This study aimed to explore the molecular mechanism of rubioncolin C(RuC) in inhibiting gastric cancer(GC). AGS and MGC803 cell lines were selected as cellular models. After treating the cells with RuC at different concentrations, the effects of RuC on the proliferation ability of GC cells were assessed using the CCK-8 method, real-time cellular analysis(RTCA), and colony formation assays. Transmission electron microscopy was used to observe subcellular structural changes. Immunofluorescence was applied to detect LC3 fluorescent foci. Acridine orange staining was used to evaluate the state of intracellular lysosomes. Western blot was employed to detect the expression of autophagy-related proteins LC3Ⅱ, P62, and lysosomal cathepsin D(CTSD). The SuperPred online tool was used to predict the target proteins that bound to RuC, and molecular docking analysis was conducted to identify the interaction sites between RuC and CTSD. The drug affinity responsive target stability(DARTS) assay was performed to detect the direct binding interaction between RuC and CTSD. The results showed that RuC significantly inhibited the proliferation and colony formation of GC cells at low concentrations, with 24-hour half-maximal inhibitory concentrations(IC_(50)) of 3.422 and 2.697 μmol·L~(-1) for AGS and MGC803 cells, respectively. After 24 hours of treatment with RuC at concentrations of 1, 2, and 3 μmol·L~(-1), the colony formation rates for AGS cells were 61.0%±1.5%, 28.0%±0.5%, and 18.2%±0.5%, respectively, while the rates for MGC803 cells were 56.0%±0.5%, 23.3%±1.0%, and 11.8%±1.0%, all of which were significantly reduced. Transmission electron microscopy revealed that RuC promoted an increase in autophagosome formation in GC cells. Immunofluorescence detection showed that LC3 fluorescent foci of GC cells increased with the increase in RuC dose. RuC up-regulated the expression of autophagy-related proteins LC3Ⅱ and P62 in GC cells. Acridine orange staining indicated that RuC altered the acidic environment of lysosomes. SuperPred online prediction identified CTSD as a potential target protein of RuC. Western blot analysis revealed that RuC induced the up-regulation of the inactive precursor of CTSD in GC cells. CTSD activity assays indicated that RuC reduced the activity of CTSD. Molecular docking simulations found that RuC bound to the substrate-binding region of CTSD, forming hydrogen bonds with the Tyr205 and Asp231 residues. Microscale thermophoresis and DARTS assays further confirmed that RuC directly bound to CTSD. In summary, RuC inhibits lysosomal activity by targeting and down-regulating the expression of CTSD, thereby inducing autophagosome accumulation in GC cells.
Humans ; Stomach Neoplasms/enzymology* ; Cathepsin D/chemistry* ; Cell Line, Tumor ; Molecular Docking Simulation ; Cell Proliferation/drug effects* ; Autophagosomes/metabolism* ; Autophagy/drug effects*

OBJECTIVES: To analyze the clinical characteristics of diffuse panbronchiolitis (DPB) in children and to enhance the clinical diagnosis and treatment of this disease. METHODS: A retrospective analysis was conducted on the clinical data of 6 children diagnosed with DPB who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2019. RESULTS: Among the 6 patients, there were 2 males and 4 females; the age at diagnosis ranged from 7 to 12 years. All patients presented with cough, sputum production, and exertional dyspnea, and all had a history of sinusitis. Two cases showed positive serum cold agglutinin tests, and 5 cases exhibited pathological changes consistent with chronic bronchiolitis. High-resolution chest CT in all patients revealed centrilobular nodules diffusely distributed throughout both lungs with a tree-in-bud appearance. Five patients received low-dose azithromycin maintenance therapy, but 3 showed inadequate treatment response. After empirical anti-tuberculosis treatment, non-tuberculous Mycobacteria were found in the bronchoalveolar lavage fluid. Follow-up over 2 years showed 1 case cured, 3 cases significantly improved, and 2 cases partially improved. CONCLUSIONS The clinical presentation of DPB is non-specific and can easily lead to misdiagnosis. In cases where DPB is clinically diagnosed but does not show improvement with low-dose azithromycin treatment, special infections should be considered.
Humans ; Male ; Female ; Bronchiolitis/drug therapy* ; Retrospective Studies ; Child ; Haemophilus Infections/diagnosis*

