Optogenetics combines optics and genetic engineering to control specific gene expression and biological functions and has the advantages of precise spatiotemporal control,noninvasiveness,and high efficiency.Genetically modified photosensory sensors are engineered into proteins to modulate conformational changes with light stimulation.Therefore,optogenetic techniques can provide new insights into oral biological processes at different levels,ranging from the subcellular and cellular levels to neural circuits and behavioral models.Here,we introduce the origins of optogenetics and highlight the recent progress of optogenetic approaches in oral and craniofacial research,focusing on the ability to apply optogenetics to the study of basic scientific neural mechanisms and to establish different oral behavioral test models in vivo(orofacial movement,licking,eating,and drinking),such as channelrhodopsin(ChR),archaerhodopsin(Arch),and halorhodopsin from Natronomonas pharaonis(NpHR).We also review the synergic and antagonistic effects of optogenetics in preclinical studies of trigeminal neuralgia and maxillofacial cellulitis.In addition,optogenetic tools have been used to control the neurogenic differentiation of dental pulp stem cells in translational studies.Although the scope of optogenetic tools is increasing,there are limited large animal experiments and clinical studies in dental research.Potential future directions include exploring therapeutic strategies for addressing loss of taste in patients with coronavirus disease 2019(COVID-19),studying oral bacterial biofilms,enhancing craniomaxillofacial and periodontal tissue regeneration,and elucidating the possible pathogenesis of dry sockets,xerostomia,and burning mouth syndrome.

Objective:To evaluate the clinical efficacy of allogeneic hematopoietic stem cell transplantation（allo-HSCT）in children with severe aplastic anemia（SAA）.Methods:Twenty-seven cases with SAA who had been treated with allo-HSCT from January 2020 to December 2022 were retrospectively analyzed and reviewed.Results:（1）A total of 27 SAA patients were enrolled，including 18 males and 9 females，with a median age of 8 (2-15) years.There were 20 cases of SAA-Ⅰ type,7 cases of SAA-Ⅱ type.Based upon donor sources，three cases of matched sibling donors hematopoietic stem cell transplantation,and 24 cases of haploidentical hematopoietic stem cell transplantation were adopted.（2）Hematopoietic reconstruction was achieved in all 27 cases.The median implantation time of neutrophils and platelets was 10（9-20）days and 12（7-26）days respectively.The cumulative incidence of acute graft-versus-host disease（GVHD）was 66.67%（18/27）.The incidence of grade Ⅰ-Ⅱ was 55.56%（15/27）and that of grade Ⅲ-Ⅳ was 11.11%（3/27）.The incidence of chronic GVHD was 7.41%（2/27）.Transplant-associated thrombotic microangiopathy (TA-TMA) occurred in 7.41%（2/27）patients,cytomegalovirus viremia in 62.96%（17/27）patients,epstein-barr virus infection in 33.33%（9/27）patients,and 14.81%（4/27）patients progressed to post-transplant lymphoproliferative disorder (PTLD).（3）The median follow-up time was 12 (2-28) months.The overall survival rate was 96.29%.Twenty-six patients survived,and one patient died due to multiple complications of severe acute GVHD,TA-TMA,cytomegalovirus infection,PTLD and secondary epilepsy.Conclusion:Allo-HSCT is an effective therapy for SAA in children.The effective rate of this research is 96.29%.Acute GVHD is still the key to therapy.The incidence rate of acute GVHD is 66.67% in this study.The blood incompatibility of donor and recipient may affect the incidence of GVHD.The intensity of GVHD prevention should be reduced after HLA-matched sibling donor-hematopoietic stem cell transplantation so as to avoid the complications of virus recurrence and PTLD.

