Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To illustrate the onset of epileptic seizures in children with brain injury admitted in pediatric intensive care unit (PICU), and to explore the risk factors and the correlation between epileptic seizures and the prognosis.Methods:Clinical data of pediatric patients with brain injury who were admitted to PICU of Peking University First Hospital from January 2013 to December 2019, and monitored by video electroencephalography (VEEG) were retrospectively collected, including general demographic information, etiological data, clinical seizures prior to VEEG performing, in-hospital mortality, brain function score, VEEG manifestations, etc.Seizures detected by VEEG were the primary outcome, and prognosis when discharged from PICU was the secondary outcome. Logistic regression was used to analyze the factors associated with seizures and poor outcome. Results:A total of 284 children were included, involving 54.9%(156/284) males.The median age of included children was 1.7(0.5, 5.0) years.Stratified by the cause of disease, 45.1%(128/284) had epilepsy, 26.1%(74/128) had genetic metabolic disease, and 14.4%(41/284) had central nervous system infection.A total of 82.0%(233/284) children had abnormal VEEG background activities, and 59.5%(169/284) had interictal epileptic discharges.Seizures were detected in 106 cases, including 39.6%(42/106) of non-convulsive seizures and 24.5%(26/106) of non-convulsive epileptic states.There were 12.0% (34/284) had poor prognosis at discharge, including 24 patients died in-hospital, and Pediatric Cerebral Performance Category scores were increased in 10 survivors.Multivariate Logistic regression analysis showed that seizures existed before VEEG monitoring and interictal epileptiform discharge were the independent risk factors for seizure.Besides, mental retardation, sepsis related encephalopathy, consciousness abnormality during VEEG, abnormal VEEG background activity, and epileptic status were significantly correlated with the poor prognosis of children with brain injury in PICU. Conclusions:The incidence of electrographic seizure is higher in children with brain injury in PICU, and VEEG monitoring is beneficial to children with brain injury that achieves an early identification of seizures and prediction of prognosis.

Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.

OBJECTIVE: To explore the clinical therapeutic strategies of refracture after Ilizarov bone transport technique in the treatment of tibial bone defect. METHODS: A retrospective study was performed on 19 patients with infected tibial bone defect treated by Ilizarov bone transport technique and then refracture from August 2010 to January 2020, including 18 males and 1 female with an average age of (37.7±13.0) years old ranging from 15 to 66 years old. Cause of injury invlved falling injury in 4 cases, crashing injury 1 case, crushing injury in 1 case and without obvious injury history in 13 cases. The ipsilateral distal femoral fracture in 2 cases occurred before the external fixator of tibia was removed, and the other 17 cases had a minimum of 1 day and a maximum of 30 months after the external fixator had been removed. The site of refracture was at regenerative zone in 8 cases, at docking site in 9 cases, at ipsilateral femoral shaft in 2 cases. According to the modified Simpson classification proposed by the author, the refracture was classified. The treatment of refracture include plaster splint, traction or external fixation. Bone healing and function were evaluated according to the standards of the Association for the Study and Application of the Method of Ilizarov(ASAMI). RESULTS: All patients were followed up, and the duration ranged from 9 to 17 months with an average of (12.3±3.2) months. According to the modified Simpson classification, there were 3 cases of type Ⅰa, 1 case of type Ⅰb, 3 cases of type Ⅰc, 1 case of type Ⅱ, 9 cases of type Ⅲ and 2 cases of type Ⅴ. All the refractures healed without infection or malunion. The fracture healing time of conservative treatment for 6 cases were 3, 5, 3, 2, 2, 2 months fespectively;and the healing time of fracture treated by surgery for 13 cases was 2 to 6 months, with an average of(4.4±1.4) months. According to ASAMI evaluation criteria, bony results showed all patients obtained excellent results, and functional results showed 6 patients got excellent results, 13 good beacause of ankle or knee stiffness. CONCLUSION The modified Simpson classification could contain most clinical types of refracture after bone transport, and the external fixation is a simple and effective method for refracture.
Male ; Humans ; Female ; Young Adult ; Adult ; Middle Aged ; Adolescent ; Aged ; Tibia/surgery* ; Tibial Fractures/surgery* ; Retrospective Studies ; Treatment Outcome ; Ilizarov Technique ; External Fixators ; Fracture Healing

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Background::Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients.Methods::From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA 2DS 2-VA score (excluding female sex from the CHA 2DS 2-VASc score). Results::Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%-1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65-0.73), higher than that of CHA 2DS 2-VA score (0.66, 95% CI: 0.62-0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA 2DS 2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%-15.7%). Conclusion::In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA 2DS 2- VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. Trial Registration::www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).

Objective: To evaluate the clinical effectiveness of combining electrical stimulation with manual massage in treating women′s myofascial pelvic pain (MPPS). Methods: A total of 93 MPPS patients were recruited and randomly divided into an infrared irradiation group (n=30), an electrical stimulation group (n=31) and a combination group (n=32). Those in the infrared group and the electrical stimulation group were given 30 minutes of infrared irradiation or electrical stimulation daily for 10 days, while the combined group was given a manual massage with electrical stimulation. The response to treatment was evaluated using a visual analogue scale (VAS) to rate discomfort, plus a physical examination, and surface electromyography results using Glazer′s protocol. The treatments′ efficacy and the recurrence of pain were evaluated 1 month after the treatment. Results: The average VAS ratings, resting potentials and their variability of the three groups all improved significantly after the treatment. The average VAS scores of the combined and electrical stimulation groups after the treatment were significantly lower than that of the infrared group. Moreover, the total effective rates of the combined group (96.87%) and the electrical stimulation group (80.65%) were significantly higher than that of the infrared group (56.67%), and the resting potential and variability of the former two groups were also significantly better. All of the above measurements among the combined group after the treatment were significantly better, on average, than in the electrical stimulation group. A month later the recurrence rate in the combined group (6.25%) was significantly lower than in the electrical stimulation group (25.81%) and the infrared group (56.67%). Conclusion Electrical stimulation combined with manual massage is effective in relieving myofascial pelvic pain.

