This study aims to investigate the anti-tumor effect and mechanism of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung carcinoma-bearing mice via the protein kinase RNA-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2α(eIF2α)/activated transcription factor 4(ATF4)/C/EBP homologous protein(CHOP) signaling pathway. Sixty SPF-grade male C57BL/6 mice were selected and assigned into a blank group and a modeling group by the random number table method. After modeling of the Lewis lung carcinoma, the mice in the modeling group were randomized into model, cisplatin(5 mg·kg~(-1), once a week), and low-, medium-, and high-dose(1.7, 3.5, and 7.05 g·kg~(-1), respectively, once a day) Guiqi Yiyuan Ointment+cisplatin(5 mg·kg~(-1)) groups(n=10). After 14 days of continuous intervention, the spleen, thymus, and tumor samples of the mice were collected, weighed, and recorded, and the spleen index, thymus index, and tumor suppression rate were calculated. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes in the tumor tissue. The morphological changes of the endoplasmic reticulum of tumor cells were observed by transmission electron microscopy. The positive expression of phosphorylated eIF2α(p-eIF2α) and ATF4 in the tumor tissue was detected by immunofluorescence. Western blot was employed to determine the protein levels of phosphorylated PERK(p-PERK), p-eIF2α, ATF4, CHOP, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinase inhibitor 1A(p21), and cyclinD1 in the tumor tissue. Real-time fluorescent quantitative PCR was employed to determine the mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, Bcl-2, p21, and cyclinD1 in the tumor tissue. Compared with the blank group, the model group showed decreases in spleen index and thymus index(P<0.05). Compared with the model group, the cisplatin group showed decreases in spleen index and thymus index(P<0.05), and the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups presented increases in spleen index and thymus index(P<0.05). In addition, the treatment groups all showed decreased tumor mass(P<0.05), increased tumor cell lysis and nuclear rupture, widened gap between rough endoplasmic reticulum, enhanced average fluorescence intensity of p-eIF2α and ATF4(P<0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P<0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P<0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P<0.05). Compared with the cisplatin group, the combination groups showed increases in spleen index and thymus index(P<0.05) as well as mean optical density(P<0.05), and the high-dose Guiqi Yiyuan Ointment+cisplatin group showed decreased tumor mass(P<0.05). In addition, the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups showcased enhanced average fluorescence intensity of p-eIF2α and ATF4(P<0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P<0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P<0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P<0.05). In conclusion, Guiqi Yiyuan Ointment combined with cisplatin can effectively inhibit the growth of Lewis lung carcinoma in mice by regulating the expression of proteins related to the PERK/eIF2α/ATF4/CHOP signaling pathway and promoting cell cycle arrest and apoptosis.
Animals ; Cisplatin/administration & dosage* ; Activating Transcription Factor 4/genetics* ; Eukaryotic Initiation Factor-2/genetics* ; eIF-2 Kinase/genetics* ; Carcinoma, Lewis Lung/pathology* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Mice ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Transcription Factor CHOP/genetics* ; Ointments/administration & dosage* ; Humans ; Cell Proliferation/drug effects* ; Antineoplastic Agents/administration & dosage*

