ObjectiveTo optimize the water extraction process of Coptidis Rhizoma （CR） and the processing of Polygalae Radix （PR） with the water decoction of CR， and to compare chemical constituents before and after processing. MethodsWith water volume， soaking time， decocting time， and decocting times as influencing factors， and the content of berberine， epiberberine， coptisine， jatrorrhizine， and palmatine and the yield of dry extract as evaluation indexes， the orthogonal test combined with multi-index comprehensive scoring method was employed to optimize the water extraction parameters of CR. With solid-liquid ratio， stir-frying temperature， and stir-frying time as influencing factors， and the content of tenuifolin， polygalaxanthone Ⅲ， and 3，6ʹ-disinapoyl sucrose and the yield of ethanol extract as evaluation indexes， the orthogonal test combined with multi-index comprehensive scoring method was applied to optimize the processing parameters of PR with the water decoction of CR. The differential chemical constituents of PR before and after processing were analyzed by ultra-performance liquid chromatography-quadrupole-Exactive Orbitrap-mass spectrometry （UPLC-Q Exactive Orbitrap MS）. ResultsThe optimal water extraction process of CR was as follows： Decocting for 3 times， 40 min each time， with 10 times the amount of water. The optimal processing technology of PR with the water decoction of CR was a solid-liquid ratio of 1∶1.5， a stir-frying temperature of 140 ℃， and stir-frying time of 20 min. A total of 31 differential components were identified before and after processing， including 17 components of PR and 15 components of CR. After processing， 14 new components such as coptisine， berberine， and palmatine emerged， and the content of arillanin A， glomeratose A， 3，6ʹ-disinapoyl sucrose， and ferulic acid was increased. The content of other intrinsic constituents of PR， such as onjisaponin D， polygalaxanthone Ⅺ， sibiricose A3， and tenuifoliside B， was generally decreased. ConclusionThe optimized characteristic processing technology of PR with the water decoction of CR is stable and feasible. Significant differences in chemical composition were observed between raw and processed PR. Processing with the water decoction of CR can effectively reduce the gastrointestinal irritant components originally present in PR while simultaneously introducing the bioactive constituents from CR. This study provides data support for the standardization research and mechanism elucidation of the ancient characteristic processing methods of the Jinling medical school.

OBJECTIVE: To compare early graft healing between over-the-top (OTT) and anatomic single-bundle (SB) anterior cruciate ligament (ACL) reconstruction. METHODS: A clinical data of 40 patients underwent ACL reconstruction, who admitted between June 2021 and October 2022 and met the selective criteria, was retrospectively analyzed. Among them, 20 patients were treated with OTT reconstruction (OTT group) and 20 with SB reconstruction (SB group). There was no significant difference between groups ( P>0.05) in the gender, age, affected side, disease duration, degree of meniscus injury, body mass index, and preoperative International Knee Documentation Committee (IKDC) score, Lysholm score, pain visual analogue scale (VAS) score, and KT-2000 measurement. At 3, 6, and 12 months, MRI was performed to measure the signal noise quotient (SNQ) of the proximal end, middle, and distal end of the graft in the two groups, as well as at the corner of the graft with lateral femoral condyle and 1 cm around the femoral fixation point in the OTT group, to observe the degree of graft healing. Before operation and at 3, 6, and 12 months, the knee function and pain were evaluated by IKDC score, Lysholm score, and VAS score. Before operation and at 12 months after operation, the KT-2000 measurement was taken to evaluation the knee joint stability. RESULTS: All operations were successfully completed in both groups and the incisions healed by first intention. All patients were followed up 12-15 months (mean, 12.9 months), with no significant difference in the follow-up time between groups ( P>0.05). After operation, the IKDC score, VAS score, and Lysholm score improved gradually over time in both groups, with significant differences between different time points ( P<0.05). The differences between groups at 3, 6, and 12 months after operation were not significant ( P>0.05). The anterior and posterior stability of the knee joint improved significantly in both groups at 12 months after operation, and the difference in KT-2000 measurements was significant when compared with the preoperative value ( P<0.05), but the difference of pre- and post-operation between groups was not significant ( P>0.05). At 3, 6, and 12 months after operation, MRI showed that the differences in the SNQ of the proximal end and middle of the grafts between the two groups were not significant ( P>0.05), and the SNQ of distal end was significantly higher in the SB group than in the OTT group ( P<0.05). At each time point, grafts in the OTT group had the highest SNQ at the corner and the lowest at the fixation point, and the differences were significant compared to the other sites ( P<0.05). In the two groups, except for the fixation point, the SNQ of the remaining sites were highest at 6 months and lowest at 12 months ( P<0.05). In addition, there were significant differences in SNQ between the different sites of grafts ( P<0.05), and the SNQ was lowest at proximal end and highest at distal end. At last follow-up, the knee grafts in both groups were in good shape and no graft necrosis or loosening of the internal fixation was observed. CONCLUSION The knee joint function and graft healing after OTT reconstruction of ACL are similar to those of SB reconstruction, but it should be noted that the healing at the corner of the graft is slower.
Retrospective Studies ; Treatment Outcome ; Anterior Cruciate Ligament Reconstruction/rehabilitation* ; Follow-Up Studies ; Tibial Meniscus Injuries/surgery* ; Patient Positioning/methods* ; Recovery of Function ; Pain Measurement ; Knee Joint/surgery* ; Humans ; Male ; Female ; Adult ; Wound Healing

