In the context of China's aging population, the issue of urinary incontinence among the elderly is becoming increasingly severe.Urinary incontinence not only significantly impacts patients' quality of life, but also imposes a substantial economic burden and psychological stress.This article explores the challenges and prospects of the early intervention of elderly urinary incontinence in China, including improving early diagnosis rates, enhancing patients' self-management abilities, and early screening and prevention for high-risk groups.With the advancement of technology and medical innovations, digital self-management tools offer new possibilities for managing urinary incontinence, helping patients to better control their condition, especially when medical resources are limited.Furthermore, this article calls for greater attention from all sectors of the society to address elderly urinary incontinence and promote the implementation of more systematic research and management strategies to improve the quality of life for China's elderly population.

Objective To knock out cdc42 gene in zebrafish using CRISPR/Cas9 technology,and investigate the effect of cdc42 on early osteochondral development.Methods After the conservation of cdc42 gene sequence of different species was analyzed by multiple sequence alignment analysis,guide RNA of cdc42 gene was designed,and cdc42 knockout zebrafish was constructed by CRISPR/Cas9 technology.The expression pattern of cdc42 was detected by whole-mount in situ hybridization,and the chondrogenesis phenotype was observed by transgenic labeled fish line Tg(col2a1a:GFP),and vertebral mineralization was observed by alizarin red staining.Results Multiple sequence alignment analysis showed that cdc42 was highly conserved in human,mouse and zebrafish,and in situ hybridization results showed that cdc42 was expressed in a variety of tissues in the head and whole body,including mandibular cartilage.With the aid of guide RNA of cdc42,cdc42 knockout zebrafish was successfully constructed by CRISPR/Cas9 technology.The cdc42 mutants exhibited shortened body length(P＜0.01)and delayed cranial development at 3 d post fertilization,with small heads and eyes(P＜0.01),as well as delayed mandibular development.The Tg(col2a1a:GFP)zebrafish showed that the mutants presented abnormal morphology of Meckel's cartilage and ceratohyal cartilage cells,with disordered arrangement of chondrocytes and increased angle and decreased length in ceratohyal cartilage(P＜0.01).The homozygous mutants died at 10～13 d after fertilization.The results of alizarin red staining suggested delayed vertebral mineralization and reduced endochondral ossification of the mutants.Conclusion CRISPR/Cas9 technology successfully knocks out the cdc42 gene in zebrafish,resulting in delayed development of jaw cartilage,delayed mineralization of the vertebrae,and decreased endochondral ossification.

Objective The study aimed to investigate the impact of rare earth elements(REEs)exposure on pregnancy outcomes of in vitro fertilization-embryo transfer(IVF-ET)by analyzing samples from spouses. Methods A total of 141 couples were included.Blood and follicular fluid from the wives and semen plasma from the husbands,were analyzed for REEs using inductively coupled plasma mass spectrometry(ICP-MS).Spearman's correlation coefficients and the Mann-Whitney U test were used to assess correlations and compare REE concentrations among three types of samples,respectively.Logistic models were utilized to estimate the individual REE effect on IVF-ET outcomes,while BKMR and WQS models explored the mixture of REE interaction effects on IVF-ET outcomes. Results Higher La concentration in semen(median 0.089 ng/mL,P=0.03)was associated with a lower fertilization rate.However,this effect was not observed after artificial selection intervention through intracytoplasmic sperm injection(ICSI)(P=0.27).In semen,the REEs mixture did not exhibit any significant association with clinical pregnancy. Conclusion Our study revealed a potential association between high La exposure in semen and a decline in fertilization rate,but not clinical pregnancy rate.This is the first to report REEs concentrations in follicular fluid with La,Ce,Pr,and Nd found at significantly lower concentrations than in serum,suggesting that these four REEs may not accumulate in the female reproductive system.However,at the current exposure levels,mixed REEs exposure did not exhibit reproductive toxicity.