Objective： To systematically evaluate the clinical efficacy and safety of Tonifying kidney and activating blood therapy for the treatment of diabetic mellitus erectile dysfunction. Methods： China National Knowledge Infrastructure(CNKI), Wanfang Data, VIP, Chinese Biomedical Database(CBM), PubMed, Cochrane Library, Embase and Web of Science were searched from inception until October 20th of 2024，for randomized controlled trials of Tonifying kidney and activating blood therapy for the treatment of diabetic erectile dysfunction. Literature screening, quality evaluation, and data extraction were carried out in accordance with relevant standards. The software of RevMan5.4 was used for the analysis of publication bias. And meta-analysis was conducted to assess the impact of this therapy on IIEF-5, total effective rate, adverse reactions. The evidence levels according to the analysis results were evaluated. Results: Totally 19 RCTs were included, involving 1 612 patients. The result of meta-analysis indicated that Tonifying kidney and activating blood therapy had advantages on the improvement of IIEF-5 scores (MD=3.59，95%CI［2.14，5.03］，P<0.01)，total effective rate (OR=4.30，95%CI［3.29，5.32］，P<0.000 01）. However, there was no statistically significant difference in the incidence of adverse reactions(OR=0.98，95%CI［0.48，2.01］，P=0.96) between the two groups. Conclusions： Tonifying kidney and activating blood therapy can improve the clinical efficacy and IIEF-5 score for the patients with diabetic erectile dysfunction. But considering the limited quantity of included studies, more high-quality studies still be needed to validate the therapeutic effect.
Humans ; Male ; Erectile Dysfunction/therapy* ; Randomized Controlled Trials as Topic ; Kidney ; Medicine, Chinese Traditional ; Diabetes Complications/therapy*

Superior vena cava syndrome(SVCS)is a group of clinical syndromes caused by obstruction of the superior vena cava and its major branches from various causes.Pulmonary artery stenosis(PS)is a complication of lung cancer or mediastinal tumours.SVCS combined with PS due to pulmonary metastases from bladder cancer is extremely rare and has not been reported in the literature.Here we reported an old male patient with pulmonary metastases from bladder cancer presenting with swelling of the head,neck and both upper limbs.SVCS combined with PS was clarified by pulmonary artery computed tomography angiography(CTA)and digital subtraction angiography(DSA).Endovascular stenting was used to treat SVCS.Angiography also showed that PS had not caused pulmonary hypertension and did not need to be treated.The swelling of the patient's head,neck and upper limbs was gradually reduced after the procedure.

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.
Humans ; Antibodies/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Carcinoma, Squamous Cell/surgery* ; Cisplatin ; Esophageal Neoplasms/surgery* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Programmed Cell Death 1 Receptor/therapeutic use* ; Retrospective Studies ; Treatment Outcome

Biliary tract cancer is a group of malignancies which originate from biliary epithelium, and adenocarcinoma is the main pathological type. Although surgical resection is the only radical treatment strategy, most biliary tract cancer patients are diagnosed at locally advanced stage or with distant metastasis. Biliary tract cancer is highly resistant to the conventional chemoradiotherapy and the emerging immunotherapy including immune checkpoint inhibitors, owing to the suppressive immune microenvironment. In a whole view, this paper discussed the anti-tumor and tumor-promoting immune responses of the various immune cells and stromal cells in the immune microenvironment of biliary tract cancer, as well as their correlation with prognosis. The understanding of the whole view of immune microenvironment in biliary tract cancer patients could further inform the design of clinical trials of immunotherapy or combination therapy.

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

OBJECTIVE: To investigate an improved culturing method for karyotyping analysis, and increase the detection rate of cytogenetic abnormalities in patients with multiple myeloma (MM), so as to provide more powerful information for the clinical diagnosis, prognosis stratification, and individualized treatment of MM patients. METHODS: Eighty newly-diagnosed MM patients were enrolled and divided into two groups. In observation group, IL-6 (10 ng/ml) and GM-CSF (30 ng/ml) were supplemented in the culture medium, while no stimulating factor was added in control group. The samples from both groups were cultured for 72 hours under the same conditions, and their karyotypes were analyzed by G-banding. The detection rate of the cytogenetic abnormalities, as well as the corresponding characteristics were compared between the two groups. RESULTS: The detection rate of the chromosome aberrations was greatly increased in the observation group compared with the control group, the overall detection rate was 72.5% and 22.5%, respectively, as well as 80.0% and 19.2% in the subgroup of ≤60 years old, 68.0% and 28.6% in the subgroup of > 60 years old, which showed significant statistical differences (P<0.05). CONCLUSION The modification of the culturing method with the addition of IL-6 (10 ng/ml) and GM-CSF (30 ng/ml) dual stimulating factors followed by incubation for 72 hours can effectively increase the detection rate of abnormal karyotypes in MM patients.
Chromosome Aberrations ; Granulocyte-Macrophage Colony-Stimulating Factor ; Humans ; Interleukin-6 ; Karyotype ; Karyotyping ; Middle Aged ; Multiple Myeloma/genetics*

