Based on the close structural and functional associations of the Shaoyang （少阳） channel and related zang-fu （脏腑） organs with the brain and the pharynx， this paper proposes that the pathogenesis of post-stroke dysphagia involves constraint and stagnation of the pivot mechanism， binding of phlegm and stasis， frenetic stirring of ministerial fire， and incoordination of the spirit mechanism， ultimately leading to loss of pharyngeal function. An acupuncture therapy centered on regulating the pivot and unblocking the orifice is established. Acupoints of the Shaoyang channel， including Fengchi （GB 20）， Wangu （GB 12）， Yifeng （SJ 17）， and Waiguan （SJ 5）， are selected to regulate the pivot and treat the root； acupoints of the Du （督） and Ren （任） channels， including Fengfu （GV 16）， Lianquan （CV 23）， and Tiantu （CV 22）， are used to unblock the orifice and treat the branch. In addition， staged treatment can be applied according to syndrome differentiation. In the acute stage with predominant phlegm turbidity， Fenglong （ST 40）， Yinlingquan （SP 9）， Jinjin （EX-HN 12）， and Yuye （EX-HN 13） are added to resolve phlegm and facilitate orifice function. During the recovery stage with excess ministerial fire scorching the pharynx， Zulinqi （GB 41） and Zhaohai （KI 6） are added to drain fire and nourish yin； when ministerial fire disturbs the spirit， Tongli （HT 5） and Neiguan （PC 6） are added to calm the spirit and the heart. During the chronic stage with blood deficiency and collateral stasis， Zusanli （ST 36） and Sanyinjiao （SP 6） are added to nourish blood and unblock collaterals. In clinical practice， the angle and depth of needling are adjusted based on the stage of dysphagia， with the combination of elongated needles and medicinal moxibustion are used to enhance the therapeutic effect.

Objective A cross-sectional survey on the postoperative home care status and barriers was conducted among elderly patients with osteoporotic fractures nationwide,in order to provide a basis for promoting the improvement of standardized home care for elderly patients with osteoporotic fractures.Methods From October to November 2023,a survey on the current situation and barriers of home environment protection was conducted among elderly patients with osteoporotic fractures in the orthopedic wards of 594 hospitals across 31 provinces(autonomous regions/municipalities directly under the central government)using a convenience sampling method.Results A total of 14,349 questionnaires were distributed,and 12,496 valid questionnaires were collected,resulting in an effective response rate of 87.09％.Among the patients,5,502 cases(44.03％)had implemented home-based prevention and treatment of osteoporosis before the fracture.2 095(16.77％)of the patients experienced a subsequent fracture,of which 65.11％of the patients who experienced a subsequent fracture received medication intervention after the initial fracture,while 19.86％of the patients who experienced a subsequent fracture did not comply with the treatment for osteoporosis after the initial fracture.Additionally,77.66％(n=1 627/2 095)of the patients received community medical services after the initial fracture.Barriers to care factors in the home environment after fracture from the patient's perspective presented the complexity of the social-ecological system model in 6 dimensions at 2 levels:micro(basic personal situation,physiological factors,psychological factors,and behavioural factors),and meso(social support factors,and healthcare worker factors).Conclusion In the vast majority of elderly patients in China,before osteoporotic fracture,home-based measures to prevent osteoporosis have not been adequately implemented;after the initial osteoporotic fracture,the pathway of re-fracture prevention and management in the patient's home environment is not yet complete and its popularity needs to be improved;the barriers to home care faced by elderly patients with osteoporotic fracture are complex.It is recommended to promote effective linkages among hospitals,community health centres and families to strengthen the closed-loop management of re-fracture prevention and management.

Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective A cross-sectional survey on the postoperative home care status and barriers was conducted among elderly patients with osteoporotic fractures nationwide,in order to provide a basis for promoting the improvement of standardized home care for elderly patients with osteoporotic fractures.Methods From October to November 2023,a survey on the current situation and barriers of home environment protection was conducted among elderly patients with osteoporotic fractures in the orthopedic wards of 594 hospitals across 31 provinces(autonomous regions/municipalities directly under the central government)using a convenience sampling method.Results A total of 14,349 questionnaires were distributed,and 12,496 valid questionnaires were collected,resulting in an effective response rate of 87.09％.Among the patients,5,502 cases(44.03％)had implemented home-based prevention and treatment of osteoporosis before the fracture.2 095(16.77％)of the patients experienced a subsequent fracture,of which 65.11％of the patients who experienced a subsequent fracture received medication intervention after the initial fracture,while 19.86％of the patients who experienced a subsequent fracture did not comply with the treatment for osteoporosis after the initial fracture.Additionally,77.66％(n=1 627/2 095)of the patients received community medical services after the initial fracture.Barriers to care factors in the home environment after fracture from the patient's perspective presented the complexity of the social-ecological system model in 6 dimensions at 2 levels:micro(basic personal situation,physiological factors,psychological factors,and behavioural factors),and meso(social support factors,and healthcare worker factors).Conclusion In the vast majority of elderly patients in China,before osteoporotic fracture,home-based measures to prevent osteoporosis have not been adequately implemented;after the initial osteoporotic fracture,the pathway of re-fracture prevention and management in the patient's home environment is not yet complete and its popularity needs to be improved;the barriers to home care faced by elderly patients with osteoporotic fracture are complex.It is recommended to promote effective linkages among hospitals,community health centres and families to strengthen the closed-loop management of re-fracture prevention and management.

BACKGROUND:The occurrence and development of various ophthalmic diseases are closely related to excessive oxidative stress,and the inhibition of oxidative stress response may produce preventive and therapeutic effects. OBJECTIVE:To explore the role of Pax6 gene expression on hydrogen peroxide-induced aging of mouse bone marrow mesenchymal stem cells(BM-MSCs). METHODS:Resuscitated BM-MSCs,Pax6/BM-MSCs,and shPax6/BM-MSCs were treated with hydrogen peroxide for 24 hours,and then β-galactosidase staining was performed.The proliferation index Ki67 expression and apoptosis were detected by flow cytometry.The expression of senescence-associated molecules(Wnt7a,p21,and p53)was detected by RT-PCR. RESULTS AND CONCLUSION:(1)After hydrogen peroxide treatment,the cells of the three groups showed senescence phenotype and β-galactosidase staining was positive.Compared with BM-MSCs group,the expression of positive cells in Pax6/BM-MSCs group was less and that in the shPax6/BM-MSCs group was more,and the difference was statistically significant(P<0.05).(2)The results of flow cytometry showed that compared with BM-MSCs group,the positive expression of Ki67 in the Pax6/BM-MSCs group increased and the level of apoptosis decreased,while the positive expression of Ki67 decreased and the level of apoptosis increased in the shPax6/BM-MSCs group;the difference was significantly different(P<0.05).(3)RT-PCR showed that compared with the BM-MSCs group,the expression of Wnt7a,p53,and p21 decreased in the Pax6/BM-MSCs group,while the expression of Wnt7a,p53,and p21 increased in the shPax6/BM-MSCs group;the difference was significantly different(P<0.05).(4)These findings indicate that overexpression of Pax6 can antagonize the aging progression of BM-MSCs induced by hydrogen peroxide,which may be related to Wnt signaling pathway.