OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

Phosphodiesterase 4 (PDE4) is an important member of the phosphodiesterase enzyme family that specifically catalyzes the hydrolysis of cyclic adenosine monophosphate (cAMP), activates the downstream phosphorylation cascade pathway by altering cAMP concentration, and is strongly associated with multiple diseases. Inhibition of PDE4 is clinically investigated as a therapeutic strategy in a broad range of disease areas, including respiratory system diseases, autoimmune disorders, central nervous system diseases, and dermatological conditions. However, the incidence of adverse reactions such as nausea and vomiting is relatively high in the marketed PDE4 inhibitors, which has stalled their clinical development. In this review, we provide an overview of the clinical progression and safety issues of the marketed PDE4 inhibitors. We also review the main causes underlying PDE4-mediated adverse effects by combining the structural analysis of the PDE4 protein, the mechanism of action of PDE4 inhibitors, and the related side effect mechanism research, aiming to provide a reference for the development of safe and effective PDE4 inhibitors.

OBJECTIVE: To observe the skin surface microcirculation of acupoints of conception vessel, governor vessel and thoroughfare vessel in patients with primary dysmenorrhea using laser speckle contrast imaging (LSCI), and provide acupoint selection basis of acupuncture-moxibustion for primary dysmenorrhea. METHODS: Ninety-nine healthy female college students with regular menstrual cycles (normal group) and 94 female college students with primary dysmenorrhea (dysmenorrhea group) were recruited. Before menstrual period, on the first day of menstruation, and on the third day after menstruation, LSCI was used to observe the surface microcirculation at the abdominal acupoints of conception vessel, i. e. Yinjiao (CV 7), Qihai (CV 6), Shimen (CV 5), Guanyuan (CV 4), Zhongji (CV 3) and Qugou (CV 2), acupoints of thoroughfare vessel, i. e. Huangshu (KI 16), Zhongzhu (KI 15), Siman (KI 14), Qixue (KI 13), Dahe (KI 12), Henggu (KI 11) and acupoints of lumbosacral region of governor vessel, i. e. Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3), Yaoshu (GV 2) as well as two non-acupoints. RESULTS: Before menstrual period, there was no significant difference in the surface blood perfusion of the acupoints between the dysmenorrhea group and the normal group (P>0.05). On the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) and right Huangshu (KI 16) in the dysmenorrhea group was higher than that in the normal group (P<0.05, P<0.01). On the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) in the dysmenorrhea group was lower than that in the normal group (P<0.05). CONCLUSION In patients with primary dysmenorrhea, on the first day of menstruation, the surface blood perfusion of Xuanshu (GV 5), Mingmen (GV 4), Yaoyangguan (GV 3) of governor vessel, and the right Huangshu (KI 16) of thoroughfare vessel is increased, while on the third day after menstruation, the surface blood perfusion of the right Henggu (KI 11) of thoroughfare vessel is decreased. These findings might provide a basis for acupoint selection in the acupuncture-moxibustion treatment of primary dysmenorrhea.
Humans ; Female ; Microcirculation ; Dysmenorrhea/therapy* ; Menstrual Cycle ; Acupuncture Points ; Acupuncture Therapy

OBJECTIVE: To explore 3.0T MRI accurate measurement of knee cartilage thickness in healthy youth provides reliable anatomical parameters for quantitative diagnosis of osteoarthritis and accurate osteotomy of joint replacement. METHODS: From January 2013 to December 2013, 30 healthy young volunteers including 14 males and 16 females with an average age of (25.8±2.4) years old ranging from 22 to 33 years were recruited in Changchun, Jilin Province, and a 3.0T MRI scan was performed on the bilateral knee joints of each volunteer. The cartilage thickness was measured on the lateral femoral condyle (LFC), medial femoral condyle (MFC), lateral tibial plateau (LTP) and medial tibial plateau (MTP). RESULTS: In four regions of the knee joint:LFC, MFC, LTP and MTP, whether young men or women, there was no significant difference in cartilage thickness between the left and right knee joints (P>0.05). There were significant differences in knee cartilage thickness between healthy young men and women (P<0.05). In the same sex group, LFC cartilage thickness was thinner in the middle, thicker in front and rear;MFC cartilage thickness was the thinnest in front and gradually thickening from the front to the rear; LTP cartilage thickness was thickest in the middle, second in the rear and thinnest in the front;MTP cartilage thickness was the thinnest in the front, was relatively uniform in the middle and rear and thicker than that in the front. CONCLUSION In Northeast China, among healthy adults aged 22 to 33, gender difference may be an important factor in the difference of cartilage thickness in various regions of the knee joint. Regardless of whether male or female healthy young people, the cartilage thickness of the entire knee joint is unevenly distributed, but there is no significant difference in cartilage thickness in the same area between the left and right knee joints.
Adult ; Adolescent ; Humans ; Male ; Female ; Young Adult ; Cartilage, Articular/diagnostic imaging* ; Knee Joint/surgery* ; Osteoarthritis ; Magnetic Resonance Imaging ; Femur