Objective:To investigate the protective effect and possible mechanism of sulforaphane (SFN) on acute liver injury in mice induced by diquat (DQ) poisoning.Methods:Forty-eight male C57BL/6 mice were divided into Control group, DQ model group (DQ group), SFN intervention group (DQ+SFN group), and SFN control group (SFN group) using a random number table method, with 12 mice in each group. Acute liver injury mice model was established by one-time intraperitoneal injection of 1 mL of 40 mg/kg DQ solution at once. SFN group was injected with 1 mL of ddH 2O. After 4 hours of molding, 0.5 mL of 5 mg/kg SFN solution was injected into the peritoneal cavity of the DQ+SFN group and SFN group, once daily for 7 consecutive days. DQ group and Control group were injected with an equal amount of ddH 2O. Then, the mice were euthanized to collect liver tissue and blood samples, and the levels of plasma biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as oxidative stress indicators such as superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) in liver tissue were measured. The changes of liver structure were observed under transmission electron microscopy. The apoptosis and reactive oxygen species (ROS) level in liver tissue were observed under fluorescence microscope. Western blotting was used to detect the protein expressions of nuclear factor E2-related factor 2 (Nrf2), hemeoxygenase-1 (HO-1), Kelch-like ECH-associated protein 1 (Keap1), and cleaved caspase-9 in liver tissue. Results:Compared with the Control group, the liver mitochondria in the DQ group showed severe swelling, partial dissolution of the matrix, and cristae rupture and loss; the levels of plasma AST and ALT significantly increased, the MDA content in the liver increased, the activities of SOD and GSH decreased, the level of ROS significantly increased, the number of apoptotic cells in the liver significantly increased, the protein expressions of Nrf2 and HO-1 significantly decreased, and the protein expressions of Keap1 and cleaved caspase-9 significantly increased. Compared with the DQ group, the mitochondrial damage in the DQ+SFN group was reduced, the levels of plasma AST and ALT were significantly reduced [ALT (U/L): 58.22±4.39 vs. 79.94±3.32, AST (U/L): 177.64±8.40 vs. 219.62±11.60, both P < 0.01], the liver MDA content decreased, and the activities of SOD and GSH increased [MDA (μmol/g: 5.63±0.18 vs. 5.96±0.29, SOD (kU/g): 102.05±4.01 vs. 84.34±5.34, GSH (mmol/g): 16.32±1.40 vs. 13.12±1.84, all P < 0.05], the production of ROS in liver tissue was significantly reduced [ROS (fluorescence intensity): 115.90±10.89 vs. 190.70±10.16, P < 0.05], and apoptotic cells were significantly reduced (cell apoptosis index: 4.39±1.00 vs. 10.71±0.56, P < 0.01), the protein expressions of Nrf2 and HO-1 were significantly increased, while the protein expressions of Keap1 and cleaved caspase-9 were significantly decreased (Nrf2/β-actin: 1.15±0.04 vs. 0.93±0.05, HO-1/β-actin: 1.75±0.12 vs. 0.78±0.04, Keap1/β-actin: 1.00±0.14 vs. 1.28±0.13, cleaved caspase-9/β-actin: 1.31±0.12 vs. 1.81±0.09, all P < 0.05). However, there was no statistically significant difference in various indicators between the SFN group and the Control group. Conclusion:SFN can activate the Keap1/Nrf2 signaling pathway to alleviate DQ induced acute liver injury in mice.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective:To investigate the efficacy and pregnancy outcome of fertility-preserving treatment for patients with stage Ⅰa, grade 2 endometrial cancer (EC).Methods:Clinical data was retrospectively collected for EC or atypical endometrial hyperplasia (AEH) patients treated in Peking University People's Hospital, Foshan First People's Hospital of Guangdong Province and First Affiliated Hospital of Sun Yat-sen University, from 2010 to 2019. Inclusion criteria for fertility-preserving treatment included: (1) Age ≤45 years. (2) EC with histological differentiation of G 1, G 2 or endometrial AEH. (3) EC disease should be stage Ⅰa, confined to the endometrium without myometrial invasion, lymph node or extrauterine metastasis. Treatment regimen: patients were given oral progestin therapy and endometrial pathology was evaluated every three months. Patients were divided into three groups as G 2 EC group, G 1 EC group and AEH group based on the histological differentiation. Oncological and pregnancy outcomes were compared among them. Results:(1) Totally 57 eligible patients were included in this study, including 11 cases with G 2 EC, 22 cases with G 1 EC, and 24 cases with AEH. (2) Oncological outcome: among the three groups of G 2 EC, G 1 EC and AH, the complete remission rates (9/11, 91% and 96%, respectively) and recurrence rates (3/9, 30% and 22%, respectively) were not significantly different (all P>0.05). Median remission time was significantly longer in