ObjectiveTo investigate the mechanism by which Haizao Yuhu Tang regulates the nuclear receptor subfamily 4 group A member 1 （NR4A1）signaling pathway to modulate CD8-positive T lymphocyte （CD8⁺T） cell exhaustion-mediated immune escape in transgenic mice with papillary thyroid carcinoma （PTC）. MethodsSixty C57BL/6J mice carrying the conditional BRAF^V600E point mutation were randomly assigned to five groups （n=12）： Model， low-dose （7.28 g·kg^-1·d^-1） Haizao Yuhu Tang， medium-dose （14.56 g·kg^-1·d^-1） Haizao Yuhu Tang， high-dose （29.12 g·kg^-1·d^-1） Haizao Yuhu Tang， and vemurafenib （PLX4032， 0.02 g·kg^-1·d^-1）. In addition， 12 BRAF^V600E-negative mice were selected as the control group. All the groups received continuous intervention for 8 weeks. After treatment， the thyroid tumor weight and volume of mice in each group were measured. Hematoxylin and eosin （HE） staining was performed to observe the morphological characteristics of thyroid tumors. Enzyme-linked immunosorbent assay （ELISA） was adopted to quantify the serum levels of interferon-γ （IFN-γ）， interleukin-2 （IL-2）， tumor necrosis factor-α （TNF-α）， C-X-C motif chemokine ligand 9 （CXCL9）， and C-X-C motif chemokine ligand 10 （CXCL10）. Flow cytometry was employed to determine the proportion of cytotoxic CD8⁺T cells in the tumor tissue. Western blot and real-time PCR were employed to determine the protein and mRNA levels， respectively， of molecules related to the NR4A1 signaling pathway. ResultsCompared with the control group， the model group showed significantly increased thyroid tumor volume and weight （P<0.01）. Compared with the model group， the low-dose， medium-dose， and high-dose Haizao Yuhu Tang groups and the vemurafenib group exhibited varying degrees of reduction in thyroid tumor volume and weight （P<0.05， P<0.01）， with the medium-dose Haizao Yuhu Tang group and the vemurafenib group showing the most pronounced therapeutic effects （P<0.01）. Compared with the model group， the low-dose， medium-dose， and high-dose Haizao Yuhu Tang groups and the vemurafenib group showed increased serum levels of IFN-γ， IL-2， TNF-α， CXCL9， and CXCL10， decreased mRNA and protein levels of NR4A1， Programmed cell death-1 （PD-1）， and Programmed cell death-ligand 1 （PD-L1）， and enhanced cytotoxic activity of CD8⁺T cells （P<0.05， P<0.01） Among these groups， the medium-dose Haizao Yuhu Tang group exhibited the optimal therapeutic effects. In addition， compared with that in the model group， T-cell factor-1 （TCF-1） expression was increased in the low-dose， medium-dose， and high-dose Haizao Yuhu Tang groups （P<0.01）， whereas no significant change in TCF-1 expression was observed in the vemurafenib group. ConclusionHaizao Yuhu Tang may restore the cytotoxic function of CD8⁺T cells by inhibiting the NR4A1 signaling pathway， thereby suppressing immune evasion in PTC and delaying PTC growth.

Objective To investigate the transcriptional and translational expression of Slitrk6 in rat spermatogene-sis.Methods The mRNA transcription level and translation level of Slitrk6 were detected by RT-qPCR and West-ern blot,respectively in testis of rats aged 2-65 days(repeat three times at each time point).Results The mRNA expression of Slitrk6 reached the highest on day 4 and day 10.SLITRK6 protein was continuously expressed during testis development in rats.Slitrk6 was found in human testis through PPI network.Conclusions Slitrk6 is potential-ly involved in mitosis and meiosis in spermatogenesis;The Slitrk6 may be one of the key genes in spermatogenesis.SLITRK6 protein is involved in mitosis and the transformation of round spermatids.The results lay a foundation for subsequent research on male infertility.

