ObjectiveTo investigate the mechanism of salt processing of Psoraleae Fructus （PF） through modern analytical techniques and biotechnology， focusing on its effects related to hepatotoxicity and anti-osteoporosis activity. MethodsThe zebrafish model was utilized to evaluate the impact of PF and salt-processed Psoraleae Fructus （SPF） on the hepatotoxicity （using 134.17 ， 178.89， 268.34 mg·L^-1 as low， medium， and high dose groups of PF， 135.04， 180.06， 270.08 mg·L^-1 as low， medium， and high dose groups of SPF， respectively） and anti-osteoporotic activity （using 33.54 ， 67.08 and 134.17 mg·L^-1 as low， medium， and high dose groups of PF， 33.76， 67.52， 135.04 mg·L^-1 as low， medium， and high dose groups of SPF， respectively）， which was using alizarin red skull staining of zebrafish as an indicator of different batches of PF. The specific dosage of a batch of PF was taken as an example. Then ultra-performance liquid chromatography-quadrupole-time of flight-mass spectrometry（UPLC-Q-TOF-MS） analysis was employed to identify the chemical composition of PF before and after salt processing， and PCA， OPLS-DA， and independent sample t-test were used to elucidating the compositional changes associated with the effects of salt processing on hepatotoxicity and anti-osteoporosis activity. ResultsUnder specific conditions， PF induced notable hepatotoxicity in zebrafish while simultaneously demonstrating protective effect against prednisolone-induced osteoporosis. In comparison to PF， SPF showed alleviated hepatotoxicity while retaining significant anti-osteoporosis activity. UPLC-Q-TOF-MS analysis revealed that after salt processing， the overall chemical composition of PF showed a downward trend， with 69 components showing a decrease in content， represented by psoralen， and 13 components showing an increase， represented by 4′-O-methyl psoralen B. Further multivariate statistical analysis revealed 11 key differential components before and after salt processing of PF， including psoralen and bakuchiol. ConclusionSalt processing effectively diminishes hepatotoxicity without impairing therapeutic efficacy against osteoporosis of PF， which may be related to the compositional changes before and after salt processing of PF and provides key evidence to reveal the scientific significance of salt processing of PF.

With the continuous development of society, a large number of new chemicals are continuously emerging, which presents a challenge to current risk assessment and safety management of chemicals. Traditional toxicology research methods have certain limitations in quickly, efficiently, and accurately assessing the toxicity of many chemicals, and cannot meet the actual needs. In response to this challenge, computational toxicology that use mathematical and computer models to achieve the prediction of chemical toxicity has emerged. In the meantime, as researchers increasingly pay attention to understanding the interaction mechanisms between exogenous chemical substances and the body from the system level, and multiomics technologies develop rapidly such as genomics, transcriptomics, proteomics, and metabolomics, huge amounts of data have been generated, providing rich information resources for studying the interactions between chemical substances and biological molecules. System toxicology and network toxicology have also developed accordingly. Of these, network toxicology can integrate these multiomics data to construct biomolecular networks, and then quickly predict the key toxicological targets and pathways of chemicals at the molecular level. This paper outlined the concept and development of network toxicology, summarized the main methods and supporting tools of network toxicology research, expounded the application status of network toxicology in studying potential toxicity of exogenous chemicals such as agricultural chemicals, environmental pollutants, industrial chemicals, and foodborne chemicals, and analyzed the development prospects and limitations of network toxicology research. This paper aimed to provide a reference for the application of network toxicology in other fields.