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.
Animals ; Mice ; Antiviral Agents/pharmacology* ; COVID-19 ; Hepatitis B virus ; Interferon Type I/metabolism* ; SARS-CoV-2/drug effects* ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/antagonists & inhibitors*

In order to establish the probabilistic risk assessment method for heavy metals and harmful elements in line with the characteristics of traditional Chinese medicine (TCM) and provide guidance for the safe use of TCM, the contents of lead (Pb), cadmium (Cd), arsenic (as), mercury (Hg) and copper (Cu) in 21 batches of Plantago asiatica L. were determined by inductively coupled plasma mass spectrometry (ICP-MS). By the comprehensive use of investigation of TCM consumption pattern and Monte Carlo simulation technology, the non-carcinogenic and carcinogenic health risks of heavy metals and harmful elements in TCM were assessed by hazard quotient (HQ) and cancer risk (CR), respectively. The greatest risk contributors were screened through sensitivity analysis. The results revealed that the mean contents of Pb, Cd, As, Hg and Cu in Plantago asiatica L. were 9.01, 0.28, 3.83, 0.01 and 12.82 mg·kg^-1, respectively. The P95, P99 and maximum values of HQ for males were 1.41, 2.83 and 10.97 mg·kg^-1, respectively. The P95, P99 and maximum values of HQ for females were 1.27, 2.63 and 9.80 mg·kg^-1, respectively. The P95, P99 and maximum values of HI for males were 1.44, 2.85 and 11.0 mg·kg^-1, respectively. The P95, P99 and maximum values of HI for females were 1.29, 2.66 and 10.0 mg·kg^-1, respectively. The P99 and maximum values for CR_As and total carcinogenic risk (TCR) were greater than 10^-4 for both men and women. The risk assessment results indicated that the non-carcinogenic and carcinogenic health risks of high exposure population caused by arsenic exposure are needed to be concern. The results of sensitivity analysis showed that the exposure frequency of TCM and the arsenic concentrations in Plantago asiatica L. were the main risk contributors. Based on Monte Carlo simulation technology and considering the characteristics of TCM, this study puts forward the first example of probabilistic risk assessment of heavy metals and harmful elements in Chinese herbal medicine, which provides a novel perspective for health risk assessment of heavy metals in TCM.

Developmental dysplasia of the hip (DDH) is a major cause of hip arthritis and ultimately total hip arthroplasty. Due to the dysplastic acetabulum, how to place the acetabular cup becomes a challenge in acetabular reconstruction for such patients. Especially in the acetabula classified as Crowe typeⅡand type Ⅲ, the dislocation of the femoral head causes bone defects above the true acetabulum, which will affect the stability of the acetabular cup when the acetabular reconstruction is performed at the true acetabulum. Many acetabular reconstruction methods such as bone grafting, the use of small acetabular cups, socket medialization technique, and high hip center technique are used to increase the host bone coverage of the cup. However, each method has its own shortcomings that can not be ignored so that there is no unified conclusion on the acetabular reconstruction methods for Crowe typeⅡand type Ⅲ hip dysplasia. This article summarized and evaluated various reconstruction methods in combination with the acetabular morphology of DDH, and put forward the research direction in the future.
Acetabulum/surgery* ; Arthroplasty, Replacement, Hip ; Developmental Dysplasia of the Hip ; Hip Dislocation/surgery* ; Hip Dislocation, Congenital/surgery* ; Hip Prosthesis ; Humans ; Treatment Outcome

Early orthodontic treatment of malocclusion is becoming the hot topic in orthodontics. The characteristics of craniofacial and dental growth and development are very important in early orthodontics. The article focuses on early correction of malocclusion and normal growth and development recovery.
Dental Care ; Growth and Development ; Humans ; Malocclusion/therapy* ; Orthodontics ; Orthodontics, Corrective

In recent years, the application of artificial intelligence technology in the field of orthodontics has gradually increased, and deep learning, as a hot direction, has also been rapidly applied in the detection, evaluation, diagnosis, prediction and effect evaluation. At present, deep learning research has the advantages of high efficiency and accuracy, but it also has limitations such as weak interpretability and insufficient data volume. This paper reviewed the proposal and development of deep learning, the application in orthodontic diagnosis and treatment, as well as the limitations and countermeasures of the popularization, and prospect of the future research.
Humans ; Artificial Intelligence ; Deep Learning ; Dental Care ; Forecasting ; Orthodontics