Background/Aims: The pathophysiology of refractory gastroesophageal reflux disease (RGERD), which differs from proton pump inhibitor dependent gastroesophageal reflux disease (DGERD), remains incompletely elucidated. This study aims to compare esophageal motility patterns, transdiaphragmatic pressure gradients (TPG), and reflux profiles between RGERD and DGERD patients, and to delineate dynamic pressure gradient-esophagogastric junction (EGJ) interactions in these patients. Methods: In this retrospective study, 274 patients who underwent 24-hour impedance-pH monitoring and high-resolution manometry, along with an assessment of proton pump inhibitor responsiveness, were classified as RGERD (32.5%), DGERD (54.4%), or non-GERD (13.1%). Clinical characteristics, TPG, esophageal motility, and reflux metrics were compared between RGERD and DGERD patients. Subgroup analysis excluding hiatal hernia (HH) was conducted to investigate the pathophysiology of RGERD. Results: The RGERD group exhibited a significantly higher proportion of chest pain compared to the DGERD group. Regarding reflux profiles, RGERD patients without HH (RGERDHH- group) experienced increased weakly acidic reflux (P < 0.001) and prolonged bolus exposure (P = 0.006) compared to their counterparts (DGERDHH- group). Mechanistically, the RGERDHH- group showed reduced lower esophageal sphincter basal pressure (P = 0.010) and EGJ contractile integral (P = 0.005). Notably, following a wet-swallow, the RGERDHH- group experienced the significant elevation in gastric pressure and TPG. Correlation analyses revealed weakly acidic reflux and bolus exposure were positively correlated with gastric pressure variation, and inversely correlated with lower esophageal sphincter basal pressure. Conclusions Transient gastric pressure elevation and compromised EGJ barrier function drive weakly acidic reflux and esophageal bolus exposure. This pressure gradient-barrier mismatch underpins the refractoriness of RGERD.

Objective: To analyze the implementation status of the “Three-Exemptions” policy for voluntary blood donation in China by taking Shandong Province as a case study, explore the sociodemographic characteristics of policy beneficiaries and the distribution differences in blood donation frequencies, so as to provide practical references for improving the honor incentive system of voluntary blood donation and stabilizing the blood donation team. Methods: Excel was used to sort out and summarize the policy documents from 31 provincial-level administrative regions of China (excluding Hong Kong, Macao and Taiwan), and its implementation models, temporal characteristics and implementation basis were analyzed. Using 238 193 policy beneficiaries in Shandong Province as the research objects, Stata was adopted for descriptive statistical analysis of sociodemographic characteristics including gender, age, educational background and occupation. The Mann-Whitney U test and Kruskal-Wallis H test were performed to compare the distribution differences of blood donation frequencies among populations with different characteristics. Results: The “Three Exemption” policy has been implemented in 29 provinces nationwide, forming five differentiated implementation models. Specifically, 45.16% of the regions adopted province-wide unified implementation, 32.26% adopted partial prefecture-level city implementation, 12.90% adopted partial clause implementation, 3.23% adopted encouraging implementation, and 6.45% had not implemented the policy. The period from 2023 to 2026 witnessed the concentrated promotion of the policy. In Shandong Province, the beneficiaries were mainly males (82.08%), middle-aged individuals aged 40-60 years (71.78%), groups with junior and senior high school education (56.57%), and staff employees (30.60%). The distribution of blood donation frequencies showed that nearly 60% (56.95%) of the beneficiaries had donated blood 20 to 29 times. Statistically significant differences in donation frequency distributions were observed across genders, age groups, educational backgrounds, and occupations (all P<0.05). Further analysis revealed that the proportion of males with 40 or more blood donations was higher than that of females (24.32% vs 15.60%), while females had a higher proportion of 20-29 blood donations than males (65.98% vs 54.99%). With the increase of age, the proportion of those with 20-29 blood donations gradually decreased, whereas the proportion of those with≥40 blood donations gradually increased. Conclusion: The coverage of the “Three Exemptions” policy for voluntary blood donation in China continues to expand. However, there is still room for optimization in terms of policy implementation standards, population structure adaptation and incentive gradient design. Future efforts should strengthen national top-level design to balance regional development gaps. Moreover, hierarchical and targeted incentive and publicity strategies combined with population structural characteristics should be implemented to enhance public enthusiasm for voluntary blood donation.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

