Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

Ulcerative colitis （UC）， a chronic， non-specific inflammatory bowel disease with typical symptoms such as abdominal pain， diarrhea， and bloody stools， demonstrates a high relapse rate and difficulty in curing. Sishenwan， first recorded in Internal Medicine Abstract （Nei Ke Zhai Yao）， are a classic prescription for treating diarrhea caused by deficiency of the spleen and kidney Yang. The core therapeutic principle of Sishenwan is warming and tonifying the spleen and kidney， and astringing the intestine and stopping diarrhea. In recent years， Sishenwan have demonstrated distinct advantages in the clinical treatment of UC. The pathogenesis of UC involves multiple factors， including immune dysregulation and gut microbiota imbalance. Although Western medicine is effective in the short term， its side effects， high relapse rate， and resistance associated with long-term use pose substantial challenges. Sishenwan have shown excellent clinical outcomes in the treatment of UC due to deficiency of the spleen and kidney Yang. Modern clinical studies indicate that Sishenwan， used alone or in combination with Western medicine or other Chinese medicine compound prescriptions， significantly improve the clinical efficacy in treating UC due to deficiency of the spleen and kidney Yang. Sishenwan effectively alleviate core symptoms such as mucus， pus， and blood in stools， and persistent abdominal pain， reduce Mayo scores and the relapse rate， and improve patients' quality of life. Research on the material basis reveals that Sishenwan contain multiple active ingredients such as psoralen， isopsoralen， and evodiamine. Mechanism studies indicate that Sishenwan inhibit the inflammatory cascade reactions by regulating the signal network through multiple targets. Sishenwan regulate cellular immunity and restore intestinal immune homeostasis. At the microecological level， Sishenwan promote the intestinal barrier repair through the "microbiota-metabolism-immunity" axis. The current research still needs to be deepened in aspects such as the mining of specific biomarkers for syndromes and the exploration of the collaborative mechanism of traditional Chinese and Western medicine. In the future， a full-chain system covering syndrome differentiation， targeting， and monitoring needs to be constructed for promoting the paradigm transformation of Sishenwan into precision drugs. This review systematically explains the treatment mechanism of Sishenwan regarding the combination of disease and syndrome and its multi-target regulatory characteristics， providing a theoretical basis and transformation direction for the treatment of UC with integrated traditional Chinese and Western medicine.

In recent years， there have been both achievements and criticisms in using the methods of evidence-based medicine to evaluate the efficacy of traditional Chinese medicine （TCM）， which is mainly due to the differences between TCM and Western medicine. To facilitate the clinical evidence-based evaluation in TCM， this paper analyzes the challenges faced in TCM clinical evaluation， particularly in the diagnosis， clinical intervention， and efficacy assessment methods. Considering the current state of TCM clinical evaluation and our clinical research experience， we believe that establishing and refining the TCM disease-syndrome diagnostic system is a prerequisite for the practice of clinical evidence-based evaluation in TCM. Furthermore， this paper discusses the specific connotation， development， and challenges of the disease-syndrome diagnostic system， especially the choice of TCM disease name or modern medical disease name in this system. Then， the clinical application scenarios are expounded from ''TCM disease name + syndrome differentiation'' and ''Western medicine disease name + syndrome differentiation''. Moreover， this paper proposed solutions for practical issues such as the standardization of disease and syndrome diagnosis， selection of clinical evaluation methods， and application of evidence-based approaches in clinical evaluation. Establishing the criteria for the disease-syndrome diagnostic system is crucial for the determination of clinical intervention regimen， the selection of clinical research methods， and the establishment of evaluation indicators， which are essential for generating high-quality clinical evidence. To sum up， this paper reviews the development and current situation of the disease-syndrome diagnostic system and proposes an exploratory approach for the standardization and application of this system in clinical evidence-based evaluation. This approach aims to facilitate the integration of TCM with modern clinical practice， thereby achieving standardized evaluation of TCM efficacy and deepening the integration of TCM with evidence-based medicine.

