OBJECTIVE To investigate the effects of total flavonoids from Carthamus tinctorius L. （TFCTL） on hepatic stellate cell （HSC） activation based on the microRNA （miRNA）-204/NUAK family SNF1-like kinase 1 （NUAK1）/Hippo signaling axis， thereby elucidating the potential mechanism underlying their antifibrotic effects. METHODS The HSC-T6 cells were divided into control group， model group， TFCTL low-concentration group （20 μg/mL）， TFCTL medium-concentration group （40 μg/mL）， and TFCTL high-concentration group （60 μg/mL）. Except for control group， the remaining groups were treated with 5 ng/mL of transforming growth factor-β to induce the activation of hepatic stellate cells， followed by the addition of corresponding drug solutions/culture medium and incubation for 24 hours. Cell apoptosis was assessed， the expression levels of α-smooth muscle actin （α-SMA）， type Ⅰ collagen （Collagen Ⅰ） and proteins associated with the Hippo/Yes-associated protein （YAP） pathway [YAP， large tumor suppressor kinase 1 （LATS1）， and mammalian STE20-like kinase 1 （MST1）] were detected. Additionally， cell transfection was used to investigate the activity of the miRNA-204/NUAK1/Hippo signaling axis at both the genetic and protein levels. RESULTS After intervention with TFCTL， the apoptosis rate of HSC-T6 cells and the protein expressions of MST1 （except for the TFCTL high-concentration group） and LATS1 were significantly increased （P＜0.05）， while the protein expressions of α-SMA， CollagenⅠ， and YAP （except for the TFCTL medium-concentration group） were significantly decreased （P＜0.05）. Further results from cell transfection experiments revealed that after transfection with miRNA-204 mimics， the mRNA it’s protein expressions of α-SMA， CollagenⅠ， NUAK1， and YAP in HSC-T6 cells were significantly decreased （P＜0.05）， while the mRNA and protein expressions of LATS1 and the mRNA expression of MST1 were significantly increased （P＜0.05）. Conversely， the results were opposite following transfection with miRNA-204 inhibitors. CONCLUSIONS TFCTL can exert anti-hepatic fibrosis effects by up-regulating the expression of miRNA-204， thereby down- regulating the expressions of NUAK1， inactivating the Hippo/YAP pathway， which in turn suppresses the activation of HSC and promotes their apoptosis.

Objective To investigate the prevalence, distribution characteristics, and influencing factors of mental health problems among the elderly, and to provide a scientific basis for policy-making.  Methods A convenience sampling method was used to investigate depression, anxiety, and cognitive function among permanent residents aged 65 and older at 59 mental health care sites for the elderly in Hubei Province. Multinomial logistic regression was employed to analyze influencing factors. Results The screening rates for depression, anxiety, and cognitive function at critical/high-risk levels among the elderly in Hubei Province were 9.7%, 5.4%, and 12.2%, respectively. Urban elderly had lower risks of depression and cognitive function at critical/high-risk levels compared to rural elderly (OR for critical depression = 0.640, P < 0.001; OR for high-risk depression = 0.595, P = 0.012; OR for critical cognitive function = 0.448, P < 0.001; OR for high-risk cognitive function = 0.188, P < 0.001). Six key population groups had higher risks of depression, anxiety, and cognitive function at critical/high-risk levels than others (OR for critical depression = 1.463, P < 0.001; OR for high-risk depression = 1.912, P < 0.001; OR for critical anxiety = 1.462, P < 0.001; OR for high-risk anxiety = 2.882, P < 0.001; OR for critical cognitive function = 1.381, P < 0.001; OR for high-risk cognitive function = 2.345, P < 0.001). A higher number of chronic diseases was associated with increased risks of critical and high-risk depression (OR for critical = 1.316, P < 0.001; OR for high-risk = 3.677, P < 0.001) and cognitive impairment (OR for critical depression = 1.316, P < 0.001; OR for high-risk depression = 3.677, P < 0.001; OR for critical anxiety = 1.512, P < 0.001; OR for high-risk anxiety = 1.801, P < 0.001). Conclusion It is recommended to expand mental health care sites in rural areas, improve the layout of mutual-support elderly care facilities, and explore sustainable models for rural elderly care. Efforts should also focus on enhancing social participation among the elderly through community-based activities, and strengthening cognitive screening and emotional regulation interventions, with particular attention to the mental health needs of older, isolated, and chronically ill individuals.