ObjectiveTo investigate the effect of Gelian Tiaotang pills on renal fibrosis in db/db mice based on the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 （NLRP3）/cysteinyl aspartate-specific proteinase （Caspase）-1/gasdermin D （GSDMD） signaling pathway. MethodsForty db/db mice were randomly assigned into model， positive control （0.001 3 g·kg·d^-1 dapagliflozin suspension）， and high-， medium-， and low-dose Gelian Tiaotang pills （3.12， 1.56， and 0.78 g·kg·d^-1 suspension of Gelian Tiaotang pills， respectively） groups， with 8 mice in each group. Eight db/m mice were selected as the normal group. The normal group and model group were given equal volumes of pure water， while the drug interventions groups were administrated with corresponding agents by gavage once a day for 12 consecutive weeks. The general conditions of mice were observed daily. The fasting blood glucose （FBG） and body mass were measured every 4 weeks. Kidneys were weighed after sampling， and the kidney index was calculated. An automatic biochemical analyzer was used to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， serum creatinine （SCr）， and blood urea nitrogen （BUN）. The pathological changes， extracellular matrix deposition， and renal fibrosis degree were examined by hematoxylin-eosin， periodic acid-schiff （PAS）， and Masson staining， respectively. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin （IL）-1β and IL-18 in the renal tissue. Immunohistochemistry （IHC） was used to detect the localization and expression of fibronectin and collagen Ⅰ in the renal tissue. Western blot was employed to determine the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， and GSDMD-N in the renal tissue. ResultsCompared with the normal group， the model group generally had poor general states and increases in the body mass， kidney weight， kidney index， and levels of FBG， TG， TC， SCr， and BUN （P<0.01）. In addition， glomerular pyknosis， increased matrix， vacuolar degeneration of renal tubular epithelial cells， and interstitial infiltration of inflammatory cells were observed in the model group （P<0.01）， together with rises in the levels of IL-1β and IL-18 in the renal tissue （P<0.01） and up-regulated protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.01）. Compared with the model group， 12 weeks of drug interventions reduced the body mass， kidney weight， and kidney index and lowered the levels of FBG， TG， TC， SCr， and BUN in the serum and IL-1β and IL-18 in the renal tissue （P<0.05， P<0.01）. Furthermore， drug interventions ameliorated the renal lesions and down-regulated the protein levels of NLRP3， Caspase-1， cleaved Caspase-1， GSDMD， GSDMD-N， fibronectin， and collagen Ⅰ in the renal tissue （P<0.05， P<0.01）. The high-dose group of Gelian Tiaotang pills had the best effects. ConclusionGelian Tiaotang pills may inhibit pyroptosis and reduce inflammatory responses by regulating the NLRP3/Caspase-1/GSDMD signaling pathway， thus delaying the process of renal fibrosis in diabetes.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

OBJECTIVE: To explore the application effect of grid locator in hip arthroscopy for the treatment of femoral acetabular impingement (FAI). METHODS: Total of 50 patients of FAI were treated by arthroscopic hip joint surgery for from January 2020 to January 2021, and were divided into two groups according to intraoperative positioning methods. Among them, 27 cases in the positioner group were treated by hip arthroscopy assisted by grid positioner including 10 males and 17 females with a mean age of (35.91±9.92) years old. In the non-locator group, 23 cases were treated with hip arthroscopy by positioning puncture according to the operator's experience including 12 males and 11 females with a mean age of (36.01±11.03) years old. Intraoperative fluoroscopy times, puncture time, adjusted puncture times and operation time of two groups were compared. The α Angle and lateral central edge(LCE) angle of hip joint were measured and compared before and after operation. Four evaluation indexes were recorded and compared, including pain visual analogue scale(VAS), hip Harris score, non-inflammatory hip joint score (NAHS), hip joint activities of daily living (HOS-ADL). RESULTS: All patients were followed up for 6 to 12 months with an average of (18.69±3.72) months. The α angle and LCE angle of hip joint at 1 month after operation were decreased in both groups(P<0.05), but there was no significant difference between groups(P>0.05). VAS, hip Harris score, NAHS and HOS-ADL score after operation were higher than those before operation(P<0.05), but there was no statistical significance between groups (P>0.05). Intraoperative fluoroscopy times(6.04±1.13), puncture time(13.19±3.52) min, puncture adjustment times(4.59±1.55) and operation time(48.28±3.38) min in the positioner group were less (shorter) than those of (13.43±2.56), (22.39±2.93) min, (10.43±3.33), (62.25±5.73) min in the non-positioner group(P<0.05). No postoperative complications occurred in both groups, and the pain was significantly relieved. CONCLUSION The application of hip arthroscopy in the treatment of femoral acetabular impingement sign can obtain good postoperative results. Compared with the traditional positioning method, the grid locator can improve the accuracy of skin positioning point, shorten the puncture time, reduce the number of fluoroscopy, and improve the efficiency of surgical puncture.
Humans ; Male ; Female ; Arthroscopy/instrumentation* ; Femoracetabular Impingement/physiopathology* ; Adult ; Middle Aged ; Hip Joint/surgery*

