Poor water solubility is the primary obstacle preventing the development of many pharmacologically active compounds into oral preparations. Self-nanoemulsifying drug delivery systems(SNEDDS) have become a widely used strategy to enhance the oral bioavailability of poorly soluble drugs by inducing a supersaturated state, thereby improving their apparent solubility and dissolution rate. However, the supersaturated solutions formed in SNEDDS are thermodynamically unstable systems with solubility levels exceeding the crystalline equilibrium solubility, making them prone to drug precipitation in the gastrointestinal tract and ultimately hindering drug absorption. Therefore, maintaining a stable supersaturated state is crucial for the effective delivery of poorly soluble drugs. Incorporating polymers as precipitation inhibitors(PPIs) into the formulation of supersaturated self-nanoemulsifying drug delivery systems(S-SNEDDS) can inhibit drug aggregation and crystallization, thus maintaining a stable supersaturated state. This has emerged as a novel preparation strategy and a key focus in SNEDDS research. This review explores the preparation design of SNEDDS and the technical challenges involved, with a particular focus on polymer-based S-SNEDDS for enhancing the solubility and oral bioavailability of poorly soluble drugs. It further elucidates the mechanisms by which polymers participate in transmembrane transport, summarizes the principles by which polymers sustain a supersaturated state, and discusses strategies for enhancing drug absorption. Altogether, this review provides a structured framework for the development of S-SNEDDS preparations with stable quality and reduced development risk, and offers a theoretical reference for the application of S-SNEDDS technology in improving the oral bioavailability of poorly soluble drugs.
Solubility ; Administration, Oral ; Polymers/chemistry* ; Drug Delivery Systems/methods* ; Humans ; Emulsions/chemistry* ; Biological Availability ; Animals ; Pharmaceutical Preparations/administration & dosage*

Objective: To explore a simple and feasible method for the isolation and purification of hepatocytes, hepatic stellate cells (HSC), and lymphocytes from mice. Methods: The cell suspension was obtained from male C57bl/6 mice by hepatic perfusion through the portal vein digestion method and then isolated and purified by discontinuous Percoll gradient centrifugation. Trypan blue exclusion was used to determine cell viability. Glycogen staining, cytokeratin 18, and transmission electron microscopy were used to identify hepatic cells. Immunofluorescence was used to detect α-smooth muscle actin combined with desmin in HSCs. Flow cytometry was used to analyze lymphocyte subsets in the liver. Results: After isolation and purification, about 2.7×10(7) hepatocytes, 5.7×10(5) HSCS, and 4.6×106 hepatic mononuclear cells were obtained from the liver of mice with a body weight of about 22g. The cell survival rate in each group was > 95%. Hepatocytes were apparent in glycogen deposited purple-red granules and cytokeratin 18. Electron microscopy showed that there were abundant organelles in hepatocytes and tight junctions between cells. HSC had expressed α-smooth muscle actin and desmin. Flow cytometry showed hepatic mononuclear cells, including lymphocyte subsets such as CD4, CD8, NKs, and NKTs. Conclusion: The hepatic perfusion through the portal vein digestion method can isolate multiple primary cells from the liver of mice at once and has the features of simplicity and efficiency.
Male ; Mice ; Animals ; Keratin-18 ; Actins ; Desmin ; Liver ; Hepatocytes ; Hepatic Stellate Cells

