Thoracic aortic aneurysm (TAA) significantly endangers the lives of individuals with Marfan syndrome (MFS), yet the intricacies of their biomechanical origins remain elusive. Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA, with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin (mTOR) signaling cascade. We uncovered that activation of the mTOR complex 1 (mTORC1) within smooth muscle cells, instigated by the oscillatory wall shear stress (OSS) that stems from disturbed flow (DF), is a catalyst for TAA progression. This revelation was corroborated through both an MFS mouse model (Fbn1 ^+/C1039G) and clinical MFS specimens. Crucially, our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS. Therapeutic administration of rapamycin suppresses mTORC1 activity, leading to the attenuation of aberrant SMC behavior, reduced inflammatory infiltration, and restoration of extracellular matrix integrity-collectively decelerating TAA advancement in our mouse model. These insights posit the mTORC1 axis as a strategic target for intervention, offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.

Objective To evaluate the feasibility of confirming syphilis reactive blood donors.Methods The serum of donors with anti-TP reaction by ELISA were confirmed by treponema pallidum particle agglutination(TPPA)and Western blotting(WB).The results of two confirmation methods that were negative,suspicious or inconsistent were followed up and compared.At the same time,the analytical index values of the screening reagent A,B and C and their combinations were e-valuated and compared using the the receiver operating characteristic curve(ROC curve)based on the results of the two confirmation methods.Results The positive rate of 223 ELISA anti-TP reactive samples(including 124 double-reagent ELISA reactive samples and 99 single-reagent ELISA reactive samples)was 57.40%confirmed by TPPA and 38.57%con-firmed by WB(89.52%vs 17.17%by TPPA and 52.42%vs 21.21%by WB for double-reagent and single-reagent ELISA reactive samples).The confirmed negative rate of TPPA was 35.43%and that of WB was 42.60%(6.45%vs 71.72%of TP-PA and 29.84%vs 58.59%of WB for double-reagent and single-reagent ELISA reactive samples).According to Kappa test,the confirmed results between the two methods were not consistent,especially for those single-regent ELISA reactive sam-ples.Thirty six cases were followed up successfully,of which 17(47.22%)confirmed changes in the test results but the changes were irregular.Based on the confirmed results of TPPA and WB,the ROC curve analysis was performed on the anti-TP screening S/CO values of double-reagent ELISA reactive samples.When combining ELISA screening reagents as A/B and A/C,the optimal S/CO values of reagent A were 1.815,5.73 and 10.205,16.165,respectively.Conclusion TPPA and WB have poor consistency in the confirmation of ELISA anti-TP reactive blood samples,and the outcome of follow-up confirmation is unclear.The S/CO threshold of ROC curve is affected by the combination of confirmatory screening reagents,and it is difficult to confirm the results of ELISA anti-TP reactive blood donors.

Objective To compare the effects of three kinds of artificial hydronephrosis in percutaneous nephrolithotomy.Methods A total of 120 patients who underwent single-tract percutaneous nephrolithotomy in the Eighth Hospital of Wuhan from May 2020 to April 2022 were selected and divided equally into three groups according to different methods of artificial hydronephrosis.Patients in group A were received preoperative indwelling ureteral catheter and injection of normal saline through ureteral catheter to dilate renal pelvis and form artificial hydronephrosis.Patients in Group B were placed with double J catheters before surgery,and the bladder was filled with physiological saline through the catheter.The renal pelvis was dilated through the double J catheters,resulting in artificial hydronephrosis.Patients in Group C were received intravenous injection of furosemide and stimulated diuretic method to actively dilate renal pelvis to form hydronephrosis.The one-time puncture success rate,channel establishment time,overall operation time,stone clearance rate and incidence of surgical complications of percutaneous nephrolithotomy after hydronephrosis were compared among the three groups.Results The operation was successfully completed in the three groups.There was no significant difference in the one-time puncture success rate and channel establishment time between group A and group B(P>0.05),which were all higher than group C(P<0.05).The overall operation time of group B was shorter than that of group A and group C(P<0.05).There were no significant differences in stone clearance rate and surgical complications among the three groups(P>0.05).Conclusion Preoperative indwelling of double J tubes to create artificial kidney hydronephrosis has advantages such as high success rate of one-time puncture,short channel establishment time,and surgical time.