Objective:To explore the clinical and imaging characteristics of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) caused by mitochondrial DNA 14453G>A (m.14453G>A) mutation.Methods:A case of MELAS caused by m.14453G>A mutation in the First Affiliated Hospital of Harbin Medical University on October 12, 2021 was reported. At the same time, the reported cases of MELAS and Leigh syndrome (LS) caused by the m.14453G>A mutation were reviewed. This enabled a comprehensive summarization, analysis, and comparison of these cases.Results:The patient was a female. She has suffered from the disease since 13-year old with seizures, accompanied by the disturbance of mood and the loss of memory. Brain magnetic resonance imaging findings consisted of lesions in frontal, parietal, occipital, temporal lobe and cerebellar. The patient was initially considered with autoimmune encephalitis and posterior reversible encephalopathy syndrome. Since direct sequencing of the complete mitochondrial genome from blood of the patient revealed m.14453G>A mutation in ND6 gene, and the mutation rate was 17.0%, the patient eventually diagnosed with MELAS based on clinical manifestations, imaging examinations, and genetic testing results. Using "m.14453G>A" as the search term, the relevant literature in China and abroad was retrieved and those with complete clinical data were identified. A total of 11 cases of m.14453G>A mutation including this case were reported, of whom 5 patients were diagnosed as MELAS, and 6 patients were diagnosed as LS. Among the 11 patients, those being adolescent or adult and with lesions in the cortex and subcortical white matter were probably be MELAS; those being infant or young child and with lesions in basal ganglia, thalamus and brainstem could be LS. Conclusions:Mitochondrial disease caused by m.14453G>A gene mutation shows a great heterogeneity, which can cause MELAS and LS. The clinical phenotype of the m.14453G>A mutation may be related to the age of onset and lesion′ s location.

Objective:To investigate the serum 25-hydroxyvitamin D [25(OH)D] level in patients with Graves' disease (GD) and its correlation with thyrotropin receptor antibody (TRAb) and bone metabolism markers.Methods:A total of 124 patients with newly diagnosed or relapsed GD were selected and divided into three groups according to serum 25(OH)D level, namely vitamin D deficiency group with 25(OH)D <12 μg/L, vitamin D insufficiency group with 25(OH)D of 12 to 20 μg/L, and vitamin D sufficiency group with 25(OH)D ≥ 20 μg/L. The levels of serum 25(OH)D, TRAb, type I procollagen N-terminal pro-peptide (PINP), type I collagen cross-linked C-terminal peptide (S-CTX), parathyroid hormone (PTH), total triiodothyronine (TT 3), total thyroxine (TT 4) and thyroid-stimulating hormone (TSH) were measured in all patients, and the differences of these biochemical indices were compared across groups. Oneway analysis of variance or Kruskal-Wallis test was used for comparison between groups, and Pearson or Spearman correlation analysis was applied for correlation test. Results:The levels of serum TT 3, TT 4, PINP, and S-CTX significantly increased ( P < 0.01) and the level of phosphorus (P) decreased ( P < 0.01) with the decreased vitamin D levels. The levels of PTH and calcium (Ca) were significantly lower in the vitamin D sufficiency group compared with the vitamin D insufficiency group and vitamin D deficiency group ( P < 0.01). Correlation analysis showed that serum 25(OH)D level was negatively correlated with the levels of TT 3, TT 4, PINP, S-CTX, PTH and Ca ( P < 0.01), and positively correlated with the levels of P and TSH ( P < 0.01). Conclusions:Decreased serum 25(OH)D level is closely related with increased bone turnover, PTH, and thyroid hormone levels in patients with GD, but not related with TRAb. Thyroid hormone levels have a certain predictive value regarding vitamin D deficiency in GD patients. It is necessary to monitor the vitamin D levels in patients with GD and provide vitamin D supplementation to reduce the incidence of osteoporosis, improve the effectiveness of antithyroid treatment and reduce the recurrence of GD.

