ObjectiveTo analyze the effects of new integration processing method in producing area and traditional method on the composition and pharmacological action of Polygoni Multiflori Radix Praeparata（PMRP）， and to illustrate the advantages of toxicity reducing and efficacy enhancing of the decoction pieces prepared by the new method. MethodFresh Polygoni Multiflori Radix（PMR） was taken from Dao-di producing area， and was processed by new integration processing method in producing area（steaming with black bean juice under pressure of 0.1 MPa and temperature at 120 ℃ for 10.5 h） and traditional method（steaming with black bean juice under water for 36 h）， respectively. Samples were collected during the processing process of the two methods， For new method， the samples were collected at 0.5， 3， 5.5， 8， 10.5 h， separately. For traditional method， the samples were collected every 4 h. High performance liquid chromatography（HPLC） was used to establish fingerprint and identify common peaks， the content of polysaccharides was determined by anthrone-sulfuric acid colorimetry at 627 nm， and the contents of anthraquinones and stilbene glycosides in different processed products were determined according to the methods under the item of determination of PMR and PMRP in the 2020 edition of Chinese Pharmacopoeia. In pharmacological experiments， 90 SD rats were randomly divided into 9 groups with 10 in each group（half of male and half of female）， including the blank group， and raw products， 24 h processed products under atmospheric pressure， 30 h processed products under atmospheric pressure， 8 h processed products under high pressure groups with low and high dosages（4.125， 16.5 g·kg^-1）. Rats were given the drug by gavage for 29 d with once a day， blood was collected from the abdominal aorta after the last administration， and the serum was isolated， the body mass and liver mass of rats were weighed and the organ index was calculated. The pathological change of liver tissue was observed by hematoxylin-eosin（HE） staining， and biochemical methods were used to detect the contents of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， alkaline phosphatase（ALP）， γ-glutamyltransferase（GGT）， lactic dehydrogenase（LDH） in serum which used as liver function indicators and the levels of superoxide dismutase（SOD）， malondialdehyde（MDA）， glutathione peroxidase（GSH-Px） in brain tissues which used as oxidation indicators. ResultA total of 14 common peaks were identified in the fingerprint of PMR， PMRP prepared by new method and traditional method， and three of the peaks were designated as stilbene glycoside， emodin and emodin methyl ether， respectively. The characteristic peak areas of each processed products changed significantly from 0 min to 25 min， indicating that different processing methods had an effect on the contents of components with high polarity in PMRP， and the trend of the changes of the two methods was similar， with the higher degree of change in the new method. The determination results showed that compared with the traditional method， the content of polysaccharide（a kind of beneficial component in PMRP obtained by the new method） significantly increased， while the contents of stilbene glycoside and bound anthraquinone（liver-damaging ingredients） significantly decreased. The pharmacological results showed that compared with the blank group， AST and LDH levels of male rats in the low and high dose groups of 24 h processed products under atmospheric pressure and AST level of male rats in the low and high dose groups of 8 h processed products under high pressure were significantly reduced（P<0.05， P<0.01）， while compared with the raw product groups with the same dose， AST and LDH levels of male rats in the low dose group of 30 h processed products under atmospheric pressure were significantly reduced（P<0.05， P<0.01）， the AST levels of male rats in the low and high dose groups of 8 h processed products under high pressure were significantly decreased（P<0.01）， and there was no statistical significance in the differences of biochemical indexes of female rats in each administration group as compared with those of the blank group. ConclusionThe new integration processing method in producing area of PMRP can reach the quality of relevant regulations in 8 h. The processed products obtained by this method have more advantages than the traditional method in terms of toxicity reducing and efficacy enhancing， and energy saving to avoid the loss of ingredients， which can provide ideas for the production of high-quality decoction pieces of PMRP， and the integration processing method in producing area of other roots and rhizomes of traditional Chinese medicines.

Background Schizophrenic patients have metabolic disorders,impaired language and information processing function.Inflammatory factors may play an important role in the occurrence and development of schizophrenia.Objective To explore the relationship of the inflammatory factor levels with metabolic levels,language fluency and information processing function in patients with schizophrenia,so as to provide references for clinical understanding of the neuropathological mechanisms of schizophrenia.Methods A total of 96 patients with schizophrenia were included in the study group,who were hospitalized in the Fourth People's Hospital of Hefei from January 2021 to December 2022 as well as met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)and Mini-International Neuropsychiatric Interview(MINI)6.0.Meanwhile,population who underwent physical examination at the same hospital were included in the control group(n=42).A high-sensitivity multi factor electrochemiluminescence analyzer was used to detect the levels of inflammatory factors IL-4,IL-5,IL-7,IL-8,IL-10 and IL-13.A fully automated biochemical analyzer was used to detect the levels of metabolic indicators such as fasting blood glucose,triglycerides,high-density lipoprotein,apolipoprotein A,creatinine and urea nitrogen.Verbal fluency and information processing function of all participants were assessed by using Verbal Fluency Test(VFT)and Stroop Color Word Test(SCWT).Results There were statistically significant differences in the levels of IL-4,IL-5,IL-7,IL-8,IL-10,IL-13 and IL-15 between the study group and the control group(P<0.05).There were statistically significant differences in BMI,waist circumference,fasting blood glucose,triglycerides,high-density lipoprotein,urea nitrogen,apolipoprotein A and creatinine levels between the two groups(P<0.05).The differences in the correct number of household appliances,animals,fruits,vegetables,names starting with"water"and"self"in VFT between the two groups were statistically significant(P<0.05).The differences in point reaction time,character reaction time and character color reaction time in SCWT between the two groups were statistically significant(P<0.05).Correlation analysis showed that except for creatinine levels,the levels of IL-4 and IL-5 in patients with schizophrenia were correlated with other indicators(P<0.05).IL-7 levels were correlated with creatinine levels,household appliances,animals,fruits,correct number of names starting with"water"in VFT,point reaction time and word reaction time in SCWT(P<0.05).IL-8 levels were correlated with triglyceride levels,household appliances,animals,fruits,vegetables,correct number of names starting with"water"and"self"in VFT and word reaction time in SCWT(P<0.05).Except for creatinine levels and the correct number of names starting with"self",IL-10 levels were correlated with all other indicators(P<0.05).Except for creatinine and urea nitrogen levels,IL-13 levels were correlated with other indicators(P<0.05).Conclusion The levels of inflammatory factors in patients with schizophrenia may be related to their metabolic levels,language fluency and information processing function.

Fetal STR typing of aborted tissue has long been a major problem in forensic DNA.Especially for the first trimester abortion tissue,it is difficult to isolate the embryonic components by histomorphological means,resulting in the inability to accurately obtain the STR typing of the fetus.The mixed STR typing results of mother and fetus can provide a key basis for the identification of suspects in cases of rape-induced pregnancy.In this study,next generation sequencing was used to successfully detect mixed STR typing of mother and suspected fetus or single STR typing of suspected fetus in 4 rape-induced early pregnancy abortion tissues.Combined with Y-STR and flank sequence information,it provides a more comprehensive and reliable genetic basis for the identification of suspects.

Calcium-activated chloride channels(CaCCs)are a class of channel proteins that trans-port chloride ions activated by intracellular calcium,which play a crucial role in regulating membrane potential,intracellular calcium balance,and cell excitability,particularly in neurons and muscle cells.In the Anoctamin(Ano)family,Ano1 is the most classic CaCC.Targeted modulators of Ano1 have poten-tial therapeutic effects against such diseases as cancer,cystic fibrosis,hypertension,diarrhea,and asthma.Since the discovery of Ano1 in 2008,several methods for screening CaCC-specific modulators have emerged including high-throughput primary screening of fluorescent proteins,electrophysiological patch clamp technique and virtual screening,and identification of small molecule modulators with diverse pharmacological effects.This paper summarizes the principles,advantages and disadvantages of the mainstream screening methods,and reviews the chemical structures and potential applications of Ano1-specific modulators discovered to date.

Objective:To evaluate the effects of different imaging frequencies and matching strategies of cone-beam computed tomography (CBCT) on dose-volume parameters in target and organs at risk (OAR) during image-guided radiotherapy for prostate cancer.Methods:A total of 561 sets of CBCT images from 21 patients treated with radical prostate radiotherapy who were admitted to Peking University First Hospital from June 2022 to May 2023 were retrospectively analyzed. All patients received volumetric intensity modulated arc therapy (VMAT) at a prescribed dose of 70 Gy divided into 25 times, 2.8 Gy per time. Clinical target volume (CTV) and OAR were delineated by the same oncologist on each CBCT image. The planned CT (pCT) was rigorously registered to CBCT after calibration of positioning errors according to different image guidance modes and frequencies, and CT values and structures were propagated to CBCT through deformable image registration (DIR). The daily dose was mapped to pCT according to the deformation vector field (DVF) for dose accumulation. The actual cumulative dose of daily online CBCT validation was compared with the weekly CBCT validation regimen (days 1, 2, 3, 6, 11, 16 and 21 online imaging). The dosimetric comparison was also made between bone-based matching and soft tissue-based matching (after automatic bone-based matching, manual prostate-based matching was performed and fine-tuning was made regarding the anterior wall of rectum). Wilcoxon signed rank-sum test was utilized to analyze dose-volume parameters between planned and cumulative doses that exhibited non-normal distribution, while paired t-test was employed for assessing shift values and average dose parameters that demonstrated normal distribution. Results:Compared with daily CBCT image guidance, the CTV_D 98% in weekly CBCT was significantly reduced [(69.08±1.58) vs. (65.24±3.64) Gy, P<0.001]. The CTV_D 98% of bone-based matching was (69.27±2.14) Gy, but the high-dose volume of the rectum were significantly increased: V 60 Gy was 3.18%±3.10%, V 65 Gy was 0.77%±1.23%. The target area coverage using soft tissue-based matching is sufficient, with a CTV_D 98% of (69.08±1.58) Gy. And the percentage volume of high-dose volume of the rectum was significantly reduced, with V 60 Gy being 2.02%±2.42% and V 65 Gy being 0.34%±0.68%. Conclusions:In prostate cancer patients undergoing moderately-fractionated radiotherapy, daily CBCT image guidance demonstrates superior target coverage compared to a weekly scheme. Soft tissue-based matching, which is automatic bone-based matching followed by manual soft tissue-based matching and fine-tuning according to the anterior rectal wall, offers better rectal protection while maintaining target coverage.

Objective:To investigate the advantage of three dimensional(3D)-printed tissue compensators in radiotherapy for superficial tumors at irregular sites.Methods:A subcutaneous xenograft model of prostate cancer in nude mice was established. Mice were randomly divided into no tissue compensator group( n=6), common tissue compensator group( n=6), and 3D-printed tissue compensator group( n=6). Computed tomography (CT) images of nude mice in the 3D-printed tissue compensator group were acquired. Compensator models were made using polylactic acid, and material properties were evaluated by measuring electron density. CT positioning images of the three groups after covering the corresponding tissue compensators were acquired to delineate the gross tumor volume (GTV). Nude mice in the three groups were irradiated with 6 MV X-rays at the prescribed dose. The prescribed dose for the three groups was 1 500 cGy. The dose distribution in the GTV of the three groups was calculated and compared using the analytical anisotropic algorithm in the Eclipse 13.5 treatment planning system. The metal-oxide-semiconductor field-effect transistor was used to verify the actual dose received on the skin surface of nude mice. Results:The air gap in the 3D-printed tissue compensator group and the common tissue compensator group was 0.20±0.07 and 0.37±0.07 cm 3, respectively ( t=4.02, P<0.01). For the no tissue compensator group, common tissue compensator group, and 3D-printed tissue compensator group, the D95% in the target volume was (1 188.58±92.21), (1 369.90±146.23), and (1 440.29±45.78) cGy, respectively ( F=9.49, P<0.01). D98% was (1 080.13±88.30), (1 302.76±158.43), and (1 360.23±48.71) cGy, respectively ( F=11.17, P<0.01). Dmean was (1 549.08±44.22), (1 593.05±65.40), and (1 638.87±40.83) cGy, respectively ( F=4.59, P<0.05). The measured superficial dose was (626.03±26.75), (1 259.83±71.94), and (1 435.30±67.22) cGy, respectively ( F=263.20, P<0.001). The percentage variation in tumor volume growth after radiation was not significantly different between the common tissue compensator group and the 3D-printed tissue compensator group ( P>0.05). Conclusions:3D-printed tissue compensators fit well to the body surface, which reduces air gaps, effectively increases the dose on the body surface near the target volume, and provides ideas for radiotherapy for superficial tumors at some irregular sites.