Objective:To explore the clinical efficacy of curcumin-mediated photodynamic therapy (PDT) for the treatment of cervical intraepithelial neoplasia (CIN) combined with human papillomavirus (HPV) infection.Methods:A prospective randomized controlled study was conducted. Eighty patients with CIN combined with HPV infection in Dingzhou People's Hospital from January 2022 to January 2023 were selected and divided into the observation group and the control group using the randomized numerical table method, with 40 cases in each group. The observation group was treated with curcumin-mediated PDT, and the control group was treated with recombinant human interferon α-2b suppository for topical application. The efficacy, HPV-DNA conversion rate, high-risk human papillomavirus (HR-HPV) load, recovery status, inflammatory cytokine level, expression of Ki-67, expression of Survivin, and occurrence of adverse reactions were compared between the two groups.Results:Eighty patients aged (35±4) years old. The age, disease duration, age of first sexual experience, CIN grading, HPV typing and other general data of the two groups were compared, and the differences were not statistically significant (all P > 0.05). The total effective rate of the observation group was higher than that of the control group [95.0% (38/40) vs. 75.0% (30/40)], and the difference was statistically significant ( χ2 = 6.28, P = 0.012). The HPV-DNA conversion rates in the observation group were higher than those in the control group at 1, 3 and 6 months after treatment [1 month: 65.0% (26/40) vs. 42.5% (17/40); 3 months: 87.5% (35/40) vs. 67.5% (27/40); 6 months: 95.0% (38/40) vs. 80.0% (32/40)], and the differences were statistically significant ( χ2 values were 4.07, 4.59 and 4.11, respectively, all P < 0.05). HR-HPV loads in the observation group were lower than those in the control group at 1, 3 and 6 months after treatment (1 month: 42.4±5.8 vs. 56.7±6.7; 3 months: 31.0±4.5 vs. 40.3±3.7; 6 months: 14.5±2.4 vs. 28.8±2.4), and the differences were statistically significant ( t values were 10.24, 10.17 and 26.77, respectively, all P < 0.001). The healing time of cervical wound in the observation group was shorter than that in the control group [(30±3) d vs. (39±5) d, t = 9.37, P < 0.001]. The levels of interleukin 4, interleukin 6, interleukin 10 and relative expressions of Ki-67 and Survivin in the observation group were lower than those in the control group at 6 months after treatment (all P < 0.001). The difference in the incidence of adverse reactions between the observation and control groups was not statistically significant [12.50% (5/40) vs. 7.50% (3/40), χ2 = 0.56, P = 0.456]. Conclusions:Curcumin-mediated PDT for the treatment of patients with CIN combined with HPV infection has a high total effective rate; it can reduce the HR-HPV load and inflammatory cytokine levels, and improve the HPV-DNA conversion rate.

Objective:To analyze the clinical significance of high risk human papillomavirus (HR-HPV) positive female cervical lesion screening HR-HPVE6/E7 mRNA detection.Methods:A total of 80 HR-HPV-positive female patients with cervical lesions were retrospectively selected in Dingzhou People′s Hospital from August 2021 to August 2023. According to the pathological examination results, the patients were divided into inflammatory response group (16 cases), cervical intraepithelial neoplasia (CIN) Ⅰ group (15 cases), CINⅡ group (22 cases), CINⅢ group (17 cases) and cervical cancer group (10 cases). The viral load and positive rate of HR-HPVE6/E7 mRNA in the five groups were compared. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic efficacy of HR-HPVE6/E7 mRNA in cervical lesions.Results:The viral load of HR-HPVE6/E7 mRNA in the cervical cancer group, CINⅢ group, CINⅡ group, CINⅠ group and inflammatory response group was gradually decreased: 3 152.62(894.26, 21 986.24), 812.62(465.05, 3 945.06), 481.64(215.62, 2 451.49), 38.62(0, 612.47), 0(0, 316.28) × 10 3 copy/L, there was statistical difference among the five groups ( P<0.05). The positive rate of HR-HPVE6/E7 mRNA in cervical cancer group (10/10) was higher than that in CINⅢ group (10/17), CINⅡ group [27.27%(6/22)], CINⅠ group (2/15) and inflammatory response group (0), and there were statistical differences ( P<0.05). ROC curve analysis results showed that the area under the curve of HR-HPVE6/E7 mRNA for diagnosis of cervical lesions was 0.901(95% CI 0.837 - 0.942), sensitivity was 92.53%, specificity was 89.12%. Conclusions:Quantitative detection of HR-HPVE6/E7 mRNA viral load has high sensitivity and specificity in the diagnosis of cervical lesions.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

For middle-aged and elderly patients with conditions such as spinal fractures and degenerative spinal diseases, spinal internal fixation is a core surgical procedure for reconstructing spinal stability, heavily relying on the biomechanical stability provided by pedicle screw systems. Whereas, these patients are often complicated by osteoporosis that can significantly compromise the stability of the bone-pedicle screw interface, leading to a marked increase in pedicle screw loosening and surgical failure rates. The bone cement-augmented pedicle screw technique, which involves injecting bone cement into the vertebral body or screw trajectory to optimize the mechanical properties of the bone-pedicle screw composite, has been proven to significantly enhance fixation strength and effectively prevent screw-related failures, thereby reducing the incidence of internal fixation failure in high-risk populations undergoing spinal fusion. However, the widespread clinical application of this technique has faced challenges such as inaccurate clinical decision-making (indication and contraindication selection), non-standardized operative practices, and insufficient awareness of complication prevention, resulting in considerable variability in clinical outcomes and even severe complications. To address this, Prof. Luo Fei from First Affiliated Hospital of Army Medical University initiated the project and the Chinese Association Orthopaedic Surgeons organized relevant experts to develop the Evidence-based clinical practice guideline for bone cement-augmented pedicle screw technique ( version 2025), based on current evidence. The guidelines put forward 8 recommendations regarding the clinical value, scope of application, and operational standards of the technique, aiming to provide evidence-based medical support and technical standardization for clinical decision-making.

Objective:To explore the clinical efficacy of curcumin-mediated photodynamic therapy (PDT) for the treatment of cervical intraepithelial neoplasia (CIN) combined with human papillomavirus (HPV) infection.Methods:A prospective randomized controlled study was conducted. Eighty patients with CIN combined with HPV infection in Dingzhou People's Hospital from January 2022 to January 2023 were selected and divided into the observation group and the control group using the randomized numerical table method, with 40 cases in each group. The observation group was treated with curcumin-mediated PDT, and the control group was treated with recombinant human interferon α-2b suppository for topical application. The efficacy, HPV-DNA conversion rate, high-risk human papillomavirus (HR-HPV) load, recovery status, inflammatory cytokine level, expression of Ki-67, expression of Survivin, and occurrence of adverse reactions were compared between the two groups.Results:Eighty patients aged (35±4) years old. The age, disease duration, age of first sexual experience, CIN grading, HPV typing and other general data of the two groups were compared, and the differences were not statistically significant (all P > 0.05). The total effective rate of the observation group was higher than that of the control group [95.0% (38/40) vs. 75.0% (30/40)], and the difference was statistically significant ( χ2 = 6.28, P = 0.012). The HPV-DNA conversion rates in the observation group were higher than those in the control group at 1, 3 and 6 months after treatment [1 month: 65.0% (26/40) vs. 42.5% (17/40); 3 months: 87.5% (35/40) vs. 67.5% (27/40); 6 months: 95.0% (38/40) vs. 80.0% (32/40)], and the differences were statistically significant ( χ2 values were 4.07, 4.59 and 4.11, respectively, all P < 0.05). HR-HPV loads in the observation group were lower than those in the control group at 1, 3 and 6 months after treatment (1 month: 42.4±5.8 vs. 56.7±6.7; 3 months: 31.0±4.5 vs. 40.3±3.7; 6 months: 14.5±2.4 vs. 28.8±2.4), and the differences were statistically significant ( t values were 10.24, 10.17 and 26.77, respectively, all P < 0.001). The healing time of cervical wound in the observation group was shorter than that in the control group [(30±3) d vs. (39±5) d, t = 9.37, P < 0.001]. The levels of interleukin 4, interleukin 6, interleukin 10 and relative expressions of Ki-67 and Survivin in the observation group were lower than those in the control group at 6 months after treatment (all P < 0.001). The difference in the incidence of adverse reactions between the observation and control groups was not statistically significant [12.50% (5/40) vs. 7.50% (3/40), χ2 = 0.56, P = 0.456]. Conclusions:Curcumin-mediated PDT for the treatment of patients with CIN combined with HPV infection has a high total effective rate; it can reduce the HR-HPV load and inflammatory cytokine levels, and improve the HPV-DNA conversion rate.

