Objective To elucidate the changes in the gut microbiota and molecular mechanism of huaier in enhancing the efficacy of oxaliplatin (OXA) chemotherapy in gastric cancer (GC). Methods The effects of huaier on the gut microbiota structure and intestinal barrier function in MKN45-bearing mice were analyzed by using 16S rRNA sequencing, RT-qPCR, and IHC. UPLC-MS and network pharmacology, as well as in vivo experimental approaches, were employed to investigate the key bioactive constituents of huaier systematically and elucidate the underlying mechanisms by which huaier exerts therapeutic effects against GC. The expression of the PI3K/AKT/SREBP pathway was detected in cancer cells and tissues via Western blot analysis. The safety profile of huaier combined with OXA was verified through serum biochemistry and HE-stained tissue section analyses. Results Huaier inhibited the PI3K/AKT/SREBP pathway by increasing the abundance of Akkermansia muciniphila, reduced lipid droplet deposition, and ultimately enhanced the sensitivity to OXA in the treatment of GC. Conclusion This study demonstrates the value of huaier in gastric cancer treatment by enhancing chemosensitivity and provides novel insights into its systemic therapeutic effects through molecular mechanisms and gut microbiota modulation.

ObjectiveA qualitative analysis method was established for the composition of Astragali Radix（AR） before and after rice stir-frying. On the basis of systematic characterization of the chemical compositions in AR and stir-fried AR with rice（ARR）， the structures of their major compounds were deduced and identified， and the differential compositions between them were analyzed. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the samples of AR and ARR in positive and negative ion modes， respectively. The compounds were analyzed and identified through self-constructed databases， literature， and reference standards， etc. And the data were analyzed by chemometrics， in order to screen for the differential components between AR and ARR. ResultsA total of 123 compounds were identified in AR and ARR， including 41 flavonoids， 19 terpenoids， 26 organic acids， 8 amino acids， 5 nucleotides， 5 carbohydrates and 19 other compounds. Among them， there were 95 common components in both， 18 unique components in AR， and 10 unique components in ARR. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） results both showed that there were significant differences in the chemical constituents of AR before and after rice stir-frying， and a total of 26 constituents with differences in the content were screened out， including L-canavanine， L-pyroglutamic acid， L-phenylalanine， cis-caffeic acid， and malonylastragaloside Ⅰ. Among them， 19 constituents of ARR were down-regulated and 7 constituents were up-regulated by comparing with AR. ConclusionThis study clarifies that the chemical composition of AR and ARR is mainly composed of flavonoids， terpenoids， and organic acids， and analyzes the components with significant differences in content between the two in combination with chemometrics， and the differential components are dominated by amino acids， organic acids and terpenoids， which can provide reference for the subsequent quality control and material basis research.

Objective To explore the influencing factors of coronary artery lesion severity in patients with acute coronary syndrome (ACS). Methods Clinical data of ACS patients admitted to Zhongshan Hospital, Fudan University from December 2017 to December 2019 were consecutively collected. The modified Gensini score was used to assess the severity of coronary artery lesions. Univariate and multivariate linear regression analyses were performed to identify independent factors associated with coronary artery lesion severity. Results A total of 1 689 ACS patients were included, with an average age of (64.04±11.45) years; 1 353 (80.11%) were male, and the mean modified Gensini score was (8.12±4.03). Multivariate linear regression analysis revealed that sex (β＝0.97, P＝0.001), age (β＝0.03, P＝0.021), estimated glomerular filtration rate (eGFR; β＝－0.03, P＜0.001), low-density lipoprotein cholesterol (LDL-C; β＝0.58, P＜0.001), apolipoprotein A1 (Apo A1; β＝－1.28, P＝0.012), lipoprotein(a) [Lp(a); β＝0.001, P＝0.033], and glycated hemoglobin A_1C (HbA_1C; β＝0.45, P＜0.001) were independent influencing factors of the modified Gensini score. Conclusions Metabolic indicators, including Apo A1, LDL-C, HbA_1C, and Lp(a), may serve as risk factors for coronary artery lesion severity in ACS patients, with Apo A1 demonstrating the strongest impact.

