Objective To observe the therapeutic effects and mechanisms of Guanyuan Mingmen Sequential Acupuncture on rats with premature ovarian insufficiency(POI)model.Methods Female SD rats were divided into the blank group,the model group,the protein kinase A(PKA)inhibitor(H89)+acupuncture group,and the acupuncture group,with 12 rats in each group.Except for the blank group,the POI model was prepared by gavage with Tripterygium Glycosides Tablets in the other three groups of rats.After the model was successfully established,the blank group and the model group were bundled once a day;in the acupuncture group,Guanyuan(RN4)point was taken during the intermotility period,and in the pre-motility period,Mingmen(DU4)point was taken;in the H89+acupuncture group,the intervention was performed in accordance with the acupuncture protocol of the acupuncture group,and H89 was injected intraperitoneally for 30 minutes prior to each acupuncture session.Continuous intervention was performed for 20 days.Samples were taken from each group of rats in the first estrus period and in proestrus period after intervention.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of follicle stimulating hormone(FSH)and estradiol(E2)during the estrous phase,Western Blot was used to measure the protein expressions of follicle stimulating hormone receptor(FSHR)and aromatase P450(P450arom)during the estrous phase,and the activity of granulocytes during the estrous phase and the proestrus phase were measured using the cell-counting kit 8(CCK-8)method.The immunohistochemistry method was used to detect the protein expression of pre-motility proliferating cell nuclear antigen(PCNA).Results(1)Compared with the blank group,the serum FSH level of the model group and H89+acupuncture group was significantly increased(P＜0.01),and the E2 level was significantly decreased(P＜0.001);there was no difference between the FSH level of the H89+acupuncture group and that of the model group(P＞0.05),and the E2 level of the H89+acupuncture group was lower than that of the model group(P＜0.05);the FSH level of the acupuncture group was lower than that of the model group and that of the H89+acupuncture group(P＜0.05),had no difference with the blank group(P＞0.05),E2 level was significantly higher than the model group and H89+ acupuncture group(P＜0.01),still being lower than the blank group(P＜0.05).(2)The protein expressions of FSHR and P450arom in the model group and H89 + acupuncture group was lower than those in the blank group;the protein expression of FSHR in the H89 + acupuncture group was not different from that in the model group(P＞0.05),while the protein expression level of P450arom was lower than that in the model group(P＜0.05);the protein expression levels of FSHR and P450arom in the acupuncture group were higher than those in the model group and H89 + acupuncture group,but still lower than those in the blank group(P＜0.05).(3)Both GCs activity and average optical density value of PCNA in the model group and H89+acupuncture group were lower than the blank group(P＜0.05);both GCs activity and average optical density value of PCNA in the H89+acupuncture group were lower than the model group(P＜0.05);the activity of GCs and average optical density value of PCNA of the acupuncture group were significantly higher than that of the model group and H89+acupuncture group(P＜0.05 or P＜0.01).Conclusion Guanyuan Mingmen Sequential Acupuncture can regulate sex hormone levels,increase GCs activity and promote GCs cell proliferation by up-regulating protein expressions of follicle stimulating hormone receptor(FSHR)/cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)pathway FSHR,P450arom,thus improving POI.

Once ischemic stroke occurs,severely insufficient blood supply causes massive neuronal apoptosis and necrosis,leading to the release of damage-associated molecular patterns(DAMPs)that exacerbate neuroinflammation and worsen brain damage.As the resident efferocytes in central nervous system,microglia possess the capability to phagocytose and eliminate ap-optotic cells by efferocytosis before necrosis occurs,thereby mit-igating the release of DAMPs and the accumulation of cellular debris.This process is crucial for neuroinflammation reduction and neurorestoration.Hence,a comprehensive understanding of the regulatory mechanism of microglial efferocytosis post-ische-mia,as well as its impact on neuroinflammation and cerebral damage,has the potential to advance diagnostic and therapeutic approaches for ischemic stroke.Here,we outline the molecular mechanisms and signaling pathways involved in microglial effero-cytosis following ischemic stroke,and summarize the research progress on drugs targeting microglial efferocytosis to enhance stroke prognosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: The prevalence of atrial fibrillation (AF) in type 2 diabetes mellitus (DM) patients under primary care in Hong Kong was yet to be explored. We aimed to evaluate the prevalence of AF in patients with DM so as to provide evidence-based recommendations to incorporate AF screening as a component in regular diabetic risk and complication assessment. The performance of automated BP machine Microlife WatchBP Office AFIB as a screening tool for the detection of AF was also evaluated.Method This was a cross-sectional study. Patients with type 2 DM who attended the regular diabetic risk and complication assessment in the participating clinics from 24 August 2021 to 27 January 2022 were recruited. Blood pressure measurement by Microlife WatchBP Office AFIB and 12-lead ECGs were performed for AF screening. Results: Among 2015 DM patients in primary care, the prevalence of AF was found to be 1.9% (95% confidence interval [CI] 1.3–2.6). The prevalence of AF increased with age, from 0.5% in patients aged < 65 years, to 2.2% in patients aged 65–74 years and 4.3% in patients aged ≥ 75 years. The sensitivity and specificity of Microlife WatchBP Office AFIB to detect AF were 80% (95% Cl 61.8–92.3) and 97.9%. (95% CI 97.3–98.5), respectively. The positive and negative predictive values were 32.8% (95% CI 21.9–45.1) and 99.7% (95% CI 99.5–99.9) respectively. Conclusions AF screening with the use of Microlife WatchBP Office AFIB is a simple procedure and can be considered as a standard assessment in the regular comprehensive diabetic risk and complication assessment in primary care setting.

