Objective To study the effect of Wuzi Yanzong Pill (WYP) on neurotrophic factors and apoptosis in the brain of mice with Parkinson's disease (PD). Methods MPTP-induced PD model in mice was established to evaluate the therapeutic effect of WYP by the behavioral gait, pole test, and brain pathological TH-positive neurons in the substantia nigra (SN). We used immunofluorescence, RT-qPCR, and Western blotting to evaluate the expression of neurotrophic factors (BDNF, GDNF, and CNTF) and apoptosis-associated genes (Bcl-2, Bax, caspase-3, and caspase-9). Results Compared with the PD model group, WYP could reduce the average swinging time of each paw (P<0.05)and pole test time (P<0.001); The number of TH positive cells (P<0.05)and TH protein expression (P<0.05) increased, which inhibited dopaminergic neuron injury. Compared with the PD model group,WYP increased the expression of BDNF, CNTF, GDNF, and Bcl-2 (P<0.05) and decreased the expression of Bax, caspase-3, and caspase-9 (P<0.05). Conclusion WYP shows therapeutic potential in PD, and its mechanism may be related to the anti-apoptotic effect and increased secretion of neurotrophic factors in SN of the brain in the MPTP-induced PD model.

Objective To analyze the detection characteristics of novel hepatitis B virus (HBV) serum biomarkers including HBV RNA, hepatitis B core-related antigen (HBcrAg), hepatitis B core antibody (anti-HBc), intrahepatic HBV total DNA (tDNA), and covalently closed circle (cccDNA) in patients with different types of HBV infection. Methods A total of 227 HBV-infected patients, who were hospitalized in the Fifth Medical Center of Chinese PLA General Hospital from January 2017 to December 2019 and underwent liver biopsy, were included in this study. The clinical data were retrospectively analyzed and serum HBV RNA, HBcrAg, anti-HBc, intrahepatic HBV tDNA and cccDNA were quantitatively detected. The characteristics and anti-HBV treatment impact on the above virological biomarkers in patients with different types of clinical illness were analyzed. Results Among 16 patients with acute hepatitis B (AHB), 4 were positive for serum HBV RNA (25.0%), 15 were positive for serum HBcrAg(93.8%), 14 were positive for HBV tDNA (87.5%), and 13 were positive for cccDNA (81.3%) in liver tissues. Among 184 patients with chronic hepatitis B (CHB), 34 were treated with nucleos(t)ide analogues (NAs), and their HBV RNA and HBcrAg contents were significantly lower than those without treatment, and the anti-HBc content was significantly higher (P<0.05). Among 18 patients with liver cirrhosis (LC), 9 were treated with NAs, the virological parameters, excepting HBV DNA, showed no significant differences between NAs-treated patients and treatment-naïve patients (P>0.05). Among 9 patients with hepatocellular carcinoma,5 were positive for serum HBV RNA (55.6%), 7 were positive for serum HBcrAg (77.8%), 8 were positive for HBV tDNA (88.9%),and 6 were positive for cccDNA (66.7%) in liver tissues. Conclusions Serum HBcrAg might be used to differentiate whether AHB is cured or not. In NAs-treated patients, even if HBV DNA decreases to the undetectable level, HBVRNA is still detectable and might cause the slow progresses of the disease, so antiviral therapy cannot be discontinued. Serum HBV RNA and HBcrAg might serve as serological substitutes for intrahepatic HBV cccDNA.

Mild traumatic brain injury (mTBI) is common in modern warfare. If the wounded cannot receive early and effective diagnosis and treatment, long-term headaches, dizziness, insomnia, memory disorders, anxiety, depression and other symptoms will be easily left behind, which will seriously affect the quality of life and combat effectiveness of service members, and bring a huge burden on families and society. In recent years, the US Department of Defense has conducted a lot of research on the pathophysiological mechanism, examination, treatment and prognosis of mTBI, and formulated some guidelines and norms. This article reviews the progress in diagnosis and treatment of mTBI, facilitating the establishment of a standardized treatment system for mTBI.