OBJECTIVE: To explore whether hydrocortisone can improve the prognosis of patients with severe community-acquired pneumonia (sCAP) by Meta-analysis. METHODS: Randomized controlled trial (RCT) on hydrocortisone in the treatment of sCAP were extracted from the database including PubMed, Cochrane library, Web of Science, and Embase, and the search time was up to April 29, 2023. The patients in the standard treatment group received standard treatment such as antibiotics and supportive care, while those in the hydrocortisone group received hydrocortisone treatment on the basis of standard treatment. Meta-analysis was used to compare the mortality, duration of mechanical ventilation, mechanical ventilation rate and incidence of adverse reactions (hyperglycemia, gastrointestinal bleeding, secondary infection) between the two groups. The risk of literature bias was assessed. The studies that might have publication bias were corrected by the subtraction and complementation method. At the same time, trial sequential analysis (TSA) was conducted. RESULTS: A total of 5 RCTs involving 1 031 patients were finally enrolled, including 494 patients in the standard treatment group and 537 patients in the hydrocortisone group. Among the 5 studies, the research site of 2 studies was in the mixed ward. Considering the inclusion characteristics of the study population, there was doubt whether its research object was sCAP patients, which might have a certain impact on the results and introduce potential bias. Meta-analysis showed that the mortality in the hydrocortisone group was significantly lower than that in the standard treatment group [6.0% vs. 14.0%; odds ratio (OR) = 0.38, 95% confidence interval (95%CI) was 0.25-0.59, P < 0.01; I² = 9%]. The studies that were asymmetric were corrected by the reduction and supplementation method. Even after filling the missing studies, hydrocortisone could still reduce the death risk of the patient (OR = 0.49, 95%CI was 0.32-0.73, P < 0.01; I² = 31%). TSA showed that the average mortality of the standard treatment group was about 14.0%, and that of the hydrocortisone group was about 6.0%, with a relative risk reduction (RRR) = 57%. The calculated sample size was 699 cases, and the actual sample size was 1 031 cases. The actual sample size exceeded the required sample size, and the Z-curve crossed the O'Brien-Fleming boundary and the curve corresponding to P = 0.05, it meant that hydrocortisone could effectively reduce the mortality of sCAP. Compared with the standard treatment group, no statistical difference in the duration of mechanical ventilation was found in the hydrocortisone group [mean difference (MD) = -3.26, 95%CI was -6.72-0.21, P = 0.07; I² = 0%], but the 8-day mechanical ventilation rate was significantly lowered (19.5% vs. 55.4%; OR = 0.24, 95%CI was 0.12-0.45, P < 0.01; I² = 0%), and also no significantly difference was found in the incidence of hyperglycemia (54.3% vs. 44.6%, OR = 1.26, 95%CI was 0.56-2.84, P = 0.58; I² = 61%), gastrointestinal bleeding (2.5% vs. 3.6%; OR = 0.70, 95%CI was 0.34-1.46, P = 0.34; I² = 0%) and secondary infection (9.2% vs. 11.5%; OR = 0.46, 95%CI was 0.06-3.35, P = 0.45; I² = 53%). CONCLUSION Hydrocortisone can reduce the mortality rate of sCAP patients, decrease their need for mechanical ventilation, and does not increase the risk of hyperglycemia, gastrointestinal bleeding, or secondary infections.
Humans ; Hydrocortisone/therapeutic use* ; Community-Acquired Infections/drug therapy* ; Pneumonia/drug therapy* ; Randomized Controlled Trials as Topic ; Respiration, Artificial ; Community-Acquired Pneumonia

Objective To report the diagnosis,treatment,and verification process of a patient with sex development disorder whose chromosomal karyotype and genetic test results are inconsistent,and conduct a literature review to improve the understanding of the mosaic status of sexual development disorders.Methods A 14-year-old patient presented with primary amenorrhea on April 3,2020,at the First Affiliated Hospital of Hebei North University,exhibiting female sexual characteristics.The patient underwent ultrasonic/magnetic resonance imaging of gonads,assessment of gonadal axis function,chromosomal karyotype,and molecular genetic testing,as well as pelvic exploration,malignant gonads resection,and hormone replacement therapy,resulting in drug-induced menstruation.During the diagnosis and treatment,it was found that the patient's chromosomal karyotype analysis was inconsistent with the molecular genetic test results.Subsequently,samples from the three germ layer cells were taken,and fluorescence in situ hybridization(FISH)was used to detect the sex chromosomes in each germ layer cell.XY probes were used to label the gonadal pathological sections to explore the distribution differences of the Y chromosome in the gonads,and changes in anti-Müllerian hormone(AMH)levels before and after surgery were compared.Databases such as Wanfang and PubMed were searched to summarize relevant cohort study literature and understand the current status of research on this disease.Results The patient's body exhibited a significant differences between the 45,X and 46,XY cell lines in different germ layers and within the same layer tissues.The proportion of 45,X in buccal mucosal cells derived from the ectoderm was 30%(6/20),in peripheral blood lymphocytes derived from the mesoderm was 9.7%(11/114),and in bladder shed cells derived from endoderm was 20.4%(22/108).The gonadal pathological sections labeled with XY probes indicated a mosaic state with a reduced Y-chromosome;where the epididymal structure area had a 45,X cell line mosaic of 50.0%,and the malignant area had a normal"Y"content.After gonadal resection,AMH levels significantly dropped from 7.28 pmol/L to＜0.07 pmol/L.Literature review revealed that patients with 45,X/46,XY have a complex phenotype spectrum,most with features of Turner syndrome,and female phenotypes are at risk of gonadal tumors.Conclusions In the diagnosis of difficult cases of sex development disorders,when performing peripheral blood karyotype testing,the number of counted cells and analyzed cells should be increased as much as possible,and multi-germ layer cell sampling should be performed.Gonads with a high"Y"mosaic rate are more prone to malignancy in the abdominal cavity.Detecting AMH levels can distinguish cryptorchidism and anorchidism in sexual development disorders with Y chromosomes.