Humans ; Pyoderma Gangrenosum ; Myeloproliferative Disorders ; Neoplasms

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.
Humans ; Male ; Female ; Adult ; Aged, 80 and over ; Antiviral Agents/therapeutic use* ; Hepatitis B, Chronic/epidemiology* ; Hepatitis B e Antigens ; Hepatitis B/drug therapy* ; Hepatitis B Surface Antigens ; Hepatitis A ; Liver Cirrhosis/drug therapy* ; China/epidemiology* ; Registries ; Hepatitis B virus/genetics* ; DNA, Viral

OBJECTIVE: To analyze the clinicopathological features, molecular changes and prognostic factors in angioimmunoblastic T-cell lymphoma (AITL). METHODS: Sixty-one cases AITL diagnosed by Department of Pathology of Peking University Cancer Hospital were collected with their clinical data. Morphologically, they were classified as typeⅠ[lymphoid tissue reactive hyperplasia (LRH) like]; typeⅡ[marginal zone lymphoma(MZL)like] and type Ⅲ [peripheral T-cell lymphoma, not specified (PTCL-NOS) like]. Immunohistochemical staining was used to evaluate the presence of follicular helper T-cell (TFH) phenotype, proliferation of extra germinal center (GC) follicular dendritic cells (FDCs), presence of Hodgkin and Reed-Sternberg (HRS)-like cells and large B transformation. The density of Epstein-Barr virus (EBV) + cells was counted with slides stained by Epstein-Barr virus encoded RNA (EBER) in situ hybridization on high power field (HPF). T-cell receptor / immunoglobulin gene (TCR/IG) clonality and targeted exome sequencing (TES) test were performed when necessary. SPSS 22.0 software was used for statistical analysis. RESULTS: Morphological subtype (%): 11.4% (7/61) cases were classified as type Ⅰ; 50.8% (31/61) as type Ⅱ; 37.8% (23/61) as type Ⅲ. 83.6% (51/61) cases showed classical TFH immunophenotype. With variable extra-GC FDC meshwork proliferation (median 20.0%); 23.0% (14/61) had HRS-like cells; 11.5% (7/61) with large B transformation. 42.6% (26/61) of cases with high counts of EBV. 57.9% (11/19) TCR⁺/IG^-, 26.3% (5/19) TCR⁺/IG⁺, 10.5% (2/19) were TCR^－/IG^－, and 5.3% (1/19) TCR^－/IG⁺. Mutation frequencies by TES were 66.7% (20/30) for RHOA, 23.3% (7/30) for IDH2 mutation, 80.0% (24/30) for TET2 mutation, and 33.3% (10/30) DNMT3A mutation. Integrated analysis divided into four groups: (1) IDH2 and RHOA co-mutation group (7 cases): 6 cases were type Ⅱ, 1 case was type Ⅲ; all with typical TFH phenotype; HRS-like cells and large B transformation were not found; (2) RHOA single mutation group (13 cases): 1 case was type Ⅰ, 6 cases were type Ⅱ, 6 cases were type Ⅲ; 5 cases without typical TFH phenotype; 6 cases had HRS-like cells, and 2 cases with large B transformation. Atypically, 1 case showed TCR^－/IG^－, 1 case with TCR^－/IG⁺, and 1 case with TCR⁺/IG⁺; (3) TET2 and/or DNMT3A mutation alone group (7 cases): 3 cases were type Ⅱ, 4 cases were type Ⅲ, all cases were found with typical TFH phenotype; 2 cases had HRS-like cells, 2 cases with large B transformation, and atypically; (4) non-mutation group (3 cases), all were type Ⅱ, with typical TFH phenotype, with significant extra-GC FDC proliferation, without HRS-like cells and large B transformation. Atypically, 1 case was TCR^－/IG^－. Univariate analysis confirmed that higher density of EBV positive cell was independent adverse prognostic factors for both overall survival (OS) and progression free survival(PFS), (P=0.017 and P=0.046). CONCLUSION Pathological diagnoses of ALTL cases with HRS-like cells, large B transformation or type Ⅰ are difficult. Although TCR/IG gene rearrangement test is helpful but still with limitation. TES involving RHOA, IDH2, TET2, DNMT3A can robustly assist in the differential diagnosis of those difficult cases. Higher density of EBV positive cells counts in tumor tissue might be an indicator for poor survival.
Humans ; Epstein-Barr Virus Infections/genetics* ; Herpesvirus 4, Human/genetics* ; T-Lymphocytes, Helper-Inducer/pathology* ; Immunoblastic Lymphadenopathy/pathology* ; Lymphoma, T-Cell, Peripheral/pathology* ; Receptors, Antigen, T-Cell

