Diabetic kidney disease （DKD） is one of the more common chronic kidney diseases，and its causes are complex. DKD is very easy to progress to end-stage renal disease，and the current therapeutic effect still needs to be improved. As an important excretive organ of the human body， the kidney has physiological functions such as discharging metabolic waste， regulating fluid balance， and maintaining the stability of the body's internal environment. These highly complex biochemical processes all depend on the energy support provided by mitochondria. Mitochondrial dysfunction is a key factor causing kidney injury， and the imbalance of mitochondrial homeostasis is an important link leading to mitochondrial dysfunction. The occurrence and development of DKD are often accompanied by the imbalance of mitochondrial homeostasis in renal cells. Mitochondrial autophagy， as a means of regulating mitochondrial homeostasis， is very important for the prevention and treatment of DKD. The PTEN-induced putative kinase 1 （PINK1）/Parkin pathway is one of the most classical pathways to regulate mitochondrial autophagy. Recent studies have found that some drugs can regulate the PINK1/Parkin signaling pathway to target mitochondrial homeostasis and exert renoprotective effects. In particular， traditional Chinese medicine has a significant effect on early and middle stage DKD by regulating PINK1/Parkin pathway-mediated mitochondrial autophagy. This article discussed the mechanism of PINK1/Parkin pathway in mitochondrial autophagy and DKD and reviewed the effect of PINK1/Parkin pathway-mediated mitochondrial autophagy on DKD. At the same time， it explored the therapeutic effect of traditional Chinese and western medicine on DKD mediated by PINK1/Parkin-mediated mitochondrial autophagy， aiming to broaden the ideas of traditional Chinese and western medicine for the prevention and treatment of DKD from the perspective of PINK1/Parkin regulating mitochondrial autophagy.

Diabetic kidney disease （DKD） is one of the more common chronic kidney diseases，and its causes are complex. DKD is very easy to progress to end-stage renal disease，and the current therapeutic effect still needs to be improved. As an important excretive organ of the human body， the kidney has physiological functions such as discharging metabolic waste， regulating fluid balance， and maintaining the stability of the body's internal environment. These highly complex biochemical processes all depend on the energy support provided by mitochondria. Mitochondrial dysfunction is a key factor causing kidney injury， and the imbalance of mitochondrial homeostasis is an important link leading to mitochondrial dysfunction. The occurrence and development of DKD are often accompanied by the imbalance of mitochondrial homeostasis in renal cells. Mitochondrial autophagy， as a means of regulating mitochondrial homeostasis， is very important for the prevention and treatment of DKD. The PTEN-induced putative kinase 1 （PINK1）/Parkin pathway is one of the most classical pathways to regulate mitochondrial autophagy. Recent studies have found that some drugs can regulate the PINK1/Parkin signaling pathway to target mitochondrial homeostasis and exert renoprotective effects. In particular， traditional Chinese medicine has a significant effect on early and middle stage DKD by regulating PINK1/Parkin pathway-mediated mitochondrial autophagy. This article discussed the mechanism of PINK1/Parkin pathway in mitochondrial autophagy and DKD and reviewed the effect of PINK1/Parkin pathway-mediated mitochondrial autophagy on DKD. At the same time， it explored the therapeutic effect of traditional Chinese and western medicine on DKD mediated by PINK1/Parkin-mediated mitochondrial autophagy， aiming to broaden the ideas of traditional Chinese and western medicine for the prevention and treatment of DKD from the perspective of PINK1/Parkin regulating mitochondrial autophagy.

Renal fibrosis （RF） is the primary pathological feature of chronic kidney disease （CKD） progression to end-stage renal disease （ESRD）， with glomerulosclerosis and tubulointerstitial fibrosis as core pathological manifestations. It involves abnormal accumulation of extracellular matrix （ECM） components such as collagen and fibronectin， ultimately leading to structural destruction and functional losses of the kidneys. Sirtuins （SIRTs）， a class of nicotinamide adenine dinucleotide （NAD+）-dependent deacetylases， play crucial roles in cellular metabolism， oxidative stress responses， inflammation regulation， and cell survival. In mammals， there are seven distinct SIRT members （SIRT1 to SIRT7）， which collectively ameliorate RF progression through multiple pathways. These include regulating the transforming growth factor （TGF）-β/Smad signaling pathway， suppressing inflammatory responses， reducing oxidative stress， modulating mitochondrial and autophagy functions， and promoting fatty acid oxidation. In recent years， traditional Chinese medicine （TCM） and its active components have demonstrated significant potential in activating or modulating the SIRT protease family and its regulatory networks to ameliorate RF in a multi-target and holistic manner. However， systematic reviews in this area remain lacking. This article elucidates the mechanisms by which the SIRT protease family regulates RF and reviews the latest research advances in TCM modulation of SIRTs for the prevention and treatment of RF， aiming to provide new insights and approaches for the TCM treatment of RF.

