Cytopharmaceutical based on macrophages is a breakthrough in the field of targeted drug delivery. However, it remains a challenge to localize and control drug release while retaining macrophage activity and exerting its immunotherapeutic effect. Herein, a localized light-triggered release macrophage cytopharmaceutical (USIP@M) was proposed, which could utilize the tumor targeting and immunotherapy effects of macrophages to reverse the immune suppression of tumor microenvironment (TME). Amphiphilic block copolymers with ultraviolet (UV)-responsive o-nitrobenzyl groups were synthesized and co-loaded with sorafenib (SF), IMD-0354 (IMD), and upconverting nanoparticles (UCNPs), which were then taken up by macrophages, and the targeted delivery of drugs was realized by using the tumor tropism of macrophages. UCNPs converted near-infrared light with strong penetrability and high safety into UV light, which promoted the photoresponsive depolymerization of block copolymers and production of exosomes from USIP@M, accelerated drug efflux and maintained the activity of macrophages. IMD simultaneously polarized carrier macrophages and tumor-associated macrophages to exert the antitumor effect of macrophages, enhance T cell immunity, and alleviate the immunosuppressive state of TME. Synergistically with the chemotherapeutic effect of SF, it could effectively kill tumors. In conclusion, based on the localized light-triggered release strategy, this study constructed a novel macrophage cytopharmaceutical that could localize and control drug release while retaining the activity of macrophages and exerting its immunotherapeutic effect, which could effectively treat solid tumors.

Objective:To investigate the knowledge, attitudes, and practices (KAP) of pulse oximetry among pediatric healthcare providers in China and analyze the factor influencing the KAP.Methods:A self-developed questionnaire was used for an online research on the KAP of 11 849 pediatric healthcare providers from 31 provinces, autonomous regions, and municipalities of China from March 11 to 14, 2022.The factors influencing the KAP of pulse oximetry among pediatric healthcare providers were examined by Logistic regression. Results:The scores of KAP, of pulse oximetry were 5.57±0.96, 11.24±1.25 and 11.19±4.54, respectively.The corresponding scoring rates were 69.61%, 74.95%, and 55.99%, respectively. Logistic regression results showed that the gender and working years of pediatric healthcare providers, the region they were located, and whether their medical institution was equipped with pulse oximeters were the main factors affecting the knowledge score (all P<0.05). Main factors influencing the attitude score of pediatric healthcare providers included their knowledge score, gender, educational background, working years, region, medical institution level, and whether the medical institution was equipped with pulse oximeters (all P<0.05). For the practice score, the main influencing factors were the knowledge score, gender, age, and whether the medi-cal institution was equipped with pulse oximeters (all P<0.05). Conclusions:Chinese pediatric healthcare providers need to further improve their knowledge about and attitudes towards pulse oximetry.Pulse oximeters are evidently under-used.It is urgent to formulate policies or guidelines, strengthen education and training, improve knowledge and attitudes, equip more institutions with pulse oximeters, and popularize their application in medical institutions.

Objective: We aimed to examine the feasibility and toxicity of EC-T dose-dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early-stage breast cancer population with high recurrence risk. Methods: 370 patients with early-stage breast cancer at high risk of recurrence were treated with EC-T dose-dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G-CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed. Results: 370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9% experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk (OR=1.268, P=0.046; OR=1.244, P=0.036). With G-CSF support, the probability of grade 3-4 dose limiting toxicity, i. e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased(P>0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P=0.814) or dose reduction (P=0.282). Conclusions EC-T dose-dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen. With G-CSF support, epirubicin 85-90 mg/m² is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.

Objective We aimed to examine the feasibility and toxicity of EC?T dose?dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early?stage breast cancer population with high recurrence risk. Methods 370 patients with early?stage breast cancer at high risk of recurrence were treated with EC?T dose?dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G?CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed. Results 370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9%experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk ( OR＝1.268, P＝0.046; OR＝1.244, P＝0.036). With G?CSF support, the probability of grade 3?4 dose limiting toxicity, i.e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased ( P＞0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P＝0.814) or dose reduction (P＝0.282). Conclusions EC?T dose?dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen.With G?CSF support, epirubicin 85?90 mg／m2 is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.

