Nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) is a cytosolic pattern recognition receptor that recognizes multiple pathogen-associated molecular patterns and damage-associated molecular patterns. It is a cytoplasmic immune factor that responds to cellular stress signals, and it is usually activated after infection or inflammation, forming an NLRP3 inflammasome to protect the body. Aberrant NLRP3 inflammasome activation is reportedly associated with some inflammatory diseases and metabolic diseases. Recently, there have been mounting indications that NLRP3 inflammasomes play an important role in liver injuries caused by a variety of diseases, specifically hepatic ischemia/reperfusion injury, hepatitis, and liver failure. Herein, we summarize new research pertaining to NLRP3 inflammasomes in hepatic injury, hepatitis, and liver failure. The review addresses the potential mechanisms of action of the NLRP3 inflammasome, and its regulation in these liver diseases.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/physiology* ; Animals ; Liver Diseases/metabolism* ; Liver/metabolism* ; Reperfusion Injury/metabolism*

Programmed cell death protein ligand-1(PD-L1)is an important immune checkpoint molecule that plays an important role in regulating the body's immune response.Several clinical studies have shown that the expression level of PD-L1 in tumors is closely related to the efficacy of immune checkpoint inhibitors.Due to the spatial and temporal heterogeneity of tumors,immunohistochemical methods commonly used in clinical practice cannot accurately and comprehensively reflect the ex-pression level of PD-L1 in patients.Given that nuclear-medicine molecular imaging technology can noninvasively,real-time,dy-namically and visually monitor the expression level of PD-L1 in vivo at the molecular level,this article mainly focuses on the re-search of peptide-based radiolabeled molecular probes targeting PD-L1,with the aim of providing guidance for the search of no-vel peptide molecular probes for immunoimaging as well as for the screening of immunotherapy-suitable patients and evaluation of therapeutic efficacy,and other clinical applications.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective:To explore the association of gait speed and cognitive function of the community-dwelling elderly.Methods:From March to December 2021, a total of 1 172 Xinxiang community-dwelling elderly people were investigated by general information questionnaire, mini-mental state examination(MMSE), patient health questionnaire depression scale and 4.6 m gait test. The elderly were divided into five groups based on the quintile grouping of gait speed values, with Q1 group (≤0.76 m/s), Q2 group (0.77-0.88 m/s), Q3 group (0.89-0.98 m/s), Q4 group (0.99-1.11 m/s) and Q5 group (≥1.12 m/s). SPSS 25.0 statistical software was used for descriptive statistics, and binary Logistic regression was used to analyze the influence of gait speed and depression on cognitive impairment of the elderly.Results:The gait speed of community-dwelling elderly people was (0.92±0.22) m/s. The scores of MMSE in Q1-Q5 groups were (24.72±3.67), (26.63±2.90), (26.58±2.66), (27.01±2.45) and (27.18±2.35), respectively, and the cognitive function was significantly different among the five gait speed groups( F=27.92, P<0.05). The results of binary Logistics regression showed that compared with Q1 group, the OR value (95% CI) of cognitive impairment in Q2-Q5 group were 0.475 (0.253-0.893), 0.426 (0.219-0.828), 0.421(0.212-0.826) and 0.371(0.179-0.766), respectively, which indicated that fast walking speed was a protective factor for cognitive function. Old age ( OR=1.096, 95% CI=1.053-1.140) and depression ( OR=14.441, 95% CI=12.670-19.829) were risk factors of cognitive impairment. Conclusion:The gait speed is associated with cognitive function among community-dwelling elderly people, and faster gait speed is a protective factor for cognitive function.