Objective:To explore the genetic characteristics of a child with 18q terminal deletion syndrome.Methods:Clinical data of a child presented at the Lianyungang Maternal and Child Health Care Hospital on July 20, 2023 was collected. Peripheral blood sample from the child was subjected to G-banded chromosomal karyotyping and chromosomal microarray analysis (CMA). Relevant literature was searched from CNKI, WanFang and PubMed databases over the past decade (from November 1, 2013 to November 1, 2023) using keywords including "18q-syndrome", "18q deletion syndrome" and "18q terminal deletion". This study was approved by Medical Ethics Committee of the Lianyungang Maternal and Child Health Care Hospital (Ethics No. LYG-MER2021017).Results:The child, a 4-year-and-6-month-old female, had manifested short stature, intellectual disability, distinctive facial features, aortic regurgitation, auditory canal atresia, and white matter lesions. She was found to have a karyotype of 46, XX, del(18)(q21), whilst the result of CMA was arr[GRCh37]18q21.33q23(60065821_77317445)×1. Both of her parents were found to have a normal karyotype. Literature review has retrieved 7 reports which involved 11 cases with a terminal 18q23 deletion. The phenotypes of cardiac abnormalities have been diverse, with pulmonary stenosis, atrial septal defect and ventricular septal defect being most common.Conclusion:The 18q terminal deletion probably underlay the multiple congenital anomalies and mental retardation in this child.

AIM: To investigate the effect of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics/pharmacodynamics (PK/PD) of daptomycin in critically ill patients. METHODS: Twenty four patients with severe infection in our hospital were randomly selected and divided into ECMO group and non ECMO group. They were intravenously injected with daptomycin 500 mg qd. After the drug reached the stability statement, venous blood was collected at different time points before and after the infusion. The plasma drug concentration was measured and the pharmacokinetic parameters were calculated. The probability target acquisition (PTA) and the cumulative fraction response (CFR) were calculated by Monte Carlo simulation. RESULTS: After dosing, the main pharmacokinetic parameters in ECMO and non-ECMO group were calculated and listed as follows: C

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for the detection of fetal anomalies among pregnant women with advanced age. METHODS: CMA results of 562 cases, in addition with the outcome of pregnancy and neonatal follow-up were reviewed. RESULTS: Among the 562 amniotic fluid samples, 73 cases (12.99%) of fetal chromosomal abnormalities were detected, which included 21 cases (3.73%) of chromosomal aneuploidies and 52 cases (9.25%) of copy number variations (CNVs). The latters included 27 cases of pathological CNVs (4.80%), 4 cases of possible pathogenic CNVs (0.71%) and 42 cases of variants with unknown clinical significance (7.47%). Compared with those under 35, the detection rate of fetal chromosomal aneuploidies for women with advanced age was higher under the indications of voluntary test, abnormal ultrasonic structures, abnormal ultrasonic soft index and risks indicated by non-invasive prenatal testing (NIPT). No significant difference was found in the detection rate of CNVs between those ≥35 and <35 and between those with age factor only and with additional indications (P> 0.05). 552 cases (98.22%) of pregnant women have completed the followed up. Among 31 women with pathological and possible pathogenic fetal CNVs detected by CMA, 25 had terminated the pregnancy, 6 (19.35%) have delivered without obvious abnormality. 41 pregnant women with fetal CNVs of unknown clinical significance have completed the follow up, among whom 3 had terminated the pregnancy, 1 newborn was found with malformation after birth, which yielded an abnormal pregnancy rate of 9.76%. 480 pregnant women with negative CMA results have completed the follow up, among whom 5 (1.04%) had abnormal pregnancy or delivered a child with birth defect. CONCLUSION There is a certain difference between the outcome of pregnancy predicted by CMA testing and the actual outcome. The pregnancies with fetal CNVs with unknown clinical significance detected by CMA have a high adverse rate, which should attract clinical attention. CMA testing should be recommended for pregnant women with advanced age regardless of whether they have other symptoms. CMA combined with other detection methods is the trend for prenatal diagnosis.
Aneuploidy ; Chromosome Aberrations ; DNA Copy Number Variations ; Female ; Humans ; Infant, Newborn ; Maternal Age ; Oligonucleotide Array Sequence Analysis ; Pregnancy ; Prenatal Diagnosis

