Sixteen compounds were isolated from the solid rice culture of the endophytic fungus Alternaria alstroemeriae WZ-419 derived from Pseudostellariae Radix, using silica gel, ODS, Sephadex LH-20 column chromatography, and preparative HPLC. Their structures were elucidated based on physicochemical properties and comprehensive spectroscopic analyses, and identified as alterpenoid A (1), tricycloalternarene A (2), altenusin (3), 4'-epialtenuene (4), altenuene (5), alternariol (6), altenuisol (7), 3-hydroxyalternariol-5-O-methylether (8), alternariol-9-methyl ether (9), alternariol 1′-hydroxy-9-methyl ether (10), stemphyperylenol (11), dihydroalterperylenol (12), alterinone A (13), 4-hydroxy-3-methoxy-5-(2E,6E-3,7,11-trimethyldodeca-2,6,10-trien-1-yl) benzoic acid (14), hexylitaconic acid (15), and altechromone A (16). Among them, compound 1 and 13 were new, and compounds 14 and 15 were isolated from the genus Alternaria for the first time. The antibacterial activities of compounds 1–16 were evaluated in vitro. Compounds 3, 6–8, 10, 11, 13, and 14 exhibited notable inhibitory effects against Gram-positive bacteria, with minimal inhibitory concentrations ranging from 8 to 64 µg/mL.This study isolated a series of antimicrobial metabolites from the endophytic fungi of Pseudostellariae Radix, providing new insights into their bioactive constituents and laying a foundation for further pharmacological investigations.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

Objective:To describe the body mass index (BMI) level and long-term trends of Chinese older adults aged 65 and above.Methods:Older adults aged 65 and above from six waves (2002-2018) of the China Longitudinal Healthy Longevity Survey were selected as the study population. Multiple cross-sectional design with six survey waves conducted in 2002, 2005, 2008, 2011, 2014, and 2018 was adopted, enrolling 15 647, 15 358, 15 622, 9 166, 6 302, and 12 417 participants, respectively. Additionally, a total of 13, 755 participants were included in the cohort study design. Relevant information was collected through questionnaires and physical examinations. The χ2 trend test was used to compare the changes in the rates of underweight and overweight/obesity over the years, and the linear mixed-e?ects model (LMM) was used to fit trajectory curves of BMI changes with advancing age in older adults. Results:The baseline ages of the participants included in 2002, 2005, 2008, 2011, 2014, and 2018 were (85.16±11.26), (84.23±11.83), (84.99±12.16), (81.10±11.86), (78.89±11.30), and (83.08±12.42) years, respectively, with a relatively high proportion of females and rural residents. In the cohort study, the 13 755 participants had a median ( Q1, Q3) follow-up time of 6.5 (5.2, 10.0) years, with a cumulative follow-up duration of 109 041 person-years. In each wave, males had higher BMI than females, urban residents had higher BMI than rural residents, and BMI gradually decreased with increasing age (all P<0.001). The mean BMI of older adults in China increased from (19.37±3.80) kg/m2 in 2002 to (22.04±4.01) kg/m2 in 2018 ( P<0.001). Across all survey years, the prevalence of underweight was consistently higher in women than in men and in rural areas than in urban areas, with an upward trend as age increased (all P<0.001). In 2018, the underweight rates in the 65-79, 80-89, 90-99, and ≥100-year-old age groups were 8.0%, 16.7%, 26.2%, and 35.5%, respectively. Meanwhile, the prevalence of overweight/obesity was higher in men than in women and in urban areas than in rural areas, showing a declining trend with advancing age (all P<0.001). The prevalence of underweight among the older adults decreased significantly from 45.2% in 2002 to 18.9% in 2018 ( P<0.001), while the prevalence of overweight/obesity increased from 11.0% in 1998 to 29.6% in 2018 ( P<0.001). The trajectory curves fitted by the LMM model showed that individuals born in later decades had higher BMI levels at the same age compared to earlier cohorts. Conclusion:From 2002 to 2018, the BMI level among Chinese older adults showed an increasing trend. The prevalence of underweight showed a declining trend, while the rates of obesity and overweight increased. However, the underweight rate remained notably high among the oldest old.

