Numerous techniques for C2 screw fixation have been recently reported. However, concerns remain regarding the risk of spinal cord or vertebral artery injury and inadequate biomechanical stability. To our knowledge, the specific transforaminal “in-out-in” screw fixation technique has not been previously reported. This study aimed to investigate the feasibility and preliminary clinical outcomes of a transforaminal “in-out-in” multi-cortical purchase screw for posterior C2 screw fixation. Between October 2022 and March 2023, 10 patients underwent posterior atlantoaxial internal fixation. All patients had severe hypoplasia of the C2 pedicle on at least one side, precluding the use of standard C2 pedicle screws. A transforaminal “in-out-in” screw was used as an alternative. No spinal cord injury, vascular injury, or other major complications were observed. No implant failure was noted at the final follow-up. In conclusion, the transforaminal “in-out-in” screw may achieve rigid three-column fixation with multiple cortical purchases. It represents a safe and effective alternative for posterior C2 fixation in patients with severely narrow C2 pedicles where traditional pedicle screw placement is not feasible.

OBJECTIVE: To explore the neuroprotective effects of Xuefu Zhuyu Decoction (XFZYD) based on in vivo and metabolomics experiments. METHODS: Traumatic brain injury (TBI) was induced via a controlled cortical impact (CCI) method. Thirty rats were randomly divided into 3 groups (10 for each): sham, CCI and XFZYD groups (9 g/kg). The administration was performed by intragastric administration for 3 days. Neurological functions tests, histology staining, coagulation and haemorheology assays, and Western blot were examined. Untargeted metabolomics was employed to identify metabolites. The key metabolite was validated by enzyme-linked immunosorbent assay and immunofluorescence. RESULTS: XFZYD significantly alleviated neurological dysfunction in CCI model rats (P<0.01) but had no impact on coagulation function. As evidenced by Evans blue and IgG staining, XFZYD effectively prevented blood-brain barrier (BBB) disruption (P<0.05, P<0.01). Moreover, XFZYD not only increased the expression of collagen IV, occludin and zona occludens 1 but also decreased matrix metalloproteinase-9 (MMP-9) and cyclooxygenase-2 (COX-2), which protected BBB integrity (all P<0.05). Nine potential metabolites were identified, and all of them were reversed by XFZYD. Adenosine was the most significantly altered metabolite related to BBB repair. XFZYD significantly reduced the level of equilibrative nucleoside transporter 2 (ENT2) and increased adenosine (P<0.01), which may improve BBB integrity. CONCLUSIONS XFZYD ameliorates BBB disruption after TBI by decreasing the levels of MMP-9 and COX-2. Through further exploration via metabolomics, we found that XFZYD may exert a protective effect on BBB by regulating adenosine metabolism via ENT2.
Animals ; Drugs, Chinese Herbal/therapeutic use* ; Blood-Brain Barrier/metabolism* ; Brain Injuries, Traumatic/metabolism* ; Adenosine/metabolism* ; Male ; Rats, Sprague-Dawley ; Rats

OBJECTIVE: Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. METHODS: HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. RESULTS: Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. CONCLUSION Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis. Please cite this article as: Feng CY, Cai CS, Shi XQ, Zhang ZJ, Su D, Qiu YQ. Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma. J Integr Med. 2025; 23(1): 79-91.
Humans ; MicroRNAs/genetics* ; Liver Neoplasms/metabolism* ; Carcinoma, Hepatocellular/metabolism* ; Mitophagy/drug effects* ; Resveratrol/pharmacology* ; Animals ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Hep G2 Cells ; Mice ; Disease Progression ; Mice, Inbred BALB C