Objective To investigate the effect and mechanism of ZCCHC12 on epithelial-mesenchymal transition and invasion of differentiated thyroid cancer cells. Methods A total of 50 patients with differentiated thyroid adenocarcinoma admitted to Hebei General Hospital from May 2017 to December 2018 were selected, and set as differentiated thyroid cancer group. In addition, 50 subjects for healthy examination in the hospital during the same period were selected as the healthy control group.The contents of PKA/cAMP response element binding protein (CREB) and p21 in serum was detected by ELISA. Western blotting was used to detect the relative expressions of CREB and p21 in HUM-CELL-0097, TPC-1 and FTC-133 cell lines. TPC-1 cells and FTC-133 cells were taken and set up blank control group (normally cultured), NC si group (transfected with non-specific siRNA),and ZCCHC12 si group (transfected with ZCCHC12 siRNA), ZCCHC12 si+NC pc group (transfected with ZCCHC12 siRNA followed by the transfection with pcDNA.3.1), ZCCHC12 si+CREB pc group (transfected with ZCCHC12 siRNA followed by the transfection with pcDNA.3.1-CREB), ZCCHC12 si+NC si group (transfected with ZCCHC12 siRNA followed by the transfection with non-specific siRNA), ZCCHC12 si+p21 si group (transfected with ZCCHC12 siRNA followed by the transfection with p21 siRNA). Western blotting was performed to detect the relative expressions of ZCCHC12, CREB, P21, E-cadherin and N-cadherin proteins. Transwell method was used to detect the cell invasion ability. Results Compared with healthy control group, the serum content of CREB increased (P<0.05), and of p21 decreased (P<0.01) in differentiated thyroid cancer group. Compared with HUM-CELL-0097 cells, the content of CREB increased (P<0.01), and of p21 decreased (P<0.01) in TPC-1 and FTC-133 cells. Compared with NC si group, the relative expressions of E-cadherin and p21 protein increased, while the relative protein expressions of CREB and N-cadherin and the number of cell migration decreased (P<0.01) in ZCCHC12 si group. The expression of p21 protein in ZCCHC12 si+CREB pc group was lower than that in ZCCHC12 si+NC pc group (P<0.01), which reversed the promoting effect of interfering ZCCHC12 on p21 protein expression. Compared with ZCCHC12 si+NC si group, the relative expression of E-cadherin protein significantly decreased, while the relative expression of N-cadherin protein and the number of cell migration were significantly increased (P<0.01) in the ZCCHC12 si+p21 si group, which reversed the inhibitory effect of ZCCHC12 interference on the epithelial-mesenchymal transition and invasive capacity in differentiated thyroid cancer cells. Conclusions Interfering with ZCCHC12 can effectively inhibit the epithelial-mesenchymal transition and invasion of differentiated thyroid cancer cells by regulating CREB and p21, providing a certain theoretical basis for the treatment of differentiated thyroid cancer.

Objective To investigate the effect of non-alcoholic fatty liver disease (NAFLD) on the overall survival of patients with hepatitis B virus-related hepatocellular carcinoma (HCC). Methods The hospitalized patients from June 2008 to December 2020 were screened according to inclusive and exclusive criteria, the clinical characteristics at the time of the initial diagnosis of HCC and time-to-event information of the enrolled patients were retrospectively collected. After stratified by the Barcelona Clinic Liver Cancer (BCLC) staging and then balanced with the stabilized inverse probability of treatment weighting(IPTW) between NAFLD and non-NAFLD group, the Kaplan-Meier survival curve, log-rank test and Cox regression were used to compare the prognosis of patients with HBV-related HCC between NAFLD group and non-NAFLD group. The endpoint of this study was HCC-related death. Results A total of 833 patients were enrolled in the study. Among them, 465 patients in resectable group and 368 in non-resectable group. There were 161 (34.6%) patients with NAFLD in resectable group, and 76 (20.7%) patients with NAFLD in non-resectable group. After stabilized IPTW weighting, all indicators showed no statistical difference between two groups. Survival analyses showed that median survival time of NAFLD patients with HBV-related HCC was significantly longer than that of non-NAFLD patients. The 3-, 5-, and 8-year cumulative survival rates of NAFLD patients in resectable group were 96.9%, 82.1% and 41.2%, which were significantly higher than 91.1%, 60.4% and 13.7% of non-NAFLD patients (P<0.01). Cox analysis showed that NAFLD was the protective factor of survive (HR=0.473, 95%CI 0.356-0.627, P<0.01). Similarly, those of NAFLD patients in non-resectable group were 76.8%, 53.7% and 18.4%, which were significantly higher than those of non-NAFLD patients (53.0%, 25.7% and 2.5%, respectively, P<0.01). Cox analysis also showed that NAFLD was the protective factor of survive(HR=0.358, 95%CI 0.247-0.518, P<0.01). Conclusion The cumulative survival rate of HBV-related HCC patients with NAFLD is higher than that of patients without NAFLD.