the G 2 EC group than those in the other two groups (8, 6 and 4 months; P=0.046). Among 9 G 2 EC patients who recurred after complete remission, three patients relapsed at 7, 18 and 53 months, respectively. All 3 patients chose fertility-sparing treatment again, and all achieved complete remission after retreatment. (3) Pregnancy outcome: among the three groups, the assisted reproduction technology rates (4/8, 5/18 and 36%, respectively) and pregnancy rates (6/8, 5/18 and 36%, respectively) had no significant difference ( P>0.05). However, time interval to pregnancy was shorter in G 2 EC patientsthan the other two groups (4, 9 and 22 months, respectively; P=0.006). Conclusions:Fertility-preserving treatment for patients with stageⅠa, G 2 endometrial cancer, may obtain a relatively high remission rate and an acceptable pregnancy rate. However, further exploration is needed due to the limited number of cases.

Transanal total mesorectal excision is a new surgical procedure which has emerged in the recent years.This procedure performs a "bottom-to-up" resection of the rectum and its surrounding mesenteries through the anus,which provides better view compared with laparoscopic or open total mesorectal excision.However,it is undeniable that as a new surgical procedure,transanal total mesorectal excision is also bound to have some complications of surgery.Therefore,how to prevent and treat the complications of transanal total mesorectal excision is still a problem that must be faced in the future.This article intends to review the prevention and treatment of surgical complications and provide some experience for the development of transanal total mesorectal excision.

Objective: To investigate the clinical features, treatment strategies and long term outcomes of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: The data of clinical features, auxiliary examinations, treatments and prognosis in children with anti-NMDAR encephalitis in Xiangya Hospital of Central South University from March 2014 to October 2017 were collected and retrospectively analyzed. A total of 71 patients were enrolled, including 33 males and 38 females. The youngest age of onset was 4 months old, and the age of onset was (9±4) years. The first-line immunotherapy treatment for anti-NMDAR encephalitis was short course corticosteroid (high-dose impulse therapy and oral maintenance therapy for 1 month in acute period) and (or) immunoglobulin. The clinical evaluation was performed 2 weeks after first-line immunotherapy treatment. The second-line immunotherapy treatment, including rituximab and (or) cyclophosphamide, would be started if the symptoms did not improve significantly and the modified Rankin scale (mRS) score ≥3. All patients were followed up and evaluated for prognosis. T-test, Mann-Whitney U, Chi square test and Fisher′s exact probability method were used for comparison between good outcome group and poor outcome group, first-line immunotherapy group and first-line immunotherapy combined with second-line immunotherapy group. Results: The more common clinical manifestations were psychiatric symptoms (n=61, 86%), dyskinesia (n=55, 77%) and convulsions (n=51, 72%). Two cases (3%) had tumors. Electroencephalogram (EEG), cerebro-spinal fluid (CSF) and brain magnetic resonance imaging (MRI) studies were abnormal in 83% (59/71), 39% (27/69) and 38% (27/71) patients, respectively. For the treatment regimens, all the 71 patients underwent first-line immunotherapy, resulting in improvement within 14 days in 40 cases (56%), and 1 case (1%) died. The rest 30 cases (42%) received second-line immunotherapy. The patients were followed up for 5.0-41.8 months, with a median of 19.3 months. At the last follow-up, 49 cases (69%) recovered completely, 15 cases (21%) had mild disability, 6 cases (8%) had severe disability, 1 case (1%) died and 3 cases (4%) had relapse. There were significant differences between the groups with good prognosis and poor prognosis on admission to pediatric intensive care unit (PICU) and consciousness disorder (10/64 vs. 5/7, 39/64 vs. 7/7, P=0.047, 0.004). There were significant differences between first-line immunotherapy group and the first-line combined second-line immunotherapy group on admission to PICU, consciousness disorder, sleep disorder and first mRS score (12% (5/41) vs. 33% (10/30), 44% (18/41) vs. 93% (28/30), 56% (23/41) vs. 90% (27/30), 3 (1-5) vs. 4 (3-5), respectively; χ²=4.645, 18.555, 9.560, Z=5.184, P=0.031, <0.01, 0.002, <0.01, respectively). Conclusions Anti-NMDAR encephalitis can occur in all ages of children. The most common clinical manifestations are psychotic symptoms, dyskinesia and convulsions. Paraneoplastic cases are less common in children. Immunotherapy is effective. The second-line immunotherapy should be given after the failure of first-line therapy (mRS score≥3).