Objective To investigate the clinical and pathological characteristics of adrenal cortical carcinoma(ACC),compare differences between hypercortisolism and non-functional ACC,and assess the diagnostic value of indicators such as Ki-67 index.Methods The clinical data of 57 ACC patients admitted to the First Medical Center of Chinese PLA General Hospital from January 2015 to March 2025 were retrospectively analyzed.According to the results of endocrine function assessment,47 of these patients were divided into hypercortisolism group(n=19)and non-functional group(n=28).The differences in clinical and pathological characteristics between the two groups were compared,and non-parametric tests and Spearman correlation analysis were used to explore the relationship between Ki-67 index and tumor stage as well as imaging features.Results Among the 57 patients,there were 20 males and 37 females,with a male-to-female ratio of 1:1.85.The age ranged from 16 to 76 years,and the age at diagnosis was(48.7±13.3)years.The tumor diameter was(10.53±4.14)cm.The tumors were located on the right side in 12 cases(21.1%),on the left side in 34 cases(59.6%),and bilaterally in 11 cases(19.3%).Among them,16 cases(28.1%)were complicated with glucose metabolism disorders,31 cases(54.3%)had hypertension,and 20 cases(35.1%)had hypokalemia.According to ENSAT staging,there were 0 cases in stage Ⅰ,15 cases(26.3%)in stage Ⅱ,24 cases(42.1%)in stage Ⅲ,and 18 cases(31.6%)in stage Ⅳ.Endocrine function assessment was completed in 47 of the 57 patients,including 28 cases(59.6%)of non-functional ACC and 19 cases(40.4%)of hypercortisolism(including 1 case of hypercortisolism combined with increased sex hormone secretion).Compared with non-functional group,hypercortisolism group had a significantly higher prevalence of hypertension(P=0.014),later ENSAT stage(P=0.010),and a higher proportion of hypervascularization(P=0.048).The median Ki-67 index was 20%(10%-40%),showing no significant correlation with either the maximum tumor diameter or SUVmax value,but it was related to ENSAT staging,with Ki-67 index in stageⅣ patients being significantly higher than that in stage Ⅱ(P=0.032).Immunohistochemistry results showed that the positive rate of Inhibin-α was 84.8%,and the positive rate of Melan-A was 40.9%.Conclusions ACC is a rare malignant endocrine tumor.ACC patients with hypercortisolism are more likely to be complicated with hypertension,have later staging,and more common hypervascular manifestations.Clinically,their endocrine function should be prioritized for assessment,and more active treatment strategies should be adopted.Diagnosis should be combined with imaging characteristics(such as hypervascularization)and immunohistochemical indicators(Ki-67,Inhibin-α,Melan-A).The significant increase in Ki-67 is in the advanced stage can serve as an important prognostic indicator to guide individualized treatment.