Objective　CARD9 can activate several pathways involved in immunity, such as NF-ΚB, MAPK, etc. However the mechanism of this process has not yet been elucidated. For conducting relevant experiments in vitro, a prokaryotic expression vector of CARD9-MBP fusion protein has to been construct, and the fusion protein need to be expressed and purified.　Methods　The coding sequence of CARD9 and MBP genes were amplified by PCR and the recombinant plasmid was correctly inserted into the pET-30a(+) vector. The recombinant plasmid was transformed into E.coli DH5α competent cells and proceeded PCR identification, restriction analysis and gene sequencing. The correct recombinant plasmid was transformed into E.coli BL21(DE3) competent cells. The target protein was induced to express by IPTG under different conditions. Relative molecular weight of the target protein was detected by SDS-PAGE electrophoresis. The CARD9-MBP fusion protein was purified by MBP maltose chromatography column and gel filtration chromatography column, and identificated by MALDI-TOF mass spectrometry after MBP-tag to be removed by HRV3C enzyme.　Results　The CARD9-MBP fusion protein was successfully constructed and confirmed by PCR and restriction analysis. The result of gene sequencing was consistent with the target sequence. The SDS-PAGE electrophoresis showed that the target protein with molecular mass (MR) about 105 000 was successfully induced to express in E.coli BL21 (DE3). A quite pure CARD9-MBP fusion protein was obtained by purification of MBP maltose chromatography column. Identification by MALDI-TOF mass spectrometry demonstrated that the target protein after MBP-tag to be removed by HRV3C enzyme is CARD9 protein. In the later stage, gel filtration chromatography column was used to obtain further pure CARD9-MBP fusion protein.　Conclusion　The prokaryotic expression vector of CARD9-MBP fusion protein was successfully constructed and a large number of soluble protein expressed. The purified target protein can be obtained by purification with MBP maltose chromatography column and gel filtration chromatography column.

Objective To study the video-electroencephalography (vEEG) background activities of very premature infants within the first 7 days after birth.Method The inclusion criteria were gestational age (GA) within 31 weeks and bedside vEEG monitoring within first 7 days of birth.Those with severe cranial ultrasound (CUS) findings,refused treatment,dead and with seizures on vEEG were excluded.The clinical information of included cases were reviewed and the continuity and sleep-wake cycle (SWC) on their EEG background activities were analysed.Result From June 2017 to April 2018,a total of 56 cases were included.Their GA were (29.4 ± 1.6) weeks,and birth weight were (1 306 ± 316) g.A total of 31 cases were diagnosed with asphyxia(1 min Apgar score less than 8),and no one with 5 min Apgar score below 5.Their umbilical artery blood pHs were 7.29 ± 0.07.Their first CUS and the CUS at corrected gestational age (cGA) full term were all within the normal range.The Gesell neurological assessment at cGA 6 months were all within the normal range.As the cGA increased,the continuity of EEG background activities became more continuous as the normal continuous/discontinuous pattern.The 95％ confidence interval of max interburst interval was 95 s.The SWC first occurred at GA 26 w,but was immature,then became mature as the cGA increased.Conclusion The EEG background activity analysis of relatively normal very premature infants within first week shows that interburst interval can be longer than the previous report,and the SWC first appear at GA 26 w.

Objective To study the influence of continuous blood purification(CBP) on cardiac out-put of pediatric patients using bioreactance. Methods Patients underwent CBP in PICU and nephrology ward from March 2014 were prospectively enrolled after approval by ethics committee. CBP therapies were all performed by Fresenius Medical Care hemodialysis machine. Cardiac output values were obtained using the non-invasive cardiac output monitoring ( NICOM) device ( Cheetah Medical). Blood pressure, heart rate, cardiac index(CI) and stroke volume index(SVI) were recorded before the therapy,at the beginning of ther-apy,during the course of therapy,and at the end of each therapy. Results Twenty-one pediatric patients (from 1. 0 year to 15. 5 years) were recruited and 69 treatments were recorded from March 2014 to Decem-ber 2016. The basic CI was 3. 4 (2. 4,6. 1) L/(min·m2),basic SVI was 43 (26,75) ml/(m2·beat). Dur-ing the beginning of therapy,mean arterial pressure(MAP),CI and SVI all dropped from the baseline ( P<0. 001),whereas heart rate increased. During the course of CBP,CI and SVI (were both recorded every 4 hours) kept on dropping and stayed at a relatively lower level. Course CI was 3. 0 (2. 4,4. 6) L/(min·m2) and course SVI was 28 (21,57) ml/(m2·beat). At the end of therapy,CI was 3. 4 (2. 5,5. 3) L/(min· m2),with no significant difference from the baseline CI (P＝0. 073). However,the SVI at the end of therapy was 35 (25,67) ml/(m2·beat),higher than the course SVI but still lower than the basic SVI,the differences were statistically significant ( P<0. 05). Conclusion CI and SVI continue to decline at the beginning of CBP treatment and remain at a lower level throughout the course of treatment. After the therapy, CI has returned to the basic level whereas SVI has not recovered.