Objective: To investigate the antibiotic resistance of Helicobacter pylori(Hp) isolates cultured from endoscopic gastric mucosal samples and influencing factors for antibiotic resistance in children. Methods: From April 2013 to February 2016, Hp cultured from mucosa samples of the gastric antrum and the body of stomach was investigated in 246 patients with ¹³C breath test positive examined by gastroscopy.Resistance to Amoxicillin, Clarithromycin, Metronidazole, Tetracycline was tested for Hp by using E-test.The clinical data were collected from the patients, and the relationship among age, gender, endoscopic diagnosis, histological performance, eradication number factors and antibiotic resistance rate were analyzed. Results: Of 246 specimens, 174 cases (70.7%) were positive.The overall antibiotic resistance rates of isolates obtained were 96.55% (168/174 cases), 57.47% (100/174 cases), 4.02% (7/174 cases), 1.15%(2/174 cases) with respect to Clarithromycin, Metronidazole, Tetracycline and Amoxicillin.An antibiotic resistance rate was 43.10% (75/174 strains), among which the Clarithromycin resistance rate was 93.33% (70/75 strains), and the Metronidazole resistance rate was 6.67% (5/75 strains). Double resistance rate was of 54.02%(94/174 strains), among which the resistances rate of Clarithromycin+ Metronidazole was 52.30%(91/94 strains), and the resistances rate of Clarithromycin+ Tetracycline was 1.72%(3/94 strains). Triple resistance rate of Clarithromycin+ Metronidazole+ Tetracycline was 1.15%(2/174 strains). Quadruple resistance rate of Clarithromycin+ Metronidazole+ Amoxicillin+ Tetracycline was 1.15%(2/174 strains). Factor analysis showed that the resistance rate of Clarithromycin in children who had failed in eradication therapy [98.7%(148/150 cases)] was higher than that in children who had not undergone eradication therapy [83.3%(20/24 cases)], and the difference was statistically significant(χ²=14.610, P<0.05). There was no significant difference in the relationship between Hp resistance to Metronidazole and Clarithromycin and the age, gender, endoscopic diagnosis and histological manifestations(all P>0.05). Conclusions Hp resistance rate to Clarithromycin, Metronidazole is very high in children, but it is relatively low to Amoxicillin and Tetracycline, and multiple antibiotic resistance is at high prevalence.

