Objective: To investigate whether acupoint penetration acupuncture (APA) could regulate chondrocyte autophagy and apoptosis via the PI3K/Akt-mTOR signaling pathway to reduce cartilage degeneration in knee osteoarthritis (KOA) rats. Methods: KOA was induced in rats via intra-articular injection of sodium iodoacetate resolution. Forty male Sprague-Dawley rats were randomly assigned to blank control, model, APA, electro-acupuncture (EA), and sham model groups (n = 8) and those in the APA and EA groups received their respective therapies. Following completion of the treatment course, histological examinations of cartilage and muscle were conducted. Levels of apoptosis- and autophagy-related factors, including Bax, Bcl-2, mTOR, ULK-1, and Beclin-1 protein, and mRNAs were assessed. Additionally, β-endorphin (β-EP) concentrations in the brain and serum were measured. Results: Histological analysis revealed that APA alleviated cartilage and muscle damage compared with the model group. APA inhibited cartilage degeneration by modulating the expression of apoptosis- and autophagy-related proteins and mRNA, thus preventing chondrocyte apoptosis. In the APA group, Bax and mTOR protein levels were significantly lower than those in the model group (both P = .024). Conversely, the Bcl-2 expression level was significantly higher than that in the EA group (P = .035). Additionally, ULK-1 expression was significantly lower than that in the EA group (P = .045). The mRNA level of Bax was significantly higher than that in the blank control group (P < .001). However, Beclin-1 levels were significantly higher than those in both the model and EA groups (both P < .001). ELISA results showed a significant decrease in the concentration of β-EP in the brains of the rats in the APA group compared with those in the model group (P = .032). Conclusions APA reduced osteoarthritis-related pain and alleviated cartilage damage by upregulating chondrocyte autophagy and down-regulating apoptosis via signaling pathways involving PI3K/Akt-mTOR in KOA rats.

Objective:To analyze the incidence and clinical phenotype of the concomitant extragenital malformations in the patients with female reproductive tract anomalies.Methods:A retrospective study was conducted using clinical data of hospitalized patients diagnosed with uterine, cervical, or vaginal malformations from January 2003 to December 2022 in Peking Union Medical College Hospital. The malformations were classified according to American Society for Reproductive Medicine müllerian anomalies classification 2021, and in each type, the incidence and specific manifestations of concomitant extragnital malformations were analyzed.Results:A total of 444 patients were included. The overall incidence of concomitant extragenital malformations was 43.5% (193/444), including urinary system, skeletal system, and other system malformations. Renal malformations on the obstructed side were present in all patients with oblique vaginal septum syndrome (100.0%, 78/78). The total incidence of concomitant extragnital malformations was as high as 8/11 in uterus didelphys, 43.5% (10/23) in unicornuate uterus, 33.6% (79/235) in Mayer-Rokitansky-Küster-Hauser syndrome, 18.8% (6/32) in septate uterus and 18.5% (12/65) in cervical agenesis. Urinary system malformations (30.6%, 136/444) and skeletal system malformations (13.5%, 60/444) were the most common concomitant malformations in all types, in which, unilateral renal agenesis and scoliosis were the most common.Conclusions:Urinary and skeletal system malformations are important features of female reproductive tract anomalies. Urologic ultrasonography and spinal roentgenogram are recommended for all patients with female reproductive tract anomalies.

Objective:To establish an automated labeling method of 18F-AlF-1, 4, 7-triazocyclohexane-1, 4, 7-triacetic acid- D-Phe1-Tyr3-Thr8-octreotide (NOTATATE) and perform neuroendocrine tumor (NET) imaging. Methods:Based on the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE was automatically prepared by one-step chelation labeling with aluminum fluoride, and its labeling conditions were optimized. The product quality was analyzed. One patient (male, 47 years old) with lower rectal segment NET and one patient (female, 52 years old) with pancreatic NET underwent 18F-AlF-NOTATATE PET/CT imaging. Results:18F-AlF-NOTATATE was successfully prepared with a total synthesis time of 35 min. The optimized radiochemical yield was (23.8±3.1)% (without decay correction, n=3), the radioactivity was (4.63±0.68) GBq, and the radiochemical purity was >95%. The stability was good, and the product quality met the requirements. 18F-AlF-NOTATATE showed clear imaging in the patient with rectal segment NET, with SUV max of 13.3 and tumor/liver ratio of 3.3. Metastatic lesions in the liver, lymph nodes, and ribs showed high SUV max and tumor/liver ratios. The imaging of the pancreatic NET patient showed an abnormal increase in local radioactive uptake at the uncinate process of the pancreatic head, with SUV max of 5.6 and SUV max of 6.3 and the tumor/liver ratio of 2.3 after 2-hours imaging. Conclusions:Using the GE-FASTLab2 synthesis module, 18F-AlF-NOTATATE can be prepared with high activity. The preparation is simple, the method is stable, and the product has high radiochemical purity. 18F-AlF-NOTATATE exhibits good imaging performance in NET patients, providing valuable information for diagnosis, treatment, and prognosis evaluation.

