BACKGROUND:Astrocytes are the most abundant cells in the central nervous system,and various subsets of astrocytes are heterogeneous,performing a variety of special functions.Single-cell RNA sequencing(scRNA-seq)technology developed in recent years has extended our understanding of astrocyte heterogeneity from the perspective of transcriptome profiling. OBJECTIVE:To summarize the heterogeneity of scRNA-seq technology in different time and space,and pathological states and expand our knowledge of astrocyte heterogeneity on both molecular and functional levels. METHODS:The relevant articles on astrocyte heterogeneity and scRNA-seq were searched on PubMed,Elsevier,and CNKI databases.The search terms were"astrocytes,scRNA-seq,heterogeneity,Alzheimer disease,spinal cord injury,multiple sclerosis"in Chinese and English.Finally,74 articles were selected for viewing after screening according to inclusion criteria. RESULTS AND CONCLUSION:scRNA-seq studies related to the heterogeneity of astrocytes have shown that astrocyte is significantly heterogeneous across four aspects:species,developmental stage,central nervous system region,and pathological state.(1)Unique expression of certain genes occurs in astrocytes of different species,and the discovery of species-specific genes is beneficial for the translation of clinical studies.(2)During astrocyte development,differential gene expression emerged in the cellular subtypes identified at each stage,which further refined the cellular lineage of astrocytes and laid the foundation for the study of astrocyte developmental trajectories and mechanisms.(3)The discovery of differential gene expression allows regional localization of different astrocyte subpopulations and assists in the diagnosis and treatment of neurological diseases.(4)Astrocyte heterogeneity revealed by scRNA-seq can provide specific markers at the time of disease diagnosis and identify potential therapeutic targets.(5)The heterogeneity of astrocytes exists in many aspects,interacts with each other and is complex.The mechanisms of its generation,maintenance and transformation remain unclear.At present,molecular research on the single-cell level is still lacking.Linking transcriptionally defined astrocyte subpopulations to cellular activity,behavior and disease markers in real time remains one of the great challenges in the field.

Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

The World Health Organization defines sexual health as a state of physical, emotional, mental and social health related to sex, which is not just the absence of disease, dysfunction, etc. In clinical practice, in addition to common male sexual dysfunction such as erectile dysfunction and premature ejaculation, rare forms of male sexual dysfunction may also be encountered. Perhaps due to our lack of understanding of this type of disease, it is easy to overlook or miss diagnosis in clinical practice. Based on the latest literature reports and our clinical experience in diagnosis and treatment, this article elaborates on its definition, clinical symptoms, diagnosis and treatment, and possible pathogenesis. It is hoped that clinician can pay attention to and accurately diagnose rare male sexual dysfunction.

Objective:To compare the safety and short-term prognosis of laparoscopic hepatectomy after conversion therapy versus pure laparoscopic hepatectomy for patients with hepatocellular carcinoma (HCC).Methods:A total of 740 patients with HCC undergoing laparoscopic hepatectomy at Sun Yat-sen Memorial Hospital of Sun Yat-sen University between January 2019 and December 2022 were screened for study eligibility, among which 433 patients were eligible, including 364 males and 69 females, aged (57.2±11.1) years. Patients who underwent laparoscopic hepatectomy after conversion therapy (including interventional therapy combined with targeted therapy or targeted therapy combined with immunotherapy, etc.) were marked as conversion resection group ( n=36), and those who underwent laparoscopic hepatectomy alone were marked as pure resection group ( n=397). After propensity score matching (PSM), 29 cases in the conversion resection group and pure resection group were finally enrolled. Preoperative (tumor number, maximum tumor diameter, etc.), intraoperative (operation time, intraoperative blood loss, etc.) and postoperative (hospital stay, drainage volume, complications, etc.) data and short-term prognosis were compared between the two groups. Survival curves and rates were analyzed using Kaplan-Meier and log-rank test. Results:The baseline characteristics including the occurrence of liver cirrhosis, the tumor number and maximum diameter showed no significant differences between the two groups after PSM (all P>0.05), indicating comparability. There were no statistical differences between the two groups in terms of operation time, intraoperative blood loss, postoperative hospital stay, postoperative drainage volume etc. (all P>0.05). The incidences of postoperative complications and severe complications (Clavien-Dindo grade ≥Ⅲ) were 34.5% (10/29) and 6.9% (2/29) in pure resection group, and 41.4% (12/29) and 10.3% (3/29) in conversion resection group, respectively, with no significant difference between the two groups (χ 2=0.29, 0, P=0.588, 1.000). The recurrence-free survival rates at 6, 12 and 18 months after surgery were 79.2%, 70.7% and 70.7% in conversion resection group and 86.2%, 82.8% and 79.3% in pure resection group, the overall survival rates at 6, 12, and 18 months after surgery were 96.4%, 89.5%, 74.6% in conversion resection group, and 100.0%, 96.6% and 93.1% in pure resection group, with no significant difference (χ 2=1.90, 1.91, P=0.168, 0.167). Conclusion:Laparoscopic hepatectomy after conversion therapy for initially unresectable HCC has comparable safety and short-term prognosis with the pure laparoscopic hepatectomy.

Unlike healthy, non-transformed cells, the proteostasis network of cancer cells is taxed to produce proteins involved in tumor development. Cancer cells have a higher dependency on molecular chaperones to maintain proteostasis. The chaperonin T-complex protein ring complex (TRiC) contains eight paralogous subunits (CCT1-8), and assists the folding of as many as 10% of cytosolic proteome. TRiC is essential for the progression of some cancers, but the roles of TRiC subunits in osteosarcoma remain to be explored. Here, we show that CCT4/TRiC is significantly correlated in human osteosarcoma, and plays a critical role in osteosarcoma cell survival. We identify a compound anticarin-β that can specifically bind to and inhibit CCT4. Anticarin-β shows higher selectivity in cancer cells than in normal cells. Mechanistically, anticarin-β potently impedes CCT4-mediated STAT3 maturation. Anticarin-β displays remarkable antitumor efficacy in orthotopic and patient-derived xenograft models of osteosarcoma. Collectively, our data uncover a key role of CCT4 in osteosarcoma, and propose a promising treatment strategy for osteosarcoma by disrupting CCT4 and proteostasis.

Objective:To investigate the intervention effect of topical shikonin on an imiquimod-induced psoriasis-like mouse model and its effect on expression of CCAAT enhancer binding protein δ (CEBPD) .Methods:Twenty specific pathogen-free BALB/c male mice were randomly and equally divided into model group, shikonin 1 group, shikonin 2 group and blank control group by using simple random sampling. Mice in the model group, shikonin 1 group and shikonin 2 group were topically treated with 50 mg of 5% imiquimod cream every day on the shaved back to establish the psoriasis-like mouse model. After 6-hour treatment, mice in the shikonin 1 group and shikonin 2 group were treated with 0.5 ml of shikonin at concentrations of 0.576 and 5.76 g/L respectively in the modeling area for 8 consecutive days; the blank control group received no treatment. Changes in the skin lesions of these mice were observed by naked eyes every day, and evaluated by using psoriasis area severity index (PASI) ; after 8-day treatment, the mice were sacrificed by cervical dislocation, the dorsal skin tissues were resected, and immunohistochemical study and Western blot analysis were performed to determine the expression of CEBPD in the mouse epidermis. Statistical analysis was carried out with SPSS 16.0 software by using one-way analysis of variance for comparisons of observation indices among different groups, as well as least significant difference- t test for multiple comparisons. Results:On day 8, the mice in the model group presented with obvious erythema, scales, and infiltrative and thickened skin lesions; compared with the model group, the skin lesions were markedly improved in the shikonin 1 group and shikonin 2 group, and the improvement was more obvious in the shikonin 2 group. On day 8, the PASI score significantly differed among the blank control group, model group, shikonin 1 group and shikonin 2 group (0, 11.0±1.22, 8.6±0.55, 5.8±1.30 points, respectively; F=128.21, P<0.01) , and there were significant differences between any two groups (all P < 0.01) . Immunohistochemical study showed a significant difference in the expression of CEBPD ( A value) among the model group, shikonin 1 group, shikonin 2 group and blank control group (0.072±0.026, 0.177±0.036, 0.290±0.062, 0.407±0.051, respectively; F=48.895, P < 0.01) , and there were also significant differences between any two groups (all P < 0.01) . Western blot analysis showed that the CEBPD expression in the mouse epidermis was highest in the blank control group, followed in descending order by the shikonin 2 group, shikonin 1 group and model group, and significantly differed among the above 4 groups ( F=10.237, P<0.05) ; moreover, there were significant differences in the CEBPD expression between the model group and blank control group, as well as between the shikonin 1 group and blank control group (both P<0.05) , while no significant difference was observed between the shikonin 2 group and the blank control group ( P > 0.05) . Conclusion:Topical shikonin could effectively interfere with the development of imiquimod-induced psoriasis-like mouse model; CEBPD expression decreased in the psoriasis-like mouse model, and could be markedly upregulated by topical application of shikonin.