Objective To investigate the thalamus and thalamic subnucleus volume changes in patients with trigeminal neuralgia(TN)and to preliminarily investigate whether there is a pain processing lateralization advantage in the thalamus.Methods The three-dimensional T1WI images of 56 TN patients and 56 matched healthy controls(HC)were collected,and thalamus and thalamic subnucleus volumes were extracted by automated segmentation via a region of interest(ROI)-based morphological analysis method.Results There was no significant difference in the whole thalamus volume between TN and HC groups.Compared with HC,the bilateral ventral lateral(VL)of the thalamus were significantly smaller in patients with right-sided trigeminal neuralgia(RTN),and no significant thalamic subnucleus volume changes were found in patients with left-sided trigeminal neuralgia(LTN).After mirror-flipping the whole-brain images of the LTN,it was found that the volume of ipsilateral thalamic VL of TN group was significantly reduced than that of HC group.The volume of ipsilateral mediodorsal lateral parvocellular(MD1)of TN group was significantly smaller than that of HC group.There was no significant difference in the volume of ipsilateral and contralateral thalamic subnucleus.Conclusion The thalamic subnucleus are exclusively reduced in volume in patients with TN,and there is no significant change in whole thalamus volume,suggesting no lateralization advantage for pain processing.

Objective:To analyze the incidence and influencing factors of lymphopenia in prostate cancer patients undergoing pelvic radiotherapy.Methods:A retrospective analysis was conducted on 123 prostate cancer patients treated at the Department of Radiation Oncology, Peking University First Hospital, from November 2011 to May 2015. Radiotherapy was administered using conventional fractionated intensity-modulated radiotherapy. Blood routine, including absolute lymphocyte count (ALC), was performed on patients before radiotherapy, weekly during radiotherapy, and at the end of radiotherapy. Severe lymphopenia was defined as an ALC <500 cells/μl. Based on whether the minimum ALC during radiotherapy was lower than 500 cells/μl, the entire cohort and 55 patients (excluding those with undelineated pelvic bone marrow due to radiotherapy planning system issues) with delineated pelvic bone marrow (divided into pelvic bone marrow, iliac bone marrow, and lower pelvic bone marrow) were stratified into a severe lymphopenia group (33 cases and 16 cases, respectively) and a mild lymphopenia group (90 cases and 39 cases, respectively). Differences in clinical factors and dosimetric parameters were compared between the groups using the chi-square test (or Fisher's exact test), t-test, and Wilcoxon rank-sum test. Univariate and multivariate logistic regression analyses were performed to identify the clinical and dosimetric factors influencing severe lymphopenia. Results:All 123 prostate cancer patients experienced lymphopenia during radiotherapy, with a median minimum ALC of 0.6×10 9/L [range: (0.2-2.3)×10 9/L]. Severe lymphopenia occurred in 26.8% (33 cases) of patients. Univariate analysis of the entire cohort showed that pre-radiotherapy baseline ALC, initial neutrophil-to-lymphocyte ratio, prostate-specific antigen value, Gleason score, and pelvic radiotherapy were promoting factors for severe lymphopenia ( P<0.05). Multivariate analysis identified pre-radiotherapy baseline ALC ( OR=0.217, 95% CI: 0.072-0.650, P=0.006) and pelvic radiotherapy ( OR=23.852, 95% CI: 2.834-200.787, P=0.004) as promoting factors for severe lymphopenia. In patients with delineated pelvic bone marrow, univariate analysis showed that pelvic bone marrow V 30 Gy and V 40 Gy, iliac bone marrow V 30 Gy and V 40 Gy, lower pelvic bone marrow V 30 Gy and V 40 Gy were promoting factors for severe lymphopenia during treatment ( P<0.05). Conclusions:Lymphopenia is common in prostate cancer patients undergoing radiotherapy, with a high incidence of severe lymphopenia. Pre-radiotherapy baseline ALC, as well as pelvic, iliac, and lower pelvic bone marrow V 30 Gy and V 40 Gy, are promoting factors for severe lymphopenia during radiotherapy.