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective:To evaluate the effect of acupuncture with invigorating viscera and purging fu, replenishing qi and nourishing yin for the T2DM patients with qi and yin deficiency syndrome.Methods:A total of 59 patients who met the inclusion criteria from January 1, 2019 to December 31, 2020 in the Endocrinology Department of the Second Affiliated Hospital of Anhui University of Chinese Medicine were divided into the acupuncture group with 30 cases and a control group with 29 cases, according to the random number table method. The control group received conventional hypoglycemic treatment. And the acupuncture group was treated with acupuncture on the basis of the control group treatment. Both groups were treated for 4 weeks. TCM syndrome scores were performed before and after treatment, respectively. Serum IL-6 was measured by ELISA, serum CRP by immunoturbidimetry, and serum fasting blood glucose (FPG), 2 hPG, HbAlc, TC, TG, HDL-C, LDL-C levels by spectrophotometry. The BMI, clinical effect rates were calculated.Results:The total effective rate was 96.7% (29/30) in acupuncture group and 75.9% (22/29) in control group, and the difference was statistically significant ( χ2=5.96, P<0.01). After treatment, the scores of fatigue, dryness of mouth and pharynx, spontaneous sweating and night sweating, shortness of breath and lazy speech in acupuncture group were significantly lower than those in the control group ( t values were 6.02, 4.31, 4.34, 3.63, respectively, all Ps<0.01). The serum CRP level in acupuncture group was significantly lower than that of the control group at 21, 48 d after treatment ( t values were -4.36, -3.75, respectively, all Ps<0.01), and IL-6 level was significantly lower than that of the control group at 14, 21, 28 d after treatment ( t values were -2.92, -5.35, -8.71, respectively, all Ps<0.01). After treatment, the serum TC [(4.62±0.68) mmol/L vs. (5.56±0.72) mmol/L, t=5.16], TG [(1.48±0.42) mmol/L vs. (2.12±0.89) mmol/L, t=3.55], LDL-C [(2.48±0.84) mmol/L vs.(3.02±0.95) mmol/L, t=2.32] in the acupuncture group were significantly lower than those in the control group ( P<0.05), HDL-C [(1.39±0.27) mmol/L vs. (1.26±0.22) mmol/L, t=-2.02] in the acupuncture group was significantly higher than that of the control group ( P<0.05). The serum FPG level at 21 d [(6.12±0.67) mmol/L vs. (6.57±0.61) mmol/L, t=-4.96], 28 d [(5.78±0.52) mmol/L vs. (6.49±0.58) mmol/L, t=-2.70] in acupuncture group were significantly lower than those in the control group ( P<0.01). The 2h PG level at 14 d after treatment [(10.23±1.06) mmol/L vs. (11.76±1.34) mmol/L, t=-4.87], 21 d [(9.05±0.98) mmol/L vs. (10.53±1.24) mmol/L, t=-5.10], 28 d [(7.45±0.69) mmol/L vs. (9.31±0.78) mmol/L, t=-9.71] in the acupuncture group were significantly lower than those in the control group ( P<0.01), and HbA1c level were decreased 14 d [(7.93±0.86)% vs. (8.52±0.97)%, t=-2.47], 21 d [(7.63±0.85)% vs. (8.15±0.92)%, t=-2.26], 28 d [(6.47±0.51)% vs. (7.51±0.62)%, t=-7.05] significantly lower than those in the control group ( P<0.01), BMI [(22.13±1.57) kg/m 2vs. (24.16±1.82) kg/m 2, t=-4.59] 28 d after treatment was significantly lower than that of the control group ( P<0.01). Conclusion:Acupuncture therapy of nourishing viscera and purging fu, nourishing qi and nourishing yin can regulate the disorder of glucose and lipid metabolism in patients with T2DM and syndrome of qi and yin deficiency.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease with unknown etiology and limited therapeutic options. Activation of fibroblasts is a prominent feature of pulmonary fibrosis. Here we report that lncRNA DACH1 (dachshund homolog 1) is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis. LncDACH1 knockout mice develop spontaneous pulmonary fibrosis, whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation, collagen deposition and differentiation of mouse lung fibroblasts. Similarly, forced expression of LncDACH1 not only prevented bleomycin (BLM)-induced lung fibrosis, but also reversed established lung fibrosis in a BLM model. Mechanistically, LncDACH1 binding to the serine/arginine-rich splicing factor 1 (SRSF1) protein decreases its activity and inhibits the accumulation of Ctnnb1. Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts. Furthermore, loss of LncDACH1 promoted proliferation, differentiation, and extracellular matrix (ECM) deposition in mouse lung fibroblasts, whereas such effects were abolished by silencing of Ctnnb1. In addition, a conserved fragment of LncDACH1 alleviated hyperproliferation, ECM deposition and differentiation of MRC-5 cells driven by TGF-β1. Collectively, LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation, suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis.