Objective:To evaluate the diagnostic efficiency and safety of endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)in lymph node staging of non-small cell lung cancer(NSCLC)in elderly patients.Methods:Thirty-five patients aged ≥70 years and 58 patients aged 60-69 years with NSCLC receiving EBUS-TBNA in our hospital from March 2015 to December 2018 were enrolled.All patients underwent EBUS for all visible mediastinal and hilar lymph nodes, and those with enlarged lymph nodes(short axis ≥6 mm)were further examined with TBNA.The diagnostic efficiency and safety of EBUS-TBNA were analyzed.Results:The sensitivity of EBUS-TBNA was 0.94, the specificity was 1.00, the Yoden index was 0.94, the positive predictive value was 1.00, and the negative predictive value was 0.82.Tumor staging was changed in 20 patients after EBU-TBNA, resulting in changes in assessment on tumor resectability in 5 cases.EBUS-TBNA had excellent agreement with postoperative pathology in evaluating resectability(Kappa=0.95). The sensitivity and specificity were 1.00 and 0.97, respectively.The incidence of complications of EBUS-TNBA was 6.5%.The elderly group had a worse performance status( P<0.05)compared with the control group, but the complication rates(5.7% vs 6.9%, P>0.05)were similar between the two groups. Conclusions:EBUS-TBNA is highly effective and safe in the diagnosis of NSCLC in patients aged 70 and older.

Objective:To investigate the role of Linc00339 in the development of triple-negative breast cancer and its related molecular mechanisms.Methods:The expression levels of Linc00339 in human normal breast epithelial cells and breast cancer cells were detected by real time fluorescent quantitative polymerase chain reaction (qRT-PCR). The Linc00339 was overexpressed in MDA-MB-231 cells by plasmid transfection test; the activity of MDA-MB-231 cells was detected by methyl thiazolyl tetrazolium (MTT) method; the adhesion, invasion and migration ability of MDA-MB-231 cells were detected by adhesion test and transwell test respectively; Western blot was used to detect the expression of APC and Wnt/β-catenin signaling pathway-related proteins in MDA-MB-231 cells. qRT-PCR was used to detect the expression of miRNA-135a, miRNA-135b and miRNA-138 in MDA-MB-231 cells. MDA-MB-231 cells were successfully transfected into nude mice to establish tumor-bearing nude mice model. The volume and weight of tumor were observed and measured. The expression levels of APC, Wnt/β - catenin signaling pathway related proteins were detected by Western blot, and the expression levels of miRNA-135a, miRNA-135b and miRNA-138 were detected by qRT-PCR.Results:Compared with the normal breast epithelial cell group (Hs578Bst), the expression level of Linc00339 in breast cancer cell lines (MCF-7, MDA-MB-468, MDA-MB-231) was significantly up-regulated, especially MDA-MB-231. The results of transfection experiments showed that the expression level of Linc00339 and cell viability were significantly up-regulated in the Linc00339 group compared with the pcDNA3.1 group. The overexpression of Linc00339 significantly increased the proliferation, adhesion and migration and invasion ability of MDA-MB-231 cells, as well as increased the volume and weight of tumor mass in tumor-bearing nude mice. Western blot results showed that Linc00339 overexpression can down-regulate APC protein expression and up-regulate Wnt/β-catenin signaling protein expression. Meanwhile, qRT-PCR results indicated Linc00339 overexpression can up-regulate miRNA-135b expression levels without affecting miRNA-135a and miRNA-138.Conclusions:This study demonstrated that Linc00339 may promote the development and progression of triple-negative breast cancer via the miR-135b/APC-mediated Wnt/β-catenin signaling pathway.

Low-level laser therapy (LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals (12-33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group (LG) or a placebo group (PG) (1:1). The LG received LLLT (810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale (NRS) of pain, pressure pain thresholds (PPTs), cold detection thresholds (CDTs), warmth detection thresholds (WDTs), cold pain thresholds (CPTs), and heat pain thresholds (HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance (ANOVA). The NRS pain scores were significantly lower in the LG group (P = 0.01). The CDTs, CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG (P < 0.033). The parameters tested also showed significantly less sensitivity on the non-treatment side of the LG compared to that of the PG (P < 0.043). There were no differences between the groups for any quantitative sensory testing (QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment. Further clinical applications are suggested.
Adolescent ; Adult ; Female ; Humans ; Low-Level Light Therapy ; methods ; Male ; Pain Management ; Pain Measurement ; Pain Threshold ; physiology ; Tooth Movement Techniques ; adverse effects ; Toothache ; etiology ; radiotherapy ; Treatment Outcome ; Young Adult

Bipolar Disorder ; genetics ; Genome-Wide Association Study ; Genomics ; methods ; Humans