OBJECTIVES: To explore the physicochemical characteristics and biocompatibility of calcium peroxide (CPO)-loaded polycaprolactone (PCL) microparticle. METHODS: The CPO/PCL particles were prepared. The morphology and elemental distribution of CPO, PCL and CPO/PCL particles were observed with scanning electron microscopy and energy dispersive spectroscopy, respectively. Rat adipose mesenchymal stem cells were isolated and treated with different concentrations (0.10%, 0.25%, 0.50%, 1.00%) of CPO or CPO/PCL particles. The mesenchymal stem cells were cultured in normal media or osteogenic differentiation media under the hypoxia/normoxia conditions, and the amount of released O₂ and H₂O₂ after CPO/PCL treatment were detected. The gene expressions of alkaline phosphatase (ALP), Runt-associated transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalcin (OCN) were detected by realtime RT-PCR. SD rats were subcutaneously injected with 1.00% CPO/PCL particles and the pathological changes and infiltration of immune cells were observed with HE staining and immunohistochemistry at day 7 and day 14 after injection. RESULTS: Scanning electron microscope showed that CPO particles had a polygonal structure, PCL particles were in a small spherical plastic particle state, and CPO/PCL particles had a block-like crystal structure. Energy dispersive spectroscopy revealed that PCL particles showed no calcium mapping, while CPO/PCL particles showed obvious and uniform calcium mapping. The concentrations of O₂ and H₂O₂ released by CPO/PCL particles were lower than those of CPO group, and the oxygen release time was longer. The expressions of Alp, Runx2, Ocn and Opn increased with the higher content of CPO/PCL particles under hypoxia in osteogenic differentiation culture and normal culture, and the induction was more obvious under osteogenic differentiation conditions (all P<0.05). HE staining results showed that the muscle tissue fibers around the injection site were scattered and disorderly distributed, with varying sizes and thicknesses at day 7 after particle injection. Significant vascular congestion, widened gaps, mild interstitial congestion, local edema, inflammatory cell infiltration, and large area vacuolization were observed in some tissues of rats. At day 14 after microparticle injection, the muscle tissue around the injection site and the tissue fibers at the microparticle implantation site were arranged neatly, and the gap size was not thickened, the vascular congestion, local inflammatory cell infiltration, and vacuolization were significantly improved compared with those at day 7. The immunohistochemical staining results showed that the expressions of CD3 and CD68 positive cells significantly increased in the surrounding muscle tissue, and were densely distributed in a large area at day 7 after particle injection. At day 14 of microparticle injection, the numbers of CD3 and CD68 positive cells in peripheral muscle tissue and tissue at the site of particle implantation were lower than those at day 7 (all P<0.01). CONCLUSIONS CPO/PCL particles have good oxygen release activity, low damage to tissue, and excellent biocompatibility.
Rats ; Animals ; Osteogenesis ; Core Binding Factor Alpha 1 Subunit ; Rats, Sprague-Dawley ; Hydrogen Peroxide/pharmacology* ; Cell Differentiation ; Oxygen ; Hypoxia ; Cells, Cultured

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Overexpressing of ATP-binding cassette (ABC) transporters is the essential cause of multidrug resistance (MDR), which is a significant hurdle to the success of chemotherapy in many cancers. Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR. Olmutinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), which has been approved in South Korea for advanced EGFR T790M-positive non-small cell lung cancer (NSCLC). Here, we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin (DOX) and rhodamine 123 (Rho 123) in ABC transporter subfamily G member 2 (ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [I]-iodoarylazidoprazosin (IAAP). However, olmutinib neither altered ABCG2 expression at protein and mRNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly, olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients.

OBJECTIVETo evaluate the rationality of T staging of gastric cancer with transverse mesocolon invasion.

METHODSData of 808 patients with primary gastric cancer undergoing surgical treatment was screened from the Data base of Gastric Cancer of Sun Yat-sen University, from April 1996 to October 2009. According to the information of transverse mesocolon invasion, all cases were divided into groups NOI (T4a stage, non organ invasion, n = 638), NTMI (T4b stage, non transverse mesolon invasion, with organ invasion, n = 126), and TMI (transverse mesocolon invasion, n = 44). The clinicopathological features, surgical procedure and prognosis were compared among the three groups.