Objective To screen antidepressant-active compounds from Polygonati Rhizoma and explore their effects and possible mechanisms against depression induced by simulated weightlessness.Methods A systems pharmacology approach was used to screen potential antidepressant-active compounds and their targets from Polygonati Rhizoma.The hindlimb unloading(HLU)rat model was employed for the study.Twenty-four healthy male Sprague-Dawley rats were randomly divided into three groups:control group(administered 0.5%carboxymethylcellulose by gavage),HLU group(hindlimb unloading),and HLU+treatment group(hindlimb unloading+active compound gavage),with 8 rats in each group.After 28 days of hindlimb unloading,depressive-like behaviors in rats were evaluated using the forced swimming test and tail suspension test.Hippocampal morphology was examined with H&E staining,and GO and KEGG enrichment analyses were conducted on the targets of active compounds.Results A total of 38 active compounds were screened from Polygonati Rhizoma,among which apigenin had an oral bioavailability of 23.06%and a drug-likeness score of 0.21.Compound-target network analysis indicated that apigenin had the highest degree and betweenness centrality values,suggesting it might be the key active component with antidepressant potential in Polygonati Rhizoma.In the forced swimming and tail suspension tests,rats in the HLU group showed a significant increase in immobility time compared to the control group,indicating successful establishment of the depression model.However,compared to the HLU group,rats in the HLU plus apigenin group exhibited significantly reduced immobility time.The H&E staining results of hippocampal tissue showed a significant reduction in the number of hippocampal neurons,along with numerous shrunken neurons and small vacuoles in nerve fibers in the HLU group.In contrast,the treatment group exhibited an increased number of hippocampal neurons,with improved cellular morphology.Target enrichment analysis indicated that apigenin targets were mainly involved in the regulation of apoptosis and cancer-related signaling pathways.Conclusion Apigenin significantly improved depressive-like behaviors in rats subjected to hindlimb unloading,and it has a protective effect on hippocampal tissue.It may provide a new natural active compound for the treatment of depression caused by spaceflight-induced weightlessness.

Objective To explore the risk factors for postoperative secondary hydrocephalus in patients with severe craniocerebral injury and construct a nomogram prediction model.Methods A total of 360 patients with severe craniocerebral injury were selected as the study subjects,and divided into hydrocephalus group(n=34)and non-hydrocephalus group(n=326)based on the occurrence of postoperative secondary hydrocephalus.Logistic regression analysis was used to screen for risk fac-tors of postoperative secondary hydrocephalus.A nomogram model for predicting postoperative second-ary hydrocephalus in patients with severe craniocerebral injury was constructed based on the identified risk factors,and its predictive performance was validated.Results Among the 360 patients,34 de-veloped secondary hydrocephalus after surgery,with an incidence rate of 9.44％(34/360).Logistic regression analysis revealed that intracranial infection,ventricular hemorrhage,midline shift ≥12 mm,preoperative Glasgow Coma Scale(GCS)score of 3 to 5,decompressive craniectomy and dura mater o-pening were independent risk factors for postoperative secondary hydrocephalus in patients with severe traumatic brain injury(P＜0.05).The concordance index of the nomogram model constructed based on these risk factors was 0.874,and the area under the curve was 0.831.Conclusion The nomogram model constructed in this study based on factors such as intracranial infection,ventricular hemorrhage,midline shift,preoperative GCS score,decompressive craniectomy and dura mater opening,effectively predicts risk of postoperative secondary hydrocephalus in patients with severe traumatic brain injury.This model has clinical significance for early prevention and treatment.

OBJECTIVE To conduct a survey of current status of surgical site infections(SSIs)among the orthope-dics department patients in the traditional Chinese hospitals of Guangdong Province so as to provide guidance for prevention and control of the SSIs.METHODS A retrospective questionnaire survey and field verification were car-ried out for the prevalence of SSIs among the orthopedics department patients of 61 secondary or above traditional Chinese hospitals(traditional Chinese medicine integrated with western medicine hospitals)in 2019.RESULTS To-tally 35 tertiary hospitals and 26 secondary hospitals were involved in the survey.A total of 167,051 patients who re-ceived orthopedic surgical procedures were investigated,355 of whom had SSIs,with the incidence 0.21％.The patients who had superficial surgical incision infections were dominant,accounting for 53.52％.The incidence rates of SSIs of grade 3 surgeries and SSIs of type Ⅰ incision were respectively 0.34％and 0.24％in the secondary hospitals,remarkably higher than those in the tertiary hospitals(all P＜0.05).There were no signficant differences in the incidence rate of SSIs of other grades of surgeries between the secondary hospitals and the tertiary hospitals.There were significant differences in the nutrition status,smoking history,complication with COPD,anemia,bath 1 night before surgery,preoperative pe-ripheral blood total white blood cell counts,type of surgery,title of surgeon,operating room,anesthesia mode,surgical site disinfectants,operation duration,American Society of Anesthesiologists(ASA)score and surgical risk index between the tertiary hospitals and the secondary hospitals(all P＜0.05).The etiological test was carried out for 331 patients with SSIs;totally 266 strains of pathogens were isolated,105(39.47％)of which were Staphylococcus aureus.CONCLUSIONS The incidence of SSIs is relatively low among the orthopedics department patients of the traditional Chi-nese hospitals(traditional Chinese medicine integrated with western medicine hospitals)in Guangdong Province.The inci-dence rates of SSIs of grade 3 surgeries and SSIs of type Ⅰ incision are remarkably higher in the secondary hospitals than in the tertiary hospitals.It is necessary to take comprehensive prevention and treatment measures according to the character-istics of the infections so as to reduce the incidence of SSIs among the orthopedics department patients.