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological disease.How-ever,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains unclear.Here,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH patients.As the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive rela-tionship with the clinical characteristics of BPH patients.Activation of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)heterodimers.Met's anti-proliferative effects were blocked by AMPK inhibitor or YAP1 over-expression in DHT-cultured BPH-1 cells.Our findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

ObjectiveTo systematically review the effects of psychosocial support-related activities on mental health of older adults. MethodsRandomized controlled trails (RCTs) on mental health benefits for older adults were retrieved from PubMed, Web of Science, EBSCO and CNKI, until August, 2022. A systematic review was conducted. ResultsSeven RCTs were included, from Spain, Chile, Canada, Finland, the United Kingdom, South Korea and the United States, mainly from psychiatry, mental health of the elderly and other journals, published after 2017. The subjects aged 60 to 80 years, accounting to 1 258 cases. Psychosocial interventions included Pilates, mindfulness, behavioral activation, cognitive stimulation, daily difficult problem solving training, pain and depression symptom management, health education and guidance, nursing coordination, group exercise (such as circuit training, pedal training or rubber band training), and water sports, etc. The frequency of intervention was 30 to 120 minutes a time, one to nine times a week, and the intensity of the intervention was low to high intensity for four to 64 weeks. Intervention sites included sports venues, community health centres, ageing services, and intervention staff included sports therapists (yoga), psychologists, health professionals, community health services, and health care workers. All interventions were carried out under supervision. The benefits of psychosocial intervention on the mental health of the older adults mainly reflected in the improving cognitive function and self-efficacy, reducing anxiety and depression, improving depressed mood or loneliness, improving sleep quality, increasing sense of social integration and relieving pain and other problems. ConclusionMental health interventions (psychological interventions or support, social interventions or support, psychosocial interventions) and mental health-related interventions (physical activity interventions) benefit older people's mental health, including improving cognitive function, alleviating anxiety and depression, improving sleep quality, and improving quality of life and well-being.

Treatment-resistant depression (TRD) is characterized by a high suicide rate and a high recurrence rate. The effect of the medicine on TRD is not ideal with obvious side effects. Psychotherapy is an important method recommended in many guidelines for the treatment of depression. However, previous studies and clinical applications have paid little attention to the application of psychotherapy in TRD. Therefore, based on recent studies, this paper reviews the effects of psychotherapy on the depressive symptoms, suicide risk, and recurrence risk in TRD. Further, the possible therapeutic mechanisms are discussed, including the improvement of interpersonal function by dealing with early trauma in TRD, therefore alleviating symptoms; intervening in the dysfunctional cognitive pattern of TRD to help them cope with negative life events, therefore reducing stress and depression. Combined with the limitations of existing studies, the following directions can be considered in the future: improving the research quality, measuring behavioral and physiological indicators to further clarify the therapeutic mechanism, identifying ways in which psychotherapy can be combined with other treatments, exploring the group and online therapy to increase accessibility of psychotherapy for TRD.

Objective:To explore the correlation between the length of peripherally inserted central catheter (PICC) through upper and lower extremities of premature infants and their body parameters, and to deduce the formula of the different length of PICC of premature infants, so as to improve the accuracy of the tip of PICC in premature infants.Methods:This study was a retrospective case series study.From January 2016 to September 2021, 758 premature infants with PICC hospitalized in Neonatal Intensive Care Unit (NICU) of Shanghai Children's Hospital were selected retrospectively by convenience sampling. We recorded the sex, gestational age, catheterization age, catheterization vessel location, birth length, length on the day of catheterization, birth weight and weight on the day of catheterization of premature infants. Pearson correlation analysis and simple linear regression were used to find the most relevant body parameters, and formula fitting was carried out to derive the optimal length of PICC for premature infants.Results:In 652 premature infants (86.02%, 652/758) , the PICC was placed in the lower limb vein, and the proportion of great saphenous vein was the highest, accounting for 41.42% (314/758) . Simple linear regression showed that the weight and length had the highest correlation with the optimal length of PICC in the superficial veins of the upper and lower extremities. The formula for the length of PICC with the puncture points of median vein, basilic vein, axillary vein, great saphenous vein, small saphenous vein, popliteal vein and femoral vein was derived.Conclusions:The formula derived from the weight and length of premature infants can provide a reference for clinical measurement of PICC length of premature infants.

Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,68Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95％and radiochemical purity of 97％.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NC1-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.