Objective To investigate the thalamus and thalamic subnucleus volume changes in patients with trigeminal neuralgia(TN)and to preliminarily investigate whether there is a pain processing lateralization advantage in the thalamus.Methods The three-dimensional T1WI images of 56 TN patients and 56 matched healthy controls(HC)were collected,and thalamus and thalamic subnucleus volumes were extracted by automated segmentation via a region of interest(ROI)-based morphological analysis method.Results There was no significant difference in the whole thalamus volume between TN and HC groups.Compared with HC,the bilateral ventral lateral(VL)of the thalamus were significantly smaller in patients with right-sided trigeminal neuralgia(RTN),and no significant thalamic subnucleus volume changes were found in patients with left-sided trigeminal neuralgia(LTN).After mirror-flipping the whole-brain images of the LTN,it was found that the volume of ipsilateral thalamic VL of TN group was significantly reduced than that of HC group.The volume of ipsilateral mediodorsal lateral parvocellular(MD1)of TN group was significantly smaller than that of HC group.There was no significant difference in the volume of ipsilateral and contralateral thalamic subnucleus.Conclusion The thalamic subnucleus are exclusively reduced in volume in patients with TN,and there is no significant change in whole thalamus volume,suggesting no lateralization advantage for pain processing.

Objective:To analyze the incidence and influencing factors of lymphopenia in prostate cancer patients undergoing pelvic radiotherapy.Methods:A retrospective analysis was conducted on 123 prostate cancer patients treated at the Department of Radiation Oncology, Peking University First Hospital, from November 2011 to May 2015. Radiotherapy was administered using conventional fractionated intensity-modulated radiotherapy. Blood routine, including absolute lymphocyte count (ALC), was performed on patients before radiotherapy, weekly during radiotherapy, and at the end of radiotherapy. Severe lymphopenia was defined as an ALC <500 cells/μl. Based on whether the minimum ALC during radiotherapy was lower than 500 cells/μl, the entire cohort and 55 patients (excluding those with undelineated pelvic bone marrow due to radiotherapy planning system issues) with delineated pelvic bone marrow (divided into pelvic bone marrow, iliac bone marrow, and lower pelvic bone marrow) were stratified into a severe lymphopenia group (33 cases and 16 cases, respectively) and a mild lymphopenia group (90 cases and 39 cases, respectively). Differences in clinical factors and dosimetric parameters were compared between the groups using the chi-square test (or Fisher's exact test), t-test, and Wilcoxon rank-sum test. Univariate and multivariate logistic regression analyses were performed to identify the clinical and dosimetric factors influencing severe lymphopenia. Results:All 123 prostate cancer patients experienced lymphopenia during radiotherapy, with a median minimum ALC of 0.6×10 9/L [range: (0.2-2.3)×10 9/L]. Severe lymphopenia occurred in 26.8% (33 cases) of patients. Univariate analysis of the entire cohort showed that pre-radiotherapy baseline ALC, initial neutrophil-to-lymphocyte ratio, prostate-specific antigen value, Gleason score, and pelvic radiotherapy were promoting factors for severe lymphopenia ( P<0.05). Multivariate analysis identified pre-radiotherapy baseline ALC ( OR=0.217, 95% CI: 0.072-0.650, P=0.006) and pelvic radiotherapy ( OR=23.852, 95% CI: 2.834-200.787, P=0.004) as promoting factors for severe lymphopenia. In patients with delineated pelvic bone marrow, univariate analysis showed that pelvic bone marrow V 30 Gy and V 40 Gy, iliac bone marrow V 30 Gy and V 40 Gy, lower pelvic bone marrow V 30 Gy and V 40 Gy were promoting factors for severe lymphopenia during treatment ( P<0.05). Conclusions:Lymphopenia is common in prostate cancer patients undergoing radiotherapy, with a high incidence of severe lymphopenia. Pre-radiotherapy baseline ALC, as well as pelvic, iliac, and lower pelvic bone marrow V 30 Gy and V 40 Gy, are promoting factors for severe lymphopenia during radiotherapy.

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.

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.