Objective We aimed to examine the feasibility and toxicity of EC?T dose?dense regimen and to demonstrate the suitable dose of epirubicin in a Chinese early?stage breast cancer population with high recurrence risk. Methods 370 patients with early?stage breast cancer at high risk of recurrence were treated with EC?T dose?dense adjuvant chemotherapy and prophylactic administration of recombinant human granulocyte stimulating factor (G?CSF). The incidence of delayed chemotherapy, drug reduction and adverse reactions were retrospectively analyzed. Results 370 patients completed the planned eight cycles of chemotherapy, 50 patients experienced chemotherapy delay, and 90 had chemotherapy dose reductions. Overall, 61.1% of the patients experienced grade 3 or 4 hematology toxicities, 4.1% of the patients experienced grade 3 gastrointestinal toxicity, 16.3% experienced grade 3 or 4 liver malfunction, and 1.9%experienced grade 3 alopecia. In the multivariate analysis, pretreatment epirubicin levels were associated with comprehensive and hematology toxicity risk ( OR＝1.268, P＝0.046; OR＝1.244, P＝0.036). With G?CSF support, the probability of grade 3?4 dose limiting toxicity, i.e. neutropenia, abnormal liver function, and gastrointestinal adverse effects did not increase as the epirubicin dose level increased ( P＞0.05). However, there were no statistically significant associations between epirubicin grade and treatment delay (P＝0.814) or dose reduction (P＝0.282). Conclusions EC?T dose?dense chemotherapy shows tolerable toxicity. High dose level is not a limiting factor for this regimen.With G?CSF support, epirubicin 85?90 mg／m2 is appropriate tolerance dose for Chinese early breast cancer patients with high recurrence risk.

Objective: To investigate the clinical outcome of expression discordance of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) in primary breast cancer and the corresponding metastatic lesions. Methods: A retrospective analysis was performed on 178 breast cancer patients with metastasis confirmed by the National Cancer Center & Cancer Hospital, Chinese Academy of Medical Sciences in the past 6 years. The data of expressions of ER, PR and HER-2 in primary and metastatic breast cancer, the metastatic sites, disease progression were collected and the relationships of the expression discordance of receptors with prognosis were analyzed. Results: The discordance rates of ER, PR and HER-2 between the primary tumor and the metastatic sites were 27.0%, 39.8% and 18.7%, respectively. The discordance rates of ER, PR and HER-2 of patients with locoregional recurrence were 21.9%, 36.6% and 12.7%, respectively, while those of patients with distant metastases were 31.3%, 42.7% and 23.8%. The median progression free survivals (PFS) of ER+/+、ER+/-、ER-/+、ER-/- of primary tumor and metastatic sites were 17.7 months, 10.3 months, 14.0 months and 9.0months, respectively (P=0.025). The median PFS of PR+/+, PR+/-, PR-/+, PR-/- were 23.0 months, 10.7 months, 14.0 months and 9.2months, respectively (P=0.002). The median PFS of HER-2+/+, HER-2+/-, HER-2-/+, HER-2-/- were 14.9 months, 15.2 months, 12.3 months and 14.0 months, respectively, without significant differences (P=0.588). Conclusions This study confirms that expression discordances of ER, PR and HER-2 between primary breast cancer and the corresponding metastatic lesions are dramatic, especially in the patients with distant metastasis. The unstable levels of ER and PR seem to be significantly associated with prognosis of breast patients.

Objective To observe the influence of subarachnoid space associated with epidural anesthesia at different posture on the hemodynamics during cesarean section.Methods One hundred and twenty uterine-incision delivery patients were chosen,the patients were separated into the left lateral decubitus group(LL group) and right lateral decubitus group(RL group) with 60 cases each by random digits table method,all the patients were blocked by subarachnoid space associated with epidural anesthesia after puncturation 2 ml 0.5％ ropivacaine was given.Then the head end epidural catheter insertion in 3-4 cm,asked maternal supine after fixed catheter enjoin.Systolic blood pressure (SBP),diastolic blood pressure (DBP),heart rate were recorded before anesthesia and at 3,5,10,15 min after anesthesia.Apgar scores of 1 and 5 min were observed as well.Results SBP and DBP at 3,5 min after anesthesia were significantly lower than those before anesthesia in RL group,SBP was (120.1 ± 11.2),(106.7 ± 17.2),(127.3 ± 13.6)mmHg (1 mmHg =0.133 kPa) respectively,DBP was (77.5 ± 6.3),(55.2 ± 21.2),(80.3 ± 10.5) mmHg,respectively,and there were significant differences (P ＜0.05).And SBP,DBP in RL group were also significantly lower than those in LL group,SBP was (123.2 ± 12.4),(110.3 ± 16.3) mmHg,DBP was (80.1 ± 9.9),(63.1 ± 13.2) mmHg,and there was significant difference (P ＜ 0.05).There was no significant difference in Apgar scores of 1 and 5 min between two groups.Conclusion The left lateral decubitus position could effectively reduce the incidence of hypotension during caesarean section under subarachnoid space associated with epidural anesthesia.

