, the prediction of AP patients without repeated hospitalization was 90.6%. The area under the ROC curve was 0.589, and the Yoden index was 0.170. Conclusion:Hypertriglyceridemia was risk factor for repeat hospitalization in AP patients and the efficacy of triglyceride in predicting repeat hospitalization in AP patients was good.

Diffusion tensor imaging analysis along the perivascular space derived intracerebral glymphatic system circulatory function on neuromyelitis optica spectrum disorder: a follow-up study for curative effect / 中华放射学杂志

Objective:To evaluate the value of curative effect in neuromyelitis spectrum disease (NMOSD) based on circulatory function evaluation of intracerebral glymphatic system by using diffusion tensor imaging analysis along the perivascular space.Methods:The clinical and imaging data of 23 patients diagnosed with NMOSD at Tianjin Medical University General Hospital from March 2018 to December 2019 were retrospectively analyzed in this study. The clinical data included expanded disability status scale (EDSS), average relapse rate (ARR) and retinal nerve fiber layer (RNFL) thickness at baseline and 1 year follow-up after treatment. Among the 23 NMOSD patients, there were 22 females and 1 male, aged from 21 to 71 (45±13) years old. All the patients underwent MR scans at both baseline and 1 year after treatment, and the scanning sequences included cerebral 3D-T 1WI, T 2WI, diffusion tensor imaging and cervical spinal sagittal 3D-T 2WI, and the cervical spinal cord volume and bilateral diffusion tensor imaging analysis along the perivascular space index (ALPS index) were calculated. The partial correlation test was used to analyze the correlations between ALPS index and the clinical indicators such as EDSS, ARR, and bilateral RNFL, with the control variables as gender, age, years of education and course of disease. The multiple linear regression model was used to analyze the independent predictors for ALPS index and EDSS after treatment. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the diagnostic value of NMOSD treatment outcome by using ALPS index. Results:When controlling for gender, age, years of education and course of disease, there were significant negative correlations between right ALPS index and EDSS ( r=-0.50, P=0.048), bilateral average ALPS index and EDSS ( r=-0.53, P=0.034), left ALPS index and ARR ( r=-0.58, P=0.018), while there was significant positive correlations between right ALPS index and RNFL ( r=0.88, P=0.008) at 1 year follow-up after treatment. Multiple linear regression analysis showed that cervical spinal cord volume was an independent impact factor of bilateral average ALPS indexes (β=0.24, 95%CI 0.10-0.38, P=0.002), and bilateral average ALPS indexes (β=-3.22, 95%CI -5.97--0.48, P=0.024) and right RNFL (β=-0.05, 95%CI -0.08--0.02, P=0.002) at baseline were the independent impact factors of EDSS after treatment. ROC curve analysis showed that the bilateral average ALPS index at baseline had the best efficacy in predicting the curative effect of NMOSD patients with AUC=0.92. Conclusions:After treatment, NMOSD patients with severe clinical disability, high frequency of disease attack, poor visual performance, and severe cervical spinal cord atrophy have more serious impairment of intracerebral glymphatic system circulatory function. The ALPS index could help in predicting the clinical curative effect of NMOSD patients.

Prophylactic Vitamin C Attenuates Radiation-induced Lung Injury by Modulating Macrophage Polarization and Alveolar Epithelial Cell Apoptosis / 中国生物化学与分子生物学报

With the ongoing epidemic of the Coronavirus disease in China and the widespread development of radiotherapy, radiation-induced lung injury has gradually become a clinical problem that has attracted much attention. The pathogenesis of radiation-induced lung injury is complex, involving an imbalance in the polarization state of alveolar macrophages and an upregulation of alveolar epithelial cell apoptosis. Previous studies have shown that vitamin C is an important antioxidant substance, and preventive use of vitamin C can effectively treat acute lung injury. However, whether prophylactic use of vitamin C can effectively prevent or treat lung injury caused by radioactive substances, and its specific molecular mechanism remains to be studied. The purpose of this study is to investigate whether the prophylactic use of vitamin C to treat the alveolar macrophage cell line RAW 264. 7 and human lung epithelial cells BEAS-2B can effectively control the abnormal polarization of macrophages and the abnormal apoptosis of lung epithelial cells. This study found that after 4 weeks and 8 weeks of radioactive X-ray irradiation, the expression of macrophage M1 polarization state markers such as iNOS was significantly up-regulated (P< 0. 05), and preventive use of vitamin C to treat macrophages and lung epithelial cells can alleviate the polarization state disorder of macrophages and the apoptosis of alveolar epithelial cells caused by external radiation exposure, which is manifested in the down-regulation of the expression of Cleaved Caspase3. In addition, the preventive application of vitamin C treatment can inhibit the MAPK signaling pathway activated by external radiation exposure. Further experimental results showed that the inhibition of the MAPK pathway is the key to inhibiting the M1 polarization of macrophages and the apoptosis of lung epithelial cells. In summary, our findings suggest that vitamin C may play a protective role in acute radiation-induced lung injury by inhibiting macrophage M1 polarization/ promoting macrophage M2 polarization and alleviating alveolar epithelial cell apoptosis. This study will help to better understand the process and mechanism of the preventive effect of vitamin C, a common vitamin, on radiation-induced lung injury.