The declining fertility has emerged as a significant concern impacting national welfare, with obesity identified as a major contributing factor. In the hypothalamus, gonadotropin-releasing hormone(GnRH) neurons release GnRH, which regulates the secretion of estrogen and testosterone via the hypothalamic-pituitary-gonadal(HPG) axis, thereby influencing sexual development and fertility. The proper function of GnRH neurons is crucial for maintaining normal sexual development and fertility. Research indicates that obesity can impact GnRH neuron function through several pathways, such as disrupting pulsatile secretion core kisspeptin neurons, causing imbalance in energy sensing and metabolic factor secretion, and triggering hypothalamic inflammation. These pathways directly or indirectly influence GnRH neuron function in the hypothalamus, which ultimately affects sexual development and impairs fertility. Therefore, this review consolidates recent advancements in understanding the mechanisms by which obesity induces dysfunction in hypothalamic GnRH neurons, offering new perspectives for early clinical interventions aimed at enhancing fertility outcomes in obese individuals.

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia seen in clinical settings, which has been associated with substantial rates of mortality and morbidity. However, clinically available drugs have limited efficacy and adverse effects. We aimed to investigate the mechanisms of action of andrographolide (Andr) with respect to AF. We used network pharmacology approaches to investigate the possible therapeutic effect of Andr. To define the role of Andr in AF, HL-1 cells were pro-treated with Andr for 1 h before rapid electronic stimulation (RES) and rabbits were pro-treated for 1 d before rapid atrial pacing (RAP). Apoptosis, myofibril degradation, oxidative stress, and inflammation were determined. RNA sequencing (RNA-seq) was performed to investigate the relevant mechanism. Andr treatment attenuated RAP-induced atrial electrophysiological changes, inflammation, oxidative damage, and apoptosis both in vivo and in vitro. RNA-seq indicated that oxidative phosphorylation played an important role. Transmission electron microscopy and adenosine triphosphate (ATP) content assay respectively validated the morphological and functional changes in mitochondria. The translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the molecular docking suggested that Andr might exert a therapeutic effect by influencing the Keap1-Nrf2 complex. In conclusions, this study revealed that Andr is a potential preventive therapeutic drug toward AF via activating the translocation of Nrf2 to the nucleus and the upregulation of heme oxygenase-1 (HO-1) to promote mitochondrial bioenergetics.
Animals ; Rabbits ; Atrial Fibrillation/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; NF-E2-Related Factor 2/pharmacology* ; Molecular Docking Simulation ; Oxidative Stress ; Energy Metabolism ; Mitochondria/metabolism* ; Inflammation/metabolism* ; Heme Oxygenase-1

OBJECTIVE: To analyze the intellectual landscape and emerging research trends of Chinese medicine (CM) in the management of pediatric asthma through a scientometric study. METHODS: Publications related to CM in the management of pediatric asthma were retrieved from the Web of Science Core Collection using relevant keywords. A scientometric study was performed using CiteSpace and VOSviewer. RESULTS: A total of 1,673 original articles and reviews from 1991 to 2019 were included in the analysis. The amount of annual publications had a gradual increase with time. USA was the major contributor both in country and institution analyses. Based on the co-citation, the published journals were grouped into 4 clusters. Keyword analysis indicated that the main hotspots were: (1) comprehensive management; (2) risk factors, mechanism, and prevalence; (3) prevention and treatment; (4) inflammation; and (5) environmental research. Lastly, we predicted that three emerging trends were quality of life promotion, immune response, and combination therapy. CONCLUSIONS CM research in the management of pediatric asthma will maintain the current trend of steady growth. This scientometric analysis may help scientists to identify the areas of interests and future directions in the field.
Asthma/drug therapy* ; Bibliometrics ; Child ; Humans ; Medicine, Chinese Traditional ; Publications ; Quality of Life