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice ; Animals ; Tumor Suppressor Protein p53/metabolism* ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Myocardium/metabolism* ; Myocardial Infarction/drug therapy* ; Apoptosis ; MicroRNAs/metabolism*

AIM: To analyze the stability of different concentrations of fluorescein sodium solution on the detection of tear break-up time(TBUT).METHODS:A retrospective study. A total of 150 cases(150 eyes)who came to our dry eye clinic with good cooperation from August 2019 to September 2021 were selected for the study, and the subjects were randomly divided into five groups, which were fluorescein sodium(FLS, 0.5%), FLS(1.0%), FLS(1.5%), FLS(2.0%)and fluorescein sodium parallel(FLSP), with 30 patients in each group(all the right eyes were the subject eyes). Each group was dripped with the corresponding fluorescein sodium. The FLSP group was the fluorescent test strip detection group. The slit lamp image scores of different concentration groups were compared, the survival time of sodium fluorescein at the instant, 2, 5, 10, 15 and 30min points was observed in each group, and the mean value of TBUT in each group was recorded.RESULTS: The image score of FLS(0.5%)group was significantly higher than that of the other four groups(t=7.746, 21.483, 116.190, 38.730, all P<0.01). The image score of FLS(1.0%)group was significantly higher than that of FLS(1.5%)and FLS(2.0%)group(t=10.742, 15.492, all P<0.01). The survival time of fluorescein in FLS(0.5%)group was significantly shorter than that of the other four groups(t=8.226, 7.458, 9.159, 12.347, all P<0.01). The survival time of fluorescein in FLS(1.5%)group was significantly longer than that of FLS(1.0%)and FLS(2.0%)group(t=15.428, 13.274, all P<0.05). TBUT in FLS(0.5%)group was significantly higher than that of the other four groups at 2min(t=22.767, 22.345, 15.494, 17.213, all P<0.01), and was significantly lower than that of the other four groups at 10min(t=23.266, 25.353, 10.183, 22.025, all P<0.01). The mean first TBUT of FLS(1.5%)group was significantly shorter than that of the other four groups(t=25.236, 21.374, 19.658, 72.341, all P<0.01), and the mean first TBUT of FLSP group was significantly longer than that of the other four groups(t=22.487, 30.267, 60.247, 40.857, all P<0.01). There was no significant correlation between TBUT and ocular surface disease index(OSDI)and tear river height(rs=-0.072, 0.219, P=0.689, 0.112). TBUT was positively correlated with tear secretion(rs=0.674, P<0.01).CONCLUSION: FLS(0.5%)had higher image quality but it was only suitable for observing staining within 5min, and the FLSP group was more suitable for clinical observation of corneal fluorescence staining for a longer period; FLS(1.5%)was the most stable and reliable concentration and dose for the detection of TBUT.

OBJECTIVE: To compare the clinical efficacy of lengthened proximal femoral nail anti-rotation(PFNA) combined with minimally invasive percutaneous plate osteosynthesis(MIPPO) and common PFNA in the treatment of AO-A3.3 intertrochanteric fracture. METHODS: The clinical data of 58 patients with AO-A3.3 intertrochanteric fracture treated from January 2015 to April 2020 were retrospectively analyzed. Among them, 27 patients were treated with extended PFNA + MIPPO plate to reconstruct the lateral wall (group A), and 31 patients were treated with closed reduction and PFNA fixation (group B). The bleeding volume, operation time, femoral neck length and tip apex distance(TAD), fracture healing time and postoperative complications were observed and compared between two groups. Harris score was used to evaluate hip joint function 10 months after operation. RESULTS: All patients were followed up for 12 to 28 months. The incision healed well after operation. The bleeding volume and operation time of group A were significantly more than that of group B (P<0.05), and the fracture healing time of group A was significantly less than that of group B(P<0.05). There was no significant difference in the length of femoral neck between two groups at 2 days after operation(P>0.05). The length of femoral neck at 6 months after operation in each group was shorter than that at 2 days after operation(P<0.05), and the shortening of femoral neck at 6 months after operation in group B was significantly shorter than that in group A(P<0.05). There was no significant difference in TAD values between two groups at the same time point(P>0.05) at 2 days and 6 months after operation. There was no significant difference in TAD values between 2 days and 6 months after operation(P>0.05). The incidence of complications in group B was significantly higher than that in group A(P<0.05). The Harris scores of hip joint function in group A were higher than those in group B 10 months after operation (P<0.05). CONCLUSION Compared with the treatment of AO-A3 femoral intertrochanteric fracture with closed reduction and PFNA fixation, the lengthened PFNA combined with MIPPO small plate for reconstruction and fixation of the lateral wall can promote the fracture healing, improve the patient's functional recovery, and significantly reduce the complications.
Humans ; Bone Nails ; Fracture Fixation, Intramedullary ; Retrospective Studies ; Hip Fractures/surgery* ; Bone Plates ; Femoral Fractures/surgery*