Dormant tumor cells constitute a population of cancer cells that reside in a non-proliferative or low-proliferative state, typically arrested in the G0/G1 phase and exhibiting minimal mitotic activity. These cells are commonly observed across multiple cancer types, including breast, lung, and ovarian cancers, and represent a central cellular component of minimal residual disease (MRD) following surgical resection of the primary tumor. Dormant cells are closely associated with long-term clinical latency and late-stage relapse. Due to their quiescent nature, dormant cells are intrinsically resistant to conventional therapies—such as chemotherapy and radiotherapy—that preferentially target rapidly dividing cells. In addition, they display enhanced anti-apoptotic capacity and immune evasion, rendering them particularly difficult to eradicate. More critically, in response to microenvironmental changes or activation of specific signaling pathways, dormant cells can re-enter the cell cycle and initiate metastatic outgrowth or tumor recurrence. This ability to escape dormancy underscores their clinical threat and positions their effective detection and elimination as a major challenge in contemporary cancer treatment. Hypoxia, a hallmark of the solid tumor microenvironment, has been widely recognized as a potent inducer of tumor cell dormancy. However, the molecular mechanisms by which tumor cells sense and respond to hypoxic stress—initiating the transition into dormancy—remain poorly defined. In particular, the lack of a systems-level understanding of the dynamic and multifactorial regulatory landscape has impeded the identification of actionable targets and constrained the development of effective therapeutic strategies. Accumulating evidence indicates that hypoxia-induced dormancy tumor cells are accompanied by a suite of adaptive phenotypes, including cell cycle arrest, global suppression of protein synthesis, metabolic reprogramming, autophagy activation, resistance to apoptosis, immune evasion, and therapy tolerance. These changes are orchestrated by multiple converging signaling pathways—such as PI3K-AKT-mTOR, Ras-Raf-MEK-ERK, and AMPK—that together constitute a highly dynamic and interconnected regulatory network. While individual pathways have been studied in depth, most investigations remain reductionist and fail to capture the temporal progression and network-level coordination underlying dormancy transitions. Systems biology offers a powerful framework to address this complexity. By integrating high-throughput multi-omics data—such as transcriptomics and proteomics—researchers can reconstruct global regulatory networks encompassing the key signaling axes involved in dormancy regulation. These networks facilitate the identification of core regulatory modules and elucidate functional interactions among key effectors. When combined with dynamic modeling approaches—such as ordinary differential equations—these frameworks enable the simulation of temporal behaviors of critical signaling nodes, including phosphorylated AMPK (p-AMPK), phosphorylated S6 (p-S6), and the p38/ERK activity ratio, providing insights into how their dynamic changes govern transitions between proliferation and dormancy. Beyond mapping trajectories from proliferation to dormancy and from shallow to deep dormancy, such dynamic regulatory models support topological analyses to identify central hubs and molecular switches. Key factors—such as NR2F1, mTORC1, ULK1, HIF-1α, and DYRK1A—have emerged as pivotal nodes within these networks and represent promising therapeutic targets. Constructing an integrative, systems-level regulatory framework—anchored in multi-pathway coordination, omics-layer integration, and dynamic modeling—is thus essential for decoding the architecture and progression of tumor dormancy. Such a framework not only advances mechanistic understanding but also lays the foundation for precision therapies targeting dormant tumor cells during the MRD phase, addressing a critical unmet need in cancer management.