OBJECTIVE: Emerging evidence suggests that exposure to ultrafine particulate matter (UPM, aerodynamic diameter < 0.1 µm) is associated with adverse cardiovascular events. Previous studies have found that Shenlian (SL) extract possesses anti-inflammatory and antiapoptotic properties and has a promising protective effect at all stages of the atherosclerotic disease process. In this study, we aimed to investigated whether SL improves UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. METHODS: We established a mouse model of MI+UPM. Echocardiographic measurement, measurement of myocardialinfarct size, biochemical analysis, enzyme-linked immunosorbent assay (ELISA), histopathological analysis, Transferase dUTP Nick End Labeling (TUNEL), Western blotting (WB), Polymerase Chain Reaction (PCR) and so on were used to explore the anti-inflammatory and anti-apoptotic effects of SL in vivo and in vitro. RESULTS: SL treatment can attenuate UPM-induced cardiac dysfunction by improving left ventricular ejection fraction, fractional shortening, and decreasing cardiac infarction area. SL significantly reduced the levels of myocardial enzymes and attenuated UPM-induced morphological alterations. Moreover, SL significantly reduced expression levels of the inflammatory cytokines IL-6, TNF-α, and MCP-1. UPM further increased the infiltration of macrophages in myocardial tissue, whereas SL intervention reversed this phenomenon. UPM also triggered myocardial apoptosis, which was markedly attenuated by SL treatment. The results of in vitro experiments revealed that SL prevented cell damage caused by exposure to UPM combined with hypoxia by reducing the expression of the inflammatory factor NF-κB and inhibiting apoptosis in H9c2 cells. CONCLUSION Overall, both in vivo and in vitro experiments demonstrated that SL attenuated UPM-aggravated myocardial ischemic injury by inhibiting inflammation and cell apoptosis. The mechanisms were related to the downregulation of macrophages infiltrating heart tissues.
Animals ; Apoptosis/drug effects* ; Particulate Matter/adverse effects* ; Mice ; Male ; Inflammation/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Inbred C57BL ; Myocardial Ischemia/drug therapy* ; Cell Line

BACKGROUND: While emotional distress, encompassing anxiety and depression, has been associated with negative clinical outcomes, its impact across various clinical departments and general hospitals has been less explored. Previous studies with limited sample sizes have examined the effectiveness of specific treatments (e.g., antidepressants) rather than a systemic management strategy for outcome improvement in non-psychiatric inpatients. To enhance the understanding of the importance of addressing mental health care needs among non-psychiatric patients in general hospitals, this study retrospectively investigated the impacts of emotional distress and the effects of early detection and management of depression and anxiety on hospital length of stay (LOS) and rate of long LOS (LLOS, i.e., LOS >30 days) in a large sample of non-psychiatric inpatients. METHODS: This retrospective cohort study included 487,871 inpatients from 20 non-psychiatric departments of a general hospital. They were divided, according to whether they underwent a novel strategy to manage emotional distress which deployed the Huaxi Emotional Distress Index (HEI) for brief screening with grading psychological services (BS-GPS), into BS-GPS ( n = 178,883) and non-BS-GPS ( n = 308,988) cohorts. The LOS and rate of LLOS between the BS-GPS and non-BS-GPS cohorts and between subcohorts with and without clinically significant anxiety and/or depression (CSAD, i.e., HEI score ≥11 on admission to the hospital) in the BS-GPS cohort were compared using univariable analyses, multilevel analyses, and/or propensity score-matched analyses, respectively. RESULTS: The detection rate of CSAD in the BS-GPS cohort varied from 2.64% (95% confidence interval [CI]: 2.49%-2.81%) to 20.50% (95% CI: 19.43%-21.62%) across the 20 departments, with a average rate of 5.36%. Significant differences were observed in both the LOS and LLOS rates between the subcohorts with CSAD (12.7 days, 535/9590) and without CSAD (9.5 days, 3800/169,293) and between the BS-GPS (9.6 days, 4335/178,883) and non-BS-GPS (10.8 days, 11,483/308,988) cohorts. These differences remained significant after controlling for confounders using propensity score-matched comparisons. A multilevel analysis indicated that BS-GPS was negatively associated with both LOS and LLOS after controlling for sociodemographics and the departments of patient discharge and remained negatively associated with LLOS after controlling additionally for the year of patient discharge. CONCLUSION Emotional distress significantly prolonged the LOS and increased the LLOS of non-psychiatric inpatients across most departments and general hospitals. These impacts were moderated by the implementation of BS-GPS. Thus, BS-GPS has the potential as an effective, resource-saving strategy for enhancing mental health care and optimizing medical resources in general hospitals.
Humans ; Retrospective Studies ; Male ; Length of Stay/statistics & numerical data* ; Female ; Middle Aged ; Adult ; Psychological Distress ; Inpatients/psychology* ; Aged ; Anxiety/diagnosis* ; Depression/diagnosis*

