ObjectiveTo investigate the intervention effects of Suanzaoren Tang on depression model rats induced by isolation combined with chronic unpredictable mild stress （CUMS）， and to examine its influence on the c-Jun N-terminal kinase （JNK）/proto-oncogene protein （c-Myc）/tumor suppressor protein 53 （p53） signaling pathway， thereby revealing its potential functional mechanism. MethodsA total of 72 male SD rats were randomly divided into six groups using a strict random number table： blank group， model group， fluoxetine group （3.6 mg·kg^-1）， and high-， medium-， and low-dose Suanzaoren Tang groups （10， 5， 2.5 g·kg^-1），with 12 rats in each group. A depression model was established using isolation combined with CUMS. Fluoxetine and different doses of Suanzaoren Tang were administered continuously for 28 days. Behavioral indicators such as sucrose water consumption and open field test scores were recorded. Western blot and immunohistochemistry （IHC） were employed to analyze the expression of key proteins in the JNK/c-Myc/p53 signaling pathway， and the terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） assay was used to evaluate the number of apoptotic cells in the hippocampus. ResultsCompared with the blank group， the model group exhibited a significantly reduced sucrose preference index （P<0.01）， a lower total score of horizontal and vertical movements in the open field test （P<0.01）， significantly increased expression of JNK， c-Myc， and p53 proteins in the hippocampus （P<0.01）， and a higher number of TUNEL-positive cells in the hippocampus （P<0.01）. Compared with the model group， the sucrose preference index and the total score of horizontal and vertical movements in the open field test significantly increased in the high- and medium-dose Suanzaoren Tang groups and the fluoxetine group （P<0.05， P<0.01）. The expression of JNK， c-Myc， and p53 proteins significantly decreased in all Suanzaoren Tang groups （high， medium， and low doses） and the fluoxetine group （P<0.05， P<0.01）. The number of TUNEL-positive cells in the hippocampus also significantly decreased in these groups （P<0.01）. ConclusionSuanzaoren Tang can regulate the expression of JNK/c-Myc/p53 proteins in the hippocampus of depression model rats， and its antidepressant mechanism may be related to its protective effect on hippocampal neurons.

Bone Transplantation/adverse effects* ; Transplantation, Autologous/adverse effects*

Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

ObjectiveTo study the changes of mitochondrial function of ovarian granulosa cells in women of different ages and the effect of Erzhi-Tiangui prescription on in vitro fertilization-embryo transfer （IVF-ET） outcomes for elderly women， so as to verify the connotation of the "Seven-Seven" theory in the Huangdi's Internal Classic （《黄帝内经》）. MethodA total of 150 infertility patients undergoing IVF-ET at the Reproductive and Genetic Center of Integrative Medicine， Affiliated Hospital of Shandong University of Traditional Chinese Medicine were recruited and assigned into "hree-Seven/Four-Seven （30 cases）， Five-Seven （60 cases）， and Six-Seven （60 cases） groups according to the "Seven-Seven" theory. The Five-Seven and Six-Seven groups were further assigned into control and Chinese medicine subgroups using the random number plus envelope method， and the Chinese medicine group was administrated with Erzhi Tiangui prescription from the start day of controlled ovulation stimulation cycle to the trigger day. The IVF outcome was observed， and Western blot was employed to determine the levels of mitofusin 1 （MFN1）， mitofusin 2 （MFN2）， and dynamin-related protein 1 （Drp1） in the ovarian granulosa cells. ResultCompared with the Three-Seven/Four-Seven group， the control subgroups of the Five-Seven and Six-Seven groups showed decreased retrieved oocytes， two pronuclear （2PN） embryos， available embryos， high-quality embryos， clinical pregnancy rate， and live birth rate （P<0.05）. Moreover， the control subgroup of the Six-Seven group showed decreased fresh embryo transfer rate（P<0.05）. Compared with the control subgroup of the Five-Seven group， that of the Six-Seven group showed reduced retrieved oocytes， 2PN embryos， available embryos， high-quality embryos， and clinical pregnancy rate （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， 2PN oocytes， and available embryos than the control subgroup in the Five-Seven groups （P<0.05）. The Chinese medicine subgroup had more retrieved oocytes， than the control subgroup in the Six-Seven groups （P<0.05）. The control subgroup of the Six-Seven group showed lower expression levels of Mfn1 and Mfn2 and higher level of Drp1 than the control subgroup of the Five-Seven group （P<0.05）， which indicated that the levels of Mfn1 and Mfn2 in ovarian granulosa cells were down-regulated while the expression of Drp1 was up-regulated with aging （P<0.05）. The Chinese medicine subgroup had higher Mfn2 level and lower Drp1 level than the control subgroup in the Five-Seven group （P<0.05）， and the Chinese medicine subgroup had higher Mfn1 and Mfn2 levels and lower Drp1 level than then control subgroup in the Six-Seven group （P<0.05）. ConclusionsThe prognosis of IVF in women after "Five-Seven" became worse with aging， and the mitochondria in ovarian granulosa cells showed decreased fusion ability and increased fission， which verified the connotation of the "Seven-Seven" theory from the mitochondrial function. Erzhi Tiangui prescription can regulate the mitochondrial function of ovarian granulosa cells in elderly women， up-regulate the expression levels of Mfn1 and Mfn2 to promote mitochondrial fusion， and down-regulate the expression of Drp1 to reduce mitochondrial fission， thus alleviating the ovarian hypofunction caused by aging， improve the development potential of oocytes， and improve the IVF outcomes of elderly women. However， this prescription has limited efficacy for the elderly women in the age range of "Six-Seven".

