Background/Aims: To evaluate the causal correlation between complement components and non-viral liver diseases and their potential use as druggable targets. Methods: We conducted Mendelian randomization (MR) to assess the causal role of circulating complements in the risk of non-viral liver diseases. A complement-centric protein interaction network was constructed to explore biological functions and identify potential therapeutic options. Results: In the MR analysis, genetically predicted levels of complement C1q C chain (C1QC) were positively associated with the risk of autoimmune hepatitis (odds ratio 1.125, 95% confidence interval 1.018–1.244), while complement factor H-related protein 5 (CFHR5) was positively associated with the risk of primary sclerosing cholangitis (PSC;1.193, 1.048– 1.357). On the other hand, CFHR1 (0.621, 0.497–0.776) and CFHR2 (0.824, 0.703–0.965) were inversely associated with the risk of alcohol-related cirrhosis. There were also significant inverse associations between C8 gamma chain (C8G) and PSC (0.832, 0.707–0.979), as well as the risk of metabolic dysfunction-associated steatotic liver disease (1.167, 1.036–1.314). Additionally, C1S (0.111, 0.018–0.672), C7 (1.631, 1.190–2.236), and CFHR2 (1.279, 1.059–1.546) were significantly associated with the risk of hepatocellular carcinoma. Proteins from the complement regulatory networks and various liver diseaserelated proteins share common biological processes. Furthermore, potential therapeutic drugs for various liver diseases were identified through drug repurposing based on the complement regulatory network. Conclusions Our study suggests that certain complement components, including C1S, C1QC, CFHR1, CFHR2, CFHR5, C7, and C8G, might play a role in non-viral liver diseases and could be potential targets for drug development.

Complex brain diseases seriously endanger human health, and early diagnostic biomarkers and effective treatments are currently lacking. Due to ethical constraints on human research, establishing monkey models is crucial to address these issues. With the rapid development of technology, transgenic monkey models of a range of brain diseases, especially autism spectrum disorder (ASD), have been successfully established. However, to establish practical and effective brain disease models and subsequently apply them to disease mechanism and treatment studies, there is still a lack of a standard tool, i.e., a system for collecting and analyzing the daily behaviors of brain disease model monkeys. Therefore, with the goal of undertaking a comprehensive and quantitative study of behavioral phenotypes, we established a standard daily behavior collection and analysis system, including behavioral data collection protocols and a monkey daily behavior ethogram (MDBE) for rhesus and cynomolgus monkeys, which are the most commonly used non-human primates in model construction. Then, we used ASD as an application example after referring to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision (DSM-5-TR), which is widely used in clinical disease diagnosis to obtain ASD core clinical symptoms. We then established a sub-ethogram (ASD monkey core behavior ethogram (MCBE-ASD)) specifically for quantitative assessment of the core clinical symptoms of an ASD monkey model based on MDBE. Subsequently, we demonstrated the high reproducibility of the system.
Animals ; Autism Spectrum Disorder ; Macaca mulatta ; Disease Models, Animal ; Behavior, Animal ; Macaca fascicularis ; Male ; Humans

Objective:To report a case of combined oxidative phosphorylation deficiency 28 (COXPD28) in China, identified the pathogenic mutation and explored the pathogenic mechanism preliminarily.Methods:The clinical characteristics of a patient with COXPD28 were retrospectively analyzed and the pathogenic mutations were identified by mitochondrial gene sequencing and whole exome sequencing. The wild-type and mutant plasmids of pathogenic genes were constructed, and effect of mutation on protein expression by quantitative real-time PCR (qPCR) and Western blot were evaluated. Statistical methods mainly used one-way ANOVA and LSD test.Results:A 21 year old female patient presented with lactic acid poisoning due to repeated chest distress and wheezing since childhood. The sequencing of the whole exon group gene found that solute carrier family 25 member 26 (SLC25A26) gene had a compound heterozygous mutation (c.34G>C, p.A12P; c.197C>A, p.A66E), which was the first report in China. In vitro function test showed that the expression levels of SLC25A26 mRNA and S-adenosylmethionine carrier (SAMC) protein in cells transfected with SLC25A26 mutant plasmid were significantly lower than those transfected with wild type plasmid. The p.A66E mutant plasmid reduced the expression level of SLC25A26 mRNA and SAMC protein to 6% and 26% of wild type plasmids respectively (both P<0.001), while p.A12P mutant plasmid decreased to 62% and 82% of wild type plasmids respectively ( P<0.001, P=0.044). When the double mutant (p.A66E+p.A12P) plasmids were co-transfected, the expression levels of SLC25A26 mRNA and SAMC protein decreased to 47% and 57% of the wild type plasmids, respectively ( P<0.001, P=0.001). Conclusion:The pathogenic mutation gene of this patient with COXPD28 is SLC25A26 gene mutation (p.A66E, p.A12P), which causes the decrease of SLC25A26 expression level, mitochondrial oxidative phosphorylation dysfunction, and induces COXPD28.

