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

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.

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.

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

Objective The traditional round incision or cross incision brain harvesting method can not meet the requirements of protecting the donor's remains. In this study, the method of brain removal through a posterior incision on the scalp of both ears was proposed, which effectively protected the donor's remains. Methods Adopting the incision 2. 0 cm above the external occipital protuberance to the most front edge of the auricle to obtain a complete brain. Results The incision did not involve the head and face skin, which was small and conducive to suture repair and reduce exudation. Conclusion The incision effectively protects the donor' s remains, and it will be conducive to the establishment and development of the brain bank.

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

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

Obstructive sleep apnea (OSA) is a sleep disorder with a high incidence and severe impact on the human body, which can induce systemic chronic inflammatory responses. Chronic inflammation is an important cause of exacerbation of OSA and its associated complications. Nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) is an inflammasome that is widely found in epithelial cells and immune cells and plays an important role in inflammatory diseases as an important component of innate immunity. Research evidence suggests that the activation of NLRP3 inflammasomes can exacerbate the damage to neurons, endothelial cells, lung and kidney caused by OSA, and these effects can be eliminated by genetic or pharmacological deletion of NLRP3. Targeting inhibition of NLRP3 inflammasome may serve as a co-therapeutic strategy for OSA-induced related complications. This article reviews NLRP3 inflammasome and its mechanism in OSA-related concurrent diseases, which can provide scientific basis for prevention and intervention of OSA and its related complications.
Humans ; Inflammasomes ; Endothelial Cells ; NLR Family, Pyrin Domain-Containing 3 Protein ; Inflammation ; Sleep Apnea, Obstructive ; Nucleotides