OBJECTIVETo observe the effect of Pingxian granules on the protein expression of apoptosis regulatory genes Bcl-2 and Bax in the hippocampus of epileptic model rats and study the molecular biological mechanism of the anti-epileptic effect of Pingxian granules.

METHODTotally 60 45-days-old Wistar rats were selected and then randomly assigned into 5 groups: the normal control group, the model group, the positive control group, the Pingxian high dose group and the Pingxian low dose group, with 12 in each group. Except the normal control group, all the groups were intraperitoneally injected with 35 mg x kg(-1) pentylenetetrazol to establish the models of epilepsy. The Pingxian high dose (1.66 g x mL(-1)) and low dose (0.42 g x mL(-1)) groups were intragastrically infused with Pingxian granules 2 mL x d(-1). The positive control group received 3.6 g x L(-1) phenobarbital suspension by gastric perfusion. The normal group and the model group were drenched with distilled water, 2 mL x d(-1), for 5 weeks. Bcl-2 and Bax protein positive cells were labeled with immunohistochemical SABC at 3, 5 w.

RESULT(1) Rats in the model group appeared the epileptic behavior at the 1st week, and became serious with the kindle frequency; grade VIepileptic behavior appeared at the 4th week. The attack frequency and grade of the Pingxian group were less and lower, the highest grade were only IV, and there were no significant differences in the attack grade and frequency. (2) With the increase in kindle frequency, the model group showed a notable decrease in the Bcl-2 expression compared with the normal control group at the 3rd and 5th weekend (P < 0.01), but a significant increase in Bax protein expression (P <0. 01). The number of the Bcl-2 protein expression in Pingxian groups and the positive control group were obviously more than the model group (P < 0.01); and the number of the Bax protein expression in Pingxian groups and the positive control group were obviously less than the model group (P < 0.01).

CONCLUSIONPingxian granules may decrease neuronal cell apoptosis by improving the protein expression of apoptosis regulatory gene Bcl-2 and inhibiting the protein expression of apoptosis regulatory gene Bax with a view of anti-epilepsy.

Animals ; Apoptosis ; drug effects ; Drugs, Chinese Herbal ; therapeutic use ; Epilepsy ; chemically induced ; drug therapy ; Female ; Hippocampus ; drug effects ; metabolism ; Immunohistochemistry ; Male ; Pentylenetetrazole ; toxicity ; Rats ; Rats, Wistar

0.05), but serum levels of, SS, SP and VIP were higher than those of control group (P05). When the intensity reached 120dB, gastrointestinal transit was accelerated significantly(P

AIM: To investigate the changes of oxidative stress in the kidneys and their roles in nephropathy in diabetic rats. METHODS: Diabetic rats were induced by streptozotocin (STZ). 36 rats were divided into three groups randomly: (1) NC group, normal control rats; (2) DM group, diabetic rats received protamine zinc insulin (PZI) 2U-4U/2 d; (3) DT group, diabetic rats received PZI 9-12 U/kg body weigh/day. 12 weeks later, rats were killed, blood glucose, blood cholesterol, serum creatinine, blood urea nitrogen, HbA1c, urinary creatinine, and urinary protein for 24 h were measured. The activities of antioxidant enzymes in renal cortex, including total superoxide dismutase (TSOD), Cu-Zn superoxide dismutase (Cu-Zn SOD), Mn superoxide dismutase (Mn SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and maleic dialdehyde (MDA) were measured by chromatometry. RT-PCR was performed to detect the expression of different antioxidant enzymes mRNA. RESULTS: For all the targets we measured, there was no significant difference between NC and DT groups. Compared with the other two groups, the levels of blood glucose, cholesterol, trigalloyl glycerol, HbA1c in DM group increased significantly. The activities of TSOD, Cu-Zn SOD and CAT decreased significantly. The activity of GSH-Px increased significantly. There was no significant difference among the activities of Mn SOD in all three groups. The level of MDA in DM group was much higher than that in NC or DT group. The relative expression levels of GSH-Px and Cu-Zn SOD mRNA in DM group were higher than those in other two groups, while the relative expression level of CAT decreased. Mn SOD mRNA was expressed without significant difference in all groups. Compared with NC or DT group, urinary protein in DM group increased significantly, while creatinine clearance rate decreased. CONCLUSIONS: Hyperglycemia affected the expression of antioxidant enzymes. Oxidative stress was caused by hyperglycemia in diabetic rats and may be an important factor in the etiology of diabetic nephropathy.