This study aims to establish the S_(180) tumor-bearing mice model, and to investigate the influence of Shenqi Erpi Granules(SQEPG) on immune function, as well as the drug's tumor-suppressive effect and mechanism. SPF grade KM mice(half male and half female) were randomly divided into 6 groups: a control group, a model group, a cyclophosphamide group(50 mg·kg~(-1)), as well as SQEPG groups in low-, medium-, and high-dose(5.25, 10.5, 21 g·kg~(-1)). The control group and the model group were given distilled water, and the other 4 groups were given the corresponding drugs by gavage. The administration continued for 10 days before the mice were sacrificed. The antitumor and immune regulation effects of SQEPG were evaluated. The effect of SQEPG on delayed type hypersensitivity reaction(DTH), carbon clearance index, and serum hemolysin antibody level was observed to reflect the effect on the immune function of tumor-bearing mice. Tumor weight was recorded to calculate the tumor suppression rate and the immune organ index. Hematoxylin-eosin(HE) staining was used to detect morphological changes in tumor tissues. Flow cytometry was employed to detect the percentage of CD4~+ and CD8~+ T-cells in the spleen tissues and the tumor tissue apoptosis levels. Immunohistochemistry was conducted to detect the KI67 protein expression level of tumor tissues. ELISA resorted to the detection of the following expression levels in tumor tissues: tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), interferon-γ(IFN-γ). Western blot was performed to detect the expression levels of caspase-3, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinases 4(CDK4), G_1/S-specific cyclin D1(cyclin D1), and vascular endothelial growth factor A(VEGFA). The results showed that, compared with the model group, the SQEPG could increase the swelling of the auricle of the tumor-bearing mice; significantly increase the phagocytic index of carbon granule contour(P<0.05 or P<0.01), and the middle dose of SQEPG could significantly increase the antibody level of hemolysin(P<0.05); different doses of SQEPG significantly inhibit the growth of the tumor, and decrease the mass of the tumor tissues(P<0.05 or P<0.01); the low dose of SQEPG significantly decreased spleen index(P<0.05), low and high doses of SQEPG increased thymus index, while medium doses of SQEPG decreased thymus index. High doses of SQEPG significantly elevated the levels of CD4~+ and CD8~+ T-cells in the spleens of the homozygous mice(P<0.01 or P<0.001), and increased the apoptosis rate of the cells of the tumor tissues(P<0.05); Meanwhile, high-dose SQEPG elevated the levels of immunity factors such as IL-2, IFN-γ and TNF-α in the serum of tumor-bearing mice(P<0.01); medium-and high-dose SQEPG significantly lowered the rate of positive expression of KI67 protein in tumor tissues(P<0.01). Compared with the model group, high-dose SQEPG significantly up-regulated the expression of caspase-3 and Bax proteins in tumor tissues(P<0.05), and significantly down-regulated the expression of CDK4, cyclin D1, and VEGFA proteins(P<0.05 or P<0.01). In conclusion, SQEPG has the effect of improving immune function and inhibiting tumor growth in tumor-bearing mice. Its mechanism of tumor-suppressive effects may be related to apoptosis promotion, cell cycle progression block, and tumor cell proliferation inhibition.
Animals ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Male ; Female ; Apoptosis/drug effects* ; Sarcoma 180/genetics* ; Humans

Objective:To investigate the factors influencing fall risk scores in elderly individuals.Methods:A total of 4 419 individuals were randomly selected using the cluster sampling method from Beijing, Nanning(Guangxi), and Yinchuan(Ningxia).Data on demographic characteristics and fall-related incidents were gathered and analyzed for their correlation with fall risk scores.Results:The fall risk score showed significant associations with various factors, such as the history of falls within one year( β=-3.607, 95% CI: -3.881 to -3.332), care methods( β=2.442, 95% CI: 2.226 to 2.658), exercise( β=0.714, 95% CI: 0.443 to 0.986), retirement( β=-0.585, 95% CI: -0.819 to -0.351), age( β=0.173, 95% CI: 0.159 to 0.187), and use of walking aids( β=-3.737, 95% CI: -4.054 to -3.421). Conclusions:Fall risk scores in older adults are influenced by a variety of factors.Factors such as no history of falls within the past year, living independently, engaging in physical activity, and being employed may contribute to lower fall risk scores in older adults.

