This study aims to investigate the pathogenesis of precancerous lesions of gastric cancer(PLGC) and explore the potential molecular mechanism of Weifuchun Capsules(WFC) in treating PLGC via the nuclear factor-κB(NF-κB)/NOD-like receptor protein 3(NLRP3) inflammasome signaling pathway. Ninety male SPF-grade Wistar rats were randomized into a normal feeding group and a modeling group. The normal feeding group received a regular diet, while the modeling group was subjected to the disease-syndrome combined modeling of PLGC. Specifically, the rats had free access to the water containing 120 μg·mL~(-1) N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) and received a diet containing 0.05% ranitidine in an irregular feeding pattern(alternations between fasting and overfeeding). After 15 weeks, the rats in the normal feeding group were randomized into control, control-NF-κB activator betulinic acid(C-BA), and control-NF-κB inhibitor pyrrolidine dithiocarbamaten(C-PDTC) groups. Meanwhile, the rats in the modeling group continuously underwent the modeling procedure and were randomized into model, WFC, model-NF-κB activator(M-BA), and model-NF-κB inhibitor(M-PDTC) groups. The model group and control group were given aseptic water by intragastric administration, once a day. WFC was given at a dose(432 mg·kg~(-1)) 6 times the equivalent dose for adults(body weight: 60 kg) by gavage, once a day. The rats in the C-BA and M-BA groups were administrated with BA by intraperitoneal injection at a dose of 10 mg·kg~(-1), twice a week. The rats in the C-PDTC and M-PDTC groups were administrated with PDTC by intraperitoneal injection at a dose of 50 mg·kg~(-1), twice a week. The interventions were carried out for 4 weeks. Histopathological changes of the gastric mucosa were observed and scored by hematoxylin-eosin(HE) and alcian blue-periodic acid Sthiff(AB-PAS) staining. The levels of inflammatory cytokines including interleukin(IL)-1β, IL-6, IL-18, tumor necrosis factor-alpha(TNF-α), and IL-10 in the gastric tissue were determined by enzyme-linked immunosorbent assay(ELISA). The expression levels of proteins associated with the NF-κB/NLRP3 inflammasome in the gastric mucosa were determined by Western blot. The positive expression areas of proteins related to NF-κB/NLRP3 inflammasome in the gastric mucosa were measured by immunohistochemistry. The results showed that compared with the control group, the model, C-BA, and M-BA groups showed significantly risen scores of mucosal inflammation, degree of inflammatory activity, gland atrophy, and intestinal metaplasia, and the model and M-BA groups showed significanly risen scores of dysplasia. Compared with the model group, the WFC group demonstrated significantly declined scores of mucosal inflammation and degree of inflammatory activity, as well as declined scores of intestinal metaplasia and dysplasia. Compared with the control group, the model and C-BA groups showed significantly elevated levels of IL-1β, IL-6, IL-18, and TNF-α in the gastric tissue, and the model group showed significantly elevated level of IL-10. In addition, the model and C-BA groups showed significantly up-regulated expression of NF-κB p65, NLRP3, cysteine-aspartic acid protease 1(caspase-1), and apoptosis-associated speck-like protein containing a CARD(ASC) in the gastric mucosa and increased positive expression areas of NF-κB p65, NLRP3, and ASC. Compared with the model group, the WFC group showed significantly decreased levels of IL-1β, IL-6, IL-18, TNF-α, and IL-10 in the gastric tissue, and the M-PDTC group showed significantly lowered levels of IL-1β, IL-18, and TNF-α in the gastric mucosa. Both WFC and M-PDTC groups demonstrated significantly down-regulated expression levels of NF-κB p65, phosphorylated NF-κB p65(p-NF-κB p65), NLRP3, and caspase-1 in the gastric mucosa, along with significant decreases in the positive expression areas of NF-κB p65, NLRP3, and ASC. In conclusion, the pathogenesis of PLGC is closely related to the activation of the NF-κB/NLRP3 inflammasome signaling pathway. WFC can alleviate mucosal inflammation, inhibit glandular atrophy, partially reverse intestinal metaplasia, and reduce dysplasia to delay the process of inflammation-cancer transformation, and meanwhile it can effectively lower the levels of inflammatory cytokines and down-regulate the expression of pathway-related proteins in the stomach. Therefore, WFC may treat PLGC by inhibiting the NF-κB/NLRP3 inflammasome signaling pathway.
Animals ; Male ; NF-kappa B/genetics* ; Rats ; Rats, Wistar ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Stomach Neoplasms/pathology* ; Inflammasomes/genetics* ; Humans ; Precancerous Conditions/metabolism* ; Capsules