OBJECTIVE: To compare effectiveness of injecting platelet-rich plasma (PRP) with different concentrations of leukocytes under ultrasound in treatment of supraspinatus tendon injury. METHODS: A clinical data of 30 patients with supraspinatus tendon injury, who met the selection criteria and were admitted between December 2022 and December 2023, was retrospectively analyzed. Thirty patients were treated with 4 injections of leukocyte-poor PRP (LP-PRP, n=10), leukocyte-rich PRP (LR-PRP, n=11), and triamcinolone ( n=9), with an interval of 7-10 days between each injection. There was no significant difference between groups ( P>0.05) in the age, gender, disease duration, affected shoulder side, Ellman classification, preoperative visual analogue scale (VAS) score, Constant score, Disabilities of the Arm, Shoulder, and Hand (DASH) score, and American Shoulder and Elbow Surgeons (ASES) score. At 1, 3, and 6 months after injection, the shoulder pain and function were evaluated by using the VAS score, Constant score, DASH score, and ASES score. MRI was conducted to observe supraspinatus tendon healing. RESULTS: No severe adverse reactions was observed in all groups. All patients were followed up 6-7 months, with an average of 6.5 months. After injection, the ASES score and Constant score gradually increased in the LR-PRP group and LP-PRP group, while the VAS score and DASH score decreased, with significant differences compared to before injection ( P<0.05). Except for no significant difference between 3 and 6 months after injection in LR-PRP group ( P>0.05), the above scores showed significant differences between different time points ( P<0.05). At 1 month after injection, the Constant score in triamcinolone group significantly increased compared to before injection, while the VAS score significantly decreased ( P<0.05). There was no significant difference in all scores between other time points in the triamcinolone group ( P>0.05). Except for 1 month after injection, there was no significant difference in Constant score and VAS score between groups ( P>0.05). At all other time points, the LR-PRP group and LP-PRP group had better scores than the triamcinolone group ( P<0.05). There was no significant difference between the LR-PRP group and the LP-PRP group ( P>0.05). MRI showed that only 4 patients in the LP-PRP group had signs of repair at the supraspinatus tendon injury site at 6 months after injection, while no significant tendon repair sign was observed in the other patients. CONCLUSION Compared with triamcinolone treatment, multiple injections of LP-PRP and LR-PRP under ultrasound can promote the recovery of shoulder joint function and significantly relieve pain in patients with supraspinatus tendon injury, and imaging improvement can be seen after LP-PRP treatment.
Humans ; Platelet-Rich Plasma ; Rotator Cuff Injuries/therapy* ; Female ; Male ; Treatment Outcome ; Pain Measurement ; Leukocytes ; Tendon Injuries/therapy* ; Middle Aged ; Ultrasonography ; Ultrasonography, Interventional ; Range of Motion, Articular ; Adult

Purpose/Significance To investigate and analyze the current status and influencing factors of digital health literacy(DHL)of the elderly,and to provide references for relevant departments.Method/Process The eHEALS scale is used to investigate the DHL status of 419 elderly people aged 60 and above in Shanghai through convenience sampling,and the influencing factors are explored through binary logistic regression analysis.Result/Conclusion Low education,smoking,and health anxiety are risk factors,while regular physical exami-nation is protective factor.Relevant departments should focus on the elderly people with lower education,and strengthen research and edu-cation on health examinations,smoking hazards,and the alleviation of anxiety.

Objectives:Fluid resuscitation is an important treatment for sepsis. However, the optimal choice of fluid is still controversial. This study aimed to investigate the effect of Sodium Bicarbonate Ringer’s Solution on the outcome of patients with sepsis.Methods:This was a single-center, prospective, randomized controlled clinical study, From July 2021 to June 2023, adult patients with Sepsis who met the diagnostic criteria of Sepsis 3.0 admitted to the Department of Critical Care Medicine of Jiangdu People's Hospital of Yangzhou were randomly assigned to the sodium bicarbonate ringer’s solution group or the normal saline group according to the random number table. Patients received either sodium bicarbonate ringer’s solution or normal saline as fluid for resuscitation and maintenance therapy. Clinicians determined the amount and rate of infusion based on volume assessment. The 30-day mortality, the degradation of endothelial glycocalyx degradation products at multiple time points, the mortality in intensive care unit (ICU), the incidence of major adverse renal events (MAKE30) within 30 days, and other clinical outcomes were compared between the two groups. Enzyme-Linked immunosorbent assay was used to determine the concentration of endothelial glycocalyx coating degradation products in peripheral blood. The count data were analyzed by χ 2 test, and the measurement data were analyzed by independent sample t test. Results:A total of 67 patients who met the inclusion criteria were enrolled during the study (32 patients in the sodium bicarbonate ringer’s solution group and 35 patients in the normal saline group). There were no significant differences in baseline data such as age, gender, underlying diseases, and SOFA score at enrollment between the two groups ( P>0.05).The 30-day mortality (28.1% vs. 40.0%), ICU mortality (15.6% vs. 20.0%) and MAKE30 (31.2% vs. 42.9%) in the sodium bicarbonate ringer’s solution group were lower than those in the normal saline group, but the differences were not statistically significant ( P>0.05). The levels of SCD-1(1317.3±206.9) pg/mL, HA (75.1±24.9) ng/mL and HS (75.6±13.8) ng/mL in the sodium bicarbonate ringer’s solution group were significantly lower than those in the normal saline group [(1514.6±264.9) pg/mL, (96.5±25.4) ng/mL, (85.8±15.8) ng/mL] on the third day (all P<0.05). Conclusion:Although the use of sodium bicarbonate ringer’s solution for resuscitation in sepsis patients cannot significantly reduce the 30-day mortality rate, but significantly reduce the degradation of polysaccharide coating, decrease the occurrence of hyperchloremia and acidosis.

