BACKGROUND:Cervical rotation-traction manipulation is effective and safe in the treatment of cervical spondylotic radiculopathy,and has been widely used in clinical work.However,its effects on the biomechanics of cervical vertebra and intervertebral disc and the area of intervertebral foramen have not been systematically clarified. OBJECTIVE:Based on the finite element analysis technique,a relevant research and analysis were carried out to provide digital evidence for the mechanism of effect of cervical rotation-traction manipulation in the treatment of cervical spondylotic radiculopathy. METHODS:The CT image data of a volunteer with no neck diseases were selected as the finite element model material at its left-handed physiological limit position.The initial construction of the finite element model was completed by Mimics 19.0 software,Geomagic Studio 2013 software,Hypermash 14.0 software,and ANSYS Workbench 2020 R2 software,respectively.Based on the literature,the grid division of cervical structure and the assignment of elastic modulus and elastic coefficient were completed.Based on the previous work of the team,the mechanical effects of cervical rotation-traction manipulation were simulated on the model.Effects of cervical rotation-traction manipulation on the mechanical parameters of each vertebral body and intervertebral disc in C3-T1 segment and on the cervical lateral foramen area were analyzed. RESULTS AND CONCLUSION:(1)During cervical rotation-traction manipulation,the stress of bone structure was significantly higher than that of soft tissue such as intervertebral disc.(2)When operating the technique,the stress at the top of each cervical vertebra was higher,the stress at the bottom was lower,and the stress at the facet joint and transverse process was lower.The stress at the top of the intervertebral disc was lower,the stress at the bottom was higher,but the highest point of the intervertebral disc stress was outside the top.(3)In addition,after loading the lifting force,the projected area of the C6/C7 intervertebral foramen increased significantly compared with that before loading.(4)It is indicated that the cervical rotation-traction manipulation has the mechanical characteristics of changing the stress structure of the cervical spine itself,and can expand the C6/7 intervertebral cervical foramen area on the opposite side of the patient's cervical rotation,so as to achieve the purpose of treating cervical spondylotic radiculopathy.

OBJECTIVE To establish the HPLC fingerprint of Xintong granules and the quantitative analysis of multi- components by single-marker method （QAMS） to determine the contents of 7 components， so as to provide a scientific basis for their quality control. METHODS HPLC method was used to establish the fingerprints for 10 batches of Xintong granules （No. S1- S10）， and similarity evaluation， cluster analysis （CA） and partial least squares-discriminant analysis （PLS-DA） were performed. At the same time， the contents of seven components， including puerarin， daidzin， calycosin-7-O- β -D-glucoside， stilbene glycoside， naringin， icariin and tanshinone ⅡA， were determined by QAMS method， and were compared with the results of external standard method. RESULTS A total of 18 common peaks were marked and 7 peaks were identified in the HPLC fingerprints for 10 batches of Xintong granules， namely puerarin （peak 4）， daidzin （peak 7）， calycosin-7-O-β-D-glucoside （peak 9）， stilbene glycoside （peak 10）， naringin （peak 12）， icariin （peak 17）， and tanshinone ⅡA （peak 18）； the similarities among them were more than 0.990， and CA and PLS-DA results showed that S4-S5，S8-S10，S1-S3 and S6-S7 were clustered into three categories， respectively. Using naringin as the internal standard， the contents of puerarin， daidzin， calycosin-7-O-β-D-glucoside， stilbene glycoside， icariin and tanshinone ⅡA were determined to be 7.868 1-10.181 2， 1.709 2-2.374 1， 0.285 2-0.326 3， 1.024 1- 1.523 9， 0.140 2-0.290 4， and 0.077 1-0.219 4 mg/g， respectively， by the QAMS. These results showed no significant differences compared to those obtained by the external standard method. CONCLUSIONS Established HPLC fingerprint and QAMS method are convenient， stable and accurate， which can provide a basis for the quality evaluation of Xintong granules.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.