Objective To explore the effect of melatonin(MT)-modified PEEK implant assisted by polydopamine(PDA)coating on osteointegration in osteoporotic rats.Methods MT was adhered to PEEK implants with PDA coating as carrier.The physicochemical properties of the materials were analyzed by SEM image,water contact angle,FTIR and protein adsorption experiment.OVX-rBMSCs were inoculated on the surface of PEEK sheet and cultured.The cytoskeleton was stained and cell adhesion morphology was observed.Cell proliferation activity was evaluated by CCK-8 assay;key enzyme activities for osteogenic differentiation were analyzed by ALP stai-ning,and expression levels of osteoblast-related genes COL-1,Runx2,OPN,OCN,BMP-2 and ALP were detected by quantitative real-time PCR.In addition,implants were implanted into the femur of osteoporotic rats and bone volume on the implant surface was de-tected and quantified by Micro-CT.Results MT was successfully loaded on PEEK;the cell adhesion was better,and the proliferation activity and osteogenic differentiation ability were significantly higher than those of control group(P＜0.01).In the rat osteoporosis mod-el,there was more new bone formation around the modified PEEK implant(P＜0.01).Conclusion MT-modified PEEK implants have excellent biocompatibility and improve osteointegration in an osteoporotic environment.

OBJECTIVES: At present, there are many reports about the treatment of cricopharyngeal achalasia by injecting botulinum toxin type A (BTX-A) into cricopharyngeal muscle guided by ultrasound, electromyography or CT in China, but there is no report about injecting BTX-A into cricopharyngeal muscle guided by endoscope. This study aims to evaluate the efficacy of endoscopic BTX-A injection combined with balloon dilatation in the treatment of cricopharyngeal achalasia after brainstem stroke, and to provide a better method for the treatment of dysphagia after brainstem stroke. METHODS: From June to December 2022, 30 patients with cricopharyngeal achalasia due to brainstem stroke were selected from the Department of Rehabilitation Medicine, the First Hospital of Changsha. They were randomly assigned into a control group and a combined group, 15 patients in each group. Patients in both groups were treated with routine rehabilitation therapy, while patients in the control group were treated with balloon dilatation, and patients in the combined group were treated with balloon dilatation and BTX-A injection. Before treatment and after 2 weeks of treatment, the patients were examined by video fluoroscopic swallowing study, Penetration-aspiration Scale (PAS), Dysphagia Outcome Severity Scale (DOSS), and Functional Oral Intake Scale (FOIS) were used to assess the swallowing function. RESULTS: In the combined group, 1 patient withdrew from the treatment because of personal reasons. Two weeks after treatment, the scores of DOSS, PAS, and FOIS in both groups were better than those before treatment (all P<0.01), and the combined group was better than the control group (all P<0.001). The effective rate was 85.7% in the combined group and 66.7% in the control group, with no significant difference between the 2 groups (P>0.05). CONCLUSIONS BTX-A injection combined with balloon dilatation is more effective than balloon dilatation alone in improving swallowing function and is worthy of clinical application.
Humans ; Deglutition Disorders/therapy* ; Esophageal Achalasia/drug therapy* ; Dilatation/adverse effects* ; Botulinum Toxins, Type A/therapeutic use* ; Brain Stem Infarctions/drug therapy* ; Treatment Outcome