Pancreatic cancer is one of the most aggressive malignancies. The poor prognosis of pancreatic cancer patients is mainly attributed to low diagnostic rate at the early stage, highly aggressive nature coupled with the inadequate efficacy of current chemotherapeutic regimens. Novel therapeutic strategies are urgently needed for pancreatic cancer. MicroRNAs (miRNAs) play an important regulatory role in key processes of cancer development. The aberrant expression of miRNAs is often involved in the initiation, progression, and metastasis of pancreatic cancer. The discovery of tumor suppressor miRNAs provides prospects for the development of a novel treatment strategy for pancreatic cancer. We reviewed recent progress on the understanding of the role of miRNAs in pancreatic cancer, highlighted the efficient application of miRNAs-based therapies for pancreatic cancer in animal models and clinical trials, and proposed future prospects. This review focuses on the promise of integrating miRNAs into the treatment of pancreatic cancer and provides guidance for the development of precision medicine for pancreatic cancer.
Animals ; Biomarkers, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; MicroRNAs/genetics* ; Pancreatic Neoplasms/genetics* ; Prognosis

Objective: To compare the disinfection effect of three-hole polypropylene infusion bottle stopper by central sterilization method and groove central sterilization method, and to explore the best method of three-hole polypropylene infusion bottle cap disinfection. Methods: A total of 1 088 bottles of three-pore polypropylene infusion bottles from 10 hospitals in Panzhihua City and the surrounding areas of Chengdu were selected for disinfection, and the effects were compared by fluorescent powder tracing method and bacterial culture method respectively. The two methods were divided into two groups: bottle stopper Central Sterilization group and groove Central Sterilization group. Each nurse sterilized two groups of liquid. Results: The total area of fluorescent powder residues after disinfection of 272 bottles of infusion bottles with different specifications M(P₂₅, P₇₅) was 0.26 (0, 2.51). The total area of fluorescent powder residues M(P₂₅, P₇₅) was 15 (8, 24). There were significant differences in the residual area of fluorescent powder between the two groups after liquid bottle disinfection (Z=-17.31, P<0.01). Thirty-four positive specimens of bacteria culture, 68 bacterial colonies and 158 bottles of infusion bottles were disinfected by central sterilization of 160 bottles. There were 15 positive samples and 30 colonies of bacteria cultured in the bottle disinfected by groove central disinfection method (χ²=2.773, P<0.05). Conclusion The groove center disinfection method is the best disinfection method for the bottle stopper of three-hole polypropylene infusion bottle.

Objective: To explore the clinical practice of delivering radiotherapy during the outbreak of 2019 novel coronavirus disease(COVID-19). Methods: During this epidemic period, available methods including but not limited to: strict disinfection, body temperature monitoring, learning relevant knowledge by all staffs to ensure the safety of radiotherapy treatment. Relevant data including proportion of radiotherapy, time from scanning to the first time of radiation delivery and degree of satisfaction in the view of staffs and patients, respectively. Results: A total of 60 patients received radiation therapy in the department of radiotherapy of Zhejiang Provincial People’s Hospital (2020-02-11). Compared with the same period in 2019 (after the Spring Festival), the total number of patients receiving radiotherapy was decreased from 72 to 60(83.3%). Among them, the number of patients receiving palliative radiation therapy decreased significantly, while the proportion of radical, preoperative and/or postoperative radiotherapy/radiochemotherapy did not significantly decrease. There was significant difference between different years (χ²=6.967, P<0.05). The median time for newly admitted patients to receive radiotherapy was two days, which was not significantly longer than the interval in 2019 (P>0.05). Staffs and patients were generally satisfied with the current prevention measures. Conclusions Using a variety of prevention and control methods, and taking full account of medical safety and patient benefits, radiation-related activities can be carried out during the epidemic.

Objective: To make a quantitative evaluation on the short term effect of particulate matter with aerodynamic diameter no more than 2.5 μm (PM_2.5) on cumulative excess mortality rate (CER) and years of life lost (YLL) in residents in Changping district of Beijing. Methods: The death data in local residents, daily mortality, meteorology data and air pollution data (PM_2.5, SO₂ and NO₂ concentrations) in Changping from 2014 to 2017 were collected. Distributed lag non-linear model was used to assess the age and gender specific cumulative lag effects of PM_2.5 on cardiovascular CER and daily YLL in Changping. Results: The effects of PM_2.5 on cardiovascular CER and YLL were obvious on lag 7 days and lag 9 days, respectively, peaking on day 14, and lasting for 21 days. On lag0-21 days, for a 10 μg/m³ increase in PM_2.5, the population based CER of cardiovascular disease death was 0.021% (95%CI: 0.004%-0.038%), and the YLL was 1.47 (95%CI: 0.23-2.70) years. Greater PM_2.5 effect were observed in males and the elderly. Conclusion PM_2.5 increased the risk of cardiovascular disease death and YLL.