Objective: To study the influence of steroid withdrawal protection strategy on height growth in pediatric patients after kidney transplantation. Methods: The prospective cohort study enrolled 40 stage 5 chronic kidney disease children receiving kidney transplantation from July 2017 to September 2022 at Guangzhou Women and Children's Medical Center. Based on the primary preoperative disease, patients with immune abnormality-associated glomerular diseases or unknown causes were assigned to the steroid maintenance group, in which patients received steroid tapering within 3 months after surgery to a maintenance dose of 2.5 to 5.0 mg/d. While patients with hereditary kidney disease or congenital urinary malformations were assigned to the steroid withdrawal group, in which patients had steroids tapered off within 3 months. The characteristics of height catch-up growth and clinical data were compared between the 2 groups at baseline, 6, 12, 18 and 24 months after kidney transplantation. T-test, repeated measurement of variance analysis, Mann-Whitney U test, and Fisher exact test were used for the comparison between the 2 groups. Results: Among the 40 children, 17 were males, 23 were females, 25 were in the steroid withdraw group ((7.8±2.8) years old when receiving kidney transplantation) and 15 cases were in the steroid maintenance group ((7.6±3.5) years old when receiving kidney transplantation). The study population was followed up for (26±12) months. The total dose per unit body weight of steroids in the steroid withdrawal group was lower than that in the steroid maintenance group ((0.13±0.06) vs. (0.36±0.19) mg/(kg·d), t=5.83, P<0.001). The height catch-up rate (ΔHtSDS) in the first year after kidney transplantation in the steroid withdraw and steroid maintenance groups was 1.0 (0.7, 1.4) and 0.4 (0.1, 1.0), respectively; in the second year, the ΔHtSDS in the steroid withdraw group was significantly higher than that in the steroid maintenance group (1.1 (0.2, 1.7) vs. 0.3 (0, 0.8), U=28.00, P=0.039). The HtSDS in the steroid withdrawal group at the five follow-up time points was -2.5±0.8, -2.0±0.8, -1.5±0.8, -1.3±0.9 and -0.5±0.3, respectively, while in the steroid maintenance was -2.4±1.3, -2.2±1.1, -2.0±1.0, -1.8±1.0 and -1.6±1.0, respectively. There were statistically significant differences in HtSDS at different follow-up time points in both 2 groups (F=19.81, P<0.01), but no statistical differences in overall impact between the 2 groups (F=1.13, P=0.204). The steroid treatment was interaction with the increase of follow-up time (F=3.62, P=0.009). At the 24^th month after transplantation, the HtSDS in the steroid withdrawal group was significantly higher than that in the steroid maintenance group (P=0.047). Six patients in the steroid withdrawal group experienced antibody-mediated immune rejection (AMR), while 3 did in the steroid maintenance group. Moreover, there was no significant difference in AMR between the two groups (χ²=0.06, P=0.814). Conclusion: The steroid withdrawal protection strategy favors the height catch-up growth in pediatric patients after kidney transplantation and does not increase the risk of postoperative antibody-mediated immune rejection.
Male ; Humans ; Child ; Female ; Child, Preschool ; Kidney Transplantation ; Prospective Studies ; Steroids/therapeutic use* ; Antibodies ; Body Weight

Child ; Humans ; Acquired Immunodeficiency Syndrome/drug therapy* ; Retrospective Studies ; Anti-Retroviral Agents/therapeutic use* ; HIV Infections/epidemiology* ; China/epidemiology* ; Anti-HIV Agents/therapeutic use*