【Objective】 To explore the relationship between the storage time of leukodepleted red blood cells and transfusion adverse reactions by analyzing the occurrence of transfusion adverse reactions of patients after leukodepleted red blood cells transfusion from four hospitals. 【Methods】 By using the electronic medical record management system, the collection and transfusion dates of leukodepleted red blood cells from four hospitals in Enshi Prefecture from 2018 to 2022, as well as the information on transfusion adverse reactions, were retrieved. 【Results】 From 2018 to 2022, a total of 697 61 bags of leukodepleted red blood cells were transfused in four hospitals, resulting in 166 cases of transfusion adverse reactions, among which 93 were allergic reactions, 63 were non hemolytic febrile reactions, and 10 were others, with a total incidence rate of transfusion adverse reactions at 0.24%. The average storage time of leukodepleted red blood cells with and without transfusion adverse reactions was (20.25±6.31) and (19.88±5.50) days, respectively. With a storage time of 7 days as the threshold, the incidence of transfusion adverse reactions was the lowest for a storage time of 15~21 days. The incidence of transfusion adverse reactions of leukodepleted red blood cells in two groups (with storage days ≤21 days and >21 days) was not statistically significant(P>0.05). 【Conclusion】 Allergic reactions were the main type of transfusion adverse reaction caused by leukodepleted red blood cells, and the incidence of transfusion adverse reactions decreased and then increased with the prolongation of the storage time of leukodepleted red blood cells. There was no significant difference in the incidence of transfusion adverse reactions with leukodepleted red blood cells stored for ≤ 21 days and >21 days.

For a long time, the cultivation of medical students’ scientific research and innovation abilitymainly depends on scattered extracurricular scientific research activities. With limited students, unsystematic teaching and inadequate administrative guarantee, it often results in obvious weakness andinefficiency. Since 2002, the Biochemistry and Molecular Biology teaching team in Shantou UniversityMedical College has been working on a “3+X” model to nurture the scientific research and innovationability of medical students. Guided by the concepts of complementary development of science andeducation, student-centeredness, and Problem-based Learning, a model is established based on the‘HEART” professionalism courses and the academy culture specific to Shantou University. We also takefull advantage of the first-tier disciplines of biology, basic medicine and clinical medicine in ShantouUniversity and collaborate with other professional teaching teams. It is conceptualized in a framework thatembraces the comprehensive connotation of scientific research and innovation ability and adopts a corecurriculum system that runs through the 5-year medical undergraduate education. In this model, " 3" means " whole-person training", " whole-process training" and " omni-directional training" for medicalstudents; " X" refers to several confirmatory dimensions of the operational effectiveness of the " 3+X" model, including organizing medical students to participate in various forms of national college students’ innovative experimental research competitions, international college students’ academic seminars, writingand publishing academic papers by medical undergraduates as the first author, etc. The model proves tobe effective in cultivating the scientific research and innovation ability of medical students, hence settinga good example to solve the current problems in the cultivation of medical students’ scientific researchand innovation ability.