OBJECTIVE: To explore the effect and mechanism of DNA methyltransferase 1 (DNMT1) knockout on the inhibition of acute myeloid leukemia (AML) by natural killer (NK) cells. METHODS: The peripheral blood NK cells of AML patients and controls were collected, and the mRNA and protein level of DNMT1 were measured by PCR and Western blot, respectively. The DNMT1 knockout mice were constructed to obtain NK^DNMT1-/- cells. The NK cells were stimulated with interleukin (IL)-12, IL-15, and IL-18 to construct memory NK cells, and then the interferon-γ (IFN-γ) levels were measured by ELISA. After co-culturing with memory NK cells and HL60 cells, the killing effect of NK^DNMT1-/- cells on HL60 cells was detected by LDH assay. Then, the HL60 cell apoptosis and NK cell NKG2D level were measured by flow cytometry. The perforin and granzyme B protein levels of NK cells were measured by Western blot. The AML model mice were constructed by injecting HL60 cells into the tail vein, meanwhile, memory NK cells were also injected, and then the mouse weights, CD33 positive rates, and survival time were detected. RESULTS: The mRNA and protein levels of DNMT1 in NK cells of AML patients were significantly higher than those in the control group (both P < 0.01), while the IFN-γ level induced by interleukin was significantly lower than that in the control group (P < 0.05). Compared with NK^DNMT1+/+ cells, the ability of NK^DNMT1-/- cells to secrete IFN-γ after interleukin stimulation was significantly increased (P < 0.05). The killing and apoptosis-inducing effects of NK^DNMT1-/- cells on HL60 cells were significantly stronger than those of NK^DNMT1+/+ cells (both P < 0.05). The NKG2D level and expression of perforin and granzyme B of NK^DNMT1-/- cells were significantly increased compared with NK^DNMT1+/+ cells (all P < 0.05). Compared with AML mice injected with NK^DNMT1+/+ cells, AML mice injected with NK^DNMT1-/- cells showed significantly increased body weight, decreased CD33 positive rate, and prolonged survival time (all P < 0.05). CONCLUSION Knocking out DNMT1 can enhance the inhibitory effect of NK cells on AML, which may be related to enhancing NK cell memory function.
Killer Cells, Natural/metabolism* ; Animals ; Leukemia, Myeloid, Acute ; Humans ; DNA (Cytosine-5-)-Methyltransferase 1 ; Mice ; Mice, Knockout ; HL-60 Cells ; Apoptosis ; Interferon-gamma/metabolism* ; Granzymes/metabolism* ; Perforin/metabolism* ; NK Cell Lectin-Like Receptor Subfamily K/metabolism*

OBJECTIVE: To investigate the effect of traditional Chinese Five-body balance exercise on patients with preserved ratio impaired spirometry (PRISm). METHODS: Fifteen patients with PRISm and 15 patients diagnosed with chronic obstructive pulmonary disease (COPD) were recruited from the Outpatient Department of Guang'anmen Hospital and Beijing Niujie Health Service Center from April to December, 2023. Participants in both groups attended supervised Five-body balance exercise training twice a week for 12 weeks. Patients with COPD continued their regular medication regimen during the intervention period. The endpoints were mean changes in the 6-min walk test (6MWT), St. George's Respiratory Questionnaire (SGRQ) score, cardiopulmonary exercise testing (CPET), pulmonary function, and scores of COPD assessment test (CAT), modified British Medical Research Council, Self-Rating Anxiety Scale, and Self-Rating Depression Scale from baseline to 12 weeks. Adverse events were monitored throughout the study. RESULTS: The PRISm group showed a significant improvement from baseline to week 12 in 6MWT, SGRQ symptom score, and forced vital capacity (FVC) compared to the COPD group (P<0.05). No significant between-group changes were observed in other outcome measurements (P>0.05). In addition, compared with baseline, both groups exhibited improvements in 6MWT, SGRQ score, and CPET at week 12 (P<0.05). The PRISm group also showed a significant increase in forced expiratory volume in 1 s and FVC, as well as a significant decrease in CAT score at week 12 (P<0.05). No adverse events were reported. CONCLUSION Patients with PRISm may benefit from Five-body balance exercise training, which can improve the exercise capacity, health-related quality of life, and lung function. (Registration No. ChiCTR2200059290).
Humans ; Spirometry ; Male ; Female ; Pulmonary Disease, Chronic Obstructive/therapy* ; Lung/physiopathology* ; Middle Aged ; Exercise Tolerance/physiology* ; Exercise Therapy ; Aged ; Medicine, Chinese Traditional ; Respiratory Function Tests ; East Asian People

