ObjectiveTo establish the quality standards for Sennae Folium（Cassia angustifolia） dispensing granules based on standard decoctions. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established for 15 batches of Sennae Folium（C. angustifolia） standard decoctions and 10 of Sennae Folium（C. angustifolia） dispensing granules from different manufacturers， and the similarity evaluation， hierarchical cluster analysis（HCA） and principal component analysis（PCA） were performed. Linear calibration with two reference substances（LCTRS） and quantitative analysis of multi-components by single-marker（QAMS） were established for the common peaks in the specific chromatograms to determine the contents of main components in the decoction pieces， standard decoctions and dispensing granules， and to calculate their transfer rates from decoction pieces to standard decoctions and dispensing granules. ResultsThe similarities of specific chromatograms of 15 batches of Sennae Folium（C. angustifolia） standard decoctions and 10 batches of Sennae Folium（C. angustifolia） dispensing granules were all greater than 0.95， and a total of 8 characteristic peaks were calibrated， and five of them were identified， including kaempferol-3，7-O-diglucoside， apigenin-6，8-di-C-glucoside， quercetin-3-O-gentianoside， sennoside B and sennoside A. HCA and PCA results showed that there were certain differences in the composition of different batches of standard decoctions， but no clustering was observed in the production area. As the standard decoctions， the extract rate of 15 batches of samples was 26.54%-45.38%， the contents of kaempferol-3，7-O-diglucoside， apigenin-6，8-di-C-glucoside， quercetin-3-O-gentianoside， sennoside B and sennoside A were 12.16-19.26， 2.57-4.94， 3.27-5.11， 6.75-11.39， 4.69-7.79 mg·g^-1， and their transfer rates from decoction pieces to standard decoctions were 45.41%-79.02%， 29.12%-55.07%， 40.52%-67.90%， 24.72%-49.12%， 27.54%-49.34%， respectively. The extract rates of Sennae Folium（C. angustifolia） dispensing granules（C8-C10） were 38.10%-39.50%， the transfer rates of the above five components from decoction pieces to dispensing granules were 72.85%-73.58%， 53.43%-53.94%， 40.19%-40.74%， 24.62%-25.00%， 28.65%-29.11%， respectively， which were generally consistent with the transfer rates from decoction pieces to standard decoctions. ConclusionCompared with the relative retention time method， LCTRS has higher prediction accuracy and is more suitable for chromatographic columns. The established quality control standard of Sennae Folium（C. angustifolia） dispensing granules based on standard decoction is reasonable and reliable， and all indicators of samples from different manufacturers are within the range specified based on the standard decoction， which can provide reference for the quality control and process research of this dispensing granules.