Objective:To investigate the clinical application value of blood oxygen level dependent functional magnetic resonance imaging (BOLD-fMRI) to the protection of language function in patients with unilateral frontal and temporal lobes glioma receiving postoperative intensity modulation radiation therapy (IMRT).Methods:A total of 27 patients with unilateral frontal and temporal lobe gliomas were treated with postoperative radiotherapy. The planning CT and BOLD-fMRI were performed before radiotherapy, and the language functional areas were delineated based on the fused images of 3D T1 and CT. IMRT technology was used to develop radiotherapy plans with and without language function area protection, naming conventional and protective radiotherapy plans respectively. The maximum radiation dose ( Dmax), average radiation dose ( Dmean), target conformal (CI) and dose uniformity (HI) of PTV of the two plans were compared and analyzed to ensure that the protective radiotherapy plan could meet the radiotherapy standard. Then, the Dmax and Dmean of the language function area were compared and analyzed to evaluate whether the Dmax and Dmean of the language function area were decreased in the protective radiotherapy plan. Results:There were no significant differences in CI, HI, Dmax and Dmean of PTV between the conventional radiotherapy plan and protective radiotherapy plan ( P>0.05). There were statistically significant differences in Dmax and Dmean of Wernicke′s and Broca′s (healthy side and affected side) between the conventional radiotherapy plan and protective radiotherapy plan ( t=3.073-12.707, P<0.05). Dmax and Dmean of Wernicke′s and Broca′s (healthy side and affected side) were decreased in the protective radiotherapy plan compared with the conventional radiotherapy plan, and the decrease was significant in the healthy side. Conclusions:BOLD-fMRI combined with IMRT can not only guarantee the target dose of patients with glioma receiving postoperative radiotherapy, but also reduces the radiation dose to the language function area. Chinese reading task and paragraph comprehension task are the stimulation mode of language function in patients after brain tumor surgery. These tasks are simple and the effect is accurate.

Objective:To clarify the anatomical characteristics and adjacent relationship of the superior segment of the inferior vena cava during laparoscopic surgery.Methods:In December 2018, two frozen and two fresh adult cadavers were dissected. The chest of the frozen cadavers was opened along the bilateral midline of the clavicle, the anterior pericardial wall was opened, and the superior vena cava and the inferior vena cava was dissected. The abdominal cavity was opened along the midline of the abdomen, the left and right hepatic lobes were turned over, the inferior vena cava and the second hilum of the posterior segment of the liver were exposed, and the hiatus of the inferior vena cava was opened and entered the pericardium.The anatomical characteristics and adjacent relationship of the superior segment of the inferior vena cava were observed, and the length of the superior segment of the inferior vena cava was measured. The fresh frozen cadaver patients underwent laparoscopic surgery.Five 12 mm trocars were placed at the side of umbilicus, right rectus abdominis about 4 cm from umbilicus, midline of abdomen about 6 cm above umbilicus, right axillary front about 2 cm below inferior edge of liver, left midline of clavicle about 2 cm below inferior edge of liver. Laparoscopic-assisted turning of the left and right hepatic lobes, exposing the posterior inferior vena cava and the second hilum of the liver, opening of the vena cava hiatus into the pericardium.The anatomical characteristics and adjacent relationship of the upper diaphragmatic segment of the inferior vena cava were observed.Results:In two autopsies, the inferior vena cava entered the chest through the cava sulcus of the liver and the phrenic foramen cava, and then through the fibrous pericardium into the right atrium. The length from the diaphragm of inferior vena cava to the right atrium was 1.67 cm, 2.57 cm. In laparoscopic operation, the diaphragm entrance of the posterior segment of the liver inferior vena cava, the second hepatic portal and the inferior vena cava could be well exposed.The diaphragm could be opened along the hole of the vena cava with a relatively non vascular anatomical layer of adipose tissue.There was a large anatomical gap between the pericardium and the right atrium, and the inferior vena cava, the superior vena cava and the right atrium could be well exposed, and the whole diaphragm could be completely and continuously exposed from the bottom to the inferior vena cava at the entrance segment of the right atrium.Conclusions:There was a relatively avascular anatomical layer beside the inferior vena cava. During laparoscopic operation, opening the diaphragm through the abdominal cavity could safely enter the pericardium and expose the inferior vena cava, the superior vena cava and the right atrium, which provides a possibility for the removal of Mayo Ⅳ grade inferior vena cava tumor thrombus through this approach.

