To enhance the therapeutic efficacy of the baicalin-berberine complex(BA-BBR) in the treatment of ulcerative colitis(UC), BA-BBR nanocrystal microspheres(BA-BBR NC MS) were prepared using the dropping method. The microspheres were characterized in terms of morphology, particle size, differential scanning calorimetry(DSC), and powder X-ray diffraction(XRD). The release profiles of BA and BBR from the microspheres were measured, and the drug release mechanism was investigated. A rat model of UC was induced by 5% dextran sodium sulfate(DSS) and treated continuously for 7 days to evaluate the therapeutic effects of different formulations. The results showed that the prepared BA-BBR MS and BA-BBR NC MS were uniform gel spheres with particle sizes of(1.77±0.16) mm and(1.67±0.08) mm, respectively. After drying, the gels collapsed inward and exhibited a rough surface. During the preparation process, the BA-BBR nanocrystals(BA-BBR NC) were uniformly encapsulated within the microspheres. The release profiles of the microspheres followed a first-order kinetic model, and the 12-hour cumulative release of BA and BBR from BA-BBR NC MS was higher than that from BA-BBR MS. Compared with BA-BBR, BA-BBR NC, and BA-BBR MS, BA-BBR NC MS further alleviated UC symptoms in rats, most significantly reducing the levels of TNF-α, IL-1β, IL-6, and MPO, while increasing the level of IL-4 in colon tissues. These results indicate that BA-BBR NC MS, based on a "nano-in-micro" design, can deliver BA-BBR to the intestine and exert significant therapeutic effects in a UC rat model, suggesting it as a promising new strategy for the treatment of UC.
Animals ; Colitis, Ulcerative/metabolism* ; Rats ; Nanoparticles/chemistry* ; Microspheres ; Male ; Berberine/administration & dosage* ; Flavonoids/administration & dosage* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Particle Size ; Tumor Necrosis Factor-alpha/immunology* ; Drug Liberation ; Drug Compounding

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 observe the effectiveness and safety of Huotujiji prescription for patients with asthenospermia of spleen-kidney yang-deficiency. METHODS: Patients with spleen-kidney-yang deficiency type of asthenospermia were divided into two groups by randomized control method. The patients in the control group were treated with L-carnitine oral solution alone. And the patients in experimental group were treated with Huotujiji prescription. Semen volume, sperm concentration, PR, TCM symptom score and spouse pregnancy were compared between the two groups before and after treatment. RESULTS: A total of 115 patients were included in the study, with 55 in the experimental group and 60 in the control group. In the experimental group, the sperm concentration before and after treatment were (160.71±53.7)×106/mL, (187.19±41.89)×106/mL, and PR were (20.37±9.42)%, (26.7±6.92)%, respectively. PR+NP were (32.06±8.49)% and (34.89±7.25)%. After the treatment, the sperm motility of both groups significantly improved compared to pre-treatment levels (P<0.05). And the experimental group's sperm concentration also showed a significant increase after the treatment (P<0.05). The pregnancy rate of spouses in the control group was 11.67%, which was 29.09% in the experimental group. The pregnancy rate of the spouses in the two groups showed a statistically significant difference (P<0.05). After 12weeks of treatment, the Traditional Chinese Medicine (TCM) symptom scores in the control group did not decrease significantly compared to those before treatment (P> 0.05). In contrast, the TCM symptom scores in the experimental group decreased significantly after treatment (P<0.05). Moreover, compared with the control group, the TCM symptom scores of the experimental group decreased significantly after treatment (P<0.05). CONCLUSION Huotujiji prescription can safely and effectively improve the sperm quality and vitality of patients with spleen-kidney-yang deficiency type of asthenospermia, improve the symptoms of patients, and increase the pregnancy rate of their spouses, which is worthy of clinical promotion.
Humans ; Male ; Drugs, Chinese Herbal/therapeutic use* ; Adult ; Yang Deficiency/drug therapy* ; Asthenozoospermia/drug therapy* ; Female ; Pregnancy ; Phytotherapy ; Sperm Motility ; Young Adult ; Spleen ; Treatment Outcome ; Sperm Count

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Aim To investigate the effect of histamine H, receptor (HjR) on the immune responses in astrocytes induced by lipopolysaccharide (LPS) and the regulatory mechanism of its signaling pathway. Methods LPS was used to establish an in vitro astrocyte inflammation model. Rat primary astrocytes were divided into the control group, LPS group, LPS + Hj R agonist group (2-pyridylethlamine, Pyri), and HjR agonist group. Astrocytes were treated with Pyri 100 p,mol • L~ for 1 h, then stimulated with LPS at 100 p,g • L~ for 24 h. Cell viability was measured using the CCK-8 assay. The expression of GFAP and HjR was detected by immunofluorescence. Glial morphological changes were observed under a microscope. The levels of proinflammatory mediators (TNF-a and IL-6) were detected by ELISA. The protein expressions of p-Akt, Akt, p-NF-KB p65, and NF-KB p65 were detected by Western blot. Results Compared with the control group, more activated astrocytes with fewer cell processes and branches were observed in the LPS group. Besides, LPS enhanced the GFAP expression level, reduced the H,R expression level and stimulated the production of TNF-a and IL-6 from astrocytes. Pre treatment with Pyri for 1 h ameliorated the glial morphological changes stimulated by LPS, inhibited LPS-induced upregulation of GFAP level and the inflammatory factors secretion. In addition, LPS stimulated astrocytes showed a higher phosphorylation of Akt and NF-KB p65, which was also ameliorated by Pyri. Conclusions H, R agonist can inhibit LPS-induced astrocyte activation and inflammatory factor secretion, and the Akt/NF-KB signaling pathway may be an important pathway for the involvement of H,R in immune regulation.