RESULTSNo significant difference was found in gender, age, lymph node metastasis, hepatic metastasis, tumor's Borrmann type, histological type, differentiation degree, value of serum CEA among the 3 groups (all P > 0.05). In the groups NOI, NTMI and TMI, the ratio of mean tumor diameter ≥ 5 cm was 39.0% (249/638), 61.1% (77/126) and 54.5% (24/44), respectively; the ratio of distal metastasis was 11.9% (76/638), 30.2% (38/126) and 43.2% (19/44), respectively; the ratio of peritoneal metastasis was 8.2% (52/638), 26.2% (33/126) and 38.6% (17/44), respectively; the ratio of TNM IV stage was 25.4% (162/638), 84.7% (107/126) and 93.7% (41/44), respectively; and the ratio of radical resection was 92.0% (587/638), 69.8% (88/126) and 77.3% (34/44), respectively; all with significant differences (P < 0.01), and the results of pairwise comparisons (Bonferroni correction, significant level α = 0.05/3 = 0.0167) showed that these parameters were significantly different between groups NOI and TMI (P < 0.0167), but non-significant between groups NTMI and TMI (P > 0.0167). The median survival time was 42.0, 16.4 and 19.0 months in the groups NOI, NTMI and TMI, respectively (P < 0.01), and the results of pairwise comparison showed that the prognosis were significant different between the groups NOI and TMI (P < 0.01), but non-significant between the groups NTMI and TMI (P > 0.05). In the cases who received radical resection, the median survival time was 47.9, 23.5 and 21.4 months in the groups NOI, NTMI and TMI, respectively (P < 0.01), and the results of pairwise comparison showed that the prognosis was significantly different between the groups NOI and TMI (P < 0.05), but not significant between groups NTMI and TMI (P > 0.05).

CONCLUSIONSThe tumor size, distal meatastasis, peritoneal metastasis, TNM stage, surgical procedure and prognosis of gastric cancer with transverse mesocolon invasion are similar to that of T4b gastric cancer, but are significantly different from that of T4a gastric cancer. Gastric cancer with transverse mesocolon invasion should be reclassified as T4b stage.

Colonic Neoplasms ; pathology ; Humans ; Mesocolon ; pathology ; Neoplasm Staging ; Stomach ; pathology ; Stomach Neoplasms ; pathology

OBJECTIVETo investigate the expression and significance of miR-125a and anti-apoptotic protein Mcl-1 in intestinal tissue after massive small bowel resection in intestinal adaptation.

METHODSSprague-Dawley rats (54 male rats, 8-week old) were divided into 3 groups randomly, including two control groups. Rats in the experiment group were subjected to 70% massive small bowel resection. Rats in the resection group underwent simple intestinal resection and anastomosis. Rats in the control group underwent laparotomy alone. A 5 cm intestine approximately 1 cm distal to the anastomosis was harvested a week after operation. Expression of Mcl-1 was assessed by immunohistochemistry and real-time PCR was used to detect the expression of miR-125a in intestinal tissue.

RESULTSThe positive expression of Mcl-1 in the experiment group was 18.8%(3/16), significantly lower than that in the control group(76.5%, 13/17) and the resection group (83.33%, 15/18)(both P<0.01). The expression of miR-125a in the experiment group was 1.92, significantly higher than that in the control group (1.01) and the resection group (1.05)(both P<0.01).

CONCLUSIONmiR-125a and anti-apoptotic protein Mcl-1 may play an important role in intestinal adaptation process and they may regulate each other through a certain pathway.

Anastomosis, Surgical ; Animals ; Disease Models, Animal ; Intestine, Small ; metabolism ; surgery ; Male ; MicroRNAs ; metabolism ; Myeloid Cell Leukemia Sequence 1 Protein ; metabolism ; Rats ; Rats, Sprague-Dawley ; Short Bowel Syndrome ; metabolism