Five novel nor-eremophilane-type sesquiterpenoids, peniroqueforins E-H and J (1-4 and 7), two new eremophilane-type sesquiterpenoids, peniroqueforins I and K (5 and 8), and a new eudesmane-type sesquiterpenoid, peniroqueforin L (9), along with four known compounds (6 and 10-12), were isolated and characterized from fungus Penicillium roqueforti (P. roqueforti). The structures and absolute configurations of these compounds were determined through comprehensive spectroscopic analyses, electronic circular dichroism (ECD) data analyses, and single-crystal X-ray diffraction methods. The anti-multi-drug resistance (MDR) cancer activity of these compounds was evaluated using SW620/Ad300 cells. Notably, the half maximal inhibitory concentration (IC₅₀) value of paclitaxel (PTX) combined with 1 in SW620/Ad300 cells was 50.36 nmol·L^-1, which was 65-fold more potent than PTX alone (IC₅₀ 3.26 μmol·L^-1). Subsequent molecular docking studies revealed an affinity between compound 1 and P-glycoprotein (P-gp), suggesting that this nor-eremophilane-type sesquiterpenoid (1) could serve as a potential lead for MDR reversal in cancer cells through P-gp inhibition.
Penicillium/chemistry* ; Humans ; Sesquiterpenes/isolation & purification* ; Cell Line, Tumor ; Molecular Structure ; Drug Resistance, Neoplasm/drug effects* ; Antineoplastic Agents/pharmacology* ; Drug Resistance, Multiple/drug effects* ; Molecular Docking Simulation

Obesity, as a chronic recurrent disease, has become a major public health challenge in China. To implement the requirements of the Healthy China Initiative (2019—2030), under domestic guidelines or consensus statements on overweight and obesity, and in alignment with the latest scientific advances globally, the Quality control protocol for adult overweight and obesity screening in health management (examination) institutions (2025 edition) was developed. This protocol was drafted by the Health Management Center of Shanghai Changzheng Hospital and formulated through multiple rounds of deliberation by experts in China’s health examination quality control field. The protocol establishes unified standards for screening facilities, personnel qualifications, and measurement or testing procedures. It defines specific screening items, outlines a standardized screening pathway, and sets requirements for the final medical review, ensuring the scientific validity, effectiveness, and safety of the screening process. The implementation of this protocol will enhance the consistency of weight management practices for adults across health examination institutions and strengthen the quality control of overweight and obesity screening programs.

Objective:A three-dimensional (3D) finite element model of the ankle joint of marathon runners was constructed to simulate the changes of the lateral collateral ligament (LCL) injury on the stability of the ankle joint and the force distribution of talar talus cartilage during exercise.Methods:The 3D MRI images of the right ankle joint of one marathon runner were acquired and imported into Mimics software in DICOM format for preliminary 3D model reconstruction of the images. The boundary conditions and loads were loaded on the model using Ansys Workbench software, and the ankle joint forces were analyzed by Ansys Workbench for marathon runners in the sports condition, and four kinds of ankle LCL injury finite element models were established, i.e., the normal model of LCL, the injury model of anterior talofibular ligament (ATFL), the injury model of AFTL merged with the calcaneofibular ligament (CFL), and the injury model of AFTL merged with the CFL and the posterior talofibular ligament (PTFL). The peak talus slide cartilage stress and its distribution were observed under the four models, and one-way ANOVA was used to compare the values of talus advancement, and the SNK- q test was used for two-by-two comparisons. Results:In the LCL normal model, the maximum stress peak of the talar slide was 0.21 MPa, which was mainly distributed in the junction area of the anterior medial (MA) and anterior lateral (LA) parts and part of the LA region. In ATFL injury, the peak stress of talar cartilage increased compared with the normal model, with a maximum value of 0.65 MPa, which was mainly distributed in the MA region. In ATFL combined with CFL injury, the peak stress increased, and the peak was mainly distributed in the MA region, and was shifted from the MA to the LA region. In ATFL combined with CFL and PTFL injuries, the peak cartilage stress in the talus slide was up to 2.29 MPa, and the maximum stress was mainly distributed in MA and LA, which had a comparable range of distribution. The anterior talar displacement values were (3.2±0.4), (3.4±0.4), (3.7±0.5), and (6.5±0.7) mm for normal LCL, AFTL injury, AFTL combined with CFL injury, ATFL combined with CFL, PTFL injuries, respectively, with a statistically significant difference ( F=109.08, P<0.001). The anterior talar displacement of ATFL combined with CFL, PTFL injuries was larger than those of normal LCL, AFTL injury, and AFTL combined with CFL injury ( P<0.05). Conclusions:A 3D finite element model is successfully constructed based on 3D MRI of the ankle joint in marathon runners. The peak and range of cartilage stresses in the talar glide change during LCL injury, and the talar glide displaces anteriorly.

Objective To study the effects of different types of fluid resuscitation on mesenteric microcirculation and inflammatory factors in rabbits with hemorrhagic shock.Methods The model of hemorrhagic shock rabbits was established by reducing the basic mean arterial pressure by 40%through draining the blood from the common carotid artery.Animals were randomly divided into control group,saline group,lactate Ringer group,acetic acid Ringer group,hydroxyethyl starch group and succinyl gelatin group with 8 animals in each group.Mesenteric microcirculation was monitored with microcirculation monitor.Mean arterial pressure(MAP),heart rate(HR),microvascular perfusion ratio(PPV)and microvascular blood flow index(MFI)were recorded before bleeding(T0),at hemorrhagic shock(T1),at the beginning of fluid resuscitation(T2),at the completion of fluid resuscitation(T3),and at the end of the experiment(T4).The contents of tumor necrosis factor-α(TNF-α),interleukin-1(IL-1)and lactic acid(Lac)were measured at T0,T2 and T4.Results Compared with hydroxyethyl starch group,there were statistically significant differences in T3 MAP(P<0.05),except for succinyl gelatin group,hydroxyethyl starch group had higher MAP at T4 than other groups,the difference was statistically significant(P<0.05).The differences in MAP between experimental control group and other groups were statistically significant at T4(P<0.05).PPV and MFI of hydroxyethyl starch group and succinyl gelatin group were higher than those of normal saline group,lactic acid Ringer group and acetic acid Ringer group at T4(P<0.05),and the lactic acid value of hydroxyethyl starch group at T4 was the lowest,compared with lactic acid Ringer group and normal saline group,the difference was statistically significant(P<0.05).There were statistical significances between all groups and experimental control group at T4(P<0.05).There were no significant differences in TNF-αand IL-1 in T0,T2 and T4 among all groups(P<0.05).Conclusion Hydroxyethyl starch solution and succinyl gelatin solution can improve the microcirculation of rabbits with hemorrhagic shock,but can not improve the level of inflammatory factors.

Objective:To investigate the changes of biventricular myocardial strain in amateur marathon runners using the cardiac MR feature tracking (CMR-FT) technique.Methods:Forty-one amateur marathon runners (marathon exercise group) and 20 age-matched healthy volunteers (control group) were recruited according to the inclusion criteria. After the kinematic parameters were obtained, all subjects underwent a CMR cine sequence imaging. The CMR images were post-processed using CVI42 software. The biventricular function parameters including end-diastole/end-systolic volume (EDV/ESV), end-diastole/end-systolic volume index (EDVI/ESVI), end-diastole/end-systolic myocardial mass (MMD/MMS), end-diastole/end-systolic myocardial mass index (MMDI/MMSI), stroke volume and index (SV/SVI), cardiac index (CI) and ejection fraction (EF), as well as the biventricular myocardial strain parameters including global radial/circumferential/longitudinal strain (GRS/GCS/GLS), global radial/circumferential/longitudinal diastolic strain rate (GRSDr/GCSDr/GLSDr) were measured and calculated. Demographic data, kinematic index, cardiac function and myocardial strain parameters were compared between the two groups.Results:Compared with the control group, the exercise group showed significant decrease heart rates ( P<0.001). It was found that the left ventricular function parameters (ESVI, MMD, MMDI, MMS, MMSI) and the right ventricular function parameters (EDVI, ESVI) of the exercise group were significantly higher than those of control group (all P<0.05); while the left ventricular strain parameters (GCS, GRSDr, GCSDr, GLSDr) and the right ventricular strain parameters (GRSDr, GLSDr) were of the exercise group were significantly lower than those of control group (all P<0.05). Conclusions:Amateur marathon runners have lower myocardial strain capacity and higher left ventricular myocardial mass. The ventricular diastolic strain rate may sensitively reflect the compensatory changes of ventricular function with the normal ejection fraction.

Objective:To evaluate the acute effects of different foot-strike patterns of running on knee cartilage in amateur marathon runners using the T 2* mapping technique. Methods:From November 2021 to February 2022, 29 amateur marathon runners were recruited in Hangzhou. The gait analysis was performed to determine their landing patterns, then the runners were divided into the fore-foot strike (FFS) group (11 cases) and the rear-foot strike (RFS) group (18 cases). The MRI of the knee joint of the dominant leg was performed before and 30 min after running, and the volume, thickness, and T 2* value of each division of knee cartilage were measured. Independent samples t-tests were used to compare the differences in baseline data before running between the groups, and paired samples t-tests were used to compare the differences before and after running within the groups. Results:The difference in knee cartilage volume and thickness between the FFS and RFS groups before running was not statistically significant ( P>0.05), and the T 2* value of the femur medial posterior in the RFS group was higher than that of the FFS group ( t=-2.47, P=0.020). Compared with pre-running, cartilage thickness of the tibia lateral posterior decreased in the FFS group after running ( t=-2.96, P=0.016), and cartilage thickness of the tibia lateral posterior and patella lateral central decreased in the RFS group ( t=-3.25, -3.02, P=0.004, 0.007). Cartilage volume of the tibia lateral posterior decreased in the FFS group after running ( t=-2.58, P=0.030), and the cartilage volume of the patella lateral central decreased in the RFS group ( t=-2.74, P=0.013). The differences in T 2* values of cartilage in each region before and after running were not statistically significant in the FFS group ( P>0.05), whereas in the RFS group, the cartilage T 2* values in the femur medial posterior, femoral trochanter central, femoral trochanter lateral, femur lateral central, tibia lateral anterior, tibia medial posterior, tibia medial central, and tibia medial anterior decreased ( P<0.05). Conclusions:After running, FFS showed changes in morphology and biochemical composition only in some subregions of tibial cartilage, whereas most of the femoral cartilage, patellar cartilage, and tibial cartilage regions were altered by RFS. The RFS pattern introduces greater acute changes in cartilage in the knee joint.

OBJECTIVE: To investigate the effect of vitamin D binding protein (DBP) gene polymorphism on susceptibility and prognosis of severe acute pancreatitis (SAP). METHODS: A prospective study was conducted. Eighty-three patients with SAP who were admitted to the department of general surgery of Tianjin Fifth Central Hospital from March 2018 to March 2021 were selected as the research objects, and 83 healthy people in the same period were selected as controls. Peripheral blood RNA was extracted and reverse transcribed into cDNA, and the genotype and allele frequency of DBP gene rs7041 locus were detected by fluorescence quantitative analyzer. Hardy-Weinberg equilibrium was used to test the genetic balance. On the day of admission, serum C-reactive protein (CRP) level was detected by scattering immunoturbidimetry, serum procalcitonin (PCT) level was detected by electrochemiluminescence, serum DBP level was detected by enzyme-linked immunosorbent assay (ELISA), and neutrophil to lymphocyte ratio (NLR) was calculated automatically by the instrument. The length of intensive care unit (ICU) stay, the length of hospital stay and prognosis during hospitalization of patients were statistically analyzed. Multivariate Logistic regression analysis was used to screen the influencing factors of SAP occurrence. RESULTS: The results of Hardy-Weinberg equilibrium test showed that the distribution of gene polymorphisms in the two groups of subjects conformed to the law of genetic equilibrium. The frequencies of TT genotype and T allele of DBP gene rs7041 locus in the patients of SAP group were significantly higher than those in the healthy control group [TT genotype: 34.94% (29/83) vs. 9.64% (8/83), T allele: 55.42% (92/166) vs. 38.55% (64/166), both P < 0.01], and the frequency of GT genotype was significantly lower than that in the healthy control group [40.96% (34/83) vs. 57.83% (48/83), P < 0.05]. There was no significant difference in the frequency of GG genotype between the healthy control group and SAP group [32.53% (27/83) vs. 24.10% (20/83), P > 0.05]. Further multivariate Logistic regression analysis showed that TT genotype [odds ratio (OR) = 2.831, 95% confidence interval (95%CI) was 1.582-5.067, P < 0.001] and T allele (OR = 2.533, 95%CI was 1.435-4.472, P < 0.001) of DBP gene rs7041 locus were independent risk factors for SAP in healthy people, while GT genotype was a protective factor for SAP (OR = 0.353, 95%CI was 0.143-0.868, P = 0.041). The levels of CRP, PCT, NLR and DBP in patients with TT genotype of DBP gene rs7041 locus were significantly higher than those in patients with GG/GT genotype on the day of admission in SAP group [CRP (mg/L): 43.25±13.25 vs. 31.86±12.83, PCT (μg/L): 1.53±0.24 vs. 1.21±0.20, NLR: 3.15±0.53 vs. 2.71±0.48, DBP (μg/L): 87.78±19.64 vs. 70.58±18.67, all P < 0.01]. The length of ICU stay in patients with TT genotype of DBP gene rs7041 locus in SAP group was significantly longer than that in patients with GG/GT genotype (days: 11.35±1.58 vs. 9.71±1.35, P < 0.01). The length of hospital stay of patients with TT genotype was longer than that of patients with GG/GT genotype (days: 23.41±3.64 vs. 23.17±3.57), and the in-hospital mortality was higher than that of patients with GG/GT genotype [34.48% (10/29) vs. 29.63% (16/54)], but the difference was not statistically significant (both P > 0.05). CONCLUSIONS The risk of SAP was significantly increased in patients with TT genotype of rs7041 locus of DBP gene, and the mechanism may be related to the increase of DBP expression. And carrying the TT genotype will prolong the ICU hospitalization time of SAP patients, but the effect on prognosis is not obvious.
Humans ; Polymorphism, Single Nucleotide ; Prospective Studies ; Vitamin D-Binding Protein/genetics* ; Acute Disease ; Pancreatitis/genetics* ; Genotype ; Prognosis

OBJECTIVE To provide reference for clinically safe application of avapritinib. METHODS The adverse drug event （ADE） reports of avapritinib from January 9th，2020，to September 30th，2022 were collected from FDA Adverse Event Reporting System （FAERS） database. For data mining and analysis，reporting odds ratio （ROR） method and proportional reporting ratio （PRR） method in the proportional imbalance method were utilized. RESULTS A total of 10 895 ADE reports with avapritinib as the main suspect drug were gathered，and 201 ADE signals involving 19 systematic organ classifications were found after eliminating invalid signals. The instruction of the drugs did not mention any of the ADE，including tinnitus，dementia，chilly limbs， the reduction of blood iron，the reduction of blood sugar，fever，the reduction of vitamin D and vitamin B12，as well as all ADE in the 2 SOCs of musculoskeletal and connective tissue illnesses，diseases of the reproductive system，and diseases of the breast. The majority of the ADE reports 670 cases with complete drug information were for the nervous system （230 cases，accounting for 34.33%） and ocular organ （277 cases，accounting for 41.34%）. Compared with other systems，daily dose and treatment course showed significant effects on ADE of neurological system and ocular organ （P＜0.05），and the patient’s age had a significant impact on the ADE of the nervous system （P＜0.05）. CONCLUSIONS A greater incidence of ADE after using avapritinib is present in patients older than 65 with a daily dose of 300 mg/d and a treatment period lasting between 31 and 90 days； patients receiving a daily dose of 300 mg/d and a treatment regimen lasting 31 to 90 days are more likely to experience ADE of the ocular organ. Attention should be given to the aberrant symptoms of the patient’s eyes and nervous system throughout clinical use of avapritinib，and prompt intervention should be given.