Effects of different extraction parts of Tibetan medicine Pulicaria insignis Drumm ex Dunn on CIA rats / 中国药理学通报

Aim To clarify the anti-rheumatoid arthritis effect of Tibetan medicine Pulicaria insignis (P. insignis),sift out the active parts against rheumatoid arthritis,and investigate the mechanism. Methods Rat rheumatoid arthritis (CIA) model was established with bovine type II collagen and incomplete Freund's adjuvant. The effects of the total extract of P. insignis, macroporous resin eluted parts with different concentrations of ethanol and Tripterygium Glycosides (GTW) on the degree of foot swelling in CIA rats were observed,the levels of tumor necrosis factor (TNF-α), intd rheumaerleukin-1β (IL-1β) antoid factor (RF) in serum of rats were detected, the pathological changes of synovial tissues were investigated, and the effects on MAPK/p38/NF-κB, TLR4/NF-κB protein expressions were explored by Western blot. Results Compared with the model group, the total extract of P. insignis and the eluted part of macroporous resin 60% ethanol could significantly reduce the degree of joint swelling in CIA rats, effectively improve the pathological changes of rats synovium tissues, and significantly reduce the levels of rat tumor necrosis factor (TNF-α), interleukin-1β (IL-1β) and rheumatoid factor (RF) in serum inflammatory factors, and markedly decrease the expression of related inflammatory proteins (TLR4, NF-κB, Myd88, p-p38, p-IκBα, iNOS, etc) in synovial tissue. Conclusions (1) P. insignis can relieve the symptoms of joint inflammation in rats with rheumatoid arthritis, and the eluted part of macroporous resin 60% ethanol of P. insignis is the effective active part for anti-rheumatoid arthritis. (2) The total and partial extracts of P. insignis can relieve arthritis symptoms in CIA rats through inhibiting the MAPK/ p38/NF-κB and TLR4/NF-κB signaling pathways.

Comprehensive assessment of mismatch repair and microsatellite instability status in molecular classification of endometrial carcinoma / 中华妇产科杂志