Objective To explore the clinical effect of amniotic membrane transplantation combined with entropion correction for ocular surface and eyelid burns.Methods A total of 80 patients with ocular surface injury and lower eyelid entropion caused by chemical or thermal burns who received surgical treatment in our hospital were selected as the research objects.All patients received amniotic membrane transplantation combined with entropion correction.All patients were examined by slit-lamp microscope and photographed before and 8 weeks after surgery.The visual acuity changes,tear film rupture time and serum levels of vascular endothelial growth factor(VEGF),trans-forming growth factor β1(TGF-β1)and insulin growth factor 1(IGF-1)were compared before and 8 weeks after surgery.Eight weeks after surgery,exfoliated epithelial cells of the central cornea and limbus were collected and analyzed by PAS staining and immunofluorescence staining.Results At 8 weeks after surgery,the patient's ocular surface condition recovered well,eyelid entropion was successfully corrected,postoperative visual acuity was significantly better than that before surgery(P<0.05).Compared with before surgery,the tear film rupture time 8 weeks after surgery was significantly prolonged(P<0.05),and the serum VEGF,TGF-β1 and IGF-1 levels 8 weeks after surgery were significantly increased(P<0.05).PAS staining showed that there was no goblet cell in the central cornea and limbus.Immunofluorescence staining showed that cytokeratin 12(CK12)was highly expressed in the corneal epithelial cells,and low expressed in corneal limbal epithelial cells near the cornea.Conclusion Amniotic membrane transplantation combined with entropion correction has a significant therapeutic effect on patients with ocular burn,which can promote ocular surface repair,correct entropion,improve postoperative visual acuity,and achieve self-amplification of cornea stem cells.It is a safe and effective treatment method.

Objective: This study aimed to analyze clinical factors related to arterial stiffening and establish a risk prediction nomogram of arterial stiffening in the octogenarian(≥80 years). Methods: This study was a retrospective cross-sectional study, which enrolled the octogenarian elderly who underwent physical examination and secondary prevention intervention in the outpatient department of Chinese People's Liberation Army General Hospital from April 2022 to August 2022. Clinical data including demographics, biochemical indicators and medical history were collected. Brachial-ankle pulse wave velocity (baPWV) was detected during the clinical visit. Participants were divided into the control group (baPWV≤1 800 cm/s) and vascular sclerosis group (baPWV>1 800 cm/s). The risk factors of arterial stiffness were analyzed by univariate and logistic regression analysis, and the nomogram model was constructed by R programming language. The predictive effect of the nomogram model was evaluated by the receiver operating characteristic curve (ROC). Results: The median age of the 525 participants was 87.0 (82.0, 92.0) years, 504 (96.0%) were male, 82 in the control group, 443 in the vascular sclerosis group. The baPWV, age, systolic blood pressure, mean arterial pressure and diastolic blood pressure were significantly lower in the control group than those in the vascular sclerosis group (all P<0.05). Logistic regression analysis showed that high-density lipoprotein cholesterol, alanine aminotransferase and amylase were protective factors, and alkaline phosphatase and creatinine were risk factors of arterial stiffening (all P<0.05). The combined nomogram model scores including age, mean arterial pressure and the above five laboratory indicators indicated that mean arterial pressure and serum creatinine levels were strongly correlated with vascular sclerosis. The ROC curve suggested that the nomogram model had good prediction ability. Conclusions: Age, mean arterial pressure, high-density lipoprotein cholesterol, alanine aminotransferase, alkaline phosphatase, amylase and creatinine are independently determinants for increased vascular stiffness. The combined prediction model in this study can provide reference for individualized clinical risk prediction of vascular sclerosis in the octogenarian elderly.
Aged, 80 and over ; Humans ; Male ; Aged ; Female ; Ankle Brachial Index ; Vascular Stiffness/physiology* ; Octogenarians ; Retrospective Studies ; Cross-Sectional Studies ; Alanine Transaminase ; Alkaline Phosphatase ; Creatinine ; Sclerosis ; Pulse Wave Analysis ; Risk Factors ; Amylases ; Lipoproteins, HDL ; Cholesterol