Objective:To analyze the clinical significance of high risk human papillomavirus (HR-HPV) positive female cervical lesion screening HR-HPVE6/E7 mRNA detection.Methods:A total of 80 HR-HPV-positive female patients with cervical lesions were retrospectively selected in Dingzhou People′s Hospital from August 2021 to August 2023. According to the pathological examination results, the patients were divided into inflammatory response group (16 cases), cervical intraepithelial neoplasia (CIN) Ⅰ group (15 cases), CINⅡ group (22 cases), CINⅢ group (17 cases) and cervical cancer group (10 cases). The viral load and positive rate of HR-HPVE6/E7 mRNA in the five groups were compared. Receiver operating characteristic (ROC) curve was drawn to analyze the diagnostic efficacy of HR-HPVE6/E7 mRNA in cervical lesions.Results:The viral load of HR-HPVE6/E7 mRNA in the cervical cancer group, CINⅢ group, CINⅡ group, CINⅠ group and inflammatory response group was gradually decreased: 3 152.62(894.26, 21 986.24), 812.62(465.05, 3 945.06), 481.64(215.62, 2 451.49), 38.62(0, 612.47), 0(0, 316.28) × 10 3 copy/L, there was statistical difference among the five groups ( P<0.05). The positive rate of HR-HPVE6/E7 mRNA in cervical cancer group (10/10) was higher than that in CINⅢ group (10/17), CINⅡ group [27.27%(6/22)], CINⅠ group (2/15) and inflammatory response group (0), and there were statistical differences ( P<0.05). ROC curve analysis results showed that the area under the curve of HR-HPVE6/E7 mRNA for diagnosis of cervical lesions was 0.901(95% CI 0.837 - 0.942), sensitivity was 92.53%, specificity was 89.12%. Conclusions:Quantitative detection of HR-HPVE6/E7 mRNA viral load has high sensitivity and specificity in the diagnosis of cervical lesions.

OBJECTIVE To optimize the salt-processing technology for Anemarrhena asphodeloides. METHODS Taking soaking time， stir-frying temperature， and stir-frying time as factors， Box-Behnken response surface methodology was employed to optimize the salt-processing technology of A. asphodeloides using the contents of mangiferin， neomangiferin， isomangiferin， timosaponin BⅡ， timosaponin AⅢ， timosaponin BⅢ， total flavonoids， and total saponins as evaluation indicators. The entropy weight method was applied to determine the weight of each indicator and calculate the comprehensive score. Based on the 17 sets of Box-Behnken response surface methodology results， a genetic algorithm （GA）-back propagation （BP） neural network was used to further optimize the salt-processing technology， with soaking time， stir-frying temperature， and stir-frying time as input layers and the comprehensive score as the output layer. The salt-processing parameters obtained from the two methods were validated and compared to determine the optimal salt-processing technology for A. asphodeloides. RESULTS The optimal salt-processing conditions obtained via the Box-Behnken response surface methodology were as follows： soaking time of 23 min， stir-frying temperature of 160 ℃ ， and stir-frying time of 12 min， yielding a comprehensive score of 63.370 2. The GA-BP neural network optimization resulted in the following conditions： soaking time of 24 min， stir-frying temperature of 163 ℃， and stir-frying time of 12 min， with a comprehensive score of 65.163 8. The GA-BP neural network optimization outperformed the results obtained by Box-Behnken response surface methodology. CONCLUSIONS This study successfully optimized the salt-processing technology for A. asphodeloides. Specifically， the technology involves adding 15 mL of 0.1 g/mL saline solution to 50 g of the herbal slices， allowing them to moisten for 24 minutes， and then stir-frying at 163 ℃ for 12 minutes.

Objective: In the present study, molecular subtypes were determined, programmed deathligand 1 (PD-L1) and tumor-associated immune cells (TAICs) were quantitatively detected, and their effect on prognosis in uterine carcinosarcoma (UCS) was analyzed. Methods: The study included 65 UCS cases. Direct sequencing of POLE exonuclease domain and immunohistochemistry of mismatch repair (MMR) deficiency proteins and p53 were used to stratify molecular subtypes. QuPath was used for quantitative immunohistochemical detection of PD-L1 and TAICs. The chi square test was used to determine the association between molecular subtypes and expression of PD-L1 and TAICs. The Kaplan–Meier method and Cox proportional hazards regression were used for plotting and survival analysis. Results: In 65 UCS cases, 1 case (1.5%) was POLE ultramutated (POLEmut) subtype, 11 cases (16.9%) were deficient MMR (dMMR) subtype, 32 cases (49.3%) were p53 mutant (p53mut) subtype, and 21 cases (32.3%) were nonspecific molecular profile (NSMP) subtype. The positive density of PD-L1 in tumor (p=0.022), CD8 in stroma (p=0.036), and CD163 in stroma (p=0.025) were significantly associated with molecular subtypes. The patients with POLEmut and dMMR subtypes had a relatively better prognosis trend than patients with NSMP and p53mut subtypes. The patients with high positive density of PD-L1 in tumor had significantly better prognosis; however, high positive density of CD163 in stroma showed significantly worse prognosis. Conclusion UCS could be classified into four molecular subtypes associated with prognosis.PD-L1 and M2 macrophages could effectively predict the prognosis of patients with UCS.