Cyclin-dependent kinase 9 (CDK9) is a member of the transcription CDK subfamily and plays a role in transcriptional regulation. Selective CDK9 degraders possess potent clinical advantages over reversible CDK9 inhibitors. Herein, we report the first ATG101-recruiting selective CDK9 degrader, AZ-9, based on the hydrophobic tag kinesin degradation technology. AZ-9 showed significant degradation effects and selectivity toward other homologous cell cycle CDKs in vitro and in vivo, which could also affect downstream related phenotypes. Mechanism research revealed that AZ-9 recruits ATG101 to initiate the autophagy-lysosome pathway, and forms autophagosomes through the recruitment of LC3, which then fuses with lysosomes to degrade CDK9 and the partner protein Cyclin T1. These dates validated the existence of non-proteasomal degradation pathway of hydrophobic driven protein degradation strategy for the first time, which might provide research ideas for chemical induction intervention on other types of pathogenic proteins.

Three taraxerane nortriterpenoids were isolated from mastic by using various modern chromatographic separation techniques. They were identified as(5R,8R,9R,10S,11S,12R,13S,17R,18R)-28-norlupa-11,12-epoxy-14-taraxerene-3,16-dione(1),(5R,8R,9R,10S,11S,12R,13S,17S,18S)-17-hydroxy-28-norlupa-11,12-epoxy-14-taraxerene-3-one(2), and(5R,8R,9R,10R,11S,12R,13R,14S,17S,18S)-14,17-epoxy-28-norlupa-11,12-oxidotaraxerone(3) through the high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), infrared(IR), ultraviolet(UV), nuclear magnetic resonance(NMR), and single-crystal X-ray diffraction techniques as well as comparison with literature data. Compounds 1-3 were C-28 nortriterpenoids and isolated from mastic for the first time, and compounds 1-2 were new ones. In the model for RAW264.7 cell anti-inflammation induced by lipopolysaccharide(LPS), compound 1 demonstrates an inhibitory effect on nitric oxide(NO) [IC_(50)=(13.38±0.68) μmol·L~(-1)], comparable to the activity of the positive control dexamethasone [IC_(50)=(14.59±1.49) μmol·L~(-1)]. Compounds 2 and 3 exhibit weaker inhibitory effects, with IC_(50) values of(24.17±2.56) and(22.25±2.84) μmol·L~(-1), respectively.
Animals ; Mice ; Triterpenes/isolation & purification* ; Drugs, Chinese Herbal/isolation & purification* ; Mastic Resin/chemistry* ; Nitric Oxide ; Molecular Structure ; Macrophages/immunology* ; RAW 264.7 Cells

Objective To explore the facilitators and barriers of palliative care volunteering,and to provide references for further advancement of palliative care volunteering.Methods Purposeful sampling was used to select 12 volunteers from a palliative care ward in Hangzhou,Zhejiang Province,between April and September 2024.Semi-structured interviews were conducted,and directed content analysis was applied to organize and analyze the data,followed by theme analysis.Results Facilitators and barriers for volunteers' participation in palliative care volunteering were extracted.The 5 sub-themes of facilitators include motivating factors and perceived benefits,support and collaboration among volunteers,professional training and healthcare recognition,increased social awareness and public acceptance,and government support and institutional safeguards.The 5 sub-themes of barriers include limitations in individual capacity,challenges in collaboration with patients,families and healthcare workers,inadequate management and service mechanisms,uneven development of palliative care and insufficient public attention to psychological problems,and inadequate relevant laws and incentives.Conclusion There are more factors affecting the development of palliative care volunteering,and healthcare professionals should adopt targeted strategies to promote the active participation of volunteers in order to promote the sustainable development of palliative care volunteering.