The study aimed to construct the second and third generation chimeric antigen receptor T cells (CAR-T) targeting the c-mesenchymal-epithelial transition factor (c-Met) protein, and observe their killing effect on human serous ovarian cancer cell SKOV-3. The expression of MET gene in ovarian serous cystadenocarcinoma, the correlation between MET gene expression and the abundance of immune cell infiltration, and the effect of MET gene expression on the tissue function of ovarian serous cystadenocarcinoma were analyzed by bioinformatics. The expression of c-Met in ovarian cancer tissues and adjacent tissues was detected by immunohistochemical staining. The second and third generation c-Met CAR-T cells, namely c-Met CAR-T(2G/3G), were prepared by lentivirus infection, and the cell subsets and infection efficiency were detected by flow cytometry. Using CD19 CAR-T and activated T cells as control groups and A2780 cells with c-Met negative expression as Non target groups, the kill efficiency on SKOV-3 cells with c-Met positive expression, cytokine release and cell proliferation of c-Met CAR-T(2G/3G) were explored by lactate dehydrogenase (LDH) release, ELISA and CCK-8 respectively. The results showed that MET gene expression was significantly up-regulated in ovarian cancer tissues compared with normal tissues, which was consistent with the immunohistochemistry results. However, in all pathological stages, there was no obvious difference in MET expression and no correlation between MET gene expression and the race and age of ovarian cancer patients. The second generation and third generation c-Met CAR-T cells were successfully constructed. After lentivirus infection, the proportion of CD8⁺ T cells in c-Met CAR-T(2G) was upregulated, while there was no significant change in the cell subsets of c-Met CAR-T(3G). The LDH release experiment showed that the kill efficiency of c-Met CAR-T(2G/3G) on SKOV-3 increased with the increase of effect-target ratio. When the effect-target ratio was 20:1, the kill efficiency of c-Met CAR-T(2G) reached (42.02 ± 5.17)% (P < 0.05), and the kill efficiency of c-Met CAR-T(3G) reached (51.40 ± 2.71)% (P < 0.05). ELISA results showed that c-Met CAR-T released more cytokine compared to CD19 CAR-T and activated T cells (P < 0.05). Moreover, the cytokine release of c-Met CAR-T(3G) was higher than c-Met CAR-T(2G) (P < 0.01). The CCK-8 results showed that after 48 h, the cell number of c-Met CAR-T(2G) was higher than that of c-Met CAR-T(3G) (P < 0.01). In conclusion, both the second and third generation c-Met CAR-T can target and kill c-Met-positive SKOV-3 cells, with no significant difference. c-Met CAR-T(2G) has stronger proliferative ability, and c-Met CAR-T(3G) releases more cytokines.
Humans ; Female ; Ovarian Neoplasms/immunology* ; Proto-Oncogene Proteins c-met/metabolism* ; Receptors, Chimeric Antigen/immunology* ; Cell Line, Tumor ; Cystadenocarcinoma, Serous/immunology* ; T-Lymphocytes/immunology*

Objective To investigate the current symptom status of maintenance hemodialysis(MHD)patients,analyze the influencing factors from the perspective of multidimensional symptom burden,extract symptom groups,and construct a symptom network.Methods A total of 490 patients who received MHD at the blood purification center of a tertiary hospital in Shanghai from March to April 2025 were selected using a convenience sampling method.30 symptoms of MHD patients were investigated using a modified dialysis symptom index table.SPSS and R software were utilized to analyze the influencing factors,extract symptom groups,and construct a multidimensional symptom network.Results A total of 488 valid questionnaires were collected,with a valid questionnaire recovery rate of 99.59％.The median number of symptoms experienced by patients was 6(interquartile range:4,8),with the top 5 symptoms being dry skin(69.88％),fatigue or tiredness(56.97％),itching(56.97％),worry(50.20％),and dry mouth(46.31％).Multidimensional analysis indicated that age,duration of dialysis,education level,and complications were influencing factors of symptom burden scores across different dimensions.6 stable symptom groups were extracted,namely skin discomfort,fatigue and pain,gastrointestinal tract,sleep disorders,water-electrolyte imbalance,and uremia.The results of the symptom network analysis revealed that difficulty of falling asleep had the highest intensity centrality(rs=2.18,2.25,2.12).Conclusion The symptom association is relatively stable,and difficulty of falling asleep is the core symptom.This finding can assist clinical medical staff in achieving efficiency and precision in symptom group management.