Objective:To evaluate the efficacy of holographic image technology in robot-assisted laparoscopic radical prostatectomy (RARP).Methods:The clinical data of 34 patients with prostate cancer who underwent RARP in our hospital during October 2020 and December 2020 was analyzed retrospectively. The average age of the patients was 67.8 (52-78) years. The mean BMI was 25.8 (18.0-32.3) kg/m 2. The median level of PSA before surgery was 13.4 (2-149) ng/ml. Median prostate volume was 31.7 (9.5-159.1) ml. EAU risk groups for biochemical recurrence of localised and locally advanced prostate cancer were list as below: 5 cases of low-risk, 7 cases of medium-risk, 22 cases of high-risk. There were 9, 16, 9 cases with the ASA score of 1, 2, 3 point, respectively. Preoperative Gleason score of 34 patients were list as below: 9 cases in score ≤6 group, 15 cases in score=7 group, 10 cases in score ≥8 group. For clinical stage before the surgery, 13 cases ≤T 2a stage, 1 case in T 2b stage, 20 cases ≥T 2c stage. The engineers established holographic images of 34 patients based on multiparametric magnetic resonance imaging (mpMRI) and the reports before the operation. Surgeons can obtain the size and location of tumors, surrounding neurovascular bundles visually by revolving, assembling, disassembling and concealing images, which was helpful for pre-surgery planning. By manipulating the holographic images extracorporeally, surgeons can discriminate Internal sphincter of urinary bladder and vesicoprostatic muscle, neurovascular bundles, membranous part, seminal vesicle easily, which improves the operation accuracy. Results:All 34 cases underwent operation successfully without transferring to open surgery. The median operative time was 157.5 (95-276) min with an estimated blood loss of 50 (20-300) ml. The median drainage removal time was 2 d and median hospitalization time was 3.5 d, respectively. The catheters were removed within an average time of 20.5 d. For postoperative Gleason score, there were 2 cases in score ≤6 group, 16 cases in score =7 group, 8 cases in score ≥8 group and 8 cases can’t make a score. For clinical stage after the surgery, 10 cases were ≤T 2a stage, 1 case was T 2b stage, 23 cases were ≥cT 2c stage. 22 cases underwent pelvic lymph node dissection, including a patient with right iliac fossa lymph node metastasis. There were 2 cases with positive surgical margin and 3 cases with Clavien-DindoⅠcomplications. The rate of 1-month and 3-month urinary continence were 47.1% and79.4%, respectively, 8 cases recovered erectile function after 3 month. Conclusions:Holographic image technology can promote cancer dissection completely, achieve urinary continence early and reduce perioperative complications tremendously. The technology is the "intraoperative security" for the accurate surgical treatment of prostate cancer.

Objective:To explore the feasibility and safty of robot assisted trans-diaphragmatic intropericardial inferior vena cava occlusion and thrombectomy in treatment of Ⅳa grade tumor thrombus without cardiopulmonary bypass and thoracotomy.Methods:The clinical data of 4 patients with renal cell carcinoma and Ⅳa grade tumor thrombus by robot assisted trans-diaphragmatic intropericardial inferior vena cava occlusion and thrombectomy from January 2013 to June 2019 were retrospectively analyzed. The median age was 53.5 (53-70) years. The average body mass index was 23.25 (20.7-26.3) kg/m 2. The tumors were located on the right side in 2 cases. The average maximum diameter of the tumor was 8.1 (3.6-11.2) cm.Preoperative tumor thrombus of all patients was classified as Ⅳa. The average preoperative length of tumor thrombus in vena cava was 12.3 (11.8-18.0) cm. All the operations were performed under multidisciplinary cooperation of urology, hepatobiliary, cardiovascular, ultrasound and anesthesiologist team. Surgical procedure: Robot assisted liver mobilization was used to expose the inferior vena cava. Under the guidance of intraoperative ultrasound, the central tendon and pericardium of diaphragm were dissected until the inferior vena cava and right atrium in the superior pericardium were exposed. The first porta hepatis and inferior vena cava were blocked in turn.The vena cava thrombectomy and inferior vena cava reconstruction were performed. Results:All the operations were completed without conversion. The median operation time was 553.5 (338-642) minutes, and the median time of the first porta hepatis occlusion was 18.1 (14-32)minutes. The median blood loss was 1 900(1 000-2 600)ml. All patients were transferred to ICU after operation. The median length of stay in ICU was 7(4-8) days, and the median time of indwelling drainage tube was 8(4-12) days. The average postoperative hospital stay was 13(11-20) days. There were 1 case of grade Ⅱ and 3 cases of grade Ⅲ complications (Clavien classification). One case had paroxysmal supraventricular tachycardia, one case had lymphatic fistula, one case had pleural effusion with atelectasis, and one case had hepatic and renal insufficiency and lymphatic fistula. The complications were improved after treatment. There was no perioperative death.Conclusions:Robot assisted trans-diaphragmatic intropericardial inferior vena cava occlusion and thrombectomy is an alternative method for the treatment of Ⅳa grade inferior vena cava tumor thrombus. Using this method, Ⅳa grade tumor thrombus can be treated without cardiopulmonary bypass and thoracotomy, with controllable complications and zero perioperative mortality.