Objective:To investigate clinical efficacy and safety of dupilumab in the treatment of atopic dermatitis (AD) .Methods:An ambispective study was conducted on 123 AD patients treated with dupilumab in Department of Dermatology, the Second Xiangya Hospital of Central South University from July 2020 to March 2022, clinical data were collected, and efficacy and safety of dupilumab were evaluated. Primary outcomes included scores of eczema area and severity index (EASI) , patient-oriented eczema measure (POEM) , peak pruritus numerical rating scale (NRS) and dermatology life quality index (DLQI) before and after 4-, 8-, 12- and 16-week treatment, and adverse reactions and events were recorded. Comparison of scores before and after treatment was performed using paired t test or repeated measures analysis of variance, Mann-Whitney U test was used for the comparison of efficacy among patients with different types of skin lesions or different IgE levels, and multiple regression model based on robust standard errors was used to analyze factors influencing the efficacy. Results:Among the 123 AD patients, 107 were enolled into the efficacy analysis, and 85 (79.44%) completed at least 4 weeks of treatment, including 6 (7.06%) achieving EASI75 and 23 (27.06%) achieving EASI50, and the EASI, NRS, POEM, DLQI scores (10.41 ± 6.72, 4.12 ± 1.74, 8.60 ± 4.29, 7.81 ± 4.38, respectively) significantly decreased compared with those before treatment (18.08 ± 10.69, 7.21 ± 2.01, 16.88 ± 5.74, 12.95 ± 5.95, respectively; all P < 0.001) in the 85 patients. Among the 107 patients, 47 (43.93%) completed at least 16 weeks of treatment. Among the 47 patients, 23 (82.14%) of 28 adults and 17 (89.47%) of 19 adolescents and children achieved 75% or greater improvement in EASI score; the EASI, NRS, POEM and DLQI scores before the treatment all significantly differred from those 4, 8, 12, 16 weeks after the treatment (all P < 0.001) , and all the scores were significantly lower at weeks 4, 8, 12 and 16 than at the previous adjacent time points (all P < 0.05) . At week 4 during the treatment, the EASI improvement rate was significantly lower in the AD patients with prurigo nodularis than in those without ( U = 151.00, P = 0.006) , while there was no significant difference in the EASI improvement rate between the AD patients with xeroderma and those without ( P > 0.05) ; at week 16 during the treatment, there was no significant difference in the EASI improvement rate between patients with prurigo nodularis or xeroderma and those without (both P > 0.05) . Multiple regression analysis based on robust standard errors at week 16 showed that the improvement degree in the EASI score was not correlated with the type of skin lesions ( β = 3.20, P = 0.075) , but correlated with age ( β = -0.22, P = 0.030) , whether patients were in adulthood ( β = 9.54, P = 0.049) , immediate family history ( β = 7.46, P = 0.017) ; the improvement degree in the NRS score was correlated with the type of skin lesions ( β = 0.55, P = 0.032) , age ( β = -0.04, P = 0.033) , weight ( β = -0.05, P = 0.020) , whether patients were in adulthood ( β = 2.06, P = 0.003) and whether patients received combined treatment with antihistamines ( β = -1.91, P = 0.001) . Adverse reactions: among the 123 patients, 6 (4.88%) developed conjunctivitis, and 2 (1.63%) developed facial erythema. Adverse events: vitiligo-like changes occurred on the right forehead of 1 patient, and 3 patients discontinued the treatment with dupilumab due to Henoch-Sch?nlein purpura, distal axonal damage in peripheral nerves in both upper limbs, and epilepsy, respectively. The causal relationship between these adverse events and dupilumab was unclear. Conclusion:Dupilumab is effective in the treatment of AD with high overall safety, and can serve as a new treatment option for AD patients with an unsatisfactory response to traditional treatment.

Humans ; COVID-19 ; Consensus ; SARS-CoV-2 ; China

Primary liver cancer is one of the common malignant tumors and its mortality ranks third in the world. Because there are no obvious symptoms in the early stage of liver cancer, most patients are diagnosed as advanced stage, without the opportunity of surgical resection. The authors report a case of hepatocellular carcinoma with portal vein tumor thrombus, which reduced significantly after hepatic artery infusion chemotherapy combined with bevacizumab and atezolizumab, showing the safety and efficacy.

To analyze the collaborative use and separation reasons of lifting-thrusting and twirling reinforcing and reducing manipulation. Lifting-thrusting manipulation and twirling manipulation are two important contents of acupuncture methods. In traditional acupuncture and moxibustion, the two methods were used in reinforcing and reducing concert, which was mainly related to the therapeutic thought guided by the
Acupuncture Therapy ; Humans ; Lifting ; Moxibustion ; Needles ; Taiwan

Large general hospitals currently play an increasingly important role in the diagnosis and treatment for acute critical patients and difficult diseases because of the development of dual referral system and hierarchical diagnosis, as well as the formation of medical treatment alliance. Patients with oral cancers are often associated with systemic diseases, which increases the complexity of the condition. Thus, meeting the demand through the traditional single medical model is difficult. As such, a multidisciplinary team (MDT) model has been proposed and has achieved a good clinical effect. To standardize the application of this model, we organized an event in which relevant experts discussed and formulated a consensus to provide standardized suggestions on the MDT process and the diagnosis and treatment of common systemic diseases as reference for clinical practice.
Consensus ; Humans ; Mouth Neoplasms/therapy* ; Patient Care Team ; Referral and Consultation