Objective To analyze the correlation between hemoglobin(Hb),anemia,and sarcopenia in the elderly population in Chongqing communities.Methods A cross-sectional study was conducted on elderly individuals who underwent healthy examinations at 5 community health service centers in Chongqing from March to August 2023.Demographic characteristics,social factors,body composition measurement,grip strength,6-meter gait speed and blood tests were assessed.Receiver operating characteristic(ROC)curve was utilized to evaluate the accuracy of Hb in predicting sarcopenia,and the Youden index was employed to determine the optimal Hb cut-off value for diagnosing sarcopenia and its components.Both unadjusted and adjusted logistic regression analyses were performed to examine the relationship between Hb and anemia with sarcopenia and its components.Results A total of 531 elderly populations were included,with an average age of(71.1±6.5)years.The overall prevalence of sarcopenia was 13.6%(72/531),including 29 males(40.3%)and 43 females(59.7%).Unadjusted analyses showed that Hb was correlated with sarcopenia,decreased muscle mass,slower gait speed,and reduced grip strength(P<0.05).After adjusting for all potential risk factors,Hb was still significantly associated with sarcopenia and reduced grip strength(P<0.05).For every 10 g/L increase in Hb,the risk of sarcopenia decreased by 2.3%,and the risk of reduced grip strength decreased by 1.7%(P<0.05).Anemia was correlated with sarcopenia,reduced muscle mass,and decreased grip strength in unadjusted analyses(P<0.05),while the correlation between anemia and reduced grip strength remained significant after adjustment for all potential risk factors(P<0.05).The optimal Hb cut-off value for diagnosing sarcopenia in males and females were 148 g/L and 128 g/L,respectively.Conclusions Hb is an independent risk factor for sarcopenia and reduced grip strength.Anemia is associated with sarcopenia,but is not an independent risk factor for sarcopenia.

Objective To investigate the factors influencing pathologic complete response(pCR)after neoadjuvant chemotherapy(NAC)and its correlation with prognosis in patients with human epidermal growth factor receptor 2(HER2)-low breast cancer.Methods A retrospective analysis was conducted on patients with HER2-low breast cancer who underwent NAC at the Second Affiliated Hospital of Jiujiang College from February 28,2018 to February 28,2021.Patients were divided into pCR group(achieved pCR,n=143)and non-pCR group(did not achieve pCR,n=300)based on pCR status.General clinicopathological data were collected and compared between the two groups,including age,surgical method,NAC regimen,postoperative radiotherapy,clinical tumor stage,tumor cT stage,tumor cN stage,pathological type,tumor Nottingham grade,hormone receptor(HR)status,Ki-67 status,menopausal status,and endocrine therapy.Binary logistic regression analysis was used to identify factors influencing pCR after NAC.Propensity score matching(1:1)was employed to balance baseline characteristics between the two groups.The matched groups'baseline data were compared.Kaplan-Meier method was used for survival analysis of the matched cohorts.Multivariate Cox proportional hazards regression models were used to analyze the independent influence of pCR on disease-free survival(DFS)and overall survival(OS)in HER2-low breast cancer after matching.Results A total of 443 patients with HER2-low breast cancer receiving NAC were included,with a mean age of(49.5±8.0)years.Binary logistic regression analysis identified clinical tumor stage(OR=0.498,95%CI 0.267-0.930),HR status(OR=0.513,95%CI 0.328-0.801),Ki-67 status(OR=2.580,95%CI 1.366-4.874),tumor Nottingham grade Ⅲ(OR=3.197,95%CI 1.147-8.910),and endocrine therapy(OR=0.513,95%CI 0.328-0.801)as independent factors influencing pCR after NAC(P<0.05).After propensity score matching,80 patients remained in each group(PCR and non-PCR).No significant differences were found in clinicopathological characteristics between the matched groups(P>0.05).The median follow-up time was 45.0 months(95%CI 43.1-46.9)for pCR group and 43.0 months(95%CI 41.0-45.0)for non-pCR group.The DFS rate was significantly higher in pCR group than that in non-pCR group(87.5%vs.70.0%,P=0.004),but there was no significant difference in OS rate(88.8%vs.85.0%,P=0.438).Multivariate Cox regression analysis showed that pCR was an independent factor influencing on DFS(HR=0.312,95%CI 0.142-0.688,P=0.004),but not OS in HER2-low breast cancer patients.Conclusions Patients with HER2-low breast cancer who have a lower clinical tumor stage,HR-negative status,high Ki-67 expression,high tumor Nottingham grade,and absence of endocrine therapy are more likely to achieve pCR.Achieving pCR prolongs DFS significantly but does not significantly improve OS in these patients.