Objective To investigate the prevalence of Anisakis infections in coastal marine fishes and awareness of anisakiasis control knowledge among local residents in Yantai City, Shandong Province in 2021, so as to provide insights into formulation of anisakiasis control interventions. Methods Marine fishes were purchased from Shunxin Port, Yantai City, Shandong Province in November 2021, and the presence of Anisakis was detected in different species of fishes and different fish sites. The correlations between body length and weight of marine fish and intensity of Anisakis infections were examined using Spearman’s rank correlation analysis, and the dietary habits and anisakiasis control knowledge were investigated using questionnaire surveys among local residents. Results A total of 201 marine fishes belonging to 20 species were dissected, and Anisakis was detected in 77 marine fishes (38.31%) belonging to 11 species (55.00%), with a mean infection intensity of 45.04 parasites per fish (3 468/77). Spearman’s rank correlation analysis revealed that the body length (r_s = 0.74, P < 0.05) and weight (r_s = 0.79, P < 0.01) of the monkfish correlated positively with the intensity of Anisakis infections, and the body length (r_s = 0.68, P < 0.05) of the flatfish correlated positively with the intensity of Anisakis infections, while no correlations were examined between the body length or weight of other marine fishes and the intensity of Anisakis infections. Of all respondents, 53.38% men and 56.67% women did not know anisakiasis control knowledge at all, and there was a significant difference in the proportion of respondents using separate chopping boards for raw and cooked food from different villages (χ² = 17.89, P < 0.01), while there was an age-specific proportion of respondents with habitats of eating raw or semi-raw seafood (χ² = 28.27, P < 0.01). Conclusions The prevalence and intensity of Anisakis infections were high in coastal marine fishes in Yantai City in 2021, and the awareness of anisakiasis control knowledge was low among local residents. Intensified health education pertaining to anisakiasis control knowledge is recommended to reduce the risk of Anisakis infections.

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (2⁴) Taguchi experiment. Using Minitab software to design a DOE experiment with 2⁴ partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.

This paper summarized Professor ZHOU Zhongying's experience in differentiating and treating hepatitis and liver cirrhosis from deficiency and excess. It is considered that the pathogenesis of hepatitis and liver cirrhosis belongs to deficiency in root and excess in branch， with depletion of liver， spleen and kidney as the root， and constraint and bind of damp-heat and stasis toxin as the branch. Moreover， mutual cause and promotion between deficiency and excess leads to the disease. For general principle of treatment， it is recommended to clear and transform pathogenic excess， supplement deficiency and rectify the healthy qi. In the early stage of hepatitis and cirrhosis， excess pathogen hyperactivity is the main manifestation， which can be treated by clearing and transforming damp-heat and stasis toxin， supplemented by regulating spleen and stomach， with modified Yinchenhao Decoction （茵陈蒿汤） and Biejiajian Pill （鳖甲煎丸）. In the middle and late stages， cases with deficiency-excess complex were more common， which should be treated by clearing damp-heat and stasis toxin， regulating and supplementing liver-spleen-kidney， using medicinals with the function of clearing heat and dispelling damp， dissolving stasis and resolving toxins to treat the branch. Moreover， Liujunzi Decoction （六君子汤）， Yiguan Decoction （一贯煎）plus Erzhi Pill （二至丸） and Buzhong Yiqi Decoction （补中益气汤） modifications are suggested respectively in correspondence to the different kinds of root deficiency including irregular liver and spleen， liver and kidney yin deficiency， and liver-spleen-kidney deficiency.