Objective:To study the clinical and genetic features of neonatal Smith-Kingsmore syndrome (SKS).Methods:The clinical data of a newborn with SKS admitted to our hospital in November 2021 were reviewed. Using "Smith-Kingsmore", "rapamycin gene", "newborn", "premature infant", "the mammalian target of rapamycin", "MTOR", "mTOR", "Smith-Kingsmore syndrome", "megalencephaly", "macrocephaly" and "hemimegalencephaly" as keywords, databases including CNKI, Wanfang Database, VIP database, PubMed, Embase, Web of Science and the Cochrane Library were searched from the date of establishment to January 1, 2022. The clinical and genetic features of neonatal SKS from published literature were summarized.Results:The case admitted to our hospital was a male preterm infant. The presenting symptoms were groan and hypotonia. The facial abnormalities included macrocrania, ocular hypertelorism, depressed nasal bridge and low-set ears. Brain MRI showed lateral ventricle enlargement. Whole-genome sequencing (WGS) showed mTOR gene nonsense heterozygous mutation (NM_004958.4:c.7255G>A:p.Glu2419Lys). Neither father nor mother had any pathogenic gene mutations. The infant had seizure at 2-month and phenobarbital was effective reducing seizure. Gross motor delay was present at 3-month. Sixteen related articles were retrieved, including eight articles with 10 neonatal cases. Among them, 6 cases were male. The main clinical features were megalencephaly or hemimegalencephaly (9/10), facial developmental malformation (8/10), hypotonia (6/10), large-for-gestational age (LGA) infants (5/10), cerebral ventricle dilation (4/10) and abnormal corpus callosum (4/10). All the gene mutations were missense mutations, including c.5395G>A(p.Glu1799Lys) mutation in 5 cases, c.4448G>T(p.Cys1483Phe) mutation in 1 case, c.4448G>T(p.Cys1483Tyr) mutation in 1 case, c.7235A>T(p.Asp2412Val) mutation in 1 case, c.5663T>G(p.Phe1888Cys) mutation in 1 case, c.5390C>T(p.Thr1799IIe) mutation in 1 case.Conclusions:The clinical phenotypes of neonatal SKS are diverse, including megalencephaly, facial malformation, LGA and hypotonia. The brain MR findings included (hemi) megalencephaly, cerebral ventricle dilation and corpus callosum hypoplasia. Most of the gene mutations are missense mutations and c.5395G>A(p.Glu1799Lys) is the hotspot.

Objective:To explore the relationship between liver iron deposition and steatosis in patients with non-alcoholic fatty liver disease (NAFLD) through MRI.Methods:163 cases of liver biopsy underwent MRI examination. R2* was used to measure liver iron content. Dixon-based proton density fat fraction (PDFF) was used to measure liver fat content. One-way ANOVA, r-correlation, ROC curve, and others were used to assess the relationship between clinical case data, serological indices, and imaging results in accordance with the pathological results of the liver biopsy.Results:R2* gradually increased as the pathological steatosis grade rose. The R2* that corresponded to no steatosis (< 5%), mild steatosis (14.95%±8.55%), moderate steatosis (46.30%±9.32%), and severe steatosis (73.86%±6.35%) were 27.56±4.40, 31.06±5.95, 38.06±4.80, and 48.10±5.55 ( P < 0.001), respectively. There was a positive correlation between R2* and liver steatosis content ( r= 0.769, P < 0.05). The area under the ROC curve and cut-off value were 0.88 and 31.77, respectively, and there was no distinct relationship with liver inflammation or fibrosis. Conclusion:R2* can quantitatively and non-invasively evaluate liver iron deposition in patients with NAFLD. A distinct relationship exists between liver steatosis and iron deposition, and iron deposition tends to increase as the steatosis aggravates.