ObjectiveTo establish the specific chromatogram and quantitative analysis of multi-components by single-marker（QAMS） based on linear calibration using two reference substances（LCTRS）， explore the consistency between Hedyotis Herba dispensing granules and standard decoction， and evaluate the quality of the dispensing granules. MethodsHigh performance liquid chromatography（HPLC） specific chromatogram was established based on 15 batches of Hedyotis Herba standard decoction and 10 batches of the dispensing granules， and LCTRS was used to locate chromatographic peaks. The actual retention times of 7 characteristic peaks in the specific chromatogram was measured on 24 different types of C₁₈ columns， taking deacetyl asperulosidic acid and asperulosidic acid as the dual standard compounds， the retention times of the other 5 characteristic peaks were predicted and validated. Based on this， QAMS was developed to determine the contents of four components（deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester， asperulosidic acid， and p-coumaric acid）. Then， the relative correction factors of deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester and p-coumaric acid were calculated using the reference peak of asperulosidic acid in the dual standard compounds， and each component was quantified accordingly. Finally， the consistency between the dispensing granules and standard decoction was assessed by taking extract rate of the standard decoction， consistency of the specific chromatograms， contents and transfer rates of the indicator components as indexes， and the quality of the dispensing granules was evaluated. ResultsThere were 7 common peaks in the characteristic chromatogram of samples of Hedyotis Herba standard decoction and the dispensing granules， and four of them were identified by reference standards， namely deacetyl asperulosidic acid（peak 1）， deacetyl asperulosidic acid methyl ester（peak 3）， asperulosidic acid（peak 6） and p-coumaric acid（peak 7）. The similarity between the dispensing granules and the standard decoction was >0.9. The absolute deviation in the predicted retention time for each component by LCTRS was lower than that of the relative retention time method. The extract rate of the 15 batches of Hedyotis Herba standard decoction ranged from 7.89% to 14.60%， the contents of deacetyl asperulosidic acid， deacetyl asperulosidic acid methyl ester， asperulosidic acid and p-coumaric acid were 6.62-19.70， 3.83-17.99， 1.57-6.69， 1.62-4.52 mg·g^-1， and the transfer rates of these components from decoction pieces to the standard decoction were 22.89%-39.60%， 34.03%-62.24%， 24.25%-43.70%， and 40.58%-73.71%， respectively. The extract rate， index component contents and transfer rates from decoction pieces to the three batches of Hedyotis Herba dispensing granules（P1-P3）， produced by manufacturer A， were similar to those of the standard decoction prepared from the same batch of decoction pieces， and all fell within the specified range. The contents of the 4 indicator components in 7 batches of the dispensing granules（P4-P10） from manufacturers B-E were all within the range of the content converted from the standard decoction based on the quantity of the dispensing granules. ConclusionThe established specific chromatogram and QAMS based on LCTRS are reasonable and reliable. Based on the evaluation indicators of standard decoction yield， consistency of specific chromatograms， contents and transfer rates of the four index components， the 10 batches of Hedyotis Herba dispensing granules from various manufacturers have exhibited good consistency with the standard decoction， indicating that the current production process is relatively reasonable.

ObjectiveTo establish the specific chromatogram of Chuanxiong Rhizoma dispensing granules（CRdg）， and to evaluate its quality by chemometrics and two reference substances for determination of multiple components（TRSDMC）. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established using 13 batches of CRdg from 7 manufacturers， and preliminary quality evaluation was performed by similarity evaluation and chemometrics analysis. Eight characteristic peaks in the specific chromatogram of CRdg were measured on 22 different types of C₁₈ columns， and the actual retention times were recorded. Taking chlorogenic acid（peak 1） and senkyunolide A（peak 8） as double standard compounds， the retention times of the eight characteristic peaks were predicted by linear calibration using two reference substances（LCTRS）， and the method was validated on three other columns of different brands. Taking chlorogenic acid as reference peak， the relative correction factor method（RCFM） was used to quantify cryptochlorogenic acid， caffeic acid， ferulic acid， senkyunolide I and senkyunolide A， and the results were compared with the external standard method（ESM）. ResultsThe similarities of specific chromatograms of 13 batches of CRdg were all >0.90， and a total of 8 characteristic peaks were calibrated， and six of them were identified， including chlorogenic acid（peak 1）， cryptochlorogenic acid（peak 2）， caffeic acid（peak 3）， ferulic acid（peak 5）， senkyunolide I（peak 6） and senkyunolide A（peak 8）. Through chemometric analysis， it was found that ferulic acid， chlorogenic acid， senkyunolide I and cryptochlorogenic acid were the main components causing quality difference in CRdg， and the accuracy of LCTRS in predicting the retention time of 8 characteristic peaks was superior to that of the relative retention time method（RRT）. Further comparison of the results obtained from RCFM and ESM showed that there was no statistically significant difference between the two methods. ConclusionA quality evaluation method for CRdg based on HPLC specific chromatogram and TRSDMC is established， its qualitative accuracy is better than that of RRT， the quantitative accuracy is similar to that of ESM， and 4 quality-differentiated components among different manufacturers are found. This method is stable and reliable， and has reference value for the quality evaluation of other dispensing granules.