ObjectiveTo investigate the mechanism of Xiaonang Tiaojing decoction（XNTJD）in improving polycystic ovary syndrome with insulin resistance（PCOS-IR）model rats based on anti-Müllerian hormone（AMH）/AMH type Ⅱ receptor（AMHRⅡ）signaling pathway. MethodForty-eight adult female SD rats were randomly divided into the blank group， model group， XNTJD group（11.4 g·kg^-1·d^-1） and Diane-35 group（0.21 g·kg^-1·d^-1）， PCOS-IR model was established by high-fat and high-sugar diet combined with letrozole in rats of all groups except the blank group， rats in the administration groups were given the corresponding dose of drugs by gavage for 15 days with an interval of 1 d every 4 d， normal saline of the same volume was given to the blank group and the model group. Estrous cycle was recorded daily during treatment. At the end of treatment， body weight and Lee's index were recorded， AMH， luteinizing hormone（LH）， LH/follicle stimulating hormone（FSH）， testosterone（T）and estradiol（E₂）levels were measured by enzyme-linked immunosorbent assay（ELISA）， fasting plasma glucose（FPG）was measured by glucometer， fasting insulin（FINS） level was measured by radioimmunoassay（RIA）， and the insulin resistance index（HOMA-IR） and insulin sensitivity index（QUICKI）were calculated， triglyceride（TG）and total cholesterol（TC）levels were measured by automatic biochemical analyzer， hematoxylin-eosin（HE）staining was used to observe the morphological changes of the ovary， the levels of AMHRⅡ， bone morphogenetic protein-15（BMP-15）and Smad5 in ovarian tissues were detected by immunohistochemistry（IHC），Western blot was used to analyze the protein expression levels of AMHRⅡ， BMP-15 and Smad5. ResultCompared with the blank group， a large number of leukocytes were observed in the vaginal exfoliated cells of rats in the model group， mainly in diestrus， the levels of body weight， Lee's index， glucose-lipid metabolism indexes（FPG， FINS， HOMA-IR， TG， TC）， AMH and sex hormones（LH， LH/FSH， T）were significantly increased（P<0.01）， and QUICKI and E₂ levels were significantly decreased（P<0.01）， there were more cystic bulges on the ovarian surface， more wet weight， more atretic and cystic dilated follicles in the ovarian tissues， and the thickness of granulosa cell layer was reduced without oocytes， the expression level of AMHRⅡ protein in ovarian tissues was significantly increased（P<0.01）， and the expression levels of BMP-15 and Smad5 proteins were significantly decreased（P<0.01）. Compared with the model group， the exfoliated cells in the vagina of rats treated with XNTJD group showed keratinocytes from the 5^th to 6^th day of treatment， and a stable estrous cycle gradually appeared， body weight， Lee's index， glucose-lipid metabolism indexes（FPG， FINS， HOMA-IR， TG， TC）， AMH and sex hormones（LH， LH/FSH， T）levels were significantly decreased（P<0.05， P<0.01）， QUICKI and E₂ levels were significantly increased（P<0.01）， ovarian surface was smoother and lighter in wet weight， oocytes and mature follicles were observed in ovarian tissues， the thickness of granulosa cell layer increased and the morphology was intact， the expression levels of BMP-15 and Smad5 proteins were significantly increased（P<0.01）and the expression level of AMHRⅡ protein was significantly decreased（P<0.01）in ovarian tissues. ConclusionXNTJD may mediate the up-regulation of BMP-15 and Smad5 in ovarian tissues of PCOS-IR rats by down-regulating AMH/AMHRⅡ， thereby improving ovarian function， sex hormones and glucose-lipid metabolism levels in PCOS-IR rats.

OBJECTIVE To study the effects of self-assembled nanoparticles from Shaoy ao gancao decoction （SGD-SAN）on the in vitro release and intestinal absorption of the main components of Glycyrrhiza uralensis . METHODS Gancao single decoction （GSD），Shaoyao single decoction （SSD），mixed suspension of Shaoyao and Gancao single decoction （MSSGD）and SGD （i.e. Shaoyao-Gancao decoction ）were prepared ，and SAN was characterized. HPLC method was adopted to determine the contents of 7 main components （liquiritin apioside ， liquiritin， isoliquiritin apioside ， isoliquiritin， liquiritigenin， glycyrrhizic acid ， isoliquiritigenin）in G. uralensis . The dialysis bag method was used to investigate the effects of the formation of SGD-SAN on in vitro release of 7 main components in G. uralensis with pH 1.2 HCl solution and pH 6.8 phosphate buffered solution （PBS）as release media. Single-pass intestinal perfusion study was performed to investigate the effects of the formation of SGD-SAN on the intestinal absorption of 7 main components from G. uralensis . RESULTS SAN with particle size of 200-300 nm and polydispersity index of 0.3-0.5 was found in GSD ，MSSGD and SGD. GSD-SAN and MSSGD-SAN were in rod shape while SGD-SAN was irregularly spherical under transmission electron microscope. The results of in vitro release study showed that the formation of SGD-SAN could significantly increase in vitro release of liquiritigenin ，isoliquiritigenin and glycyrrhizic acid ，and had no effect on other components of G. uralensis in pH 1.2 HCl solution. The formation of SGD-SAN also had no effect on the release of each component from G. uralensis in pH 6.8 PBS. The results of intestinal perfusion experiments showed that the formation of SGD-SAN could significantly promote the absorption of each component from G. uralensis in the ileum. CONCLUSIONS- The formation of SGD-SAN significantly improves the in vitro release of poorly soluble components from G. uralensis and promotes the intestinal absorption of main components from G. uralensis ，which is the physical structure basis for the compatibility and synergy of Paeonia lactiflora and G. uralensis .