Objective By literature review to retrospectively study the diagnosis and treatment process of decitabine combined with ruxolitinib in treatment of elderly patient with atypical chronic myeloid leukemia (aCML) for improving the understanding of aCML. Methods To report a case data of elderly aCML patients with CSF3R T618I mutation and the clinical treatment process using decitabine combined with ruxolitinib. Search CNKI, Wanfang data knowledge service platform, PubMed database (as of December 2021). Combined with literature reports to summarize the clinical characteristics of aCML and the effectiveness and safety in treatment applying decitabine combined with ruxolitinib. Results A case of 72-year-old man, admitted to our hospital since fatigue and dizziness for more than 1 month, and diagnosed as aCML with obviously increased white blood cells, granulocytic proliferation and granulocytic dysplasia with primitive cells <20%, and CSF3R T618I mutation detected by next-generation sequencing (NGS) analysis. After targeted therapy with ruxolitinib and 4 courses of treatment with decitabine, the patient achieved complete remission (CR) on morphology and had a good response on molecular. The patient's primary disease remained stable by maintenance therapy with ruxolitinib. A total of 11 cases treated with hypomethylating agents such as decitabine and azacitidine in aCML were found in literature, including 8 cases treated with decitabine alone [the CR rate was 87.5%(7/8)],2 cases treated with azacitidine alone [the effective rate was 50.0%(1/2)], and 1 case treated with decitabine combined with CAG(recombinant human granulocyte colony-stimulating factor + cytarabine + aclacinomycin) chemotherapy and achieved CR. A total of 4 cases treated with ruxolitinib alone in CSF3R T618I mutant aCML were found in literature and the overall efficiency was 50.0%(2/4). No case treated with drug combination in treatment of decitabine and ruxolitinib were found by searching literature. Conclusion aCML is a kind of rare disease, the diagnosis is based on morphological grounds only. The drug combination of decitabine and ruxolitinib is effective and well tolerable in this elderly patient with aCML.

Objective To analyze the genotypic characteristics of resistance-associated mutation in reverse-transcriptase(RT) domain of hepatitis B virus (HBV) in treatment-experienced chronic hepatitis B (CHB) patients with low-level viremia (LLV). Methods CHB patients with LLV, who admitted to the Fifth Medical Center of Chinese PLA General Hospital from September 2007 to August 2019, were retrospectively enrolled. Their serum HBV DNA was extracted, and a nested PCR was used to amplify an HBV RT fragment, 1225 bp in length (nt54-nt1278), containing the HBV RT gene (nt130-nt1161) and S gene (nt155-nt835).PCR products were bidirectionally sequenced, and a molecular evolutionary tree analysis of the RT/S gene sequence was performed with MEGA 4 software, with the Hepacivirus database (http://www.ncbi.nlm.nih.gov/projects/genotyping/formpage.Cgi) with the standard sequence as the reference for HBV genotyping. Results Among the 2096 patients, 82.4% were male, mean age was(45.6±12.0) years, HBV DNA was (2.5±0.5) log₁₀ IU/ml. Lamivudine resistance related mutations accounted for 58.0%, with M204V and L180M+M204V as the main forms; Adefovir dipivoxil resistance associated mutations accounted for 21.2%, with A181V and N36T as the predominant forms; Entecavir resistance associated mutations accounted for 17.9%, with L180M+M204I/V+T184L/A/S/I and L180M+M204V+S202G being the predominant forms; Multidrug resistance accounted for 2.9%, with L180M+M204I/V+A181V and L180M+M204V+A181V+N236T+S202G being the predominant forms. Conclusion Lamivudine and Adefovir resistance are the main drug-resistant mutation genotypes in the treated CHB patients with LLV, which reduces the gene barrier of entecavir resistance and increases the proportion of entecavir resistance. Therefore, the first-line nucleos(t)ide analogues with strong effect and low resistance should be selected for antiviral treatment.

Objective To analyze the risk factors of esophago-gastric fundal varices (EGV) in patients with hepatitis B virus (HBV)-related compensated cirrhosis, and to compare the clinical performance of multiple noninvasive prediction models for EGV evaluation. Methods A retrospective analysis was performed on the clinical data of patients with hepatitis B cirrhosis from two centers from January 2017 to December 2019. All patients underwent biochemical examination, gastroscopy, and liver stiffness measurement (LSM). AST-to-platelet ratio index (APRI), Fibrosis 4 index (FIB-4) and LSM-spleen diameter (SD)-to-platelet ratio score (LSPS) were calculated. According to the results of gastroscopy, they were divided into EGV and non-EGV group. The high-risk factors of EGV were explored by binary logistic regression. The receiver operating characteristic curve (ROC) was plotted, and the area under the curve (AUC) was calculated to evaluate the clinical performance of each indicator in predicting EGV. Results A total of 470 patients were enrolled, including 292 in the non-EGV group and 178 in the EGV group. Logistic regression analysis showed low PLT (platelet)(OR=0.99, 95%CI 0.98-0.99), high SD (spleen diameter)(OR=1.02, 95%CI 1.01-1.03) and high LSM(OR=1.04, 95%CI 1.02-1.07) were high risk factors for EGV (all P<0.05). The AUC of LSPS in predicting EGV [0.75(95%CI 0.71-0.79)] was significantly higher than that of PLT [0.72(95%CI 0.67-0.76)], SD [0.69(95%CI 0.64-0.73)], LSM [0.67(95%CI 0.63-0.72)], APRI [0.69(95%CI 0.65-0.74)] and FIB-4 [0.66(95%CI 0.62-0.71)](P<0.05). The LSPS score in EGV group was significantly higher than that in non-EGV group [2.7(1.3, 5.0) vs. 1.0(0.5, 1.7), P<0.001]. With the aggravation of EGV, LSPS score showed an upward trend (r=0.426, P<0.001). The cutoff value of LSPS for high risk of EGV was >3.5, the corresponding specificity and positive predictive value (PPV) ratio were 93.6% and 79.8% respectively. The cutoff value of LSPS for low risk of EGV was<1.3, its sensitivity and negative predictive value were 75.5% and 81.1% respectively. Conclusions Incorporating three risk factors including low PLT, high LSM and SD, the LSPS in predicting EGV in patients with compensated hepatitis B cirrhosis is better than ARPI, FIB-4, or LSM, and can reduce the need for gastroscopy.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly infectious and pathogenic.Although it mainly involves the respiratory system, it can also invade the nervous system and lead to a variety of neurological symptoms and diseases, further complicating the clinical conditions of the patients. In order to assist physicians and neurologists in understanding the pathogenesis, clinical features, diagnostic procedures, therapeutic principles, and clinical outcomes of the diseases,the experts of Neurology Branch of Chinese Medical Doctor Association wrote this expert recommendation based on present research articles and clinical practices about the epidemiology, clinical symptoms, diagnostic algorithms, treatment and prognosis of neurological diseases caused by coronavirus disease 2019, in order to provide reference for clinical diagnosis and treatment.

Vesicovaginal fistula (VVF) is an abnormal anatomical structure formed between the bladder and vagina, which usually occurs after gyneco-obstetric or pelvic surgery. VVF is one of the most common female genitourinary fistulas, causing serious distress to patients' physical and mental health and the quality of life. At present, the majority of VVF patients have poor outcomes in conservative therapy such as continuous bladder drainage and electrocoagulation, surgical repair is the main treatment option. The traditional surgical methods include transvaginal repair and transabdominal open repair. In recent years, with the development of minimally invasive techniques such as laparoscopic/robot-assisted laparoscopic surgery, the selection of VVF repair procedures has become more diverse, and the safety and efficacy of the operation have been continuously improved. However, there is no uniform standard for the timing and optimal surgical method for VVF repair. This article reviews the current progress in the treatment of VVF, and provides a reference for surgeons to formulate the optimal options for individual differences.