Objective: This cross-sectional study aimed to investigate the characteristics of malocclusions in scoliotic patients through clinical examinations. Methods: Fifty-eight patients with idiopathic scoliosis (IS) and 48 patients with congenital scoliosis (CS) participated in the study. A randomly selected group of 152 orthopedically healthy children served as the control group. Standardized orthodontic and orthopedic examination protocols were used to record the occlusal patterns and type of scoliosis. Assessments were made by three experienced orthodontists and a spinal surgery team. The differences in the frequency distribution of occlusal patterns were evaluated by the chi-squared test. Results: In comparison with patients showing IS, patients with CS showed a higher incidence of Cobb angle ≥ 45° (p = 0.020) and included a higher proportion of patients receiving surgical treatments (p < 0.001). The distribution of the Angle Class II subgroup was significantly higher in the IS (p < 0.001) and CS (p = 0.031) groups than in the control group. In comparison with the healthy controls, the CS and IS groups showed significantly higher (p < 0.05) frequencies of asymmetric molar and asymmetric canine relationships, upper and lower middle line deviations, anterior deep overbite, unilateral posterior crossbite, and canted occlusal plane, with the frequencies being especially higher in CS patients and to a lesser extent in IS patients. Conclusions Patients with scoliosis showed a high frequency of malocclusions, which were most obvious in patients with CS.

Objective:To investigate the complications and prevention strategies of Dynesys stabilization in the treatment of lumbar degenerative disease.Methods:Two hundred and forty-three patients underwent lumbar spine stabilization with Dynesys owing to lumbar degenerative disease were retrospectively analyzed from July 2008 to December 2016. The mean follow-up time was 5.6 years (48-148 months). There were 152 patients with lumbar disc herniation and 91 patients with lumbar spinal stenosis. 167 cases underwent single-level operation, 71 cases underwent two-level operation, and 5 cases underwent three-level operation. All patients had low back pain, radiating pain in the lower extremities, and/or intermittent claudication. Clinical outcomes were evaluated using Oswestry disability index (ODI) and visual analogue scale (VAS). The occurrence of perioperative complications (with in 3 months) and postoperative complications (after 3 months) after the operation were recorded and analyzed. Radiographic adjacent segment degeneration (ASD) was evaluate dusing University of California at Los Angeles Grading Scale (UCLA).Results:All patients underwent surgery successfully. ODI score of patients improved from 55.1%±16.8% preoperatively to 15.6%±5.8% at the final follow-up, the difference was statistically significant ( t=34.6, P<0.01). VAS score decreased from 6.4±2.3 preoperatively to 1.1±0.4 at the final follow-up, the difference was also statistically significant ( t=35.4, P<0.01). There were 25 cases (10.29%) with complications, and 3 cases (1.23%) underwent secondary operation. Perioperative complications occurred in 13 patients (5.35%), including 5 cases of cerebros pinal fluid leakage, 5 cases of poor wound healing (2.06%), and 3 cases of deep wound infection (1.23%). Twelve patients (4.94%) had long-term postoperative complications, including 6 patients (2.47%) of unilateral screw loosening at the 5-year follow-up, 3 patients (1.23%) of screw fracture, and 3 patients (1.23%) of symptomatic ASD, among whom 2 patients underwent secondary operation, and 1 patient underwent conservative treatment. There was no recurrence at the operated segments in all patients. At the final follow-up, 41 patients (16.87%) had radiographic ASD. The UCLA score atthe final follow-up was significantly different from that preoperatively ( Z=2.60, P=0.01). Conclusion:Dynesys dynamic system combined with decompression in the treatment of degenerative lumbar spine diseases can achieve good long-term clinical outcome, with low incidence of complications and ASD.

Adolescent ; Adult ; Age Distribution ; Aged ; Basic Reproduction Number ; COVID-19/virology* ; China/epidemiology* ; Disease Outbreaks ; Female ; Humans ; Male ; Middle Aged ; SARS-CoV-2 ; Sex Ratio ; Young Adult

Objectives: Fitting and forecasting the trend of COVID-19 epidemics. Methods: Based on SEIR dynamic model, considering the COVID-19 transmission mechanism, infection spectrum and prevention and control procedures, we developed SEIR^{+ CAQ} dynamic model to fit the frequencies of laboratory confirmed cases obtained from the government official websites. The data from January 20, 2020 to February 7, 2020 were used to fit the model, while the left data between February 8-12 were used to evaluate the quality of forecasting. Results: According to the cumulative number of confirmed cases between January 29 to February 7, the fitting bias of SEIR^{+ CAQ} model for overall China (except for cases of Hubei province), Hubei province (except for cases of Wuhan city) and Wuhan city was less than 5%. For the data of subsequent 5 days between February 8 to 12, which were not included in the model fitting, the prediction biases were less than 10%. Regardless of the cases diagnosed by clinical examines, the numbers of daily emerging cases of China (Hubei province not included), Hubei Province (Wuhan city not included) and Wuhan city reached the peak in the early February. Under the current strength of prevention and control, the total number of laboratory- confirmed cases in overall China will reach 80 417 till February 29, 2020, respectively. Conclusions The proposed SEIR^{+ CAQ} dynamic model fits and forecasts the trend of novel coronavirus pneumonia well and provides evidence for decision making.

Objective The number of confirmed and suspected cases of the COVID-19 in Hubei province is still increasing. However, the estimations of the basic reproduction number of COVID-19 varied greatly across studies. The objectives of this study are 1) to estimate the basic reproduction number ( R 0 ) of COVID-19 reflecting the infectiousness of the virus and 2) to assess the effectiveness of a range of controlling intervention. Method The reported number of daily confirmed cases from January 17 to February 8, 2020 in Hubei province were collected and used for model fit. Four methods, the exponential growth (EG), maximum likelihood estimation (ML), sequential Bayesian method (SB) and time dependent reproduction numbers (TD), were applied to estimate the R 0 . Result Among the four methods, the EG method fitted the data best. The estimated R 0 was 3.49 (95% CI : 3.42-3.58) by using EG method. The R 0 was estimated to be 2.95 (95% CI : 2.86-3.03) after taking control measures. Conclusion In the early stage of the epidemic, it is appropriate to estimate R 0 using the EG method. Meanwhile, timely and effective control measures were warranted to further reduce the spread of COVID-19.

Objectives:The COVID-19 has been the public health issues of global concern, but the incubation period was still under discussion. This study aimed to estimate the incubation period distribution of COVID-19.Methods:The exposure and onset information of COVID-19 cases were collected from the official information platform of provincial or municipal health commissions. The distribution of COVID-19 incubation period was estimated based on the Log- normal, Gamma and Weibull distribution by interval-censored data estimation method.Results:A total of 109 confirmed cases were collected, with an average age of 39.825 years. The median COVID-19 incubation period based on Log-normal, Gamma, and Weibull distribution were 4.958 ( P25- P75: 3.472-7.318) days, 5.083 ( P25- P75: 3.511-7.314) days, and 5.695 ( P25- P75: 3.675-7.674) days, respectively. Gamma distribution had the largest log-likelihood result. Conclusions:The distribution of COVID-19 incubation period followed the Gamma distribution, and the interval-censored data estimation method can be used to estimate the incubation period distribution.