Objective: To investigate the clinical characteristics, treatments, and prognostic factors among patients with gestational trophoblastic neoplasia (GTN) exhibiting brain metastases who underwent craniotomy. Methods: Thirty-five patients with GTN who had brain metastases and subsequently underwent craniotomies between January 1990 and December 2018 at Peking Union Medical College Hospital were identified using the GTN database. Their clinical manifestations, treatments, outcomes, and prognostic factors were retrospectively analyzed. Results: All 35 patients underwent decompressive craniotomy, hematoma removal, and metastatic tumor resection combined with multiagent chemotherapy. Eighty percent (28/35) achieved complete remission, 11.4% (4/35) achieved partial remission, and 8.6% (3/35) had progressive disease. Not counting 2 patients who were lost to follow-up, 81.8% of the patients (27/33) were alive after a median follow-up of 72 months. The 5-year overall survival rate was 80.4%. Univariate analysis revealed that a history of chemotherapy failure (p=0.020) and a >1-week interval between craniotomy and chemotherapy commencement (p=0.027) were adverse risk factors for survival. Multivariate analysis showed that previous chemotherapy failure remained an independent risk factor for poor survival (odds ratio=11.50; 95% confidence interval=1.55–85.15; p=0.017). Conclusion Decompressive craniotomy is a life-saving option if metastatic hemorrhage and intracranial hypertension produce a risk of cerebral hernia in patients with GTN who have brain metastases. Higher survival rates and improved prognoses can be achieved through perioperative multidisciplinary cooperation and timely standard postoperative chemotherapy.

Objective:To investigate the risk factors for nonunion after surgery for femoral shaft fractures in order to reduce them.Methods:The clinical data were retrospectively analyzed of the 804 patients with femoral shaft fracture who had been treated from January 2014 to December 2020 at Department of Orthopaedics, Xijing Hospital. There were 575 males and 229 females, aged from 18 to 96 years (average, 43.7 years). The patients were divided into 2 groups according to whether nonunion had occurred after surgery: a nonunion group of 112 cases and a fracture healing group of 692 cases. The preoperative general data, such as age, gender and fracture type, as well as intraoperative and postoperative data, such as operation time, internal fixation method, reduction method and internal fixation failure, were compared between the 2 groups. Items with P<0.05 were included in the multivariate logistic regression analysis to identify the risk factors for nonunion. Results:There were statistically significant differences between the nonunion group and the fracture healing group in smoking history, drinking history, injury mechanism, injury type, multiple injuries, fracture AO classification, fixation method, internal fixation failure, postoperative infection and use of non-steroid anti-inflammtory drugs ( P<0.05). Multivariate logistic regression analysis showed that smoking ( OR=3.261, 95% CI: 2.072 to 5.133, P<0.001), high energy injury ( OR=2.010, 95% CI: 1.085 to 3.722, P=0.026), multiple injuries ( OR=3.354, 95% CI: 1.985 to 5.669, P<0.001), AO type 32-C fracture (type 32-C fracture used as a reference, P=0.034), internal fixation failure ( OR=3.517, 95% CI: 1.806 to 6.849, P<0.001), external stent fixation (external stent fixation used as a reference, P=0.009) were the risk factors for nonunion after femoral shaft fractures. Conclusions:After surgery for patients with femoral shaft fracture, special attention should be paid to those with a smoking habit, high-energy injury, multiple injuries, AO type 32-C fracture, external stent fixation or a failed internal fixation, because they are high-risk groups prone to postoperative nonunion.

Objective:To explore the effect of cognitive behavioral intervention combined with early functional exercise on kinesiophobia in patients with lumbar disc herniation after surgery.Methods:From September 2020 to September 2021, the convenient sampling was used to select 90 patients with kinesiophobia after lumbar disc herniation surgery in Department of Orthopedics in Nanjing First Hospital as the research objects. They were divided into the intervention group and the control group by the random number table, with 45 cases in each group. The control group received routine nursing, while the intervention group received cognitive behavioral intervention combined with early functional exercise on the basis of routine nursing. The scores of Tampa Scale for Kinesiophobia (TSK) , Fear Avoidance Beliefs Questionnaire (FABQ) , Exercise Adherence Rating Scale (EARS) and Japanese Orthopaedic Association (JOA) were compared between the two groups at the time of admission, at discharge and 1 and 3 months after the operation.Results:After the intervention, the TSK and FABQ scores of the patients in the intervention group were lower than those in the control group at the time of discharge, 1 month after surgery and 3 months after surgery; the EARS and JOA scores of patients in the intervention group were higher than those in the control group at the time of discharge, 1 month and 3 months after operation, and the differences were all statistically significant ( P<0.05) . Conclusions:Cognitive-behavioral intervention combined with early functional exercise can effectively reduce the level of kinesiophobia and fear-avoidance beliefs in patients with postoperative lumbar disc herniation, improve their exercise compliance and effectively improve their physical function.