Objective To explore the application value of Fast Dixon technique in MR hip joint scanning.Methods Fifty young volunteers were recruited to perform axial and coronal MR scans of the hip joint.The scanning sequence was Fast Dixon T2WI sequence and conventional Dixon T2WI sequence.A double-blind five-point scale was used to subjectively evaluate the image quality of the two types sequences.The signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the axial image were measured at the maximum level of the bladder display.Results In the scores of"good contrast between surrounding tissue and femoral head signal"and"overall image quality",the Fast Dixon T2WI sequence was better than the conventional Dixon T2WI sequence,and the difference was statistically significant(P<0.05).There was no significant difference in the average scores of"whether bladder artifacts affected the diagnosis"and"whether the fat suppression effect was good"between Fast Dixon T2WI sequence and conventional Dixon T2WI sequence(P>0.05).In the objective image quality evaluation,the SNR and CNR of Fast Dixon T2WI sequence were better than those of conventional Dixon T2WI sequence,and the difference was statistically significant(P<0.05).Conclusion The image quality score of the hip joint of young volunteers with Fast Dixon T2WI sequence combined with multiple averaging excitation technique is significantly higher than that of conventional Dixon T2WI sequence.The Fast Dixon T2WI sequence can increase the effect of inhibiting fat and motion artifacts without increasing the scanning time,and the joint face ratio is good.Fast Dixon technique can replace the traditional Dixon technique,thus becoming an optimal choice for hip joint MR scanning.

Objective To explore the inhibitory effect of saikosonin a(SSa)on pentylenetetrazol-induced acute epilepsy seizures in a mouse model of depression and explore the mechanism mediating this effect.Methods Male C57BL/6J mouse models of depression was established by oral administration of corticosterone via drinking water for 3 weeks,and acute epileptic seizures were induced by intraperitoneal injection of a single dose of pentylenetetrazole.The effect of intraperitoneal injection of SSa prior to the treatment on depressive symptoms and epileptic seizures were assessed using behavioral tests,epileptic seizure grading and hippocampal morphology observation.ELISA was used to detect blood corticosterone levels of the mice,and RT-qPCR was performed to detect the pro-and anti-inflammatory factors.Microglia activation in the mice was observed using immunofluorescence staining.Results The mouse model of corticosterone-induced depression showed body weight loss and obvious depressive behaviors with significantly increased serum corticosterone level(all P<0.05).Compared with those with pentylenetetrazole-induced epilepsy alone,the epileptic mice with comorbid depression showed significantly shorter latency of epileptic seizures,increased number,grade and duration of of seizures,reduced Nissl bodies in hippocampal CA1 and CA3 neurons,increased number of Iba1-positive cells,and significantly enhanced hippocampal expressions of IL-1β,IL-10,TNF-α and IFN-γ.Pretreatment of the epileptic mice with SSa significantly prolonged the latency of epileptic seizures,reduced the number,duration,and severity of seizures,increased the number of Nissl bodies,decreased the number of Iba1-positive cells,and reduced the expression levels of IL-1β,IL-10,TNF-α,and IFN-γ in the hippocampus(P<0.05).Conclusion Depressive state aggravates epileptic seizures,increases microglia activation,and elevates inflammation levels.SSA treatment can alleviate acute epileptic seizures in mouse models of depression possibly by suppressing microglia activation-mediated inflammation.

Objective To explore the inhibitory effect of saikosonin a(SSa)on pentylenetetrazol-induced acute epilepsy seizures in a mouse model of depression and explore the mechanism mediating this effect.Methods Male C57BL/6J mouse models of depression was established by oral administration of corticosterone via drinking water for 3 weeks,and acute epileptic seizures were induced by intraperitoneal injection of a single dose of pentylenetetrazole.The effect of intraperitoneal injection of SSa prior to the treatment on depressive symptoms and epileptic seizures were assessed using behavioral tests,epileptic seizure grading and hippocampal morphology observation.ELISA was used to detect blood corticosterone levels of the mice,and RT-qPCR was performed to detect the pro-and anti-inflammatory factors.Microglia activation in the mice was observed using immunofluorescence staining.Results The mouse model of corticosterone-induced depression showed body weight loss and obvious depressive behaviors with significantly increased serum corticosterone level(all P<0.05).Compared with those with pentylenetetrazole-induced epilepsy alone,the epileptic mice with comorbid depression showed significantly shorter latency of epileptic seizures,increased number,grade and duration of of seizures,reduced Nissl bodies in hippocampal CA1 and CA3 neurons,increased number of Iba1-positive cells,and significantly enhanced hippocampal expressions of IL-1β,IL-10,TNF-α and IFN-γ.Pretreatment of the epileptic mice with SSa significantly prolonged the latency of epileptic seizures,reduced the number,duration,and severity of seizures,increased the number of Nissl bodies,decreased the number of Iba1-positive cells,and reduced the expression levels of IL-1β,IL-10,TNF-α,and IFN-γ in the hippocampus(P<0.05).Conclusion Depressive state aggravates epileptic seizures,increases microglia activation,and elevates inflammation levels.SSA treatment can alleviate acute epileptic seizures in mouse models of depression possibly by suppressing microglia activation-mediated inflammation.