OBJECTIVES: To develop a new Chinese medicine (CM)-based drug and to evaluate its safety and effect for suppressing acute respiratory distress syndrome (ARDS) in COVID-19 patients. METHODS: A putative ARDS-suppressing drug Keguan-1 was first developed and then evaluated by a randomized, controlled two-arm trial. The two arms of the trial consist of a control therapy (alpha interferon inhalation, 50 µg twice daily; and lopinavir/ritonavir, 400 and 100 mg twice daily, respectively) and a testing therapy (control therapy plus Keguan-1 19.4 g twice daily) by random number table at 1:1 ratio with 24 cases each group. After 2-week treatment, adverse events, time to fever resolution, ARDS development, and lung injury on newly diagnosed COVID-19 patients were assessed. RESULTS: An analysis of the data from the first 30 participants showed that the control arm and the testing arm did not exhibit any significant differences in terms of adverse events. Based on this result, the study was expanded to include a total of 48 participants (24 cases each arm). The results show that compared with the control arm, the testing arm exhibited a significant improvement in time to fever resolution (P=0.035), and a significant reduction in the development of ARDS (P=0.048). CONCLUSIONS Keguan-1-based integrative therapy was safe and superior to the standard therapy in suppressing the development of ARDS in COVID-19 patients. (Trial registration No. NCT04251871 at www.clinicaltrials.gov ).
Administration, Inhalation ; Adult ; China ; Coronavirus Infections ; diagnosis ; drug therapy ; mortality ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Follow-Up Studies ; Humans ; Integrative Medicine ; Interferon-alpha ; administration & dosage ; Lopinavir ; administration & dosage ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; diagnosis ; drug therapy ; mortality ; Risk Assessment ; Severe Acute Respiratory Syndrome ; diagnosis ; drug therapy ; mortality ; Severity of Illness Index ; Survival Rate

Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.

OBJECTIVE: To investigate the composition of gut microbiota and its correlation with the severity of behavior symptoms in children with autism spectrum disorder (ASD). METHODS: A total of 30 children with ASD were enrolled as the ASD group, and 20 healthy children matched for age and sex were enrolled as the healthy control group. Related clinical data were analyzed. The V3-V4 hypervariable regions of the bacterial 16S rRNA gene in fecal samples were sequenced. The severity of behavior symptoms in children with ASD was assessed using the autism behavior checklist. The Spearman's correlation analysis was used to investigate the correlation between gut microbiota and the severity of behavior symptoms in children with ASD. RESULTS: There was a significant difference in the composition of gut microbiota between the two groups. Compared with the healthy control group, the ASD group had significant reductions in Shannon index and Shannoneven index (P<0.05), as well as a significant reduction in the percentage of Firmicutes and a significant increase in the percentage of Acidobacteria in feces (P<0.05). In the ASD group, the dominant bacteria were Megamonas, Megasphaera, and Barnesiella, while in the healthy control group, the dominant bacteria were Eubacterium_rectale_group, Ezakiella, and Streptococcus. In the children with ASD, the abundance of Megamonas was positively correlated with the scores of health/physical/behavior and language communication (P<0.05). CONCLUSIONS The development of ASD and the severity of behavior symptoms are closely associated with the composition of gut microbiota.
Autism Spectrum Disorder ; Bacteria ; Child ; Feces ; Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S

OBJECTIVE: To evaluate the correlation between the injury patterns of the medial patellofemoral ligament (MPFL) on magnetic resonance imaging in an acute first-time lateral patellar dislocation (LPD) and incidence of a second-time LPD. MATERIALS AND METHODS: Magnetic resonance images were prospectively analyzed in 147 patients after an acute first-time LPD with identical nonoperative management. The injury patterns of MPFL in acute first-time LPDs were grouped by location and severity for the analysis of the incidence of second-time LPD in a 5-year follow-up. Independent t tests, chi-square tests and Kruskal-Wallis tests were performed as appropriate. RESULTS: Forty-six cases (46/147, 31.3%) of second-time LPD were present at the 5-year follow-up. Fourteen (14/62, 22.6%) and 31 cases (31/80, 38.8%) were present in the partial and complete MPFL tear subgroups, respectively. Twenty-five cases (25/65, 38.5%), 11 cases (11/26, 42.3%), and 8 cases (8/47, 17%) were present in the isolated femoral-side MPFL tear (FEM), combined MPFL tear (COM), and isolated patellar-side MPFL tear (PAT) subgroups, respectively. Compared with the partial MPFL tears, complete tears showed higher incidence of a second-time LPD (p = 0.04). The time interval between the two LPDs was shorter in the complete MPFL tear subgroup (24.2 months) than in the partial tear subgroup (36.9 months, p = 0.001). Compared with the PAT subgroup, the FEM and COM subgroups showed a higher incidence of a second-time LPD (p = 0.025). The time intervals between the two LPDs were shorter in the FEM and COM subgroups (20.8 months and 19.2 months) than in the PAT subgroup (32.5 months, p = 0.049). CONCLUSION: A complete MPFL tear, isolated femoral-side tear and combined tear in a first-time LPD predispose a second-time LPD.
Follow-Up Studies ; Humans ; Incidence* ; Knee ; Ligaments* ; Magnetic Resonance Imaging* ; Patellar Dislocation* ; Prospective Studies ; Recurrence ; Tears