Objective:To compare the clinical efficacy of O-arm navigation-assisted percutaneous vertebroplasty (PVP) versus C-arm-guided PVP in the treatment of postoperative recurrent vertebral fractures following Kümmell′s disease.Methods:A retrospective cohort study was conducted to analyze the clinical data of 48 patients with postoperative recurrent vertebral fractures following Kümmell′s disease who were admitted to Zhengzhou Orthopedic Hospital from January 2021 to September 2024, including 16 males and 32 females, aged 51-85 years [(69.8±6.6)years]. Among them, 21 patients had stage I Kümmell′s disease and 27 stage II. Fractured vertebrae involved T 8-T 10 in 4 patients, T 11-L 2 in 29, and L 3-L 5 in 15. Twenty-five patients underwent O-arm navigation-assisted PVP (O-arm-assisted group) and 23 underwent C-arm-guided PVP (C-arm-guided group). The two groups were compared in terms of the operative time, intraoperative blood loss, bone cement volume, and bone cement filling saturation rate in the injured vertebral body. The visual analogue scale (VAS) scores and Oswestry disability index (ODI) values were also compared before operation, at 1 day, 1 month, 6 months after operation, and at the last follow-up. The excellent-good rate based on the MacNab criteria at the last follow-up and incidence of postoperative complications were detected. Results:All the patients were followed up for 6-24 months [(13.3±3.5)months]. There were no significant differences in the operative time, operative blood loss or bone cement volume between the two groups ( P>0.05). The O-arm-assisted group demonstrated a bone cement filling saturation rate of 96% (24/25) in the fractured vertebrae, significantly higher than 65% (15/23) in the C-arm-guided group ( P<0.05). The VAS scores before operation, at 1 day, and 1 month after operation were (8.4±1.0)points, (1.9±0.7)points, and (1.8±0.6)points, respectively in the O-arm-assisted group, while they were (8.3±0.8)points, (2.0±0.6)points, and (1.9±0.5)points, respectively in the C-arm-guided group ( P>0.05). The ODI values before operation, at 1 day, and 1 month after operation were 76.6±8.2, 20.4±4.5, and 19.8±4.1, respectively in the O-arm-assisted group, and 74.9±9.1, 21.3±3.6, and 20.9±3.2, respectively in the O-arm-assisted group ( P>0.05). At 6 months after operation and at the last follow-up, the VAS scores were (1.4±0.5)points and (1.5±0.5)points in the O-arm-assisted group, with significant improvement compared to (1.8±0.4)points and (1.9±0.3)points in the C-arm-guided group ( P<0.01); the ODI values were 17.8±3.2 and 18.2±3.5 in the O-arm-assisted group, with significant improvement compared to 19.9±3.1 and 21.3±4.0 in the C-arm-guided group ( P<0.05). Both groups demonstrated significant improvements in VAS scores and ODI values at 1 day, 1 month, 6 months after operation, and at the last follow-up, compared to those preoperatively ( P<0.05), while no statistically significant differences were found in VAS scores or ODI values at any postoperative timepoints ( P>0.05). According to the MacNab criteria, the O-arm-assisted group had a 100% (25/25) excellent-good rate, compared to 74% (17/23) in the C-arm-guided group ( P<0.05). The complication rate was 4% (1/25) in the O-arm-assisted group, significantly lower than 35% (8/23) in the C-arm-guided group ( P<0.05). Conclusion:O-arm navigation-assisted PVP for postoperative recurrent vertebral fractures following Kümmell′s disease offers advantages in precise cement delivery with sufficient dispersion, enhanced pain relief, functional recovery, improved quality of life, and reduced complication rates when compared to C-arm navigation-assisted PVP.