Objective Metformin (MET) can reduce blood glucose, act against inflammation, lessen oxidative stress and prevent fibrosis. This study was to investigate the protective effect of MET against acute lung injury (ALI) induced by paraquat poisoning (PQP) in rats. Methods Totally 78 healthy adult SPF male SD rats were randomly divided into five groups, normal control, PQP model control, and low-, medium- and high-dose MET. The PQP model was established in the latter four groups of rats by intraperitoneal injection of paraquat solution at 30 mg/kg and, at 2 hours after modeling, the rats in the three MET intervention groups were treated intragastrically with MET at 100, 400 and 800 mg/kg/d respectively, while those in the normal and PQP model control groups with the same amount of normal saline, all for 7 successive days. Six of the animals from each group were sacrificed at 1, 3 and 7 days and their lung tissues harvested for measurement of the wet/dry weight ratio of the pulmonary tissue and contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in the plasma, determination of the levels of serum interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by ELISA, and observation of the pathological changes in the pulmonary tissue by HE staining. Results In the normal control, PQP model control and low-, medium- and high-dose MET groups, the contents of MDA were (2.53±0.36), (3.68±0.26), (3.57±0.52), (3.56±0.83) and (3.68±0.60) nmol/mL respectively on the 1st day of intervention and (2.53±0.36), (5.18±0.56), (5.09±0.88), (3.80±0.91) and (3.96±0.78) nmol/mL at 7 days; those of SOD were (256.18±18.18), (229.24±18.26), (224.65±19.27), (223.20±19.37) and (226.45±11.62) U/mL on the 1st day and (256.18±18.18), (152.06±17.03), (150.76±18.18), (205.95±13.16) and (208.37±12.23) U/mL at 7 days; those of IL-1β were (10.57±2.24), (21.97±5.03), (22.33±4.88), (21.78±5.21) and (22.11±4.19) pg/mL on the 1st day and (10.57±2.24), (91.86±8.40), (91.36±10.65), (63.52±7.06) and (60.35±6.70) pg/mL at 7 days; those of IL-6 were (21.35±2.62), (45.61±3.71), (44.83±5.97), (46.17±7.33) and (45.78±6.55) pg/mL on the 1st day and (21.35±2.62), (84.38±10.21), (85.88±6.70), (49.08±7.70) and (50.26±7.65) pg/mL at 7 days; and those of TNF-α were (32.37±3.74), (71.89±6.98), (72.52±8.23), (71.13±4.50) and (70.15±6.47) pg/mL on the 1st day and (32.37±3.74), (197.04±14.80), (201.59±13.61), (140.17±14.84) and (139.86±11.12) pg/mL at 7 days. Compared with the normal controls, the rats in the PQP model control and the MET intervention groups showed significant increases in the wet/dry weight ratio of the pulmonary tissue and contents of MDA, IL-1β, IL-6 and TNF-α (all P < 0.05), but a decrease in the SOD level in the plasma at 1, 3 and 7 days (P < 0.05). In comparison with the PQP model controls, the animals in the medium- and high-dose MET groups exhibited remarkable decreases in the wet/dry weight ratio of the lungs and contents of MDA, IL-1β, IL-6 and TNF-α (all P < 0.05), but an increase in the SOD level at 7 days (P < 0.05). Massive inflammatory cell infiltration, diffuse pulmonary hemorrhage, alveolar collapse and extensive alveolar septal thickening were observed in the PQP model control and low-dose MET groups but significantly alleviated in the medium- and high-dose MET groups at 7 days. Conclusion Metformin can protect paraquat-poisoned rats against acute lung injury by reducing pulmonary edema and the expressions of inflammation- and oxidation-related factors in the pulmonary tissue.