Objective:To compare the efficacy and safety of standard treatment with or without adjuvant chemotherapy in patients with highly malignant non-metastatic prostate cancer.Methods:In this prospective non-randomized controlled study, consecutive non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or Gleason score of 5 admitted to Peking University First Hospital were enrolled. Four to six cycles of chemotherapy using docetaxel ± carboplatin regimen were added or not after standard radical therapy. The primary end point was 5-year event-free survival (EFS), and the secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. The survival curve was drawn by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test.Results:A total of 176 patients were consecutively enrolled from November 2019 to January 2022 of which 138 patients received only standard radical therapy (control group), and 38 patients received adjuvant chemotherapy after standard radical therapy (chemotherapy group). The median follow-up time was 13.4 (2.0-34.0) months. All patients survived. The 30-month EFS rates in the chemotherapy and control groups were 100% and 85.6%, respectively ( P=0.064). There were no events in the chemotherapy group, while there were 12 cases of events in the control group, including 6 cases of biochemical recurrence and 6 cases of imaging progression. The 30-month MFS rates in two groups were 100% and 91.9%, respectively ( P=0.205). After the 1 vs. 2 propensity score matching, the EFS and MFS rates in two groups were 100% vs. 85.7% ( P=0.056), and 100% vs. 92.2% ( P=0.209), respectively. The incidence rates of grade 2 and above urinary toxicity in the chemotherapy and control groups were 2.6% and 7.2% ( P=0.354), respectively. The incidence rates of grade 2 and above rectal toxicity were 5.3% and 5.1% ( P=0.711), respectively. Grade 3 and above chemotherapy-related toxicity in the chemotherapy group were leukopenia (31.6%), thrombocytopenia (2.6%) and alopecia (13.2%). Conclusion:The addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall EFS of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

Objective To investigate the molecular mechanism of YingZhongXiao Ointment(YZXO)in the treatment of goiter based on network pharmacology and experimental validation.Methods TCMSP,TCMID,BATMAN-TCM,TCM-MESH,were used to screen the effective active ingredients and targets of YZXO.GeneCards,OMIM,Pharm GKB and Drug Bank databases were used to obtain goiter disease targets.After mapping the drug targets to the disease targets,the intersecting targets were screened,and then the intersecting targets were used to construct a PPI network and screen the core targets,which were subjected to GO and KEGG enrichment analysis.Results In this study,227 active ingredients,314 targets and 847 goiter targets were screened,and 78 potential targets for goiter treatment were obtained after mapping.449 biological processes were obtained from GO enrichment analysis,and 118 pathways were identified from KEGG enrichment analysis,including PI3K-Akt,mitogen-activated protein kinase(MAPK),tumor necrosis factor(TNF)and other signalling pathways.The results of animal experiments showed that compared with the model group,the gene expression of PI3K/Akt/m TOR signalling pathway in thyroid tissue of rats in each dose group and LT4 group was decreased(P<0.01 or P<0.05),p-PI3K/PI3K、p-Akt/Akt was decreased(P<0.01),the protein content of VEGF and PCNA was decreased(P<0.01 or P<0.05),and the protein content of Fas and FasL was increased(P<0.05 or P<0.01).Conclusion This study suggests that the mechanism of YZXO treated goiter by Resolving the Fire may be related to downregulation of PI3K/Akt/m TOR signalling pathway,inhibition of abnormal thyroid cell proliferation and promotion of thyroid cell apoptosis.

Objective:To construct indicators of the ideological and political resource database construction for the curriculum of "Epidemiology".Methods:Two rounds of expert consultation were conducted in 15 experts from 4 universities and 1 textbook publishing house using the Delphi method, and the importance and feasibility scores of the indicators were calculated with the degree of concentration and coordination of experts' opinions.Results:In the two rounds of consultation, the experts' positive coefficient of the two questionnaires were both 100.00% (15/15), the authoritative coefficients of experts were both 0.83, and the Kendall's W was 0.27 ( P<0.05) and 0.33 ( P<0.05), respectively. Consensus was reached on 4 primary indicators and 31 secondary indicators. Conclusion:The process of this study is scientific, and the indicators for the construction of ideological and political resource database for the curriculum of "Epidemiology" are authoritative, which can promote the establishment of ideological and political resource database for the curriculum of "Epidemiology".