Objective: To explore the concordance and causes of different mismatch repair (MMR) and microsatellite instability (MSI) detection results in endometrial carcinoma (EC) molecular typing. Methods: A total of 214 EC patients diagnosed from January 2021 to April 2023 were selected at the Department of Pathology, Peking University Third Hospital. The immunohistochemistry (IHC) results of MMR protein were reviewed. Tumor specific somatic mutations, MMR germline mutations, microsatellite scores and tumor mutation burden (TMB) were detected by next-generation sequencing (NGS) with multi-gene panel. Methylation-specific PCR was used to detect the methylation status of MLH1 gene promoter in cases with deficient MLH1 protein expression. In cases with discrepant results between MMR-IHC and MSI-NGS, the MSI status was detected again by PCR (MSI-PCR), and the molecular typing was determined by combining the results of TMB and MLH1 gene promoter methylation. Results: (1) In this study, there were 22 cases of POLE gene mutation subtype, 55 cases of mismatch repair deficient (MMR-d) subtype, 29 cases of p53 abnormal subtype, and 108 cases of no specific molecular profile (NSMP). The median age at diagnosis of MMR-d subtype (54 years old) and the proportion of aggressive histological types (40.0%, 22/55) were higher than those of NSMP subtype [50 years old and 12.0% (13/108) respectively; all P<0.05]. (2) Among 214 patients, MMR-IHC test showed that 153 patients were mismatch repair proficient (MMR-p), 49 patients were MMR-d, and 12 patients were difficult to evaluate directly. MSI-NGS showed that 164 patients were microsatellite stable (MSS; equal to MMR-p), 48 patients were high microsatellite instability (MSI-H; equal to MMR-d), and 2 patients had no MSI-NGS results because the effective sequencing depth did not meet the quality control. The overall concordance between MMR-IHC and MSI-NGS was 94.3% (200/212). All the 12 discrepant cases were MMR-d or subclonal loss of MMR protein by IHC, but MSS by NGS. Among them, 10 cases were loss or subclonal loss of MLH1 and (or) PMS2 protein. Three discrepant cases were classified as POLE gene mutation subtype. In the remaining 9 cases, 5 cases and 3 cases were confirmed as MSI-H and low microsatellite instability (MSI-L) respectively by MSI-PCR, 6 cases were detected as MLH1 gene promoter methylation and 7 cases demonstrated high TMB (>10 mutations/Mb). These 9 cases were classified as MMR-d EC. (3) Lynch syndrome was diagnosed in 27.3% (15/55) of all 55 MMR-d EC cases, and the TMB of EC with MSH2 and (or) MSH6 protein loss or associated with Lynch syndrome [(71.0±26.2) and (71.5±20.1) mutations/Mb respectively] were significantly higher than those of EC with MLH1 and (or) PMS2 loss or sporadic MMR-d EC [(38.2±19.1) and (41.9±24.3) mutations/Mb respectively, all P<0.01]. The top 10 most frequently mutated genes in MMR-d EC were PTEN (85.5%, 47/55), ARID1A (80.0%, 44/55), PIK3CA (69.1%, 38/55), KMT2B (60.0%, 33/55), CTCF (45.5%, 25/55), RNF43 (40.0%, 22/55), KRAS (36.4%, 20/55), CREBBP (34.5%, 19/55), LRP1B (32.7%, 18/55) and BRCA2 (32.7%, 18/55). Concurrent PTEN, ARID1A and PIK3CA gene mutations were found in 50.9% (28/55) of MMR-d EC patients. Conclusions: The concordance of MMR-IHC and MSI-NGS in EC is relatively high.The discordance in a few MMR-d EC are mostly found in cases with MLH1 and (or) PMS2 protein loss or MMR protein subclonal staining caused by MLH1 gene promoter hypermethylation. In order to provide accurate molecular typing for EC patients, MLH1 gene methylation, MSI-PCR, MMR gene germline mutation and TMB should be combined to comprehensively evaluate MMR and MSI status.

ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification / 医学前沿

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

Advances in live-imaging aging reporter mice / 生理学报

Aging is an independent risk factor for chronic diseases in the elderly, and understanding aging mechanisms is one of the keys to achieve early prevention and effective intervention for the diseases. Aging process is dynamic and systemic, making it difficult for mechanistic study. With recent advances in aging biomarkers and development of live-imaging technologies, more and more reporter mouse models have been generated, which can live monitor the aging process, and help investigate aging mechanisms at systemic level and develop intervention strategies. This review summarizes recent advances in live-imaging aging reporter mouse models based on widely used aging biomarkers (p16Ink4a, p21Waf1/Cip1, p53 and Glb1), and discusses their applications in aging research.

Clinical thinking of acupuncture for snoring based on "disharmony qi leads to restlessness" / 中国针灸

This study summarizes the clinical thinking of acupuncture for snoring based on "disharmony qi leads to restlessness". According to the pathological characteristics of qi stagnation and blood stasis, phlegm dampness and internal obstruction in snoring patients, combined with the etiology, pathogenesis and location of the disease, the innovative viewpoint of "disharmony qi leads to restlessness" is proposed. It is believed that the key to snoring treatment lies in "regulating qi ". In clinical practice, acupuncture can directly regulate the qi of the disease's location, regulate the qi of the organs and viscera, and regulate the qi of the meridians to achieve overall regulation of the body's internal and external qi, smooth circulation of qi and blood, and ultimately achieve the therapeutic goal of harmonizing qi, stopping snoring, and improving sleep quality.

Application of three-dimensional printed guiding device for electrode implantation in sacral neuromodulation in children / 现代泌尿外科杂志