ObjectiveTo explore the correlation between general anesthesia and mild cognitive impairment in older adults so as to provide new ideas for early prevention and timely intervention of mild cognitive impairment（MCI）. MethodsBased on the baseline survey of the Hubei memory and aging cohort study（2018-2023）， the participants completed a thorough neuropsychological assessment and physical examination， and self-reported a history of general anesthesia and surgery. The association of general anesthesia and MCI in the elderly was analyzed using the logistic regression model. In addition， the stratification and interaction analysis of anesthesia history， anesthesia number and physical intellectual exercise were conducted separately. ResultsA total of 5 069 older adults aged 65 and above were included in this study， including 3 692 city dwellers and 1 377 rural people， among whom were 2 584 women （51%）. Out of the 1 472 participants with history of general anesthesia， 249 people （17.4%） had MCI. After controlling for confounding factors， there was a 39.6% increased risk of MCI in older adults who underwent general anesthesia ［OR=1.396，95%CI（1.169，1.668），P<0.001］， suggesting that general anesthesia may be an independent influence on MCI. For the older adults who had one general anesthesia ［OR=1.235，95%CI（1.001，1.523），P=0.049］， two general anesthesia ［OR=1.779，95%CI （1.292，2.450），P<0.001］， and three OR more general anesthesia ［OR=2.395，95%CI （1.589，3.610），P<0.001］， their risks of MCI were increased by 23.5%， 77.9%， and 139.5%， respectively. Compared with the older adults without a history of general anesthesia who did not exercise， the risk of developing MCI was significantly negatively correlated with the exercise group， cognitive exercise group， and combined exercise and cognitive exercise groups （all P<0.001）. The risk of developing MCI in the exercise group was 60.2% of that in the no exercise group ［OR = 0.602， 95% CI（0.456， 0.795）］， the risk in the cognitive exercise group was 42.4% of that in the no exercise group ［OR = 0.424， 95% CI（0.294， 0.613）］， and the risk in the combined exercise and cognitive exercise group was 27.0% of that in the no exercise group ［OR = 0.270， 95% CI （0.208， 0.353）］. In the older adults with a history of general anesthesia， compared with the no exercise group， the risk of developing MCI was significantly negatively correlated with the cognitive exercise group and the combined exercise and cognitive exercise group （all P < 0.05）. The risk of developing MCI in the cognitive exercise group was 47.7% of that in the no exercise group ［OR=0.477， 95% CI （0.256，0.892）］， the risk in the combined exercise and cognitive exercise group was 34.5% of that in the no exercise group ［OR=0.345， 95% CI （0.220， 0.540）］， while the risk in the exercise-only group did not show a significant difference. ConclusionThe risk of MCI increased significantly in older adults with a history of general anesthesia， and this risk increased with the times of anesthesia. Physical and mental exercise reduces the risk of MCI. it is recommended that older adults with a history of anesthesia incorporate physical and mental exercise into their daily lives to prevent mild cognitive impairment.

Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

OBJECTIVE: To explore the incidence, clinical features, genetic variant characteristics and prognosis of Glutaric acidemia type I (GA1) among neonates from Henan Province. METHODS: A total of 814 625 neonates undergoing screening for inherited metabolic diseases by tandem mass spectrometry (MS/MS) at the Third Affiliated Hospital of Zhengzhou University from January 2016 to December 2022 were selected as the study subjects. A retrospective method was adopted to collect the clinical data of the patients. Whole exome sequencing was carried out to detect GCDH gene variants in individuals with positive results by GA1 newborn screening, and Sanger sequencing was used to verify the candidate variants. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was rated. This study was approved by the Medical Ethics Committee of the Hospital (Ethics Number: 2019 Medical Ethics Review No. 67). RESULTS: Eight cases of GA1 were diagnosed among the 814 625 neonates. Blood glutaryl carnitine (C5DC) and urine glutaric acid (GA) levels of the 8 children were higher than the normal reference values. In total 12 variants were detected, all of which were missense variants. c.1064G>A (p.Arg355His) was the most common one, accounting for 21.4% (3/14). Three GCDH gene variants, including 1297G>C (p.Ala433Pro), c.467G>A (p.Gly156Asp) and c.1125T>G (p.Cys375Trp), were previously unreported. REVEL software analysis predicted that all of the three variants were harmful. 3D protein structure modeling indicated that the three variants may cause amino acid residue alterations, and c.1297G>C (p.Ala433Pro) and c.1125T>G (p.Cys375Trp) may result in increase in hydrogen bonds and affect the function of GCDH protein. By December 2023, one of the eight children had deceased, and another child had severe clinical symptoms with poor prognosis. Six children had a good prognosis, of which two had mild motor development delay and four had normal development without clinical symptoms. CONCLUSION The incidence of GA1 in newborns screened by MS/MS in Henan Province is 1/101 828, and the carrier rate of pathogenic GCDH variants is 1/160. The c.1064G>A (p.Arg355His) may be the hotspot variant of the GCDH gene among children with GA1 in Henan. Discovery of the three novel variants has enriched the mutational spectrum of the GCDH gene and provide a basis for the early diagnosis, treatment, prognosis and genetic counseling of this disease.
Humans ; Amino Acid Metabolism, Inborn Errors/epidemiology* ; Glutaryl-CoA Dehydrogenase/chemistry* ; Infant, Newborn ; Female ; Neonatal Screening/methods* ; Male ; Brain Diseases, Metabolic/epidemiology* ; China/epidemiology* ; Retrospective Studies ; Mutation ; Genetic Variation ; Glutarates