Objective To investigate the current symptom status of maintenance hemodialysis(MHD)patients,analyze the influencing factors from the perspective of multidimensional symptom burden,extract symptom groups,and construct a symptom network.Methods A total of 490 patients who received MHD at the blood purification center of a tertiary hospital in Shanghai from March to April 2025 were selected using a convenience sampling method.30 symptoms of MHD patients were investigated using a modified dialysis symptom index table.SPSS and R software were utilized to analyze the influencing factors,extract symptom groups,and construct a multidimensional symptom network.Results A total of 488 valid questionnaires were collected,with a valid questionnaire recovery rate of 99.59％.The median number of symptoms experienced by patients was 6(interquartile range:4,8),with the top 5 symptoms being dry skin(69.88％),fatigue or tiredness(56.97％),itching(56.97％),worry(50.20％),and dry mouth(46.31％).Multidimensional analysis indicated that age,duration of dialysis,education level,and complications were influencing factors of symptom burden scores across different dimensions.6 stable symptom groups were extracted,namely skin discomfort,fatigue and pain,gastrointestinal tract,sleep disorders,water-electrolyte imbalance,and uremia.The results of the symptom network analysis revealed that difficulty of falling asleep had the highest intensity centrality(rs=2.18,2.25,2.12).Conclusion The symptom association is relatively stable,and difficulty of falling asleep is the core symptom.This finding can assist clinical medical staff in achieving efficiency and precision in symptom group management.

Protein phosphorylation modification is an important mechanism of physiological regulation that is closely related to protein biological functions. In particular, protein kinases are responsible for catalyzing the phosphorylation process of proteins, and phosphatases are responsible for catalyzing the dephosphorylation process of phosphorylation-modified proteins, which together mediate the achievement of dynamic and reversible phosphorylation modifications of proteins. Abnormal phosphorylation levels of proteins contribute to the development of many diseases, such as cancer, neurodegenerative diseases, and chronic diseases. Therefore, rational design of small molecules to regulate protein phosphorylation is an important approach for disease treatment. Based on the mechanism of protein phosphorylation regulation, small molecule drug design strategies can be classified into three types, protein kinase modulators, phosphatase modulators, and bifunctional molecules with proximity-mediated mechanism. This review emphasizes the above three small molecule design strategies for targeting protein phosphorylation regulation, including molecular design ideas, research progress and current challenges, and provides an outlook on small molecule modulators targeting protein phosphorylation modification.

Objective To observe the value of self-supervised deep learning artificial intelligence(AI)noise reduction technology based on the nearest adjacent layer applicated in ultra-low dose CT(ULDCT)for urinary calculi.Methods Eighty-eight urinary calculi patients were prospectively enrolled.Low dose CT(LDCT)and ULDCT scanning were performed,and the effective dose(ED)of each scanning protocol were calculated.The patients were then randomly divided into training set(n=75)and test set(n=13),and a self-supervised deep learning AI noise reduction system based on the nearest adjacent layer constructed with ULDCT images in training set was used for reducing noise of ULDCT images in test set.In test set,the quality of ULDCT images before and after AI noise reduction were compared with LDCT images,i.e.Blind/Referenceless Image Spatial Quality Evaluator(BRISQUE)scores,image noise(SDROI)and signal-to-noise ratio(SNR).Results The tube current,the volume CT dose index and the dose length product of abdominal ULDCT scanning protocol were all lower compared with those of LDCT scanning protocol(all P＜0.05),with a decrease of ED for approximately 82.66％.For 13 patients with urinary calculi in test set,BRISQUE score showed that the quality level of ULDCT images before AI noise reduction reached 54.42％level but raised to 95.76％level of LDCT images after AI noise reduction.Both ULDCT images after AI noise reduction and LDCT images had lower SDROI and higher SNR than ULDCT images before AI noise reduction(all adjusted P＜0.05),whereas no significant difference was found between the former two(both adjusted P＞0.05).Conclusion Self-supervised learning AI noise reduction technology based on the nearest adjacent layer could effectively reduce noise and improve image quality of urinary calculi ULDCT images,being conducive for clinical application of ULDCT.