Deep brain stimulation(DBS),including optical stimulation and electrical stimulation,has been demonstrated considerable value in exploring pathological brain activity and developing treatments for neural disorders.Advances in DBS microsystems based on implantable microelectrode array(MEA)probes have opened up new opportunities for closed-loop DBS(CL-DBS)in situ.This technology can be used to detect damaged brain circuits and test the therapeutic potential for modulating the output of these circuits in a variety of diseases simultaneously.Despite the success and rapid utilization of MEA probe-based CL-DBS microsystems,key challenges,including excessive wired communication,need to be urgently resolved.In this review,we considered recent advances in MEA probe-based wireless CL-DBS microsystems and outlined the major issues and promising prospects in this field.This technology has the potential to offer novel therapeutic options for psychiatric disorders in the future.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Developing universal CARs with improved flexible targeting and controllable activities is urgently needed. While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells, the weak affinity between them is one of the limiting factors for efficacy. Herein, we systematically investigated the impact of Fcγ receptor (FcγR) affinity on CAR-T cells properties by constructing universal CARs using Fcγ receptors with different affinities for IgG1 antibodies, namely CD16a, CD32a, and CD64. We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies. In xenografted mice, 64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model. However, in the CD20 high expression Raji model, 64CAR caused excessive activation of CAR-T cells, which resulted in cytokine release syndrome (CRS) and the decline of antitumor activity, and 32CAR with a moderate affinity brought the best efficacy. Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.

This study aimed to investigate the incidence of patent processus vaginalis (PPV) in pediatric patients with a unilateral nonpalpable testis and explore the associated factors. From May 2014 to April 2017, 152 boys who were diagnosed with a unilateral nonpalpable testis and underwent laparoscopy in Shanghai Children's Hospital (Shanghai, China) were included in this study. The data were collected and reviewed, and the results were analyzed regarding the age at operation, side, development, and position of the nonpalpable testis. The mean age of the patients was 2.6 (standard deviation: 2.3) years. The testis was absent in 14 cases, nonviable in 81 cases, and viable in 57 cases. The incidence of PPV was 37.5% (57 of 152) on the ipsilateral side and 16.4% (25 of 152) on the contralateral side. The ipsilateral PPV was more prevalent when the nonpalpable testis occurred on the right side ( P < 0.01). Besides, patients with a viable testis had a greater incidence of ipsilateral PPV than those with a nonviable or absent testis ( P < 0.01). Moreover, this rate was the highest when the testis was in the abdominal cavity and the lowest when the testis was in the scrotum (both P < 0.01). However, the incidence of contralateral PPV was independent of all the factors. In conclusion, in children with a nonpalpable testis, the incidence of an ipsilateral PPV was significantly related to the side, development, and position of the testis, while it was independent of these factors on the contralateral side.
Male ; Child ; Humans ; Infant ; Child, Preschool ; Testis ; China ; Testicular Hydrocele/surgery* ; Laparoscopy ; Scrotum ; Hernia, Inguinal/surgery* ; Cryptorchidism/surgery*

Dopamine D₃ receptor (D₃R) is implicated in multiple psychotic symptoms. Increasing the D₃R selectivity over dopamine D₂ receptor (D₂R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D₃R selective ligands. Through a structure-based virtual screen, ZLG-25 (D₃R K_i = 685 nmol/L; D₂R K_i > 10,000 nmol/L) was identified as a novel D₃R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D₃R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD₃R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.