Background Self-perceived burden,anxiety and depression are among the most important factors affecting quality of life.At present,there is a lack of understanding on the research status and influencing factors of self-perceived burden in liver transplant recipients.Previous studies have shown that self-perceived burden,anxiety,depression and quality of life are correlated in pairs,but the effecting path among the three are not yet clear.Objective To explore the correlation of self-perceived burden and anxiety/depression with quality of life in liver transplant recipients,so as to provide guidance for psychological nursing intervention in clinical patients.Methods A total of 200 patients liver transplant recipients were enrolled from the liver transplantation inpatient and outpatient clinics of Jiangsu Province Hospital and Qinhuai Medical Area,General Hosptial of Eastern Theater Command of People's Liberation Army of China from March 2022 to February 2023.Patients were evaluated using Self-perceived Burden Scale(SPBS),Hospital Anxiety and Depression Scale(HADS)and the Chinese version of Post Liver Transplant Quality of Life Questionnaire(pLTQ).Spearman correlation analysis was used to examine the correlation among the scales.A structural equation model using Mplus 8.3 was utilized to testify the relationship among self-perceived burden,anxiety/depression and quality of life in liver transplant recipients.Bootstrap method was used to test the effecting pathway.Results There were statistically significant differences in SPBS scores of liver transplant recipients with different levels of education and fannual family income(H=9.656,18.796,P<0.05).There were statistically significant differences in HADS scores of liver transplant recipients with different numbers of somatic symptoms(H=9.859,P<0.05).There were statistically significant differences in the Chinese version of pLTQ scores of liver transplant recipients with different levels of education,postoperative survival time and numbers of somatic symptoms(H=6.892,8.023,16.099,P<0.05).The total and each dimension scores in SPBS of liver transplant recipients were positively correlated with the total score and anxiety/depression dimension scores in HADS(r=0.464～0.586,0.460～0.593,0.286～0.408,0.464～0.583,P<0.01)and negatively correlated with the total score and each dimension scores in the Chinese version of pLTQ(r=-0.572～-0.416,-0.599～-0.441,-0.365～-0.213,-0.559～-0.428,P<0.01).Structural equation model denoted that self-perceived burden negatively affected quality of life(β=-0.186,P<0.01).Anxiety/depression also negatively affected quality of life(β=-0.679,P<0.01).The self-perceived burden indirectly affected the quality of life of liver transplant recipients through anxiety and depression,with an effect value of-0.429,accounting for 69.76％of the total effect.Conclusion The quality of life in liver transplant recipients may be related to their self-perceived burden and anxiety/depression.Self-perceived burden may affect the quality of life of liver transplant patients through anxiety and depression.

Objective:To investigate the characteristics of early motor development in small for gestational age (SGA) infants at high risk of brain injury.Methods:This study retrospectively enrolled a total of 81 SGA infants and appropriate for gestational age (AGA) infants who were at high risk of brain injury and attended outpatient follow-up visits in Xi'an Children's Hospital from February to October 2022. Seventeen SGA infants (SGA group) and 24 AGA infants (AGA group) were assessed for motor development using the Test of Infant Motor Performance (TIMP) at 2-5 weeks of corrected age (CA) and 20 SGA infants (SGA group) and 20 AGA infants (AGA group) were assessed at 14-17 weeks of CA. Independent samples t-test, rank-sum test, and Chi-square test were used to compare the demographic characteristics, high-risk factors of brain injury, and TIMP scores between the two groups. Results:At 2-5 weeks and 14-17 weeks of CA, the birth weights of SGA group were both less than those of AGA group [(1 817.1±440.3) vs. (2 630.0±560.9) g, t=－4.98; (1 752.0±434.4) vs. (2 226.3±699.8) g, t=－2.58; both P<0.05], but there were no significant differences in gestational age at birth or high-risk factors of brain injury between the two groups (all P>0.05). (1) At 2-5 weeks of CA: SGA group had lower total TIMP score [(71.6±13.7) vs. (80.5±11.5) scores, t=－2.26, P=0.029], elicited item score [61.0 scores (41.0-85.0 scores) vs. 69.1 scores (49.0-96.0 scores), Z=－2.15, P=0.037], sitting position score [8.8 scores (3.0-19.0 scores) vs. 11.2 scores (5.0-22.0 scores), Z=－2.07, P=0.038], and prone position score [(9.8±3.1) vs. (12.3±3.1) scores, t=－2.19, P=0.034] when compared with AGA group. (2) At 14-17 weeks of CA: The standing position score of the SGA group was lower than that of the AGA group [6.5 scores (4.0-11.0 scores) vs. 7.7 scores (2.0-11.0 scores), Z=－2.05, P=0.040], but no statistical difference was observed in the total TIMP score or the scores of sitting, supine, prone, turning, and lateral positions between the two groups (all P>0.05). Conclusion:Early motor performance of SGA infants is inferior to AGA infants before five months of age, which is embodied in the poor head control at 2-5 weeks of CA that further affects the stability of standing posture in them at 14-17 weeks of CA.