[Purpose]To analyze cancer incidence and mortality in Anhui cancer registration areas in 2019 and the trends from 2015 to 2019.[Methods]Data from 42 cancer registration areas in Anhui Province in 2019 meeting quality control requirements were collected.The incidence,mor-tality,age-standardized rates by Chinese standard population and world standard population,age-specific rate,accumulation rate(0～74 years old)and the top 10 cancers of high incidence and mortality were calculated by urban and rural areas,sexes and age groups.The standard population of China in 2000 was used for age-standardized incidence or mortality rate(ASIRC or ASMRC),and the Segi world standard population was used for age-standardized incidence or mortality rate(ASIRW or ASMRW),respectively.Joinpoint was used to analyze the incidence and mortality trends from 2015 to 2019,and the annual percentage change(APC)was estimated.[Results]In 2019,the reported incidence rate(crude rate)in Anhui cancer registration areas was 282.87/105(313.24/105 for male,251.19/105 for female),ASIRC and ASIRW were 183.85/105 and 178.94/105,respectively,with the cumulative incidence rate of 20.35％.There was no significant change in the incidence of malignant tumors from 2015 to 2019(APC=-1.00％,P＞0.05).The reported mortality rate(crude rate)was 167.20/105(214.67/105 for male,117.67/105 for female),ASMRC and ASMRW were 98.41/105 and 97.15/105,and the cumulative mortality rate was 10.68％.There was no significant change in the mortality rate of malignant tumors from 2015 to 2019(APC=-3.44％,P＞0.05).The incidence and mortality rate of lung cancer ranked the first in urban and rural popu-lations of all genders.The incidence rate of female breast cancer ranked the third and the mortali-ty rate ranked the sixth of all malignancies.The incidence and mortality of malignant tumors in men were higher than those in women,and higher in rural areas than those in urban areas,and the main cancer types of rural and urban areas tended to be the same.[Conclusion]From 2015 to 2019,there was no significant change in the incidence and mortality of malignant tumors in the cancer registration areas of Anhui Province,but it is still necessary to prevent and treat lung can-cer and female breast cancer.

Objective:To investigate the effects of lipids and lipopolysaccharide (LPS) in Artemisia pollen on the induction of allergic rhinitis in a murine model. Methods:BALB/c mice were randomly divided into seven groups using the random number table method as follows: defatted pollen group (TZ group, n=5), defatted pollen+ LPS group (TZLPS group, n=5), non-defatted pollen group (WTZ group, n=5), non-defatted pollen+ LPS group (WTZLPS group, n=5), PBS group ( n=5), PBS+ LPS group (PBSLPS group, n=5), and blank control group ( n=6). On days 1, 8, and 15, the mice in the TZ and TZLPS groups received a subcutaneous injection in the neck region with 0.1 ml of defatted Artemisia pollen extract (20 μg/ml); the WTZ and WTZLPS groups were administered 0.1 ml of non-defatted Artemisia pollen extract (20 μg/ml), while the PBS and PBSLPS groups were injected with 0.1 ml of PBS (0.1 mol/L). From days 22 to 28, the mice were subjected to intranasal challenge to induce allergic rhinitis symptoms. The TZ, WTZ, and PBS groups received nasal administration of 10 μl per nostril of defatted Artemisia pollen extract (500 μg/ml), non-defatted Artemisia pollen extract (500 μg/ml), and PBS (0.1 mol/L), respectively. For the TZLPS, WTZLPS, and PBSLPS groups, an additional 260 EU (5.2 μl) of LPS was co-administered per nostril alongside the corresponding base solutions. The blank control group received no intervention during this phase. The behaviors of the mice were observed; the levels of specific IgE, IgG1 and IgG2a in serum samples were detected by ELISA; the pathological changes in nasal mucosa and lung tissues were observed by HE staining, and the expression of both IL-4 and IL-5 was observed by immunohistochemistry. One-way analysis of variance and Kruskal-Wallis test were used for statistical analysis. Results:Following Artemisia pollen antigen challenge, the total TZ group (TZLPS group+ TZ group) exhibited significantly higher behavioral scores as compared with the total PBS group (PBSLPS group+ PBS group) and the blank control group (both P<0.001). Serum analysis revealed that the total TZ group showed markedly elevated levels of Artemisia-specific IgE compared with the total WTZ group (WTZLPS group+ WTZ group) and the total PBS group ( P<0.05, P<0.001), along with significantly higher IgG1 levels than the total PBS and blank control groups ( P<0.05, P<0.001), while no significant differences in IgG2a levels were observed among these groups (all P>0.05). In local inflammatory responses, eosinophil infiltration and IL-4/IL-5 expression in both nasal mucosa and lung tissues of mice in the total TZ group were significantly higher than those in the total PBS and blank control groups (all P<0.001). Notably, eosinophil counts in nasal mucosa of mice in the total TZ group surpassed those in the total WTZ group ( P<0.05), whereas no significant differences in IL-4/IL-5 expression in mouse nasal mucosa were detected between the total TZ and total WTZ groups (both P>0.05). LPS supplementation in pollen extracts showed no significant effects on the specific IgE, IgG1, or IgG2a levels in serum across groups (all P>0.05), nor did it alter eosinophil activation or IL-4 expression in mouse nasal mucosa (all P>0.05). However, compared with the TZ group, eosinophil counts and IL-4 expression in lung tissues of mice in the TZLPS group were significantly increased (both P<0.001). Conclusions:This study successfully establishes a mouse model of Artemisia pollen allergy, and finds that the defatting treatment of Artemisia pollen can induce more intense inflammatory response. The presence or absence of LPS in pollen has no significant effect on allergic inflammation in the nasal mucosa, but it can cause different degrees of damage to the lung tissues of mice.