Objective: To determine the spatiotemporal distribution of Schistosoma (S.) japonicum infections in humans, livestock, and Oncomelania (O.) hupensis across the endemic foci of China. Methods: Based on multi-stage continuous downscaling of sentinel monitoring, county-based schistosomiasis surveillance data were captured from the national schistosomiasis surveillance sites of China from 2005 to 2019. The data included S. japonicum infections in humans, livestock, and O. hupensis. The spatiotemporal trends for schistosomiasis were detected using a Joinpoint regression model, with a standard deviational ellipse (SDE) tool, which determined the central tendency and dispersion in the spatial distribution of schistosomiasis. Further, more spatiotemporal clusters of S. japonicum infections in humans, livestock, and O. hupensis were evaluated by the Poisson model. Results: The prevalence of S. japonicum human infections decreased from 2.06% to zero based on data of the national schistosomiasis surveillance sites of China from 2005 to 2019, with a reduction from 9.42% to zero for the prevalence of S. japonicum infections in livestock, and from 0.26% to zero for the prevalence of S. japonicum infections in O. hupensis. Analysis using an SDE tool showed that schistosomiasis-affected regions were reduced yearly from 2005 to 2014 in the endemic provinces of Hunan, Hubei, Jiangxi, and Anhui, as well as in the Poyang and Dongting Lake regions. Poisson model revealed 11 clusters of S. japonicum human infections, six clusters of S. japonicum infections in livestock, and nine clusters of S. japonicum infections in O. hupensis. The clusters of human infection were highly consistent with clusters of S. japonicum infections in livestock and O. hupensis. They were in the 5 provinces of Hunan, Hubei, Jiangxi, Anhui, and Jiangsu, as well as along the middle and lower reaches of the Yangtze River. Humans, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the north of the Hunan Province, south of the Hubei Province, north of the Jiangxi Province, and southwestern portion of Anhui Province. In the 2 mountainous provinces of Sichuan and Yunnan, human, livestock, and O. hupensis infections with S. japonicum were mainly concentrated in the northwestern portion of the Yunnan Province, the Daliangshan area in the south of Sichuan Province, and the hilly regions in the middle of Sichuan Province. Conclusions: A remarkable decline in the disease prevalence of S. japonicum infection was observed in endemic schistosomiasis in China between 2005 and 2019. However, there remains a long-term risk of transmission in local areas, with the highest-risk areas primarily in Poyang Lake and Dongting Lake regions, requiring to focus on vigilance against the rebound of the epidemic. Development of high-sensitivity detection methods and integrating the transmission links such as human and livestock infection, wild animal infection, and O. hupensis into the surveillance-response system will ensure the elimination of schistosomiasis in China by 2030.

Cell membrane affinity chromatography has been widely applied in membrane protein (MP)-targeted drug screening and interaction analysis. However, in current methods, the MP sources are derived from cell lines or recombinant protein expression, which are time-consuming for cell culture or purification, and also difficult to ensure the purity and consistent orientation of MPs in the chromatographic stationary phase. In this study, a novel in situ synthesis membrane protein affinity chromatography (iSMAC) method was developed utilizing cell-free protein expression (CFE) and covalent immobilized affinity chromatography, which achieved efficient in situ synthesis and unidirectional insertion of MPs into liposomes in the stationary phase. The advantages of iSMAC are: 1) There is no need to culture cells or prepare recombinant proteins; 2) Specific and purified MPs with stable and controllable content can be obtained within 2 h; 3) MPs maintain the transmembrane structure and a consistent orientation in the chromatographic stationary phase; 4) The flexible and personalized construction of cDNAs makes it possible to analyze drug binding sites. iSMAC was successfully applied to screen PDGFRβ inhibitors from Salvia miltiorrhiza and Schisandra chinensis. Micro columns prepared by in-situ synthesis maintain satisfactory analysis activity within 72 h. Two new PDGFRβ inhibitors, salvianolic acid B and gomisin D, were screened out with K _D values of 13.44 and 7.39 μmol/L, respectively. In vitro experiments confirmed that the two compounds decreased α-SMA and collagen Ӏ mRNA levels raised by TGF-β in HSC-T6 cells through regulating the phosphorylation of p38, AKT and ERK. In vivo, Sal B could also attenuate CCl₄-induced liver fibrosis by downregulating PDGFRβ downstream related protein levels. The iSMAC method can be applied to other general MPs, and provides a practical approach for the rapid preparation of MP-immobilized or other biological solid-phase materials.