Objective:To investigate the clinical outcome of the coronal Y-shaped osteotomy in the apical vertebra for treating congenital complex rigid scoliosis.Methods:A retrospective analysis was conducted on 66 cases who underwent Y-shaped osteotomy treatment for congenital complex rigid scoliosis in the uppermost vertebra at the Department of Orthopedics,the Second Hospital of Shanxi Medical University from June 2007 to August 2020. There were 19 males and 47 females,with an age of (13.1±5.3) years(range:2 to 30 years).Classification of congenital scoliosis:25 cases (37.9%) were incomplete,13 cases (19.7%) were dysarthritic,and 28 cases (42.4%) were mixed. There were 25 cases (37.9%) with thoracic or rib malformations. 45 cases (68.2%) were complicated with spinal cord malformation.The main radiological indicators included Cobb angle of the curvature,Cobb angle of the local bend,apical vertebral translation (AVT),trunk shift (TS),thoracic trunk shift (TTS),radiographic shoulder height (RSH),coronal balance and sagittal vertebral axis. The preoperative,postoperative immediate,and last follow-up radiological indicators were collected and the operation time,blood loss,hospitalization time,and operation-related complications were recorded. Data were compared by repeated measure ANOVA and paired- t test. Results:All patients underwent surgery successfully. The duration of the first surgery was (221.4±52.8) minutes,and the blood loss during the first surgery was (273.2±41.8) ml. The length of the first hospital stay was (8.8±1.7) days.Unilateral fixation was performed in 19 cases (28.8%),while bilateral fixation was performed in 47 cases (71.2%). The fused segments were 7.5±2.9,and the vertebral pedicle screw density was (68.5±20.6)%. The follow-up time for the 66 patients was (36.7±17.0) months(range:24 to 102 months).The main curve Cobb Angle was improved from (58.5±18.9)°before surgery to (21.1±11.8)°after surgery,and was (23.6±15.3) ° at the last follow-up( F=273.957, P<0.01),with a correction rate of 66.2%. Segmental curve Cobb Angle was improved from (47.9±18.0)° to (16.0±11.3)° after surgery,and was (16.8±12.8) °at the last follow-up ( F=270.483, P<0.01)with a correction rate of 69.2%. The AVT,TS,TTS and RSH values improved significantly at the final follow-up (all P<0.05),while coronal balance and sagittal vertical axis were maintained without significant differences between pre-operation and post-operation(both P>0.05). A total of 5 patients underwent staged operation,all of which were residual scoliosis aggravated after the first stage of orthosis operation and had good prognosis after the second stage of operation. Conclusions:Y-shaped osteotomy for the treatment of congenital rigid scoliosis results in good clinical and radiological outcomes without serious complications. This procedure can be considered as an option for the treatment of congenital complex rigid scoliosis.

Objective:To investigate the clinical outcome of the coronal Y-shaped osteotomy in the apical vertebra for treating congenital complex rigid scoliosis.Methods:A retrospective analysis was conducted on 66 cases who underwent Y-shaped osteotomy treatment for congenital complex rigid scoliosis in the uppermost vertebra at the Department of Orthopedics,the Second Hospital of Shanxi Medical University from June 2007 to August 2020. There were 19 males and 47 females,with an age of (13.1±5.3) years(range:2 to 30 years).Classification of congenital scoliosis:25 cases (37.9%) were incomplete,13 cases (19.7%) were dysarthritic,and 28 cases (42.4%) were mixed. There were 25 cases (37.9%) with thoracic or rib malformations. 45 cases (68.2%) were complicated with spinal cord malformation.The main radiological indicators included Cobb angle of the curvature,Cobb angle of the local bend,apical vertebral translation (AVT),trunk shift (TS),thoracic trunk shift (TTS),radiographic shoulder height (RSH),coronal balance and sagittal vertebral axis. The preoperative,postoperative immediate,and last follow-up radiological indicators were collected and the operation time,blood loss,hospitalization time,and operation-related complications were recorded. Data were compared by repeated measure ANOVA and paired- t test. Results:All patients underwent surgery successfully. The duration of the first surgery was (221.4±52.8) minutes,and the blood loss during the first surgery was (273.2±41.8) ml. The length of the first hospital stay was (8.8±1.7) days.Unilateral fixation was performed in 19 cases (28.8%),while bilateral fixation was performed in 47 cases (71.2%). The fused segments were 7.5±2.9,and the vertebral pedicle screw density was (68.5±20.6)%. The follow-up time for the 66 patients was (36.7±17.0) months(range:24 to 102 months).The main curve Cobb Angle was improved from (58.5±18.9)°before surgery to (21.1±11.8)°after surgery,and was (23.6±15.3) ° at the last follow-up( F=273.957, P<0.01),with a correction rate of 66.2%. Segmental curve Cobb Angle was improved from (47.9±18.0)° to (16.0±11.3)° after surgery,and was (16.8±12.8) °at the last follow-up ( F=270.483, P<0.01)with a correction rate of 69.2%. The AVT,TS,TTS and RSH values improved significantly at the final follow-up (all P<0.05),while coronal balance and sagittal vertical axis were maintained without significant differences between pre-operation and post-operation(both P>0.05). A total of 5 patients underwent staged operation,all of which were residual scoliosis aggravated after the first stage of orthosis operation and had good prognosis after the second stage of operation. Conclusions:Y-shaped osteotomy for the treatment of congenital rigid scoliosis results in good clinical and radiological outcomes without serious complications. This procedure can be considered as an option for the treatment of congenital complex rigid scoliosis.