【Objective】 To investigate the application value of three-dimensional printed guiding device in sacral neuromodulation in children. 【Methods】 A total of 17 patients admitted during Jan.2017 and Nov.2022 were divided into two groups: control group (n=8), using traditional method to locate sacral foramen for puncture; three-dimensional printed guiding device group (n=5), using three-dimensional printing technology to make individual guiding device for puncture. The clinical indexes of the two groups were evaluated, including puncture time, puncture numbers, intraoperative X-ray exposure times, postoperative evaluation time and second-stage conversion rate. The evaluation indexes of postoperative complications were wound bleeding, wound infection, wound rupture, electrode fracture, displacement or prolapse. 【Results】 In the control group, 1 case was diagnosed as bladder-bowel dysfunction, the remaining 7 were neurogenic bladder; in the three-dimensional printed guiding device group, all 9 cases were diagnosed as neurogenic bladder. The puncture time was shorter in the three-dimensional printed guiding device group than in the control group [85(70-90) min vs.138(133-208) min], the puncture numbers were fewer [15(12-20) vs.22(18-26)], and the X-ray exposure times were fewer [12(12-17) vs.19(16-23)] (all P<0.05). The initial stimulation voltage, postoperative evaluation time and second-stage conversion rate were not statistically significant. 【Conclusion】 Compared with the traditional method, the use of three-dimensional printed guiding device can reduce the puncture numbers and shorten the puncture time in the process of sacral neuromodulation in children.

Effect of Guizhi Fuling Capsule on Apoptosis of Myeloma Cells Through Mitochondrial Apoptosis Pathway / 中国结合医学杂志

OBJECTIVE@#To observe the effects of Guizhi Fuling Capsule (GZFLC) on myeloma cells and explore the mechanisms.@*METHODS@#MM1S and RPMI 8226 cells were co-cultured with different concentrations of serum and the cell experiments were divided into negative (10%, 20% and 40%) groups, GZFLC (10%, 20%, and 40%) groups and a control group. Cell counting kit-8 (CCK-8) assays and flow cytometry were used to detect the viability and apoptosis levels of myeloma cells. The effects on mitochondria were examined by reactive oxygen specie (ROS) and tetrechloro-tetraethylbenzimidazol carbocyanine iodide (JC-1) assays. Western blot was used to detect the expression of B cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cleaved caspase-3, -9, cytochrome C (Cytc) and apoptotic protease-activating factor 1 (Apaf-1). RPMI 8226 cells (2 × 107) were subcutaneously inoculated into 48 nude mice to study the in vivo antitumor effects of GZFLC. The mice were randomly divided into four groups using a completely randomized design, the high-, medium-, or low-dose GZFLC (840, 420, or 210 mg/kg per day, respectively) or an equal volume of distilled water, administered daily for 15 days. The tumor volume changes in and survival times of the mice in the GZFLC-administered groups and a control group were observed. Cytc and Apaf-1 expression levels were detected by immunohistochemistry.@*RESULTS@#GZFLC drug serum decreased the viability and increased the apoptosis of myeloam cells (P<0.05). In addition, this drug increased the ROS levels and decreased the mitochondrial membrane potential (P<0.01). Western blot showed that the Bcl-2/Bax ratios were decreased in the GZFLC drug serum-treated groups, whereas the expression levels of cleaved caspase-3, -9, Cytc and Apaf-1 were increased (all P<0.01). Over time, the myeloma tumor volumes of the mice in the GZFLC-administered groups decreased, and survival time of the mice in the GZFLC-administered groups were longer than that of the mice in the control group. Immunohistochemical analysis of tumor tissues from the mice in the GZFLC-administered groups revealed that the Cytc and Apaf-1 expression levels were increased (P<0.05).@*CONCLUSION@#GZFLC promoted apoptosis of myeloma cells through the mitochondrial apoptosis pathway and significantly reduced the tumor volumes in mice with myeloma, which prolonged the survival times of the mice.

Construction of a model for early identification of spotted fever and severe fever with thrombocytopenia syndrome / 预防医学

Objective@#To construct a model for clinical identification of spotted fever (SF) and severe fever with thrombocytopenia syndrome (SFTS), so as to provide insights into early identification of SF and SFTS.@*Methods@#The clinical data of laboratory-confirmed SF and SFTS patients in secondary and tertiary hospitals in Lu'an City, Anhui Province from May 2017 to May 2021 were retrieved from Chinese Disease Prevention and Control Information System. Factors affecting SF were identified using a logistic regression model, and the model for early identification of SF and SFTS was created. The model fitting effect was evaluated using Hosmer-Lemeshow test, and the value of the model for identification of SF and SFTS was evaluated using the area under the receiver operating characteristic curve (AUC).@*Results@#Data of 62 SF cases and 115 SFTS cases were included. Multivariable logistic regression analysis showed that rash (β=5.994), C-reactive protein (β=4.409), white blood cell (β=-3.176) and platelet (β=-3.234) were included in the model, which were scored 6, 4, -3 and -3, with a total score ranging from -5 to 10. Hosmer-Lemeshow test revealed a high model fitting effect (χ2=3.245, P=0.662). The AUC of the model was 0.992, and the sensitivity and specificity were 0.935 and 0.991 if the cutoff was 1.@*Conclusion@#A model for early identification of SF and SFTS that includes four variables of rash, C-reactive protein, white blood cell and platelet has been created, which has a high accuracy.