OBJECTIVE: To explore the method of measuring root volume with cone-beam computed tomography (CBCT) three-dimensional reconstruction technology, and to study root length and root volume of upper and lower central incisors in patients with skeletal Class Ⅲ malocclusion treated by surgical orthodontic treatment. METHODS: Twenty patients with skeletal Class Ⅲ malocclusion undergoing surgical orthodontic treatment were selected. CBCT data at three time points, before decompensation treatment (T0), after decompensation treatment (before orthognathic surgery, T1), and the end of post-operative orthodontic treatment (T2) were collected. Three-dimensional reconstruction technology was used to measure the root length and root volume of the upper and lower central incisors (including total root volume, cervical root and apical root), calculate the percentage of reduction volume, and measure the distance of tooth movement after orthodontic treatment. Data were statistically analyzed by SPSS 20.0 software. Least significant difference (LSD) method was used for pair comparison between the groups subject to normal distribution, and non-parametric test was used for comparison between the groups not subject to normal distribution. The differences of root length and root volume of upper and lower incisors were compared, and the characteristics of root absorption were analyzed. RESULTS: Root length and root volume of the upper and lower central incisors were reduced during the surgical orthodontic treatment (P < 0.05) in cases. Both the root volume of cervical root and apical root were significantly reduced (P < 0.05), the reduction of apical root was more significant. The percentage of root volume reduction of the upper central incisor was (30.51±23.23)%, and lower central incisor (23.24±11.96)%. Compared with the upper central incisor, the root volume reduction amount and percentage of the lower central incisor were smaller, and apical root volume reduction of the upper central incisor was greater than that of the lower central incisor, which was statistically significant (P < 0.05). During pre-surgical orthodontic treatment, maxillary central incisor palatal moving was in a controlled tipping manner, and the mandibular central incisor tipped labially. CONCLUSION In patients with skeletal Class Ⅲ malocclusion, root length and total root volume of upper and lower central incisors decreased during surgical orthodontic treatment. Root volume measurement indicated that the cervical root also had root resorption. The difference in root resorption of the upper and lower central incisors might be related to the distance and direction of teeth movement. CBCT three-dimensional reconstruction will compensate for the limitation of root length measurement in evaluating root resorption.
Cone-Beam Computed Tomography/methods* ; Humans ; Incisor/diagnostic imaging* ; Malocclusion, Angle Class III/surgery* ; Maxilla/surgery* ; Root Resorption/etiology*

Cavernous nerve injury is an important cause of erectile dysfunction (ED). Although protective nerve technology has been widely used in nerve-sparing radical prostatectomy (nsRP), the incidence of ED is still very high after surgery. The purpose of our study was to evaluate erectile function (EF) and penile length in the non-erectile state (PLNES) following scheduled phosphodiesterase 5 inhibitor (PDE5i), vacuum erectile device (VED) treatment, and combination therapy after nsRP. One hundred patients with localized prostate cancer and normal EF were randomized to scheduled PDE5i group, VED treatment group, a combined treatment group, and the control group without any intervention. The International Index of Erectile Function-5 (IIEF-5) scores and PLNES were evaluated after 6 months and 12 months of treatment. Sexual Encounter Profile (SEP-Question 2 and SEP-Question 3) were evaluated after 12 months of treatment. Ninety-one of the 100 randomized patients completed the study. We found that the 5 mg tadalafil once a day (OaD) combined with VED can help improve IIEF-5 scores in nsRP patients after both 6 months and 12 months. VED alone or combined with tadalafil OaD can help patients maintain PLNES. VED combined with tadalafil OaD can improve the rate of successful penetration (SEP-Question 2) after 12 months. There were no significant differences in the return to target EF after 12 months among the groups. No significant correlation was noted between the variables and return to target EF (IIEF ≥ 17), and between the variables and effective shortening of the patient's penis (shortening ≥ 1 cm) after 12 months of intervention.
Erectile Dysfunction ; Humans ; Male ; Penile Erection ; Phosphodiesterase 5 Inhibitors ; Prospective Studies ; Prostatectomy ; Prostatic Neoplasms ; Tadalafil ; Treatment Outcome ; Vacuum

Magnetic anchoring and traction technique is one of the core technologies of magnetic surgery. With the "non-contact" traction force of the outer magnet on the inner magnet, we can drive the inner magnet and the gripper to multiple directions, and pull tissue or organ to required position in operations, so as to get a clearer surgical field of view. On the basis of the previous animal experiments, we applied magnetic anchoring and traction device in 3 human (males aged 63-71 years) thoracoscopic esophagectomies. Using the magnetic anchoring device, we could pull the esophagus dorsally or ventrally to assist in exposing the anatomical plane without special equipment or pleural puncture for retraction of the esophagus. The interference between operating instruments reduced. The mean blood loss in operation was 83 mL, the mean total operation time was 253 min and the mean length of hospital stay was 10 d. Postoperative follow-up showed that all 3 patients had good short-term prognosis. There was no swellling or pain in magnetic anchoring zone of chest wall.