OBJECTIVE To conduct a survey of current status of surgical site infections(SSIs)among the orthope-dics department patients in the traditional Chinese hospitals of Guangdong Province so as to provide guidance for prevention and control of the SSIs.METHODS A retrospective questionnaire survey and field verification were car-ried out for the prevalence of SSIs among the orthopedics department patients of 61 secondary or above traditional Chinese hospitals(traditional Chinese medicine integrated with western medicine hospitals)in 2019.RESULTS To-tally 35 tertiary hospitals and 26 secondary hospitals were involved in the survey.A total of 167,051 patients who re-ceived orthopedic surgical procedures were investigated,355 of whom had SSIs,with the incidence 0.21％.The patients who had superficial surgical incision infections were dominant,accounting for 53.52％.The incidence rates of SSIs of grade 3 surgeries and SSIs of type Ⅰ incision were respectively 0.34％and 0.24％in the secondary hospitals,remarkably higher than those in the tertiary hospitals(all P＜0.05).There were no signficant differences in the incidence rate of SSIs of other grades of surgeries between the secondary hospitals and the tertiary hospitals.There were significant differences in the nutrition status,smoking history,complication with COPD,anemia,bath 1 night before surgery,preoperative pe-ripheral blood total white blood cell counts,type of surgery,title of surgeon,operating room,anesthesia mode,surgical site disinfectants,operation duration,American Society of Anesthesiologists(ASA)score and surgical risk index between the tertiary hospitals and the secondary hospitals(all P＜0.05).The etiological test was carried out for 331 patients with SSIs;totally 266 strains of pathogens were isolated,105(39.47％)of which were Staphylococcus aureus.CONCLUSIONS The incidence of SSIs is relatively low among the orthopedics department patients of the traditional Chi-nese hospitals(traditional Chinese medicine integrated with western medicine hospitals)in Guangdong Province.The inci-dence rates of SSIs of grade 3 surgeries and SSIs of type Ⅰ incision are remarkably higher in the secondary hospitals than in the tertiary hospitals.It is necessary to take comprehensive prevention and treatment measures according to the character-istics of the infections so as to reduce the incidence of SSIs among the orthopedics department patients.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Colorectal cancer is currently one of the most common malignant tumors in the world,and its incidence and mortality rates have gradually increased in recent years.As insidious symptoms characterize early colorectal cancer,most of the patients have already developed into late or advanced stages in the primary survey.For stage Ⅳ metastatic colorectal cancer(mCRC),surgery supplemented with chemotherapy or radiotherapy for mCRC patients has a low 5-year survival rate.With the development of immunology in recent years,PD-1/PD-L1 inhibitors have made breakthroughs in treating malignant tumors.They also have improved the therapeutic efficacy of some mCRC patients,especially those with microsatellite instability-high/mismatch repair deficient.The guidelines recommend this approach.However,patients with microsatellite stable/mismatch repair proficiency,which accounts for more than 90%,are poorly treated with PD-1/PD-L1 inhibitors.Fortunately,there are several clinical studies that reported that some of this type of mCRC can gain some benefit.In this review,we examined the anti-tumor mechanism of PD-1/PD-L1 inhibitors and the latest progress of PD-1/PD-L1 inhibitor's clinical application in patients of mCRC with different genotypes.We discussed the prospect of PD-1/PD-L1 inhibitor combination therapy to provide a reference to the benefit of this type of patients and provide information for optimizing the dosing regimen of PD-1/PD-L1 inhibitors in the treatment of mCRC.

Objective:To evaluate the relationship between the occipitocervical angle(basilar vertebral angle [O-C 2 angle], mento-pharyngeal angle [M-P angle], and cervical range of motion [CROM]) and difficult airway after occipitocervical fusion surgery in the patients. Methods:This was a retrospective study. The clinical data from patients who underwent occipitocervical fusion surgery at our hospital from March 2018 to March 2023 were retrospectively collected. Preoperative and last follow-up airway assessment data and cervical lateral X-rays were collected to measure the O-C 2 angle, M-P angle and CROM. Patients were divided into negative group (Mallampati grade Ⅰ or Ⅱ, suggesting no difficulty in intubation) and positive group (Mallampati grade Ⅲ or Ⅳ, suggesting possible difficulty in intubation) based on the last follow-up modified Mallampati classification. Results:A total of 53 patients were finally included, with 18 cases in positive group and 35 in negative group. There were no statistically significant differences in the O-C 2 angle and CROM between preoperative and last follow-up in the 53 patients ( P>0.05), and the M-P angle was significantly decreased at the last follow-up compared with that before operation ( P<0.05). Compared with negative group, O-C 2 angle and M-P angle were significantly decreased at the last follow-up ( P<0.05), and no significant change was found in CROM in positive group ( P<0.05). Compared with that before operation, the M-P angle was significantly decreased at the last follow-up in both groups, and the O-C 2 angle was significantly decreased at the last follow-up in positive group ( P<0.05). The areas under the receiver operating characteristic curves of O-C 2 angle, M-P angle and CROM in predicting difficult airway were 0.895, 0.888 and 0.519 respectively. Conclusions:The decrease in the O-C 2 angle and M-P angle after occipitocervical fusion surgery can increase the risk of difficult airway, and both can be used for airway assessment in the patients undergoing this kind of surgery.