Objective:To compare the efficacy of three-dimensional visualization-assisted intermuscular versus conventional intermuscular cervical expansive open-door laminoplasty (CEOL) in the treatment of cervical spinal cord injury without fracture or dislocation (CSCIWFD).Methods:A retrospective cohort study was conducted to analyze the clinical data of 58 patients with CSCIWFD admitted to Zhengzhou Orthopedic Hospital from October 2021 to January 2024, including 39 males and 19 females, aged 36-77 years [(52.9±8.9)years]. Among them, 26 patients were treated with three-dimensional visualization-assisted intermuscular CEOL (three-dimensional visualization group), while 32 patients were treated with conventional intermuscular CEOL (conventional intermuscular group). All patients were treated with CEOL in 4 segments (C 3-C 6), comprising 104 surgical segments in the three-dimensional visualization group and 128 in the conventional intermuscular group. The following outcomes were compared between the two groups, including the operative duration, intraoperative blood loss, accuracy rate of open-door and hinge placement at the surgical levels, visual analogue scale (VAS) of the neck and shoulder and Japanese Orthopedic Association (JOA) score preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up, American Spinal Injury Association (ASIA) impairment scale preoperatively and at the last follow-up, and postoperative complication rate. Results:All patients were followed up for 12-24 months [(17.5±3.1)months]. The operative duration and intraoperative blood loss were (117.0±12.3)minutes and (151.3±30.9)ml in the three-dimensional visualization group, which were shorter or less than (131.9±15.0)minutes and (184.7±42.9)ml in the conventional intermuscular group ( P<0.01). The accuracy rate of open-door and hinge placement at the surgical levels was 94.2% (98/104) in the three-dimensional visualization group, significantly higher than 83.6% (107/128) in the conventional intermuscular group ( P<0.05). The VAS scores of the neck and shoulder preoperatively, at 1 week, 1 month, 3 months, 6 months postoperatively, and at the last follow-up were 6.0(5.0, 7.0)points, 3.5(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.0, 3.0)points, 2.0(1.0, 2.3)points, and 2.0(1.0, 2.0)points in the three-dimensional visualization group, which were not statistically different from 5.0(4.3, 6.8)points, 4.0(3.0, 4.0)points, 3.0(2.0, 3.0)points, 2.0(1.3, 2.0)points, 2.0(1.0, 2.8)points, and 2.0(1.0, 2.0)points in the conventional intermuscular group ( P>0.05). The VAS scores of the neck and shoulder in the two groups were significantly decreased at 1 week, 1 month and 3 months postoperatively from the preoperative values ( P<0.05), while they were stabilized at 6 months postoperatively and at the last follow-up compared with those at 3 months postoperatively, with no significant difference among them ( P>0.05). The JOA scores were (8.1±2.8)points, (10.0±2.6)points, (10.5±2.6)points, (11.6±2.3)points, (12.7±2.3)points, and (13.7±2.4)points in the three-dimensional visualization group, which were not statistically different from (8.8±2.2)points, (10.3±2.1)points, (10.8±2.0)points, (12.0±2.0)points, (12.9±2.0)points, and (13.8±2.1)points in the conventional intermuscular group ( P>0.05). The JOA scores of the two groups showed continuous improvement at 1 week, 1 month, 3 months, 6 months postoperatively and at the last follow-up in comparison with the preoperatively values ( P<0.05). Although no significant difference was observed between the two groups in ASIA grade preoperatively and at the last follow-up ( P>0.05), the ASIA grade at the last follow-up was significantly improved compared with that before surgery in both groups ( P<0.05). The postoperative complication rate was 12% (3/26) in the three-dimensional visualization group, significantly lower than 38% (12/32) in the conventional intermuscular group ( P<0.05). Conclusion:Compared with the conventional intermuscular approach, the three-dimensional visualization-assisted intermuscular CEOL offers advantages in reducing surgical trauma, improving surgical precision, and lowering the postoperative complication rate in the treatment of CSCIWFD.