Circadian rhythm is a biological endogenous process regulated by the suprachiasmatic nucleus of the hypothalamus, which transmits light signals to peripheral clocks and synchronizes the body with the external environment through balanced expression of circadian rhythm genes. Working the night shift, sleep disorders, and exposure to artificial light can lead to disturbances in circadian rhythm and genetic imbalances. A substantial body of research has demonstrated that circadian rhythm plays a significant role in the treatment of autoimmune diseases and neurodegenerative disorders, with increasing attention being directed toward their impact on oral health. Disturbances in circadian rhythm primarily affect psycho-neuro-immune mechanisms, oxidative stress responses, and oral microflora through pathways such as the hypothalamic-pituitary-adrenal axis (HPA axis), brain and muscle ARNT-like 1 (BMAL1)-brain-derived neurotrophic factor (BDNF) signaling, and BMAL1-nuclear factor kappa-B (NF-κB) interactions. These disruptions may influence the progression of oral diseases. Certain pharmacological agents (e.g., melatonin, vitamin D, nobiletin, and propofol) have been shown to regulate mood disorders, immune function, and sleep-wake cycles by upregulating BMAL1 expression, thus alleviating disturbances in circadian rhythm. In addition, non-pharmacological interventions, such as sleep management strategies, psychotherapy approaches, and light therapy, also modulate these processes through HPA axis regulation. Currently, the specific mechanisms by which circadian rhythm regulates BDNF levels, T cell subsets, and inflammatory signals—thereby influencing both pathogenesis and treatment outcomes for oral diseases—remain unclear. Future research should focus on elucidating these molecular mechanisms as well as identifying therapeutic targets related to circadian rhythm within the oral health context. Further, multidisciplinary collaboration encompassing pharmacy, sleep behavior studies, and psychology will be instrumental in advancing prevention strategies and treatments for oral diseases.

Objective: To analyze the factors associated with high level fear of negative evaluation (FNE) among junior high school students and to construct a nomogram risk prediction model, so as to provide scientific tools for psychological health intervention for junior high school students. Methods: A convenience sampling combined with cluster random sampling method was used to select 5 485 junior high school students from 4 cities (Wuhan, Huanggang, Xianning and Xiaogan) for an online questionnaire survey in March 2025. The total sample was randomly split into a training set ( n =3 839) and a validation set ( n =1 646). Univariate analysis was performed in the training set using Chi-square test and t-test. Variables with statistical significance were subsequently included in multivariate Logistic regression to identify independent predictors and to construct a nomogram based risk prediction model. The discriminative ability and clinical utility of the model were evaluated in the validation set using the area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA). Results: There were 1 649 junior high school students with low level FNE and 2 190 with high level FNE in the training set. The self control ability of junior high school students with lowlevel and high level FNE showed a statistically significant difference (23.96±3.96, 21.48±3.37, t=25.15, P < 0.01 ). Statistically significant differences in the detection rate of high level FNE were observed among junior high school students with different genders, family types, parenting styles, academic rankings, psychological flexibility, mobile phone addiction tendencies, emotional management training, exercise frequency, left behind experiences, and places of origin ( χ 2=82.01- 1 126.68 , all P <0.01). The results of Logistic regression analysis revealed that, the following factors were identified as significant factors influencing high level FNE among junior high school students:exercise frequency ( OR=0.21, 95%CI =0.17-0.26); parenting style ( OR=0.48, 95%CI =0.40-0.58); left behind experience ( OR=3.88, 95%CI =3.27-4.61); smartphone addiction proneness ( OR=2.19, 95%CI =0.89-0.93); self-control ability ( OR=0.91, 95%CI =0.89-0.93); and psychological flexibility ( OR=0.16, 95%CI =0.10-0.28) (all P <0.05). The AUC for the training and validation set were 0.88 (95% CI =0.87-0.89) and 0.87 (95% CI =0.85-0.89), respectively. The Hosmer-Lemeshow goodness of fit test yielded χ 2=8.57, 15.20 (both P >0.05). Conclusion The risk prediction model with high level FNE demonstrates good accuracy and can assist educators and parents in timely screening of junior high school students with high level FNE, thereby providing a basis for implementing targeted interventions.