Objective:To conduct a survey on major surgeon′s mental trauma caused by iatrogenic biliary injury (IBI) during laparoscopic cholecystectomy (LC), and explore its influencing factors.Methods:The retrospective cross-sectional survey was conducted. Surgeons who have registered in Chinese College of Surgeons of Chinese Medical Doctor Association and Chinese Surgical Society of Chinese Medical Association were recruited to participate as respondents between December 1, 2018 and January 1, 2019. The survey was conducted by the questionnaires of influencing factors for surgeon′s mental trauma caused by IBI during LC. The questionnaires were distributed to participants via WeChat on the Wenjuanxin platform. Observation indicators: (1) results of questionnaire survey; (2) analysis of influencing factors for severe mental trauma of major surgeons caused by IBI during LC. Measurement data with normal distribution were expressed as Mean± SD, and count data were expressed as absolute numbers or percentages. The chi-square test was used for univariate analysis. Factors with P<0.10 in the univariate analysis were included in multivariate analysis, and Logistic regression model was used for multivariate analysis. Results:(1) Results of questionnaire survey. A total of 606 questionnaires were retrieved. ① Basic information of major surgeons: of the 606 major surgeons, there were 596 males and 10 females, aged (41±7)years, with a range from 18 to 62 years. Of the 606 major surgeons, 59.24%(359/606) came from non-teaching hospitals, and 64.03%(388/606) encounted the most impressive case of IBI during LC when they were in the primary or intermediate professional title. For 76.24%(462/606) of the major surgeons, the first case of IBI during LC was the most impressive case, and 69.80%(423/606) believed that careful operation during LC could avoid IBI. ② Patient information: of the patients with the most impressive IBI during LC in each major surgeon′s memory, there were 400 females and 206 males. The proportion of patients younger than 35 years old, in 35-65 years old and older than 65 years old was 9.57%(58/606), 65.51%(397/606), and 24.92%(151/606), respectively. ③ IBI related information: 57.43%(348/606) of the major surgeons indicated that they could receive help from senior surgeons in time for the occurrence of IBI during LC, and 78.88%(478/606) of the major surgeons invited senior surgeons to participate in the initial repair. For the most impressive case of IBI during LC, 66.83%(405/606) of the primary repair surgeries were performed during LC, 11.06%(67/606) were performed within postoperative 3 days and 22.11%(134/606) were performed after 3 days. The main repair methods included local repair, bile duct to end anastomosis, and bilioenteric anastomosis, accounting for 24.92%(151/606), 30.20%(183/606), 33.17%(201/606), respectively. The proportion of patients requiring partial hepatectomy, with perioperative death, and requiring multiple repair was 2.48%(15/606), 2.15%(13/606), and 9.24%(56/606), respectively. ④ Subsequent processing on major surgeons: after the occurrence of IBI during LC, 64.85%(393/606) of the major surgeons gained the understanding of patients and their families, 35.15%(213/606) of the major surgeons were involved in medical disputes, 15.68%(95/606) of the major surgeons received administrative punishment from the hospital. About the compensation, 14.36%(87/606) of the major surgeons had to pay for the compensation by themselves, and only 6.77%(41/606) of the major surgeons had medical liability insurance. There were 9.24%(56/606) of the major surgeons invloved in violent conflicts during the medical disputes. ⑤ Psychology-related information of major surgeons: of the 606 major surgeons, 544 had mental trauma including 279 with severe mental trauma. After the occurrence of IBI during LC, 82.01%(497/606) of the major surgeons experienced anxiety and/or depression for more than one month; 63.37%(384/606) of the major surgeons expected to avoid LC or showed tension during LC; 44.72%(271/606) of the major surgeons had a physiological response when recalling the case; 36.14%(219/606) of the major surgeons initiated the idea of not being a surgeon; 6.44%(39/606) of the major surgeons asked psychologists for help; and 5.61%(34/606) of the major surgeons had taken psychiatric drugs such as antianxiety and anti-depression drugs for more than one month. (2) Analysis of influencing factors for severe mental trauma of major