Objective To investigate the clinical value of WNT1 inducible signaling pathway protein 1(WISP-1)and vascular endothelial growth factor-A(VEGF-A)as novel molecular markers of esophageal squamous cell carcinoma(ESCC)in elderly patients.Methods Elderly patients with ESCC were divided into 65-70 years old group and>70 years old group.Immunohistochemical staining and RT-PCR were used to detect the expression levels of WISP-1 and VEGF-A proteins and mRNAs,respectively.Log rank test was used to analyze correlation between clinicopathological features and prognosis of ESCC in the elderly.Results The positive expression rate of WISP-1 in ESCC tissues was significantly higher than that in para-cancer tissues(53.33% vs.35.42%,P=0.045).The positive expression rate of WISP-1 in patients over 70 years old and with lymph node metastasis was significantly higher than that in patients aged 65-70 years and without lymph node metastasis(P=0.047 and 0.032).The positive expression rate of VEGF-A protein in ESCC tissues was significantly higher than that in para-cancer tissues(50.00% vs.20.83%,P=0.001).The positive expression rate of VEGF-A in patients with depth of infiltration T3-T4 stage,lymph node metastasis,and TNM Ⅲ-Ⅳ stage was significantly higher than that in patients with T1-T2 stage,no lymph node metastasis,andⅠ-Ⅱ stage(P=0.030,0.006,and 0.010,respectively).The mRNA expression levels of these two molecules were significantly higher in ESCC tissues than in para-cancer tissues(P<0.05),and the results of univariate analysis showed that the expression levels of WISP-1 and VEGF-A were correlated with the prognosis of ESCC in the elderly(P<0.05).The results of multivariate analysis showed that lymph node metastasis was the independent risk factor affecting the prognosis of elderly patients with ESCC.Conclusion WISP-1 and VEGF-A are associated with malignant behavior in elderly patients with ESCC.The expression of WISP-1 increased with age,and it has potential as a novel molecular marker of ESCC in elderly patients.

Objective:To examine the postoperative prosthesis-related complications, short-term surgical outcomes and patient satisfaction with breast reconstruction between patients who underwent endoscopic assisted versus conventional nipple sparing mastectomy and immediate prothesis breast reconstruction.Methods:This study was a retrospective cohort study. A retrospective analysis was performed on clinical data of 104 women with breast cancer who received nipple sparing mastectomy and immediate prothesis breast reconstruction from August 2021 to August 2022 at the Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. They were divided into two groups according to the surgical approach. A total of 53 patients, aged (43.3±9.9) years (range: 25 to 66 years), underwent endoscopic nipple sparing mastectomy (E-NSM group) and immediate prothesis breast reconstruction. The other 51 patients aged (39.9±7.8) years (range: 25 to 54 years) underwent conventional open surgery (C-NSM group). Short-term surgical outcomes including operation time, postoperative hospital stay, postoperative blood loss, and postoperative drainage volume in 2 days were recorded. Patient satisfaction with breast reconstruction was compared using the Wilcoxon rank sum test. Postoperative prothesis-related complications were investigated to determine the experience to deal with them.Results:No postoperative prosthesis-related infection, prosthesis loss, or necrosis of the nipple-areola complex occurred in the E-NSM group, while 1 patient suffered from hematoma, whose wound was skinned with resuture after disinfection. Five patients in the C-NSM group had prosthesis-related infection, 2 of them received prosthesis removal surgery combined with sufficient antimicrobial agent, another one underwent surgery for subcutaneous placement of the drain, as well as antimicrobial agent therapy, and the rest of them healed up only with antimicrobial agent therapy. All recovered well after treatment. One patient recovered from necrosis of the nipple-areola complex through periodic iodophor disinfection and dressing which ended in improvement of necrotic areas, another patient who had hematoma accepted the same treatment mentioned above and also healed. All the patients mentioned above are now in stable conditions. Patients in the E-NSM group had higher satisfaction with the cosmetic results of the breast prosthesis implant than those in the C-NSM group ( Z=-4.511, P<0.01). Conclusions:Both surgical approaches were proven to be safe and effective with a low rate of postoperative prosthesis-related complications. Patients in the E-NSM group were more satisfied with the cosmetic results of breast reconstruction than those in the C-NSM group.