Objective:To construct and analyze the visual nomogram predictive model for the prognosis of elderly advanced lung adenocarcinoma patients after surgery based on the Surveillance, Epidemiology, and End Results (SEER) database.Methods:SEER*Stat8.4.0.1 software was used to screen out the data from 17 register in SEER database between 2000 and 2019, and finally 4 453 lung adenocarcinoma patients aged ≥ 65 years who underwent surgical treatment and were diagnosed as stage Ⅲ and Ⅳ according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging criteria were enrolled. The data were randomly divided into the training set (3 117 cases) and the validation set (1 336 cases) in a 7:3 ratio; the epidemilogical data and clinicopathological characteristics of the two groups were compared. LASSO regression was used for data dimensionality reduction to select the best predictors from the prognostic factors of patients. Cox proportional risk model was used to perform univariate and multivariate analyses of the screened variables, and based on R software rms package and the prognostic independent risk factors, the nomogram was constructed to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) rates of the patients. The validation set was validated by using Bootstrap method with 1 000 equal repeated samples with playback, and the accuracy of the nomogram model was verified by using the C-index, receiving operating characteristic (ROC) curves and calibration curves.Results:There were no statistically significant differences in age, gender, race, tumor location, Grade grading, surgery methods, the number of lymph node dissection, radiotherapy, tumor diameter, tumor metastasis, marriage, living condition, TNM staging, radiochemotherapy of training set and validation set (all P > 0.05). In training set, 18 variables were included into LASSO regression analysis and were performed with dimensionality reduction; ultimately, 11 optimal predictive variables were selected, including age ≥ 85 years ( HR = 2.34, 95% CI: 1.803-3.037, P < 0.01), male ( HR = 1.326, 95% CI: 1.228-1.432, P < 0.01), Grade grading Ⅲ-Ⅳ ( HR = 1.333, 95% CI: 0.844-2.105, P < 0.01), undissected lymph nodes ( HR = 2.261, 95% CI: 2.023-2.527, P < 0.01), tumor diameter ≥3.7 cm ( HR = 1.445, 95% CI: 1.333-1.566, P < 0.01), bone metastasis ( HR = 1.535, 95% CI: 1.294-1.819, P < 0.01), brain metastasis ( HR = 1.308, 95% CI: 1.117-1.532, P < 0.01), lung metastasis ( HR = 1.229, 95% CI: 1.056-1.431, P = 0.01), living in rural areas ( HR = 1.215, 95% CI: 1.084-1.363, P < 0.01), TNM staging Ⅳ ( HR = 1.155, 95% CI: 1.044-1.278, P = 0.01), postoperative radiotherapy ( HR = 1.148, 95% CI: 1.054-1.250, P < 0.01); lung adenocarcinoma patients with the above 11 factors had worse prognosis. Based on the variables, the nomogram predictive model was constructed to predict 1-, 3-, and 5-year CSS rates of elderly advanced lung adenocarcinoma patients. Bootstrap method was used for repeated sampling for 1 000 times to verify the modeling effect of nomogram. In the model group, C-index was 0.654 (95% CI: 0.641-0.668), 0.666 (95% CI: 0.646-0.685), respectively in the training set and the validation set. The nomogram was drawn to predict ROC curves of 1-, 3-, and 5-year CSS rates for elderly advanced lung adenocarcinoma patients after operation in the training set and validation set; the area under the curve (AUC) of 1-year, 3-year, and 5-year CSS rates was 0.730 (95% CI: 0.708-0.754) and 0.689 (95% CI: 0.672-0.710), 0.687 (95% CI: 0.668-0.711) and 0.731 (95% CI: 0.697-0.765), 0.712 (95% CI:0.684-0.740) and 0.714 (95% CI: 0.683-0.745), respectively in the training and validation sets. The calibration curve showed a high consistency between the predicted probability of the model and the actual probability. Conclusions:The nomogram model constructed by optimal predictive variables for predicting the prognosis of elderly advanced lung adenocarcinoma patients after surgery may be a convenient tool for survival prediction of these patients.