OBJECTIVE: To analyze the effectiveness of three internal fixation methods, namely hollow screw combined with Kirschner wire tension band, hollow screw combined with anchor nail, and modified 1/3 tubular steel plate, in the treatment of avulsion fracture of tibial tubercle (AFTT) in adolescents. METHODS: Between January 2018 and September 2023, 19 adolescent AFTT patients who met the selection criteria were admitted. According to different internal fixation methods, patients were divided into group A (8 cases, hollow screw combined with Kirschner wire tension band), group B (6 cases, hollow screw combined with anchor nail), and group C (5 cases, modified 1/3 tubular steel plate). There was no significant difference in the baseline data of age, gender, side, cause of injury, Ogden classification, and time from injury to operation among the three groups ( P>0.05). The range of motion (ROM), weight-bearing time, normal activity time of knee joint, and the hospital for special surgery (HSS) score at last follow-up were recorded and compared among the three groups. Recorded whether the fracture was displaced, whether the fracture line was blurred at 1 month after operation, whether there was epiphyseal dysplasia, and whether there was incision infection and other complications. RESULTS: There was no significant difference in hospital stay between the groups ( P>0.05). All patients were followed up 10-24 months, with an average of 14.3 months; there was no significant difference between the groups ( P>0.05). All the incisions healed well without soft tissue irritation or fracture nonunion, and no limb shortening deformity or epiphyseal dysplasia was found during follow-up. At 1 month after operation, the knee joint ROM and hospitalization expenses in group A were better than those in groups B and C, the fracture healing time, knee joint weight-bearing time, and normal activity time of knee joint were better than those in group C, and the hospitalization expenses in group C were better than those in group B, with significant differences ( P<0.05); there was no significant difference in the other indicators between the groups ( P>0.05). In group A, the fracture line was blurred 1 month postoperatively, the fracture ends were in close contact, and there was no fracture displacement; in groups B and C, the fracture line was clear in 2 cases, and 1 case in group C had slight fracture displacement; except for 1 case in group B, there was no fracture split in the other two groups. There was no significant difference in the incidences of blur of fracture line, fracture displacement, and intraoperative bone split between the groups at 1 month after operation ( P>0.05). At last follow-up, the HSS scores of knee joints in the three groups were excellent and good, and there was no significant difference between the groups ( P>0.05). CONCLUSION Hollow screw combined with Kirschner wire tension band technique is effective in treating adolescent AFTT, which has the advantages of stabilizing fracture, accelerating fracture healing and rehabilitation, early feasible knee joint functional exercise, and reducing hospitalization expenses.
Humans ; Tibial Fractures/surgery* ; Adolescent ; Male ; Fracture Fixation, Internal/instrumentation* ; Female ; Fractures, Avulsion/surgery* ; Bone Wires ; Bone Screws ; Bone Plates ; Treatment Outcome ; Range of Motion, Articular ; Bone Nails ; Weight-Bearing ; Fracture Healing

OBJECTIVE: To explore effectiveness of intermediate screw assisted reduction and fixation technique in the treatment of Schatzker type Ⅴ and Ⅵ tibial plateau fractures. METHODS: A clinical data of 22 patients with Schatzker type Ⅴ and Ⅵ tibial plateau fractures, who were admitted between June 2022 and December 2023 and met the selection criteria, was retrospectively analyzed. During operation, the intermediate screw assisted reduction and fixation technique was used. There were 14 males and 8 females with an average age of 46.3 years (range, 17-65 years). The fractures were caused by traffic accident in 13 cases, by falls in 5 cases, and by falling from height in 4 cases. According to Schatzker classification criteria, 9 cases were type Ⅴ and 13 cases were type Ⅵ. The interval between injury and operation was 5-12 days (mean, 7.9 days). The operation time, intraoperative fluoroscopy times, and length of hospital stay were recorded. The range of motion of knee joint and Hospital for Special Surgery (HSS) score were recorded at last follow-up. X-ray films were taken to review the fracture healing. Rasmussen score, tibial plateau varus angle (TPVA), and posterior tibial slope (PTS) were estimated before operation, at immediate after operation, and at last follow-up in order to evaluate the fracture reduction effect and postoperative outcome. RESULTS: The operation time was 85-140 minutes (mean, 103.9 minutes). Intraoperative fluoroscopy was performed 7-15 times (mean, 10.1 times). All incisions healed by first intention after operation, and no complication such as nerve or blood vessel injury occurred. The length of hospital stay ranged from 8 to 17 days (mean, 12.4 days). All patients were followed up 10-22 months (mean, 14.8 months). At last follow-up, the range of motion of knee joint was 110°-140° (mean, 125°). HSS score was rated as excellent in 16 cases, good in 5 cases, and fair in 1 case, with an excellent and good rate of 95.5%. X-ray films reexamination showed that all fractures healed with the healing time of 12-17 weeks (mean, 14.8 weeks). No internal fixation failure occurred. Rasmussen score, TPVA, and PTS at immediate after operation and at last follow-up were significantly superior to those before operation ( P<0.05). And there was no significant difference between immediately after operation and last follow-up ( P>0.05). CONCLUSION The treatment of Schatzker type Ⅴ and Ⅵ tibial plateau fractures with intermediate screw assisted reduction and fixation technique is reliable, which can reduce the difficulty of reduction and fixation, improve the efficiency of reduction and fixation, reduce the operation time, achieve satisfactory reduction and fixation effect and postoperative prognosis, and achieve good recovery of knee joint function.
Humans ; Tibial Fractures/diagnostic imaging* ; Male ; Female ; Adult ; Middle Aged ; Bone Screws ; Fracture Fixation, Internal/instrumentation* ; Retrospective Studies ; Adolescent ; Aged ; Young Adult ; Treatment Outcome ; Range of Motion, Articular ; Operative Time ; Length of Stay ; Tibial Plateau Fractures

OBJECTIVE: To evaluate the effectiveness of V-shaped stealth decompression technique using ultrasonic bone scalpel in anterior surgery for adjacent two-level cervical spondylosis. METHODS: A clinical data of 41 patients with adjacent two-level cervical spondylosis, who admitted between January 2020 and December 2023 and met the selection criteria, was analyzed retrospectively. Among them, 22 cases were treated with anterior cervical discectomy and fusion (ACDF) assisted by V-shaped stealth decompression technique using ultrasonic bone scalpel (group A) and 19 cases with anterior cervical corpectomy and fusion (ACCF) (group B). There was no significant difference between the two groups in age, gender, disease duration, surgical segment, preoperative Japanese Orthopedic Association (JOA) score, neck dysfunction index (NDI), pain visual analogue scale (VAS) score, and the anteroposterior diameter of the spinal canal in the responsibility space of axial CT ( P>0.05). The operation time, intraoperative blood loss, postoperative drainage volume, hospital stay, complications during follow-up, JOA score, NDI, and VAS score at last follow-up, and the incidences of intervertebral fusion at 3 months after operation, and cage subsidence at last follow-up were compared between the two groups. RESULTS: The operations in the two groups were successfully completed. The operation time, intraoperative blood loss, postoperative drainage volume, and hospital stay in group A were significantly less than those in group B ( P<0.05). Two cases (9.1%) in group A and 4 cases (21.1%) in group B developed complications, with no significant difference in the incidence between the two groups ( P>0.05). All patients in the two groups were followed up 6-12 months (mean, 9.3 months). There was no significant difference in follow-up time between the two groups ( P>0.05). At last follow-up, the JOA score and VAS score in both groups significantly improved when compared with those before operation ( P<0.05). The change values of VAS score and the improvement rate of JOA score in group A were significantly superior to group B ( P<0.05). There was no significant difference in the change values of NDI and JOA score between the two group ( P>0.05). Imaging reexamination showed that the rate of intervertebral fusion at 3 months after operation was significantly higher in group A (81.8%) than in group B (52.6%) ( P<0.05), and all patients obtained bony intervertebral fusion at last follow-up. At last follow-up, 2 cases (9.1%) in group A and 11 cases (57.9%) in group B had cage sinking, and the difference in the incidence was significant ( P<0.05). No loosening or fracture of internal fixators occurred in all patients. CONCLUSION Using ultrasonic bone scalpel can transform single vertebral ACCF into two-segment ACDF in anterior cervical spondylosis surgery. The V-shaped stealth decompression technique is safe and efficient, with the advantages of minimal trauma, fewer postoperative complications, and rapid recovery of patients.
Humans ; Spondylosis/surgery* ; Male ; Female ; Middle Aged ; Decompression, Surgical/instrumentation* ; Retrospective Studies ; Cervical Vertebrae/surgery* ; Spinal Fusion/instrumentation* ; Diskectomy/instrumentation* ; Adult ; Treatment Outcome ; Aged ; Ultrasonic Surgical Procedures/methods* ; Operative Time

Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.

Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.