ObjectiveTo establish the specific chromatogram of Chuanxiong Rhizoma dispensing granules（CRdg）， and to evaluate its quality by chemometrics and two reference substances for determination of multiple components（TRSDMC）. MethodsHigh performance liquid chromatography（HPLC） specific chromatograms were established using 13 batches of CRdg from 7 manufacturers， and preliminary quality evaluation was performed by similarity evaluation and chemometrics analysis. Eight characteristic peaks in the specific chromatogram of CRdg were measured on 22 different types of C₁₈ columns， and the actual retention times were recorded. Taking chlorogenic acid（peak 1） and senkyunolide A（peak 8） as double standard compounds， the retention times of the eight characteristic peaks were predicted by linear calibration using two reference substances（LCTRS）， and the method was validated on three other columns of different brands. Taking chlorogenic acid as reference peak， the relative correction factor method（RCFM） was used to quantify cryptochlorogenic acid， caffeic acid， ferulic acid， senkyunolide I and senkyunolide A， and the results were compared with the external standard method（ESM）. ResultsThe similarities of specific chromatograms of 13 batches of CRdg were all >0.90， and a total of 8 characteristic peaks were calibrated， and six of them were identified， including chlorogenic acid（peak 1）， cryptochlorogenic acid（peak 2）， caffeic acid（peak 3）， ferulic acid（peak 5）， senkyunolide I（peak 6） and senkyunolide A（peak 8）. Through chemometric analysis， it was found that ferulic acid， chlorogenic acid， senkyunolide I and cryptochlorogenic acid were the main components causing quality difference in CRdg， and the accuracy of LCTRS in predicting the retention time of 8 characteristic peaks was superior to that of the relative retention time method（RRT）. Further comparison of the results obtained from RCFM and ESM showed that there was no statistically significant difference between the two methods. ConclusionA quality evaluation method for CRdg based on HPLC specific chromatogram and TRSDMC is established， its qualitative accuracy is better than that of RRT， the quantitative accuracy is similar to that of ESM， and 4 quality-differentiated components among different manufacturers are found. This method is stable and reliable， and has reference value for the quality evaluation of other dispensing granules.

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

During the hyperacute phase of intracerebral hemorrhage (ICH), the mass effect and blood components mechanically lead to brain damage and neurotoxicity. Our findings revealed that the mass effect and transferrin precipitate neuronal oxidative stress and iron uptake, culminating in ferroptosis in neurons. M6A (N6-methyladenosine) modification, the most prevalent mRNA modification, plays a critical role in various cell death pathways. The Fto (fat mass and obesity-associated protein) demethylase has been implicated in numerous signaling pathways of neurological diseases by modulating m6A mRNA levels. Regulation of Fto protein levels in neurons effectively mitigated mass effect-induced neuronal ferroptosis. Applying nanopore direct RNA sequencing, we identified voltage-dependent anion channel 3 (Vdac3) as a potential target associated with ferroptosis. Fto influenced neuronal ferroptosis by regulating the m6A methylation of Vdac3 mRNA. These findings elucidate the intricate interplay between Fto, Vdac3, m6A methylation, and ferroptosis in neurons during the hyperacute phase post-ICH and suggest novel therapeutic strategies for ICH.
Ferroptosis/physiology* ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics* ; Animals ; Neurons/metabolism* ; Transferrin/pharmacology* ; Mice ; Methylation ; Mice, Inbred C57BL ; Adenosine/metabolism* ; RNA, Messenger/metabolism* ; Male ; Oxidative Stress/physiology*

Objective:To investigate the incidence of radiation pneumonitis (RP) induced by 125I seed implantation for the treatment of malignant lung tumors and analyze related dosimetric parameters. Methods:A retrospective analysis was conducted on 31 cases of malignant lung tumors treated with 125I seed implantation from January 2017 to December 2022 at Hebei Provincial Tumor Radioactive Seeds Implantation Diagnosis and Treatment Center. These cases consisted of eight patients with squamous cell carcinoma, 10 patients with adenocarcinoma, and 13 patients with metastatic cancer in other sites. At 1-6 months after treatment, these patients received postoperative chest CT scans, with the efficacy evaluated based on the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), including the objective response rate (ORR) and the disease control rate (DCR). The efficacy of RP was evaluated using the Radiation Therapy Oncology Group (RTOG) criteria. Postoperative dosimetric parameters, including D90 (minimum peripheral dose received by 90% of the target volume), V8 (percentage of lung volume receiving 8 Gy), V32 (percentage of lung volume receiving 32 Gy), and Dmean (mean radiation dose) of the affected lung, were statistically analyzed. The relationships of the RP occurrence with postoperative D90, V8, V32, and Dmean were analyzed by comparison with relevant external radiotherapy data, to identify the parameters that are correlated closely with RP occurrence. Results:All the patients underwent successful surgeries. The postoperative efficacy evaluation after six months showed complete response (CR) in 11 cases, partial response (PR) in 11 cases, stable disease (SD) in eight cases, and progressive disease (PD) in one case, with an overall response rate (ORR) of 71.0%, and a disease control rate (DCR) of 96.8%. Three patients suffered RP, with an incidence rate of 9.7%. Postoperative V8, V32, and Dmean could not serve as predictive indicators for RP. Follow-up observation revealed that three RP cases (3/5) exhibited postoperative D90 exceeding 170 Gy and no RP cases (0/26) showed postoperative D90 below 170 Gy. Conclusions:In the treatment of malignant lung tumors with 125I seed implantation, there is a certain correlation between RP and postoperative D90, while there is no correlation between it and V8, V32, and Dmean.

Animal experiment courses are important for developing students'practical skills in medical and life science education.They help to cultivate students'experimental skills,scientific reasoning,and innovative thinking ability.However,the traditional teaching method used in animal experiment courses tend to focus on a single topic and have minimal student participation.Courses should aim to promote students'active learning and innovative thinking abilities,and this paper discusses the ways teaching in animal experiment courses can be reformed.First,the paper introduces the background and significance of teaching in animal experiment courses and emphasizes the importance of cultivating the students'abilities.Second,it puts forward the principles of improved animal experiment course teaching,including designing student-centered lessons,providing opportunities for problem solving and practical exploration,and promoting interdisciplinary integration.At the same time,we integrate an ethical review of the welfare of experimental animals in China.Then,from the aspects of course design,teaching method,and evaluation method,this paper expounds several concrete measures of teaching reform in animal experiment courses in detail.When designing a course,attention should be paid to the selection of challenging and exploratory experimental projects,and students'interests and professional needs should be fully considered.Using improved teaching method,students should be encouraged to actively participate in explorative and cooperative classes,be guided through problem solving tasks,and encouraged to cultivate innovative thinking.Diversified evaluation method,such as experimental reports,group discussions,and project presentations,should be used to comprehensively evaluate students'practical and innovative thinking abilities.Finally,with practical verification and effect evaluation,the experiences and outcomes from a reform of animal experiment course teaching are summarized,and suggestions for further improvements are put forward.

Objective:To investigate the application value of porcine small intestinal sub-mucosa (SIS) acellular matrix mesh in laparoscopic inguinal hernia repair (LIHR).Methods:The prospective multicenter randomized controlled single-blind non-inferiority-type study was conducted. The clinical data of 216 patients who underwent LIHR in 4 medical centers, including Beijing Chaoyang Hospital of Capital Medical University et al, from April 2021 to August 2022 were selected. Patients were divided into two groups using a central randomization system. Patients in the experimental group were implanted domestic SIS mesh, and patients in the control group were implanted imported mesh of similar material origin. The baseline characteristics of enrolled patients were evaluated using the full analysis set, and the effectiveness indicators were evaluated using the protocol set. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the ttest. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Wilcoxon rank sum test. Count data were expressed as absolute numbers and/or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. If the lower limit of 95% confidence interval( CI) of the difference in effective rates between the experimental group and the control group was greater than the non-inferiority cut-off value of ?10%, the experimental group was considered non-inferior to the control group. Results:(1) Situations of the enrolled patients. A total of 216 patients were selected for eligibility, with 46 patients dropping out due to violation of the trial protocol, and the remaining 170 patients were included in the full analysis set. Nine patients were dislodged due to loss to follow-up, and 161 patients completed follow-up. One case in the experimental group was excluded due to violating the inclusion and exclusion criteria, while the remaining 160 patients were included in the protocol set (80 cases in the experimental group and 80 cases in the control group). There was no significant difference in the gender, age, body mass index (BMI), surgical method, Gilbert type of hernia, volume of intraoperative blood loss, operation time of patients between the experimental group and the control group ( P>0.05), confounding bias ensured comparability. (2) Study endpoints. ① Primary study endpoint. During the postoperative 6 month of follow-up, none of patient in the experimental group or the control group had hernia recurrence, with the recurrence rate as 0. Results of non-inferiority test showed that the difference of hernia recurrence between the two groups was 0 (95% CI as ?4.58% to 4.58%), with the lower limit of ?4.58% greater than the non-inferiority cut-off value of ?10%, which fulfilled the non-inferiority hypothesis. ② Secondary study endpoints. Cases with plasmapheresis during the follow-up were 18 in the experimental group and 29 in the control group, respectively, showing no significant difference between the two groups ( χ2=3.65, P>0.05). There were 4 cases with postoperative pain and 1 case with postoperative malaise in the experimental group, and there were 8 cases with postoperative pain and 0 case with postoperative malaise in the control group, showing no signifi-cant difference in the above indicators between the two groups ( P>0.05). None of patient in the experimental group or the control group had incision infection, enterocutaneous fistula, intestinal obstruction, intestinal canal injury, allergy and rejection, testicular inflammation and/or atrophy, or any other complication. Conclusion:Compared with imported mesh of similar material origin, domestic porcine SIS mesh is safe and effective in LIHR.

Objective:To investigate the clinical efficacy and prognostic factors of 125I seeds implantation in the treatment of patients with advanced lung cancer after radiotherapy and chemotherapy. Methods:From January 2017 to December 2019, 44 patients (39 males, 5 females, age 41-84 years) with advanced lung cancer after radiotherapy and chemotherapy who received 125I seeds implantation in Hebei General Hospital were retrospectively analyzed. All patients were followed up for ≥12 months, and the clinical efficacies were observed. χ2 test was used to analyze the difference of effective rates between groups. The cut-off value of postoperative dose delivered to 90% gross tumor volume ( D90) was obtained by ROC curve analysis. Kaplan-Meier method was used to calculate the survival rate and log-rank test was used for univariate analysis. Cox proportional hazards model was used for multivariate analysis to find the influencing factors for clinical efficacy. Results:The total effective rate was 72.73%(32/44) after 6 months treatment. The cut-off value of D90 was 120 Gy with the AUC of 0.771. The short-term effective rate of D90≥120 Gy group was better than that of D90<120 Gy group (18/19 vs 56.00%(14/25); χ2=8.17, P=0.004). The 1-year survival rate was 77.27%(34/44). Univariate analysis showed that age ( χ2=3.99, P=0.046), preoperative Hb ( χ2=10.60, P=0.001), tumor maximum diameter ( χ2=11.50, P=0.001) and postoperative D90( χ2=5.81, P=0.016) could affect the survival of patients. Multivariate analysis showed that preoperative Hb (hazard ratio ( HR)=0.023, 95% CI: 0.001-0.882, P=0.043) and tumor maximum diameter ( HR=40.889, 95% CI: 1.458-1 146.586, P=0.029) were prognostic factors. Conclusions:125I seeds implantation shows a good effect in the treatment of lung cancer patients after the progress of radiotherapy and chemotherapy. The short-term effect of patients with D90≥120 Gy is better than that of patients with D90<120 Gy. Preoperative Hb and tumor maximum diameter are prognostic factors of survival after implantation.