Pollen allergen-induced allergic rhinitis(AR),also known as seasonal allergic rhinitis(SAR),typically manifests during the period of pollen dissemination by anemophilous plants.The prevalence of SAR has more than doubled over the past three decades.The etiology of SAR is multifaceted,involving factors such as pollen allergens,environmental and climatic conditions,genetic predispositions,and the immunological status of the individual.Animal models provide a critical tool for elucidating the mechanisms underlying AR and advancing the development of effective preventive and therapeutic strategies.This review synthesizes the recent pertinent domestic and international literature on pollen-sensitized AR animal experiments.It systematically delineates the factors influencing the efficacy of these models,including the selection of animal strains,the production and associated challenges of sensitizing agents,specifically pollen antigens,the utilization and limitations of adjuvants,the procedural steps involved in model creation,and the method ologies for evaluating model effectiveness.The insights provided are intended to offer guidance and support for the development of appropriate animal models of pollen-induced AR,thereby facilitating both fundamental and applied research in this area.

Objective:To explore the efficacy of percutaneous vertebroplasty (PVP) using the partition injection technique in the treatment of Kümmell’s disease of stages Ⅰ and Ⅱ.Methods:A retrospective study was conducted of the 30 patients with stage Ⅰ or Ⅱ Kümmell’s disease (the partition group) who had been treated by PVP using the partition injection technique at Department of Spinal Surgery, Zhengzhou Orthopedic Hospital from January 2020 to January 2022. The data of another 30 patients who had been treated at the same department and the same period using conventional PVP for stage Ⅰ or Ⅱ Kümmell's disease were selected as the conventional group. In the partition group, there were 13 males and 17 females, with an age of (72.3±10.1) years and disease duration of (3.1±1.5) months. Seventeen thoracic and 13 lumbar vertebrae were affected. In the conventional group, there were 11 males and 19 females, with an age of (75.5±12.7) years and disease duration of (3.5±1.8) months. Eighteen thoracic and 12 lumbar vertebrae were affected. Surgical time, volume of bone cement injected, bone cement leakage, and bone cement distribution were compared between the 2 groups. The heights of the anterior and middle vertebral bodies, kyphotic Cobb angle, visual analog scale (VAS) pain score, and Oswestry disability index (ODI) were assessed postoperatively at 1 day, 6 months, and the last follow-up and compared between the 2 groups.Results:No significant differences were found in the baseline data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (17.3±3.1) months. There were no significant differences in the surgical time or bone cement leakage between the 2 groups ( P>0.05). The volume of bone cement injected in the partition group was significantly higher [(6.3±1.5) mL] than that in the conventional group [(4.9±1.0) mL] ( P<0.05). Bone cement distribution was significantly better in the partition group than that in the conventional group ( P<0.05). At postoperative 1 day, 6 months, and the last follow-up, the partition group was significantly better than the conventional group in anterior vertebral body height, middle vertebral body height, and kyphotic Cobb angle ( P<0.05). At the 6-month and the last follow-ups, the partition group was also significantly better than the conventional group in VAS pain score and ODI ( P<0.05). Conclusion:In the treatment of Kümmell’s disease of stages Ⅰ and Ⅱ, compared with conventional PVP, PVP using the partition injection technique may lead to better long-term outcomes due to its better bone cement distribution, more adequate cement injection, and better restoration of vertebral body heights and correction of local deformity.

A patient with anti-MDA5-positive dermatomyositis complicated by hepatic dysfunction developed rhabdomyolysis after an intravenous injection of gadopentetate dimeglumine for magnetic resonance imaging.Analysis of clinical manifestations and medication correlation confirmed gadopentetate dimeglumineinduced rhabdomyolysis.Gadopentetate dimeglumine can cause rhabdomyolysis in dermatomyositis patients.Clinical conditions should be closely monitored when using gadopentetate dimeglumine to guard against adverse reactions.