Objective: To measure and analyze parameters of the three-dimensional (3D) model of the condylar movement envelope surface (ES) and provide a reference for the design of the temporomandibular prosthesis. Methods: Thirty-four healthy adults aged (25.4±2.8) years were recruited from the Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology as subjects. There were 9 males and 25 females, most of them were university students and others outside the university have received undergraduate education or above. Condylar movement ES were obtained using the previous method on the 3D trajectory of condyle. The simulations of condylar movement were projected according to opening movements, protrusion movements, and lateral movements respectively. The total area of the ES and the area proportions of models formed by above different mandibular movements were measured and calculated. The adults' head and maxillofacial 3D models reconstructed by cone beam CT were registered with ES in Geomagic Studio. The inner and outer poles of the condyle, the corrective sagittal axis of the ES, and the median sagittal plane (MSP) were calibrated in registration models using Geomagic Studio, and the parameters were measured as follows: the anteroposterior and medialateral diameters of the condyle, the anteroposterior diameters and the transverse diameters (anterior, middle and posterior parts) of the ES, the angles between the corrective sagittal axis of the ES and MSP (ES-MSP). Pearson correlation analysis was performed by SPSS 24.0. Results: The total area of the ES was (760±133) mm², the opening movement part accounted for (63.3±15.2)%, the protrusion movement part accounted for (14.9±9.6)%, the lateral movement part accounted for (21.8±13.3)%. Parameter measurements were as follows: mediolateral diameters of condyle was (19.8±2.3) mm; anteroposterior diameter of the ES was (21.2±3.1) mm, the transverse diameters (anterior, middle and posterior parts) of the ES were (20.6±2.4), (20.4±2.4), (22.0±2.6) mm, respectively; the transverse diameters of the ES were about 2 mm larger than that of the condyle. The angle between the corrective sagittal axis of ES and the MSP was 6.8°±6.2°. The coefficient of variation (CV) in these parameters showed: CV of the transverse diameters (anterior, middle and posterior parts) of the ES and mediolateral diameter of the condyle were 0.98, 0.99, 0.93, respectively (P<0.001). CV of aera of ES and mediolateral diameter of the condyle was 0.64 (P=0.002). CV of aera of ES and anteroposterior diameter of ES was 0.62 (P=0.004). Conclusions: The 3D envelope surface model formed by mandibular opening movements accounted for the largest proportion of the ES. The corrective sagittal axis of the ES was at an angle to the MSP, the transverse diameters (anterior, middle and posterior parts) of the ES were approximately 2 mm larger than the mediolateral diameter of the condyle, the transverse diameters (anterior, middle and posterior parts) of the ES were highly positively correlated with the mediolateral diameter of the condyle.
Humans ; Adult ; Male ; Female ; Mandibular Condyle ; Cone-Beam Computed Tomography ; Mandible ; Movement ; Temporomandibular Joint

Three new coumarins, integmarins A-C (1-3), and a new coumarin glycoside, integmaside A (4) were isolated from the leaves and stems of Micromelum integerrimum. Their structures were elucidated on the basis of 1D and 2D NMR and MS data, and their absolute configurations were assigned according to the ECD data of the in situ formed transition metal complexes and comparison of experimental and calculated ECD data. Compounds 1 and 2 are two rare coumarins with butyl and propyl moieties at the C-6 position; compound 3 is a novel coumarin with a highly oxidized prenyl group, and compound 4 is a rare bisdihydrofuranocoumarin glycoside.
Coumarins/isolation & purification* ; Glycosides/isolation & purification* ; Molecular Structure ; Plant Leaves/chemistry* ; Plant Stems/chemistry* ; Rutaceae/chemistry*