Biosensor analysis technology is a kind of technology with high specificity that can convert biological reactions into optical and electrical signals. In the development of drugs for Alzheimer's disease (AD), according to different disease hypotheses and targets, this technology plays an important role in confirming targets and screening active compounds. This paper briefly describes the pathogenesis of AD and the current situation of therapeutic drugs, introduces three biosensor analysis techniques commonly used in the discovery of AD drugs, such as surface plasmon resonance (SPR), biolayer interferometry (BLI) and fluorescence analysis technology, explains its basic principle and application progress, and summarizes their advantages and limitations respectively.

OBJECTIVE To study the interventional effect and mechanism of 1，8-cineole on pancreatic β cell ferroptosis induced by type 2 diabetes. METHODS In vitro ferroptosis model was established in pancreatic β cells of mice by using high glucose. The effects of low-dose and high-dose 1，8-cineole （0.25， 0.5 μmol/L） on the level of Fe2+ in pancreatic β cells were investigated. The effects of 1，8-cineole （0.5 μmol/L） combined with ferroptosis inducer Erastin （20 μmol/L） and ferroptosis inhibitor Ferrostatin-1 （20 μmol/L） on the protein expressions of glutathione peroxidase-4 （GPX4） and cyclooxygenase-2 （COX2） were also detected. The type 2 diabetes model mice were established by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin. The effects of low-dose and high-dose 1，8-cineole （50， 200 mg/kg） on the pathological morphology of pancreatic tissue， the content of iron as well as the protein expressions of GPX4 and COX2 were investigated. RESULTS The results of the cell experiment showed that compared with the model group， pretreatment with 1，8-cineole significantly reduced intracellular Fe2+ levels and upregulated GPX4 protein expression， while downregulated COX2 protein expression in pancreatic β cells （P＜0.05）. After combining with Ferrostatin-1， the expression trends of the above two proteins were the same， while there was no statistically significant difference after combining with Erastin. The results of animal experiments showed that compared with the model group， after intervention with 1，8-cineole， the structure of the pancreatic islets in mice recovered intact and their morphology improved； the iron content of pancreatic tissue and protein expression of COX2 were decreased significantly （P＜0.05）， while protein expression of GPX4 was increased significantly （P＜0.05）. CONCLUSIONS 1，8-cineole could ameliorate pancreatic β cell injury induced by diabetes， the mechanism of which may be related to reducing intracellular iron deposition and regulating ferroptosis-related proteins.

Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98％in 2014 to 85.01％in 2022(P＜0.001),and HA case infection incidence decreased from 1.21％to 0.83％(P＜0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P＜0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P＜0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.

Objective To investigate disease characteristics and hospitalization costs of children with Mycoplasma Pneumoniae pneumonia(MPP)admitted to Shanghai municipal medical hospitals from 2019 to 2023.Methods Depending on the Shanghai Municipal Hospital Pediatric Alliance,we retrospectively investigated community acquired MPP pediatric patients hospitalized in 22 municipal hospitals with pediatric qualifications(including 4 children's hospitals)in Shanghai from Jan 2019 to Dec 2023.We collected the patients'diagnosis codes,gender,age,length of hospital stay,hospitalization costs,and whether they progressed to severe Mycoplasma pneumoniae pneumonia(SMPP).Results From 2019 to 2023,a total of 29 045 hospitalized children with MPP were treated,with 6 035 cases(20.8%)identified as SMPP in the 22 hospitals.Trend analysis revealed a rising trend with years in the proportion of SMPP patients(χ2trend=365.498,P<0.001).Among the 4 children's hospitals,there were 18 710 cases with MPP,including 4 078 cases(21.8%)of SMPP.The proportion of SMPP patients also showed an increasing trend with years(χ2trend=14.548,P<0.001),and the proportion in 2023(23.0%)was higher than that in previous years with statistical significance.There were statistical differences in the seasonal distribution of MPP cases between different years,with higher proportions in summer and autumn overall.The age distribution of hospitalized MPP children varied among different years,with school-age children accounting for the majority(56.8%)in 2023.There was no difference in the distribution of severe cases between different genders,but there were differences in the proportion of severe cases among different age groups in different years,with a gradual increase in severe cases among children aged 1 to 3 years(χ2trend=191.567,P<0.001).The average length of hospital stay for MPP during the epidemic was higher than that during non-epidemic periods,and there were statistically significant differences in the average length of hospital stay between different years(P<0.001).The individual hospitalization costs during the epidemic were higher than in other years,and there were statistically significant differences in individual hospitalization costs between different years(P<0.001).The total hospitalization costs were still higher in 2019 and 2023.The individual hospitalization costs for SMPP were higher than for non-SMPP cases.Conclusion MPP outbreaks occurred in Shanghai in 2019 and 2023,with the higher proportions in summer and autumn overall.Compared to previous years,the number of hospitalized MPP children in Shanghai was higher in 2023,with a higher proportion of SMPP cases,especially among children under 3 years old.The individual per capita hospitalization expenses for SMPP cases were higher than for non-SMPP cases.

In clinical practice, red blood cell infusion needs to be based on the patient′s hemoglobin level. However, different guidelines recommend different thresholds for red blood cell infusion and the timing of blood transfusion initiation is still controversial due to the presence of these different thresholds. Meanwhile, the use of allogeneic blood products carries a certain risk of transfusion-related infections or organ damage. Therefore, initiating red blood cell infusion requires more evidence. This review discusses some new methods, namely central venous oxygen saturation, arterial venous oxygen difference, near-infrared spectroscopy, and perioperative transfusion trigger score. It aims to help evaluate blood transfusion trigger and provide reference for doctors when making transfusion decisions.