BACKGROUND: This study aimed to develop a comprehensive instrument for evaluating and ranking clinical practice guidelines, named Scientific, Transparent and Applicable Rankings tool (STAR), and test its reliability, validity, and usability. METHODS: This study set up a multidisciplinary working group including guideline methodologists, statisticians, journal editors, clinicians, and other experts. Scoping review, Delphi methods, and hierarchical analysis were used to develop the STAR tool. We evaluated the instrument's intrinsic and interrater reliability, content and criterion validity, and usability. RESULTS: STAR contained 39 items grouped into 11 domains. The mean intrinsic reliability of the domains, indicated by Cronbach's α coefficient, was 0.588 (95% confidence interval [CI]: 0.414, 0.762). Interrater reliability as assessed with Cohen's kappa coefficient was 0.774 (95% CI: 0.740, 0.807) for methodological evaluators and 0.618 (95% CI: 0.587, 0.648) for clinical evaluators. The overall content validity index was 0.905. Pearson's r correlation for criterion validity was 0.885 (95% CI: 0.804, 0.932). The mean usability score of the items was 4.6 and the median time spent to evaluate each guideline was 20 min. CONCLUSION The instrument performed well in terms of reliability, validity, and efficiency, and can be used for comprehensively evaluating and ranking guidelines.
Reproducibility of Results ; Surveys and Questionnaires ; Practice Guidelines as Topic ; Humans

Objective: To explore the molecular features of chronic myelomonocytic leukemia (CMML) . Methods: According to 2022 World Health Organization (WHO 2022) classification, 113 CMML patients and 840 myelodysplastic syndrome (MDS) patients from March 2016 to October 2021 were reclassified, and the clinical and molecular features of CMML patients were analyzed. Results: Among 113 CMML patients, 23 (20.4%) were re-diagnosed as acute myeloid leukemia (AML), including 18 AML with NPM1 mutation, 3 AML with KMT2A rearrangement, and 2 AML with MECOM rearrangement. The remaining 90 patients met the WHO 2022 CMML criteria. In addition, 19 of 840 (2.3%) MDS patients met the WHO 2022 CMML criteria. At least one gene mutation was detected in 99% of CMML patients, and the median number of mutations was 4. The genes with mutation frequency ≥ 10% were: ASXL1 (48%), NRAS (34%), RUNX1 (33%), TET2 (28%), U2AF1 (23%), SRSF2 (21.1%), SETBP1 (20%), KRAS (17%), CBL (15.6%) and DNMT3A (11%). Paired analysis showed that SRSF2 was frequently co-mutated with ASXL1 (OR=4.129, 95% CI 1.481-11.510, Q=0.007) and TET2 (OR=5.276, 95% CI 1.979-14.065, Q=0.001). SRSF2 and TET2 frequently occurred in elderly (≥60 years) patients with myeloproliferative CMML (MP-CMML). U2AF1 mutations were often mutually exclusive with TET2 (OR=0.174, 95% CI 0.038-0.791, Q=0.024), and were common in younger (<60 years) patients with myelodysplastic CMML (MD-CMML). Compared with patients with absolute monocyte count (AMoC) ≥1×10(9)/L and <1×10(9)/L, the former had a higher median age of onset (60 years old vs 47 years old, P<0.001), white blood cell count (15.9×10(9)/L vs 4.4×10(9)/L, P<0.001), proportion of monocytes (21.5% vs 15%, P=0.001), and hemoglobin level (86 g/L vs 74 g/L, P=0.014). TET2 mutations (P=0.021) and SRSF2 mutations (P=0.011) were more common in patients with AMoC≥1×10(9)/L, whereas U2AF1 mutations (P<0.001) were more common in patients with AMoC<1×10(9)/L. There was no significant difference in the frequency of other gene mutations between the two groups. Conclusion: According to WHO 2022 classification, nearly 20% of CMML patients had AMoC<1×10(9)/L at the time of diagnosis, and MD-CMML and MP-CMML had different molecular features.