Objective To accurately encode pelvic organ prolapse and ensure data accuracy.Methods ICD-10 coding analysis was performed in combination with the professional knowledge of the International Classification of Diseases(ICD-10)and specific clinical cases of pelvic organ prolapse.Results Vaginal anterior wall prolapse,regardless of severity,was encoded as N81.1;vaginal posterior wall prolapse,regardless of severity,as N81.6;uterine prolapse grade Ⅰ and Ⅱ,regardless of the presence or absence of vaginal anterior and posterior wall prolapse,as N81.2;uterine prolapse grade Ⅲ,whether the prolapse of the anterior and posterior vaginal walls is combined,or what level of the severity of the prolapse,as N81.3;cervical prolapse staging,regardless of severity or presence of vaginal anterior and posterior wall prolapse,as N81.2.In addition,the N81.-code does not include genital prolapse complicating pregnancy(O34.5),prolapse and hernia of ovary and fallopian tube(N83.4),vaginal fornix prolapse after hysterectomy(N99.3).Conclusion To ensure accurate coding,the composite coding rules must be cross-checked with volume one.ICD-10 failed to reflect the severity of vaginal prolapse in clinical practice.To consider the severity,coding should be extended in the N81.-segment.It is essential for coders to actively acquire clinical knowledge,rein-force professional knowledge,and enhance their responsibility to improve their coding proficiency and ensure data accuracy.

Objective To investigate the relationship between the levels of CD4+/CD8+and D-dimer(D-D)in peripheral blood and the outcome of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis(EBV-HLH).Methods Ninety patients with EBV-HLH who were treated in Beijing Friendship Hospital from September 2021 to August 2023 were included as observation group,and additional 90 patients with infectious mononucleosis(IM)treated in the hospital contemporarily were selected as the control group.The levels of CD4+/CD8+and D-D in peripheral blood were compared between the two groups of patients to examine the correlation between the levels of CD4+/CD8+and D-D in peripheral blood and EBV-DNA load in patients with EBV-HLH,compare the outcome of patients within 3 months in terms of the levels of CD4+/CD8+and D-D in peripheral blood,evaluate the effects of CD4+/CD8+and D-D levels in peripheral blood on the risk of death from EBV-HLH,and analyze the interaction between the levels of CD4+/CD8+and D-D in peripheral blood.Results The patients in observation group showed significantly lower peripheral blood CD4+/CD8+ratio and significantly higher D-D than the patients in control group(P＜0.05).The peripheral blood CD4+/CD8+ratio was negatively correlated with EBV-DNA load(P＜0.05),and D-D was positively correlated with EBV-DNA load(P＜0.05)in EBV-HLH patients.The patients with high peripheral blood CD4+/CD8+ratio were assocaited with lower 3-month mortality rate compared to the patients with low CD4+/CD8+ratio.The patients with high D-D level were associated with higher 3-month mortality rate compared to the patients with low D-D level(P＜0.05).In EBV-HLH patients with low levels of peripheral blood CD4+/CD8+,the risk of death was 6.125 times that of the patients with high levels of CD4+/CD8+.High level D-D was associated with 14.348 times risk of death compared to the patients with low level D-D.CD4+/CD8+and D-D had synergistic effect on death of EBV-HLH patients.Conclusions Peripheral blood CD4+/CD8+levels decreased and D-D levels increased in EBV-HLH patients.Peripheral blood CD4+/CD8+levels and D-D levels and their changes may be useful for predicting the outcome of patients.

Objective:To compare the short-term clinical efficacy and patient satisfaction of single-port assisted endoscopic breast-conserving surgery versus open approach in the treatment of female breast cancer patients.Methods:This study retrospectively analyzed the clinical data of 129 female breast cancer patients admitted to Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University from March 2022 to June 2023. In this study, 56 patients underwent breast-conserving surgery assisted by single-port endoscopy (endoscopic group) and 73 patients underwent conventional open breast-conserving surgery (conventional group).Results:Compared to the conventional group (73 cases), the endoscopic group (56 cases) had slightly longer operation time [(200.0±43.2) min vs. (185.3±56.5) min] and intraoperative blood loss [(34.0±25.4) ml vs. (27.2±21.8) ml, P>0.05]. The endoscopic group had a significantly shorter surgical incision length than the conventional group [(4.7±0.7) cm vs. (8.0±1.1) cm, P<0.05], the difference in postoperative tumor margin was not significant (endoscopic group: 3.5% vs. conventional group: 5.7%, P>0.05). In terms of postoperative complications, the endoscopic group had a significantly lower incidence of radiation-related skin reactions than the conventional group ( P<0.05). The endoscopic group had a higher satisfaction rate in terms of postoperative aesthetics (73.2% vs. 56.2%, P<0.05). Conclusions:The short-term clinical efficacy of breast-conserving surgery for female breast cancer by single-port assisted endoscopy is not inferior to that of conventional open breast-conserving surgery, with added better cosmetic results.