Risk factors for yersiniosis: a case-control study / 预防医学

Objective@#To investigate the risk factors for yersiniosis, so as to provide insights into prevention of yersiniosis.@*Methods@#The patients with yersiniosis admitted to the clinics in the surveillance site of Chengbei Township of Jin'an District and Chengnan Township of Yu'an District in Lu'an City from 2013 to 2021 were included as the case group, and the healthy family members matched to cases were selected as the family control group, while normal residents with a 1︰2 match in the same village, gender, and age difference within 5 years were included in the community control group. Participants' demographics, hand-washing and eating habits, living environment hygiene, poultry and livestock feeding were collected using questionnaire surveys, and factors affecting yersiniosis were identified using a multivariable conditional logistic regression model.@*Results@#There were 43 cases in the case group, with a median (interquartile range) age of 45 (34) years, 91 cases in the family control group, with a median (interquartile range) age of 36 (36) years and 86 cases in the community control group, with a median (interquartile range) age of 46 (34) years. Multivariable conditional logistic regression analysis showed that compared with the family control group, the habit of drinking unboiled water (OR=6.721, 95%CI: 1.765-25.588), and direct consumption of food stored in the refrigerator (OR=7.089, 95%CI: 1.873-26.829) were risk factors for yersiniosis in the case group; and compared with the community control group, not washing hands after contacting with poultry and livestock (OR=50.592, 95%CI: 2.758-927.997), habit of eating raw vegetables and fruits (OR=5.340, 95%CI: 1.022-27.887), direct consumption of food stored in the refrigerator (OR=19.973, 95%CI: 2.118-188.336), and unclean refrigerator (OR=12.692, 95%CI: 1.992-80.869) were risk factors for yersiniosis in the case group. Compared with the family and community control groups, not washing hands after contacting with poultry and livestock (OR=4.075, 95%CI: 1.427-11.637), habit of drinking unboiled water (OR=4.153, 95%CI: 1.331-12.957), habit of eating raw vegetables and fruits (OR=4.744, 95%CI: 1.609-13.993), and direct consumption of food stored in the refrigerator (OR=5.051, 95%CI: 1.773-14.395) were risk factors for yersiniosis in the control group.@*Conclusion@#Unhealthy habits such as eating raw vegetables and fruits, drinking unboiled water, direct consumption of food stored in the refrigerator, unclean refrigerator, and not washing hands after contacting poultry and livestock may increase the risk of yersiniosis.

The past, present and future of sleep medicine in China / 北京大学学报(医学版)

Sleep is a highly conserved phenomenon in endotherms, and has a universal physiological function across all species. In mammals, sleep can be divided into two stages: rapid eye movement (REM) sleep and non-REM (NREM) sleep, which alternate in a cyclic manner. Humans spend about one-third of their lives asleep. Sufficient sleep is necessary for humans to sustain everyday functioning. Sleep plays an important role in regulating energy metabolism, immune defense, endocrine function, and the consolidation of memory process. With the development of social economy and the change of life style, sleep duration of the residents has gradually decreased and the incidence of sleep disturbances has increased. Sleep disturbances can lead to severe mental disorders, such as depression, anxiety disorders, dementia, and other mental diseases, and may increase the risk of physical diseases, such as chronic inflammation, heart disease, diabetes, hypertension, atherosclerosis and others. Maintaining good sleep is of great significance for developing social productive forces, promoting sustainable development of economic society, and is a necessary condition for carrying out the "Healthy China Strategy". The sleep research in China started in 1950s. After decades of development, researchers have made great progress in the molecular mechanisms of sleep and wakefulness, the pathogenesis of sleep disorders and the development of new therapies. With the advancement of science and technology and the public's attention to sleep, the level of clinical diagnosis and therapy of sleep disorders in China is gradually brought in line with international standards. The publication of diagnosis and treatment guidelines in the field of sleep medicine will promote the standardization of the construction. In the future, it is still necessary to promote the development of sleep medicine in the following aspects: Strengthening the professional training and discipline construction, improving the cooperation of sleep research, promoting the intelligent diagnosis and treatment of sleep disorders, and developing the new intervention strategies. Therefore, this review will comprehensively summarize the origin, current situation, and future expectations of sleep medicine in China, including discipline construction of sleep medicine, the number of sleep project grants, research findings, the status and progress of diagnosis and treatment of sleep disorders, and the development direction of sleep medicine.