Humans ; Aged ; Middle Aged ; Leukemia, Myelomonocytic, Chronic/genetics* ; Prognosis ; Splicing Factor U2AF/genetics* ; Mutation ; Myelodysplastic Syndromes/genetics* ; Leukemia, Myeloid, Acute/genetics*

Objective: To evaluate the efficacy of in-situ full size split liver transplantation(fSLT) for adult recipients using the living donor liver transplantation(LDLT) technique and to compare the characteristics of the left hemiliver graft (LHG) and the right hemiliver graft(RHG)transplantation. Methods: Deceased donor and recipient data of 25 consecutive cases of fSLT at Department of Hepatopancreatobiliary Surgery, Ningbo Medical Center Lihuili Hospital from March to December 2021 was retrieved and the patients divided into two groups:LHG group and RHG group. Among the 13 donors,11 were male and 2 were female,aged (M(IQR))38(19) years(range: 25 to 56 years),with height of 168(5) cm(range:160 to 175 cm) and weight of 65(9) kg(range: 50 to 75 kg). The median age of the 25 recipients was 52(14) years(range:35 to 71 years),17 were male and 8 were female,15 had primary liver cancer and 10 had benign end-stage liver disease,model for end-stage liver disease score was 10(9) points(range:7 to 23 points). Of the 25 recipients,10 recipients had previously undergone hepatobiliary surgery. The follow-up period was to January 2022. Demographic,clinicopathological,surgical outcomes and postoperative complications were evaluated and compared between the two groups. Continuous quantitative data were compared using Mann-Whitney U test. Classification data were expressed as frequencies,and were compared between groups using χ² test or Fisher exact probability method. Results: Using LDLT technique,in-situ full-left/full-right liver splitting was performed and 13 viable pairs of hemiliver grafts were harvested with acquisition time of 230(53) minutes(range:125 to 352 minutes) and blood loss of 250(100) ml(range:150 to 1 000 ml). A total of 25 hemiliver grafts(13 LHG and 12 RHG) were allocated to patients listed for liver transplantation in our center by China Organ Transplant Response System. In the LHG group(13 cases),there were more females and more patients with benign end-stage liver disease than in the RHG group(12 cases)(P<0.05). The body weight and graft weight of recipients in the LHG group were lower than that in RHG group(both P<0.05). There were no significant differences in other baseline data between the two groups(all P>0.05). The graft to recipient weight ratio(GRWR) was 1.2(0.4)%(range:0.7% to 1.9%) for 25 recipients,1.1(0.5)%(range:0.7% to 1.6%)for the LHG group and 1.3(0.5)%(range:0.9% to 1.9%)for the RHG group. There was no significant difference between the two groups (P>0.05). Sharing patterns of hepatic vessels and the common bile duct are as follows:all the trunk of middle hepatic vein were allocated to the LHG group. The proportion of celiac trunk,main portal vein and common bile duct assigned to LHG and RHG was 10∶3 (P=0.009), 9∶4 (P>0.05) and 4∶9 (P=0.027),respectively. The vena cava of 12 donors in early stage retained in LHG and that of last one was shared between LHG and RHG (P<0.01). The median cold ischemia time of 25 hemiliver grafts was 240(90) minutes(range:138 to 420 minutes). For the total of 25 fSLT,the median anhepatic phase was 50(16) minutes(range:31 to 98 minutes) and the operation time was 474(138)minutes(range:294 to 680 minutes) with blood loss of 800(640) ml(range:200 to 5 000 ml). There were no significant differences in all of operation data between two groups. In the LHG group,3 patients with GRWR≤0.8% had postoperative small-for-size syndrome which improved after treatment. Postoperative Clavien-Dindo grade≥Ⅲ complications were observed in 6 cases(24.0%),4 cases(4/13) in the LHG group and 2 cases(2/12) in the RHG group,respectively. The difference was not statistically significant. Among them,5 cases improved after re-operation and intervention,1 case in LHG group died of secondary infection 2 weeks after operation,and the mortality was 4.0%. Analysis of serious postoperative complications and death has suggested that conventional caval interposition should not be used for LHG transplantation. Conclusion: Relying on accurate donor-recipient evaluation and the apply of LDLT technique,the morbidity and mortality of in-situ fSLT in adults is acceptable.
Adult ; Aged ; End Stage Liver Disease/surgery* ; Female ; Humans ; Liver/surgery* ; Liver Transplantation/methods* ; Living Donors ; Male ; Middle Aged ; Postoperative Complications ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome