Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD⁺) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi-pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.

Objective To observe the correlations of lumbar bone mineral density(BMD)with serum uric acid(SUA),hepatic fat and abdominal fat based on quantitative CT(QCT).Methods A total of 522 subjects who underwent lumbar QCT were retrospectively enrolled.Subjects with different genders were divided into hyperuricemia(HUA)group and normal SUA group according to SUA levels,and QCT parameters were compared between groups.Meanwhile,subjects with different genders were also divided into normal bone mass group(normal group),osteopenia group and osteoporosis(OP)group,and SUA and QCT parameters were compared among groups.Pearson correlation analyses were performed to explore the correlations of lumbar BMD with age,SUA,visceral adipose tissue(VAT),subcutaneous adipose tissue(SAT)and liver fat content.Results There were 325 males,with 105 ones in HUA group and 220 ones in normal SUA group.There were 197 females,with 26 ones in HUA group and 171 ones in normal SUA group.VAT,SAT and percentage of liver fat content in HUA group of different genders were all higher than those in normal SUA group(all P＜0.05).Among 325 males,there were 196 ones in normal group,105 ones in osteopenia group and 24 ones in OP group among males,and VAT increased successively in the above groups(all P＜0.05).Among 197 females,there were 147 ones in normal group,30 ones in osteopenia group and 20 ones in OP group,and VAT and SAT increased successively in the above groups(all P＜0.05).Lumbar BMD was moderately and weakly negatively correlated with age and VAT in males(r=-0.618,-0.286,both P＜0.001),which was moderately,lowly and weakly negatively correlated with age,VAT and SAT in females,respectively(r=-0.772,-0.451,-0.273,all P＜0.001).Conclusion Increased SUA levels resulted in increased abdominal and liver fat content,and the latter was negatively correlated with lumbar BMD.

Objective:To analyze the association between healthcare workers mental health,institu-tional supplies and facilities,inter-organizational coordination during infectious disease outbreaks,and the healthcare institution resilience.Methods:An online questionnaire survey was conducted among the healthcare workforce from 146 institutions in Beijing from January 13,2023 to February 9,2023,and a total of 1 434 eligible respondents were included.The sample comprised 408 responses from tertiary hos-pitals,117 from secondary hospitals,and 909 from primary care institutions.The resilience indicator for healthcare institutions was defined as the degree to which medical services met patient demands,with in-fluencing factors including physical factors,such as material shortages and facility space adaptation or ex-pansion,organizational factors such as information sharing and patient referral,and psychological factors were evaluated using job satisfaction(extrinsic satisfaction,intrinsic satisfaction),burnout(emotional exhaustion,depersonalization,reduced personal accomplishment),and depression status.Ordered mul-ticlassification Logistic regression was used to examine the impact of various factors on the degree to which healthcare services met patient needs;additionally,demographic factors that might influence institutional resilience were controlled.Results:During the emergency response phase,93％of hospitals maintained the capacity to meet patient needs,though tertiary hospitals demonstrated significantly higher rates of service inadequacy(21.05％).Material shortages were reported across all institutions,with tertiary hos-pitals experiencing more frequent multi-item shortages.Inter-institutional collaboration patterns revealed substantial variation:87.50％of primary care facilities,42.86％of secondary hospitals,and 31.58％of tertiary hospitals.Healthcare workers across all levels reported mild depressive symptoms and moderate-to-severe burnout levels.Regression analysis showed high satisfaction(overall satisfaction β=0.04,ex-trinsic satisfaction β=0.06,and intrinsic satisfaction β=0.08),low degree of job burnout(emotional exhaustion β=-0.04,depersonalization β=-0.07 and reduced personal accomplishment β=0.01),low degree of depression(β=-0.06)were significantly associated with higher healthcare institution re-silience.In addition,material shortages were significantly associated with lower resilience,and renova-tion and expansion of treatment spaces,and information sharing,were all associated with higher resilience.Demographic factors(age,gender,marital status,educational background,etc.)had no sig-nificant impact on resilience.Conclusion:Mental health status significantly influences healthcare institu-tion resilience.As human resources constitute the core asset of healthcare institutions,strategic optimiza-tion of workforce allocation and psychological support interventions can effectively strengthen resilience.Moreover,healthcare institution resilience is positively impacted by orderly material supply chains,timely resource distribution,and adaptive reconfiguration of clinical spaces.Finally,facilitating information sharing also enhances institutional resilience.

BACKGROUND:With the aging of the population,the incidence of osteoporosis is increasing year by year,and osteoporotic spinal fracture,as one of the common complications,brings great pain and inconvenience to patients.As an effective treatment,percutaneous vertebroplasty has been widely used in clinical practice.However,cement leakage as a potential risk of this procedure has been the focus of researchers.OBJECTIVE:To investigate the causes and management strategies of cement leakage after percutaneous vertebroplasty for osteoporotic vertebral compression fractures.METHODS:A total of 100 osteoporotic vertebral compression fractures patients who underwent percutaneous vertebroplasty in the Department of Orthopedics of Beijing Pinggu District Hospital from March 2017 to February 2021 were selected as the study subjects.According to the 12-month follow-up results,the patients were divided into bone cement leakage group(n=27)and non-bone cement leakage group(n=73).Cox proportional risk regression analysis was used to screen the influencing factors of bone cement leakage after surgery,so as to construct and evaluate the nomogram model for predicting the risk of bone cement leakage after surgery.Visual analog scale score and Oswesry dysfunction index of 27 patients were observed before surgery,3 days and 12 months after surgery following bone cement leakage treatment.RESULTS AND CONCLUSION:(1)Among the 27 patients with bone cement leakage,24 patients had internal leakage of intervertebral disc endplate,no obvious symptoms or discomfort,and no special treatment.Pulmonary embolism occurred in 1 case,and the patient was treated with the help of respiratory department.Two patients with symptoms underwent percutaneous intervertebral foramen endoscopic bone cement removal.(2)CT value,fracture severity,bone cement viscosity,cortical fracture,and injection amount of bone cement were the independent influencing factors for postoperative bone cement leakage(P<0.05).(3)The calibration degree and differentiation degree of the nomogram model were good,and it had good clinical practicability.(4)For 27 patients with external bone cement leakage after surgery,visual analog scale score at 3 days and 12 months after surgery was significantly lower than that before surgery,and the difference was statistically significant(P<0.05).Oswesry dysfunction index score at 12 months after surgery was significantly lower than that at 3 days after surgery,and the difference was statistically significant(P<0.05).(5)The results show that the amount of bone cement injection,bone cement viscosity,cortical fracture,CT value,and fracture severity are the risk factors of bone cement leakage after percutaneous vertebroplasty.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Objective:To analyze the genetic characteristics of the prevalent strains of Varicella-Zoster virus (VZV) in the population of Dali, Yunnan, and to understand its evolutionary status in the population of Dali.Methods:Herpes fluid and 163 sera were collected from 249 patients clinically suspected to have varicella or herpes zoster in the Department of Dermatology of the Second People′s Hospital of Dali city, Yunnan province, China, from 2023 to 2024. The levels of VZV-specific IgG and IgM antibodies in serum were detected using enzyme-linked immunoassay. Viral DNA was extracted from the herpes fluid, and the cycle threshold ( Ct) of the samples was detected using quantitative real-time polymerase chain reaction (qPCR), and some samples with Ct ≦ 22 were selected for sequencing by next-generation sequencing technology (next-generation sequencing). Next-generation sequencing (NGS) was used to obtain 90 whole genome sequences of VZV, and the sequencing result were compared with the sequences of reference strains for multiple sequence comparison and evolutionary analysis. Snapgene was used to translate the nucleotides into amino acids, and the result were compared with the amino acid sequences of the reference strain. Results:Of the 90 VZV whole-genome sequences, one whole-genome sequence was from an adult varicella patient, and the remaining 89 whole-genome sequences were from herpes zoster patients. The serum-specific IgG antibody positivity rate was 99.4%, and the IgM antibody positivity rate was 52.8%. The result of both single nucleotide polymorphism (SNPs) site typing and genome-wide phylogenetic tree analysis showed that 83 of the 90 VZV whole-genome sequences in this study were on the same branch as Clade 2, and 7 VZV whole-genome sequences were on the branch of Clade 9.Conclusions:The main endemic branch in Dali region in 2023-2024 was Clade 2, with the emergence of Clade 9 branch; there were amino acid mutations in the proteins encoded by ORF22 and ORF68 in 83 VZV whole genome sequences of Clade 2 branch, and the mutations did not cause significant changes to the protein structure.

OBJECTIVE To investigate the management status of small pressure steam sterilizers in dental institu-tions across seven major regions of China and provide references for establishing standardized monitoring and eval-uation protocols for sterilization efficacy.METHODS From Aug.to Nov.2023,a convenience sampling method was employed to select 885 dental institutions of various levels from seven geographical regions.An online survey using a self-designed questionnaire was conducted to assess the management status of small pressure steam steri-lizers in dental institutions.RESULTS A total of 885 questionnaires were distributed,with 770 valid responses col-lected,covering 770 dental institutions at all levels.The survey involved 2 056 small pressure steam sterilizers,of which 43.14％were pre-vacuum type and 89.40％were benchtop models.Tertiary dental institutions had the high-est proportion of imported small pressure steam sterilizers(60.15％),with most devices in use for 5-10 years(36.88％).Secondary and low er-level institutions predominantly used domestically produced small pressure steam sterilizers(74.60％),which used for 3-5 years accounting for the highest proportion(34.29％).While 85.58％of dental institutions employed dedicated sterilization personnel,only 45.84％performed proper maintenance for small pressure steam sterilizers.Training rates were 80.00％for department of stomatology in ungraded general hospitals and primary medical institutions,76.19％in prejob and 71.43％during the work for department of sto-matology in primary clinics,respectively.CONCLUSIONS Although most dental institutions demonstrate sound policy formulation,challenges persist in equipment maintenance,policy implementation and grassroots training.Future efforts should be made on strengthening maintenance and inspection of equipment,enhancing sys-tem supervisory mechanisms,and optimizing training systems to ensure dental treatment safety.

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.

Objective To assess the therapeutic effects of ultrasound(US)assisted administration of nusinersen in spinal muscular atrophy(SMA)patients with scoliosis.Methods The clinical data of 7 SMA patients with scoliosis treated with US assisted administration of nusinersen were retrospectively reviewed.The locating time,level of puncture points,puncture time,the number of puncture attempts,pain scores and adverse events were recorded.Meantime,the learning curve(LC)of US assisted administration of nusinersen for SMA patients with scoliosis was analyzed using cumulative sum(CUSUM).Results Thirty-one procedures were performed on 7 SMA patients with scoliosis.The success rate was 100％.The locating time was 11.9(5.1,15.4)min,the puncture time was 12.6(6.0,16.9)min,the number of puncture attempts were 2.0(1.0,3.0),the pain scores were 2.1(1.0,3.0).During the follow-up period of six months,only 1 patient had dizziness and soreness of waist.No serious adverse events were observed.The locating time,puncture time and the number of puncture attempts decreased as the number of procedures increased.Evaluation of the CUSUM curve revealed that 14 cases were needed to achieve proficiency.Conclusion US assisted administration of nusinersen is a valid and safe technique,deserving further clinical promotion and application on SMA patients with scoliosis.

Objective To evaluate the influencing factors of aspiration in neurological critically ill patients by Meta-analysis.Methods PubMed,Embase,Web of Science,CNKI,and Wanfang Data were searched from inception to 1 October,2023,to obtain relevant studies on influencing fac-tors of aspiration in neurological critically ill patients.The literature screening,data extraction and quality evaluation were completed by two researchers.RevMan 5.4 and Stata 13.0 software were ap-plied for pooled Meta-analysisand assessed publication bias,respectively.Results A total of 8 arti-cles,including 1,315 neurocritical care patients,were included in this study.Nine influencing factors related to aspiration were extracted for Meta-analysis.The Meta-analysis results showed that the three influencing factors that caused aspiration in neurocritical care patients were stroke history(OR=5.03,95％CI,2.71 to 9.32,P＜0.000 01),National Institutes of Health Stroke Scale(NIHSS)score＞10(OR=3.35,95％CI,1.75 to 6.42,P=0.000 3),and gastric residual volume＞150mL(OR=7.13,95％CI,2.55 to 9.96,P=0.001).Conclusion This study provides a scientific basis for clinical healthcare professionals to early identify high-risk patients for aspiration,take targeted inter-vention measures,and prevent the occurrence of aspiration.