Objective To investigate the effects and molecular mechanism of Homer protein homolog 1a (Homer 1a) overexpression on nerve injury in mice with traumatic brain injury (TBI). Methods Sixty male C57BL/6 mice were randomly divided into five groups: sham group, TBI group, empty lentivirus (Lv-NC) group, Homer 1a overexpression lentivirus (Lv-Homer 1a) group and Lv-Homer 1a + 740 Y-P group, with 12 mice in each group. The lentivirus was orthotopic injected into the cerebral cortex of mice 5 d before modeling, while 740 Y-P was injected intraperitoneally 1 d before modeling. The TBI model was established using the free-fall impact method, and the modified neurological severity scores (mNSS) of the mice was assessed 72 h post-surgery. The water content of brain tissue was quantified, and the histopathological damage and neuronal loss in brain tissue were assessed using HE staining and Nissl staining respectively. The formation of autophagosomes in brain tissue was observed by transmission electron microscopy. The protein expression levels of Homer 1a, microtubule-associated protein 1 light chain 3B (LC3B), Beclin 1, phosphatidylinositol 3-kinase (PI3K), phosphorylation PI3K(p-PI3K), protein kinase B (AKT), p-AKT, mammalian target of rapamycin (mTOR), and p-mTOR in brain tissue were detected by Western blot analysis. Results Compared to the sham group, the mice in the TBI group exhibited a significant increase in mNSS and cerebral water content. Moreover, severe brain tissue pathological damage was observed, accompanied by a substantial loss of neurons and an increase in autophagosome formation. The protein expressions of Homer 1a and Beclin 1, as well as the protein ratio of LC3B-II/LC3B-I, in brain tissues were significantly elevated, while the protein ratios of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR were significantly reduced. Compared to the TBI group, the Lv-Homer 1a group exhibited reduced mNSS and brain water content. Additionally, there was an improvement in pathological brain tissue damage and neuron loss. Furthermore, there was an increase in autophagosome formation and expression of autophagy-related proteins, while the protein ratios of p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR were decreased. Compared to the Lv-Homer 1a group, the nerve injury in the Lv-Homer 1a+740 Y-P group was exacerbated, accompanied by a reduction in autophagosome formation and expression of autophagy-related proteins, while the PI3K/AKT/mTOR signaling pathway was activated. Conclusion Overexpression of Homer 1a effectively mitigates neurological damage in TBI mice, potentially through modulation of autophagy mediated by the PI3K/AKT/mTOR signaling pathway.
Animals ; TOR Serine-Threonine Kinases/genetics* ; Autophagy ; Brain Injuries, Traumatic/pathology* ; Male ; Proto-Oncogene Proteins c-akt/genetics* ; Phosphatidylinositol 3-Kinases/genetics* ; Homer Scaffolding Proteins/metabolism* ; Mice, Inbred C57BL ; Signal Transduction ; Mice