From November, 2010 to February, 2018, 11 children with variants of Guillain-Barré syndrome (GBS) were treated in Xiangya Hospital of Central South University. Clinical manifestations included cranial nerve involvement in 9 cases, limb weakness in 9 cases, ataxia in 8 cases, abnormal sensation in 7 cases, weakened or disappeared tendon reflex in all cases, albuminocytologic dissociation of cerebrospinal fluid in 6 cases, and neurogenic changes in electromyography in 8 cases. Immune globulin and steroids were given to 5 cases and 1 case, respectively, while the combination of immune globulin with steroids was given to 1 case, and symptomatic treatment was given to 4 cases. All treatments were effective, remaining no apparent side effect for nervous system. The diagnosis of GBS variants was based on clinical manifestation. Patients who had cranial nerve involvement, ataxia and weakened or disappeared tendon reflex should be paid attention. Albuminocytologic dissociation of cerebrospinal fluid and electromyography were helpful to diagnosis. GBS variants were self-limited disease. Immunotherapy can ease the patients' critical condition.
Child ; Electromyography ; Guillain-Barre Syndrome ; Humans ; Immunoglobulins, Intravenous ; Immunotherapy

OBJECTIVE: To summarize and analyze the postoperative short-term complications of laparoscope-assisted transanal total mesorectal excision (taTME) for rectal cancer patients after neoadjuvant therapy. METHODS: A prospectively established database on taTME patients at Peking University Cancer Hospital was screened with the following conditions: data retrieval from June 2016 to August 2018, pathologically confirmed adenocarcinoma, receiving preoperative neoadjuvant chemoradiotherapy or chemotherapy. The transabdominal procedure and the transanal procedure were performed simultaneously in the taTME operation. Occurrence of complications during perioperative period (within postoperative 3 months) in these patients, especially anastomosis-related complications and their management were analyzed. The relevant complications were recorded according to the Clavien-Dindo (CD) grading criteria. The severity of anastomotic leakage and anastomotic stenosis was evaluated according to criteria developed by the International Rectal Cancer Research Group. RESULTS: A total of 29 patients were enrolled in this study. In the 29 patients, 25 (86.2%) were male and 4 (13.8%) were female, the median age was 60 (range, 30 to 72) years, the median body mass index was 25.8 (range, 19.8 to 36.4) kg/m, the median distance from the tumor to anal verge was 4 (range, 2 to 8) cm. All the patients completed laparoscope-assisted taTME operations successfully without conversion to laparotomy, intra-operative severe complication or death. The median operation time was 300 (range, 198 to 405) minutes, and the median intra-operative blood loss was 100 (range, 50 to 200) ml. All the TME specimens were complete according to the Nagtegaal standard. All the patients underwent prophylactic ileostomy. Hartmann procedure was performed in one case due to poor blood supply in the proximal bowel without the possibility of anastomosis. Anal sphincter preservation rate was 96.6% (28/29). The median postoperative exhaust time was 2 (range, 1 to 10) days, and the median postoperative hospital stay was 9 (range, 7 to 24) days. Fifteen patients (51.7%) had postoperative complications, among which serious complication (CD grade IIIb and above) accounted for 6.9% (2/29). No perioperative death was observed. Five patients (17.2%) presented anastomosis-related complications, including 2 cases of grade C anastomotic leakage due to anastomotic rupture, who underwent abdominal perineal resection 1 month after operation; 2 cases of grade B anastomotic leakage, who improved after conservative treatment; 1 case of grade A anastomotic stenosis, who improved with anal expansion 1 month after operation. The incidence of postoperative infection was 24.1% (7/29), including 6 cases of pelvic infection and 1 case of trocar site infection, all of which were CD grade II. One case had incomplete intestinal obstruction (CD grade II); 1 case had gastroplegia; 1 case had abdominal trocar hernia. All the patients were followed up for a median of 12.0 (range, 3.9 to 29.9) months. Seven cases did not undergo ileal stoma closure. The anal sphincter preservation rate was 75.9% (22/29). CONCLUSION Pelvic infection and anastomosis-related complications are common after laparoscope-assisted taTME surgery for rectal cancer patients following neoadjuvant chemoradiotherapy, which require active management and appropriate treatment.
Adult ; Aged ; Anal Canal ; Female ; Humans ; Laparoscopes ; Male ; Middle Aged ; Neoadjuvant Therapy ; Postoperative Complications ; Rectal Neoplasms ; therapy