To determine heat-shock protein (Hsp)90 expression is connected with cellular apoptotic response to heat stress and its mechanism, chicken (Gallus gallus) primary myocardial cells were treated with the Hsp90 promoter, aspirin, and its inhibitor, geldanamycin (GA), before heat stress. Cellular viability, heat-stressed apoptosis and reactive oxygen species level under different treatments were measured, and the expression of key proteins of the signaling pathway related to Hsp90 and their colocalization with Hsp90 were detected. The results showed that aspirin treatment increased the expression of protein kinase B (Akt), the signal transducer and activator of transcription (STAT)-3 and p-IKKα/β and the colocalization of Akt and STAT-3 with Hsp90 during heat stress, which was accompanied by improved viability and low apoptosis. GA significantly inhibited Akt expression and p-IKKα/β level, but not STAT-3 quantity, while the colocalization of Akt and STAT-3 with Hsp90 was weakened, followed by lower cell viability and higher apoptosis. Aspirin after GA treatment partially improved the stress response and apoptosis rate of tested cells caused by the recovery of Akt expression and colocalization, rather than the level of STAT-3 (including its co-localization with Hsp90) and p-IKKα/β. Therefore, Hsp90 expression has a positive effect on cellular capacity to resist heat-stressed injury and apoptosis. Moreover, inhibition of Hsp90 before stress partially attenuated its positive effects.
Apoptosis* ; Aspirin ; Cell Survival ; Chickens* ; Heat Stress Disorders ; Heat-Shock Proteins* ; Hot Temperature* ; HSP90 Heat-Shock Proteins ; In Vitro Techniques* ; Proto-Oncogene Proteins c-akt ; Reactive Oxygen Species ; Transducers

Objective To provide evidence for effective implementation of influenza and pneumonia immune strategies, we investigated the awareness of influenza and pneumonia and the willingness of vaccination among chronic disease patients.Methods A stratified multistage cluster sampling method was used to investigate 720 patients less than 75 years of age.Results Overall, 717 completed responses were received.The awareness rates of influenza and pneumonia diseases were 59.83% and 59.55%, respectively.However, the awareness rates of influenza and pneumonia vaccine were 17.71% and 6.00%, respectively.The vaccination rate of influenza vaccine was 1.26% while no patients received pneumonia vaccination.Among those not vaccinated the most frequent reasons for not receiving the vaccine included "Believed oneself unlikely to be infected with influenza/pneumonia" and "No recommendation has been received for influenza/pneumonia vaccination".The influence on recommendations by doctors at vaccine clinic and by general practitioner had no significant statistical difference (P>0.05).Conclusion The main reasons for such low awareness and willingness may be due to their poorly knowledge on the risk of influenza/pneumonia diseases, and related vaccines.Health education and intervention should be taken to heighten the vaccination rates of influenza/pneumonia vaccines.

Objective To clarify the necessity of therapeutic drug monitoring (TDM ) of voriconazole ,and give relevant clinical tips ,by comparing the plasma concentration of different clinical specialties before and after adjustment of dose .Methods This is a retrospective study of voriconazole TDM data .It involves 435 cases voriconazole plasma trough concentration meas-urement results of 154 inpatients to make a preliminary assessment .Results 4 .3% plasma concentration were higher than 5 .5 μg/ml ,26 .5% plasma concentration were less than 1 .0 μg/ml in renal transplantation department ;while 52 .3% plasma concentration were higher than 5 .5 μg/ml ,no less than 1 .0 μg/ml in infectious disease department .Conclusions Therapeutic drug monitoring is necessary for rational use of voriconazole .The majority of plasma concentrations in renal transplantation pa-tients were <1 .0 μg/ml ,lower than recommended treatment concentration range ;while most infectious disease patients have> 5 .5 μg/ml ,higher than recommended treatment concentration range .Clinical pharmacists can be more closely involved in the clinical use of voriconazole based on the results of the therapeutic drug monitoring .