Objective:To explore the clinical application value of a combined model based on the radiomics features of magnetic resonance imaging(MRI)and MRI signs in predicting recurrence after radical resection for hepatocellular carcinoma(HCC).Methods:A retrospective analysis was conducted on the imaging data of 100 patients with radical resection for HCC who admitted to Zibo 148 Hospital from May 2016 to May 2020.All patients underwent abdominal enhanced MRI examination before surgery,and they were followed up for at least 2 years after the surgery.They were randomly divided into training group(70 cases)and verification group(30 cases)as a ratio of 7:3.According to the postoperative follow-up results,the training group existed 12 cases of recurrence and 58 cases without recurrence,and the verification group existed 5 cases of recurrence and 25 cases without recurrence.The 3D-slicer software was used to extract radiomics features of preoperative MRI images of each HCC patient.The intra-group correlation coefficient(ICC)of the extracted imaging features of the observers was calculated.The maximum related minimum redundancy(mRMR)algorithm and LASSO regression were selected to analyze the established radiomics labels after dimensionality reduction and screening.Univariate and multivariate logistic regression analysis were used to screen the independent risk factors of predicting recurrence in MRI signs,and they were used respectively to construct radiomics models with the radiomics labels of plain scan,arterial phase,portal phase and hepatobiliary phase.The receiver operating characteristic(ROC)curve was used to assess the diagnostic efficacy of each radiomics model in predicting recurrence.Results:The ICC range of two physicians in selecting radiomics features from the MRI images of all patients were between 0.903 and 0.957,which consistency was favorable(ICC≥0.9).Compared with other predictive models,the highest area under curve(AUC)values of ROC curve of the radiomics model of plain scan of training group[0.951(95%CI:0.901-1.000)]and verification group[0.968(95%CI:0.917-1.000)]were respectively 0.951 and 0.968 in predicting recurrence after radical resection for liver cancer.Conclusion:The combined model that is constructed on the basis of MRI radiomics features has favorable predictive value for the recurrence of patients after radical resection for HCC.Among of them,the radiomics model of plain scan has a certain guiding role in the clinical implementation of personalized treatment plans under the absence of enhancement,and in underdeveloped areas.

Objective:To dynamically assess liver fibrosis using magnetic resonance elastography (MRE) and explore factors associated with fibrosis reversal in patients with metabolic dysfunction-associated steatohepatitis (MASH).Methods:This study included data from patients diagnosed with MASH by liver biopsy who underwent at least two MRE examinations. Patients were divided into a fibrosis reversal group and a non-reversal group according to whether MRE values decreased by 20% during follow-up. Differences in clinical data between the groups were compared using analysis of variance, the Kruskal-Wallis test, and the chi-square test. Univariate and multivariate logistic regression analyses were used to explore independent risk factors for fibrosis reversal in MASH.Results:A total of 46 cases were included in this study (mean age 50.1±12.3 years, BMI 26.1±3.1 kg/m2). Among them, the reversal group accounted for 26.1%. The rate of decrease in MRI proton density fat fraction (PDFF) was significantly higher in the reversal group (-50.0% vs. -8.1%, P=0.001) than in the non-reversal group between the two MRE examinations. The reversal group showed a more significant change rate of decreases in fasting insulin (-37.3% vs. -3.6%, P=0.011), insulin resistance index (-38.6% vs. -6.5%, P=0.044), and ALP (-24.9% vs. 0, P=0.004). Multivariate logistic regression analysis indicated that the rate of change in MRI PDFF was an independent predictor of fibrosis reversal ( OR=0.96, 95% CI: 0.92-1.00, P=0.046). Conclusion:A decrease in MRI proton density fat fraction levels is independently associated with liver fibrosis reversal in MASH, suggesting that intervention targeting liver fat content may be an effective treatment strategy.

