Objective:To observe the intervention mechanism of phlegm-stasis co-treatment for the JNK signaling pathway in the myocardium of diabetes rats.Methods:Totally 50 male SD rats of SPF grade were selected. Diabetes model was established by single intraperitoneal injection of 55 mg/kg streptozotocin (STZ) solution. After continued feeding for 3 weeks, the rats were divided into normal group, model group, alachloramine group, blood stasis removing group, phlegm removing group and phlegm-blood stasis co-treatment group according to random number table method, with 6 rats in each group. Xiaoxianxiong Decoction (4.05 g/kg), Xuefu Zhuyu Decoction (7.02 g/kg), Didang Xianxiong Decoction (8.10 g/kg) were administered to the stomach respectively in the phlegm removing group, the blood stasis removing group and the phlegm-blood stasis co-treatment group. Alachloramine (3 mg/kg) was administered to the stomach by gavage in the alachloramine group. After 8 weeks, HE staining was used to observe the morphological changes of myocardial tissue in diabetic rats. Masson staining was used to observe the deposition of collagen fibers in the myocardial interstitium in rats. The expression of JNK1 protein was determined by immunohistochemistry. JNK1 mRNA, IRS1 mRNA and NLRP3 expression levels were detected by Real-time PCR. Western blot was used to detect the protein expressions of IRS-1, p-Akt and NLRP3.Results:The myocardial cells in the model group were disorganized, with hypertrophy, blurred texture, inflammatory infiltration of interstitium, increased collagen fibers, and focal necrosis. All treatment groups could improve fibrosis, inflammatory infiltration and reduce myocardial collagen deposition in different degrees. Compared with the model group, the mRNA and protein expressions of JNK1 and NLRP3 bodies decreased ( P<0.01), the IRS-1 mRNA and protein increased ( P<0.01), and p-Akt protein expression increased ( P<0.01). Conclusions:The phlegm and stasis co-treatment can effectively improve the cardiomyopathy of diabetes rats, and the effect is better than the phlegm-resolving method or the stasis resolving method alone. The mechanism may be related to the inhibition of JNK signaling pathway activation, reduce the expressions of JNK1 and NLRP3, and increase the IRS-1 and Akt.

Objective:To evaluate the rationality of the "Sandwich Principle teaching mode" adopted in our teaching of internal medicine and verify the necessity of its "Intergroup intersecting discussion".Methods:33 students majoring in traditional Chinese medicine were divided into control group (taught by standard process of sandwich principle) and experiment group (taught by simplified process of sandwich principle). The Dundee Ready Education Environment Measure (DREEM) was used to evaluate students' feelings toward the two teaching modes.Results:The total score of DREEM in the control group was higher than that in the experiment group, with statistically significant difference; the total score in the academic perception subscale in the control group was higher than that in the experiment group, among which the scores of "I have faith in passing the exam this year" and other 2 items were better than that in the experiment group, with statistically significant difference ( P<0.05); there were no statistical difference in the total scores of other perception subscales between the two groups( P>0.05), but the scores of the 9 items including "the atmosphere is very harmonious in the clinical teaching process" in the control group were significantly better than those in the experiment group, with statistically significant difference( P<0.05). Conclusion:The teaching mode of Sandwich Principle can create a positive and effective learning environment for supporting students. "Intergroup intersecting discussion" can encourage students to actively participate in the teaching process, and help increase their academic confidence and sense of achievement in learning. It is also helpful to build a harmonious teacher-student relationship and create a relaxing and pleasant learning environment so that students can gain a better learning experience. Therefore, "Intergroup intersecting discussion" is indispensable in medical teaching.

Objective: We aimed to investigate the differences of transcriptome profile between 2 groups of high-grade serous ovarian cancer (HGSOC) patients with distinct outcomes and identify potential biomarkers for recurrence. Methods: RNA sequencing was performed in 2 groups of HGSOC patients with similar demographic characteristics but exhibiting distinct progression-free survival (PFS). Transcriptome data of poor response (PR; PFS ≤6 months) and good response (GR; PFS ≥12 months) group were compared. We employed xCell to evaluate the abundance of 63 cells in tumor microenvironment. The predictive value of recurrence-related tumor infiltration cells was validated in cohort data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) dataset. The weighted correlation network analysis was performed to identify the genes related to cell infiltration. Results: PR patients exhibited a distinct tumor infiltration immune cells-related transcriptional profile compared to GR patients, such as lower signatures of leukocyte differentiation, activation and chemotaxis. The fraction of T-helper 2 (Th2) cells infiltration was significantly higher in PR group than in GR group. High infiltration of Th2 was significantly associated with unfavorable prognosis in the GEO cohort (area under the curve=0.84 at 6 months recurrence) and TCGA cohort (p=0.008). Genes enriched to extracellular matrix organization and integrin binding were relevant to Th2 infiltration. Conclusion Patients with HGSOC having shorter PFS exhibited a distinct gene signature that related to tumor-infiltrating immune cells. The level of Th2 infiltration could facilitate patient recurrence risk stratification and may be a promising biomarker for prognosis prediction and immune-related treatment.

Objective:To explore the clinical and genetic characteristics of a child with autosomal recessive primary microcephaly (MCPH).Methods:A case study has been carried out on a boy who had presented at the Inner Mongolia Maternity and Child Health Care Hospital for microcephaly and mental deficiency in September 2022. Prenatal ultrasound images were retrospectively analyzed, and whole exome sequencing and Sanger sequencing were carried out for his family. A literature review was also carried out using keywords such as " ASPM gene", "microcephaly", "prenatal diagnosis", "primary microcephaly", " ASPM", "MCPH5", "MCPH", "autosomal recessive microcephaly", and "prenatal diagnosis on ultrasonography" on the PubMed database, Wanfang Data and China National Knowledge until September 2023. This study was approved by Medical Ethics Committee of the Inner Mongolia Maternity and Child Health Care Hospital (Ethics No. 2021-093-1). Results:The proband had shown progressive reduction in biparietal diameter (BPD) and head circumference (HC) during the fetal period. He was found to harbor compound heterozygous variants of the ASPM gene, which included a paternally derived c. 8044C>T (p.R2682X) and a maternally derived c.8652dup (p.A2885Sfs*35). Both variants were classified as pathogenic (PVS1+ PM2_Supporting+ PP4; PVS1+ PM2_Supporting+ PM3) based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). For other fetuses in his family, prenatal ultrasound and genetic testing were all normal. Literature research has identified 11 relevant articles, which included 14 MCPH cases. All of the MCPH5 cases had shown various degrees of reduced BPD/HC on fetal imaging (100%, 15/15). Developmental delay, intellectual disability, and attention deficits were noted in all survived cases, with one case having seizures (12.5%, 1/8). Their genotypes had included homozygotes (46.2%, 6/13) and compound heterozygotes (53.8%, 7/13) for nonsense variants (45%, 9/20) and frameshifting variants (55%, 11/20). Conclusion:The compound heterozygous variants c. 8044C>T (p.R2682X) and c. 8652dup (p.A2885Sfs*35) of the ASPM gene probably underlay the reduced BPD and HC in this proband with MCPH.

Objective To evaluate the frequencies and polymorphisms of CCR5-△32,CCR2-641 and SDF1-3'A alleles conferring resistance to HIV-1 infection in Chinese population from Han ethnic origin.Methods This cohort was comprised of 1251 subjects(915 men and 336 women)aged 15 -80 years and none was HIV-1 positive.Genotyping of allelic CCR5-△32,CCR2-641 and SDF1-3' A variants was performed using PCR or PCR/RFLP assay,and further confirmed by direct DNA sequencing.Results Our finding shows that the△32 deletion mutation in the CCR5 gene does occur in this population and can be inherited in a Mendelian fashion in indigenous Han Chinese at a very low frequency of 0.00119(n= 1254).The frequencies of mutant CCR2-641 and SDF1-3'A alleles were 0.20023(n = 1251)and 0.2873(n = 893),in this population,which are higher than those found in American Caucasians.Furthermore the polymorphisms of CCR2-641 and SDF1-3' A alleles in the Han Chinese population were different from those in American Caucasians.Statistical analysis showed that the genotype distribution of CCR5-△32,CCR2-641 and SDF1-3' A alleles was in equilibrium according to the Hardy-Weinberg equation.Conclusion The CCR5-△32 mutation may not be a major resistant factor against HIV-1 infection in indigenous Han Chinese.The significance of higher frequencies of CCR2-641 and SDF1-3' A alleles (0.20023 and 0.2791)in the Han population remains to be clarified in HIV-1-positive carriers and AIDS patients.

Cancer remains one of the leading causes of death globally and metastasis always leads to treatment failure. Here, we develop a versatile hydrogel loading photothermal agents, chemotherapeutics, and immune-adjuvants to eradicate orthotopic tumors and inhibit metastasis by combinational therapy. Hydrogel networks were synthesized via the thiol-Michael addition of polydopamine (PDA) with thiolated hyaluronic acid. PDA acted as a cross-linking agent and endowed the hydrogel with excellent photothermal property. Meanwhile, a chemotherapeutic agent, doxorubicin (DOX), was loaded in the hydrogel via π‒π stacking with PDA and an immune-adjuvant, CpG-ODN, was loaded via electrostatic interaction. The release of DOX from the hydrogel was initially slow but accelerated due to near infrared light irradiation. The hydrogels showed remarkably synergistic effect against 4T1 cancer cells and stimulated plenty of cytokines secreting from RAW264.7 cells. Moreover, the hydrogels eradicated orthotopic murine breast cancer xenografts and strongly inhibited metastasis after intratumoral injection and light irradiation. The high anticancer efficiency of this chemo-photothermal immunotherapy resulted from the strong synergistic effect of the versatile hydrogels, including the evoked host immune response. The combinational strategy of chemo-photothermal immunotherapy is promising for highly effective treatment of breast cancer.

Radiation therapy is an effective method to kill cancer cells and shrink tumors using high-energy X-ray or γ-ray. Radiation pneumonitis (RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here, we prepared curcumin-loaded mesoporous polydopamine nanoparticles (CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles (MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π‒π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2B cells from γ-ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of 15 Gy ⁶⁰Co γ-ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.

The heavily harsh plateau environment including low pressure, hypoxia, cold, dryness and strong ultraviolet radiation, seriously threatens the physical and mental health of those who quickly enter the plateau area. Lungs are the sensitive organs for high altitude injury. High-altitude lung diseases include the acute high-altitude lung disease (i.e., high-altitude pulmonary edema), the chronic high-altitude lung disease (i.e., high-altitude pulmonary artery hypertension) and the high-altitude de-adapted reaction. This review summarizes the pathogenic mechanisms and the main therapeutic drugs of high-altitude lung diseases based on the recent research. Moreover, the related formulations and administration routes are also reviewed here. It will provide support and counsel for the diagnosis and treatment of high-altitude lung diseases.