Objective:To explore the treatment of iatrogenic injury to the medial collateral ligament (MCL) in total knee arthroplasty (TKA).Methods:From January 2009 to December 2016, 14 patients were treated at Department of Arthropathy, Zhengzhou Orthopedics Hospital for iatrogenic MCL injury in primary TKA (injury group). They were 3 males and 11 females with an age of (72.6±3.9) years. The MCL injury was body rapture in 9 cases and avulsion of femoral insertion in 5 ones. Interlacing suture was used for body rapture and reparative reconstruction with wire anchors or nails was performed for avulsion of femoral insertion. A restrictive condylar prosthesis was used instead in the 4 patients whose medial stability failed to be restored after repair of body rapture. A control group of 21 cases was enrolled who had suffered from no iatrogenic MCL injury in primary TKA at the corresponding period. There were 5 males and 16 females with an age of (73.2±3.9) years. The 2 groups were compared in terms of American Knee Society Score (KSS) and knee flexion.Results:There was no significant difference between the 2 groups in preoperative general data, showing comparability between groups ( P>0.05). The injury group was followed up for 18 to 36 months (mean, 33 months). Joint loosening was observed at 18 months after operation in 3 patients with nonrestrictive prosthesis who had to receive secondary revision. At the 36-month follow-up of the remaining 11 patients, normal knee extension and flexion was observed, the stress test of valgus showed no inner relaxation, their KSS increased significantly from preoperative 50.0±22.7 to 93.3±4.7, and their knee flexion was improved significantly from 90.4°±10.3° to 110.7°±8.8° ( P<0.05). There were no significant differences in KSS score or knee flexion between the 2 groups at 3, 6, 12 or 36 months after operation ( P>0.05). Conclusion:Iatrogenic MCL injury in primary TKA should be repaired and reconstructed by one-stage surgery because the patients can achieve curative results similar to those for the patients free from iatrogenic MCL injury in primary TKA.

Whether direct manipulation of Parkinson's disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6-10 months), and thus provides a practical transgenic monkey model for future PD studies.
Animals ; Brain ; CRISPR-Cas Systems/genetics* ; Dependovirus/genetics* ; Haplorhini ; Phenotype ; Protein Kinases/genetics*

Whether direct manipulation of Parkinson’s disease (PD) risk genes in the adult monkey brain can elicit a Parkinsonian phenotype remains an unsolved issue. Here, we used an adeno-associated virus serotype 9 (AAV9)-delivered CRISPR/Cas9 system to directly co-edit PINK1 and DJ-1 genes in the substantia nigras (SNs) of two monkey groups: an old group and a middle-aged group. After the operation, the old group exhibited all the classic PD symptoms, including bradykinesia, tremor, and postural instability, accompanied by key pathological hallmarks of PD, such as severe nigral dopaminergic neuron loss (>64%) and evident α-synuclein pathology in the gene-edited SN. In contrast, the phenotype of their middle-aged counterparts, which also showed clear PD symptoms and pathological hallmarks, were less severe. In addition to the higher final total PD scores and more severe pathological changes, the old group were also more susceptible to gene editing by showing a faster process of PD progression. These results suggested that both genetic and aging factors played important roles in the development of PD in the monkeys. Taken together, this system can effectively develop a large number of genetically-edited PD monkeys in a short time (6–10 months), and thus provides a practical transgenic monkey model for future PD studies.

OBJECTIVES: To evaluate the efficacy of different ways of cocktail analgesic mixture injection on total knee arthroplasty (TKA). METHODS: A total of 50 patients with knee osteoarthritis treated by TKA from July to September 2018 were randomly divided into two groups (=25). The Group 1 underwent anterior intra-articular injection before prosthesis implanted while the Group 2 underwent posterior intra-articular injection before prosthesis implanted. Visual Analogue Scale (VAS) of all patients for pain during activity and at rest, maximal flexion degree of the knee at the 48th h and the 72th h after surgery, the time of raise leg, usage rate of patient-controlled analgesia (PCA), and complications were evaluated and analyzed. RESULTS: VAS for pain at rest of patients in the Group 1 was significantly less than that in the Group 2 at the 6th, 12th, and 24th h after surgery (all <0.05). Maximal flexion degree of the knee at the 48th h and the 72th h after surgery in the Group 1 was better than that in the Group 2 (both <0.05). The Group 1 costed less time than the Group 2 on the ability to perform an active straight leg raise (=0.027). CONCLUSIONS The anterior intra-articular cocktail analgesic mixture injection can strongly relieve the pain early after TKA, which can improve knee function and achieve painless rehabilitation in most patients, with safety.
Analgesics ; Arthroplasty, Replacement, Knee ; Humans ; Injections, Intra-Articular ; Osteoarthritis, Knee ; surgery ; Pain Measurement ; Pain, Postoperative ; prevention & control

Objective To explore the current status and influencing factors of oral health knowledge and behavior among the elderly living in Gongshu District of Hangzhou City.Methods A total of 600 elderly individuals were selected by multi-stage stratified cluster random sampling and interviewed with a self-designed questionnaire which included demographic characteristics and oral health knowledge and behavior.The status and influencing factors of oral health behavior were analyzed by single and multiplefactor analysis methods.Results A questionnaire survey was conducted among 600 elderly residents,with a response rate of 99.3％ (596/600) and an effective response rate of 94.1％ (561/600).The rate of good oral hygiene was 50.4％.Those elderly with different age,education level,medical insurance and oral hygiene showed significant difference in qualified rate of oral health behavior (x2 values were 10.79,21.32,5.72 and 16.33,respectively; all P＜0.05).In Logistic regression model,education level was positively correlated with oral health behavior among the elderly,and the qualified rate of oral health behavior of the elderly with education level of junior school or above was 2.69 times higher than that of illiterate elderly (x2=10.53,P=0.001).Conclusion The awareness rate of oral health knowledge among the elderly living in Gongshu District of Hangzhou City is at a relatively higher level,though oral health behavior is moderate.Age,education level,medical insurance and oral hygiene could be impacting factors of oral health behavior.

Objective To analyze outcome of pulmonary tuberculosis(TB) patients in different household in Shenzhen in 2008, and provide scientific basis for development of TB control strategy. Methods The data from monthly,quarterly,annual report as well as the TB report card and other related information were collected and analyzed. Results A total of 4 826 active pulmonary tuberculosis patients were found in 2008, in which 86.0% were mobile population;2 349 cases of new smear positive pulmonary tuberculosis patients were found;Mobile population cure rate of new smear positive(75.0%) was significantly lower than that of household population(P＜0.01). Mobile population moving out or loss rate of new smear positive(13.5%) was significantly higher than that of household population(P＜0.01). Conclusion Mobile population cure rate of new smear positive was lower and moving out or loss rate of new smear positive(13.5%) was higher. Mobile population TB control in Shenzhen was the key and difficult.

Objective To understand the situation of drug resistance( DR) and multi-drug resistance( MDRTB) tuberculosis in Shenzhen and provide scientific evidence for TB control in Shenzhen. Methods According to drug resistance TB guidelines issued by WHO/IUALD, all new smear positive cases and.new registered retreatment smear positive cases in 2005 and 2009 were included in the surveillance. A total of 1856 strains of mycobacterium tuberculosis were isolated and drug susceptibility test were performed with the proportional method. Results In 2005, the overall DR rate was 18. 3% , 17. 2% and 31. 3% for initial and acquired DR respectively, overall MDR rate was 4. 74% ,3.25% and 21.9% respectively for initial and acquired MDR. In 2009, the overall DR rate was 17.4% , 16% and 39. 3%for initial and acquired DR respectively,overall MDR rate was 3.8% ,3.02% and 16.4% respectively for initial and acquired MDR. In 2005,2009, the rates of acquired DR and acquired MDR were significantly higher than the rates of initial DR and initial MDR. Conclusion The incidence of TB drug resistance in Shenzhen was high and merits attention.