Radionuclide drug conjugates(RDC)represent the culmination of interdisciplinary integra-tion.By virtue of their precise targeting capability,high diagnostic sensitivity,and remarkable therapeutic effi-cacy in tumor diagnosis and treatment,RDC has emerged as promising theranostic agents with immense applica-tion potential.This article systematically reviews the progress in RDC development in China from 2009 to 2024,encompassing an overview of RDC,its structure and classification,trends in clinical research,advances in clinical trials,and national policy support.The aim is to provide valuable insights for researchers in related fields,thereby facilitating further development and application of RDC-based therapeutics.

Objective:To explore the distribution characteristics of HBsAg levels in treatment-na?ve and treatment-experienced patients with chronic hepatitis B (CHB) in China.Methods:Data were obtained from the China Registry of Hepatitis B (CR-HepB) platform from the establishment of the platform to April 11, 2024. Patients with CHB who were treatment-na?ve and treatment-experienced with nucleos(t)ide analogs (NAs) were included. Relevant clinical data were collected. The distribution of hepatitis B surface antigen (HBsAg) status, as well as the levels in populations of different age groups after different antiviral treatment durations, were retrospectively analyzed. Normally and non-normally distributed measured data were represented by Mean± SD, and M( Q1, Q3). Results:A total of 13 505 treatment-na?ve patients and 6 390 treatment-experienced patients were included in the analysis. The proportions of treatment-na?ve patients with HBsAg<100, <500, and <1 500 IU/mL were 10.51%, 28.47%, and 46.85%, and the corresponding proportions of treatment-experienced patients were 12.88%, 29.84%, and 52.07%. The proportions of treatment-na?ve patients with HBsAg levels≥1 500, ≥3 000, and≥8 000 IU/mL were 53.15%, 38.17%, and 15.62%, and the corresponding proportions of treatment-experienced patients were 47.93%, 31.77%, and 10.39%. HBsAg level showed a trend of gradual decrease with the increase of antiviral treatment time. The proportion of treatment-experienced patients with HBsAg<100 IU/mL increased from 12.73% when the treatment duration was less than three years to 26.92% when the treatment duration was≥10 years, while the proportion of patients with HBsAg levels≥3 000 IU/mL or≥8 000 IU/mL decreased from 34.66% to 23.08% and from 12.19% to 5.77%, respectively. The proportion of patients with HBsAg<100, <500, and<1 500 IU/mL increased with age, while the proportion of patients with HBsAg≥1 500, ≥3 000, and ≥8 000 IU/mL decreased sequentially.Conclusions:The CR-HepB platform provides a basis for clarifying the serum HBsAg levels in treatment-na?ve and treatment-experienced CHB patients in China. The HBsAg status indicates that with a prolonged antiviral treatment duration, there is a gradual decline trend in HBsAg level.

This study aims to inquire about the fluctuations of ubiquitin-specific protease 47 on neu-roblastoma cells(Neuro-2a,N2a)infected by rabies virus(RABV).USP47 expression levels were detected after RABV infection in N2a cells through RT-qPCR,protein immunoblotting,and virus titer determination.The levels of RABV nucleoprotein and phosphoprotein gene and protein,and RABV titers in supernatants were analyzed during overexpression and knockdown of USP47.The results showed that RABV infection increased USP47 gene level in N2a cells.When overexpression of USP47,the levels of RABV N and P were increased,and the virus titers were also improved.Mo-reover,the level of interleukin-6(IL-6)genes decreased.Knocking down USP47 expression reduced levels of RABV N and P genes and proteins,lowered the virus titer,and elevated the IL-6 gene lev-el.The results suggest that USP47 promotes RABV infection and suppresses IL-6 expression.This finding lays the foundation for further investigation into the molecular mechanisms by which USP47 regulates RABV infection.

Radionuclide drug conjugates(RDC)represent the culmination of interdisciplinary integra-tion.By virtue of their precise targeting capability,high diagnostic sensitivity,and remarkable therapeutic effi-cacy in tumor diagnosis and treatment,RDC has emerged as promising theranostic agents with immense applica-tion potential.This article systematically reviews the progress in RDC development in China from 2009 to 2024,encompassing an overview of RDC,its structure and classification,trends in clinical research,advances in clinical trials,and national policy support.The aim is to provide valuable insights for researchers in related fields,thereby facilitating further development and application of RDC-based therapeutics.