surgeons caused by IBI during LC. Results of univariate analysis showed that the hospital type of the major surgeons, participation of senior surgeons in the repair, surgical method of the primary repair, IBI requiring repeated repair, medical disputes, administrative punishment from the hospital, compensation paid by the major surgeon, having medical liability insurance, violent conflicts in medical disputes were related factors for severe mental trauma of the major surgeons caused by IBI during LC ( χ2=7.688, 3.932, 19.764, 13.837, 61.488, 24.904, 30.976, 5.344, 26.285, P<0.05) . Results of multivariate analysis showed that the surgical method of the primary repair, IBI requiring repeated repair, medical disputes, administrative punishment from the hospital, compensation paid by the major surgeon, violent conflicts in medical disputes were independent risk factors for severe mental trauma caused by IBI during LC of the major surgeons ( odds ratios=1.203, 2.198, 2.922, 1.830, 2.405, 2.171, 95% confidence interval: 1.033-1.402, 1.143-4.226, 1.944-4.391, 1.083-3.093, 1.076-5.375, 1.002-4.702, P<0.05). Having medical liability insurance was an independent protective factor for severe mental trauma of the major surgeons caused by IBI during LC ( odds ratios=0.336, 95% confidence interval: 0.126-0.896, P<0.05). Conclusions:Most surgeons in China are troubled by IBI during LC, and nearly half of them suffer from severe mental trauma. Surgical method of the primary repair, IBI requiring repeated repair, medical disputes, administartive punishment from the hospital, compensation paid by the major surgeon, and violent conflicts in medical disputes are independent risk factors for severe mental trauma of major surgeons caused by IBI during LC. Having medical liability insurance is an independent protective factor for severe mental trauma of major surgeons caused by IBI during LC.

OBJECTIVE: To identify potential mutations of F11 gene in a pedigree affected with hereditary coagulation factor XI (FXI) deficiency and explore its molecular pathogenesis. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), coagulation factor VIII activity (FVIIIC), coagulation factor IX activity (FIXC), coagulation factor XI activity (FXIC), coagulation factor XII activity (FXIIC) and lupus anticoagulation (LA) of the proband and eight family members were determined. FXI antigen (FXIAg) was determined by enzyme-linked immunosorbent assay (ELISA). For the proband, potential mutations in the exons, flanking introns and 5'-, 3'-untranslated regions of the F11 gene were screened by direct DNA sequencing. The results were confirmed by reverse sequencing. Suspected mutations were detected in other family members. ClustalX-2.1-win and four online bioinformatic tools (PolyPhen-2, PROVEAN, SIFT, and Mutation Taster) were used to study the conservation and possible impact of the mutations. The structure of the mutational sites was processed with Swiss-PdbViewer. RESULTS: The propositus had prolonged APTT (69.6 s), whose FXIC and FXIAg were reduced to 6.0% and 10.7%, respectively. Her mother, elder sister, one younger sister, little brother, daughter and son showed slightly prolonged APTT and moderate FXIC and FXIAg levels. Gene sequencing revealed that the propositus carried a heterozygous nonsense mutation c.738G>A (p.Trp228stop) in exon 7 and a heterozygous mutation c.1556G>C (p.Trp501Ser) in exon 13. Her mother, elder sister and daughter were heterozygous for the p.Trp228stop mutation, while one younger sister and little brother and son were heterozygous for p.Trp501Ser. Her husband and the youngest sister were of the wild type. Phylogenetic analysis suggested that Trp501 was highly conserved among all homologous species. The p.Trp501Ser was predicted to be "probably damaging","deleterious", "affect protein function" and "disease causing" corresponding to PolyPhen-2, PROVEAN, SIFT and Mutation Taster. Model analysis demonstrated that the non-polar Trp501 has two benzene rings, forming a hydrogen bond with Gln512 in the wild type. Once substituted by Ser501, the side chain may form another hydrogen bond with the benzene of His396. This may affect the normal space conformation and stability of FXI protein. CONCLUSION The compound heterozygous mutations of the F11 gene probably accounted for the low FXI concentration in this pedigree.
Factor XI ; genetics ; Factor XI Deficiency ; genetics ; Female ; Heterozygote ; Humans ; Male ; Mutation ; Pedigree ; Phylogeny