Objective To investigate the serum levels of soluble programmed death-1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in chronic hepatitis B (CHB) patients with clinical cure, the correlation between programmed death-1 (PD-1) and lymphocytes by flow cytometry, and the recovery of hepatitis B virus (HBV)-specific immunity. Methods A total of 26 CHB patients with clinical cure, 26 treatment-naïve CHB patients, and 26 healthy controls who were diagnosed at the outpatient service of Peking University First Hospital from January to May of 2022 were enrolled, and related clinical data and peripheral blood samples were collected. ELISA was used to measure the serum levels of sPD-1 and sPD-L1, and flow cytometry was used to measure the expression of PD-1 in peripheral blood lymphocytes. CHB patients with clinical cure were compared with the treatment-naïve CHB patients and the healthy controls. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between three groups, and the chi-square test was used for comparison of categorical data between groups. The Pearson correlation analysis or the Spearman correlation analysis was used to investigate the correlation between two continuous variables. Results For the 26 CHB patients with clinical cure, the mean time of antiviral therapy was 8.33 years, with entecavir as the antiviral drug. The CHB patients with clinical cure had significantly higher levels of sPD-1 and sPD-L1 than the healthy controls ( P < 0.05) and significantly lower percentages of PD-1 + cells/lymphocytes and PD-1 + CD8 + T cells/lymphocytes than the treatment-naïve CHB patients ( P < 0.05). In the treatment-naïve CHB patients, the serum levels of sPD-1 and sPD-L1 were moderately negatively correlated with HBsAg level ( r =-0.524 and -0.583, both P < 0.05). The serum levels of sPD-1 and sPD-L1 were moderately positively correlated with PD-1 + CD8 + T cells/lymphocytes ( r =0.535 and 0.419, both P < 0.05). In the CHB patients with clinical cure, the serum levels of sPD-1 and sPD-L1 were not correlated with age, sex, alanine aminotransferase, T cells/lymphocytes, CD8 + T cells/lymphocytes, PD-1 + T cells/lymphocytes or PD-1 + CD8 + T cells/lymphocytes (all P > 0.05). Conclusion The serum levels of sPD-1 and sPD-L1 in treatment-naïve CHB patients are mainly associated with exhausted CD8 + T cells in peripheral blood, while there is no significant correlation between serum sPD-1/sPD-L1 and exhausted CD8 + T cells in peripheral blood in CHB patients with clinical cure.

Organ transplantation is the most effective treatment for all categories of end-stage organ diseases. To resolve the shortage of donors in organ transplantation, widespread attention has been diverted to xenotransplantation. At present, clinicians mainly highlight the problems related to xenotransplantation rejection and viral infection. The physiology of xenotransplantation has been rarely studied. Kidney performs endocrine function by producing erythropoietin (EPO), renin and activating vitamin D. Although these pathways are usually well preserved in allogeneic transplantation, species-specific differences, especially those between pigs and non-human primates, may still affect the physiological function of transplant organs. In this article, the changes of EPO, renin-angiotensin-aldosterone system (RAAS) and active vitamin D₃ of pig and human after xenotransplantation were illustrated, aiming to provide reference for subclinical research of xenotransplantation.

Objective To improve the analysis of ¹³⁴Cs, ¹³⁷Cs, and ⁶⁰Co in aerosol samples by the national key radiation environment laboratories. Methods Intercomparison of analysis results of ¹³⁴Cs, ¹³⁷Cs, and ⁶⁰Co in standard aerosol samples was performed among the national key radiation environment laboratories according to Gamma spectrometry method of analyzing radionuclides in biological samples (GB/T 16145-1995 ), and the intercomparison results were evaluated by the standard deviation. Results Six laboratories were involved in the intercomparison. For ¹³⁴Cs, 50% of the laboratories showed a relative deviation less than 10%, and 50% showed a relative deviation of 10%-20%. For ¹³⁷Cs, 33.3% of the laboratories showed a relative deviation less than 10%, and 76.7% showed a relative deviation of 10%-20%. For ⁶⁰Cs, all laboratories showed a relative deviation less than 10%. The overall intercomparison results were acceptable. Conclusion The laboratories in this intercomparison show generally good results.

During the gene editing process mediated by CRISPR/Cas9, precise genome editing and gene knock-in can be achieved by the homologous recombination of double-stranded DNA (dsDNA) donor template. However, the low-efficiency of homologous recombination in eukaryotic cells hampers the development and application of this gene editing strategy. Here, we developed a novel CRISPR/Cas9-hLacI donor adapting system (DAS) to enhance the dsDNA-templated gene editing, taking the advantage of the specific binding of the LacI repressor protein and the LacO operator sequence derived for the Escherichia coli lactose operon. The codon-humanized LacI gene was fused as an adaptor to the Streptococcus pyogenes Cas9 (SpCas9) and Staphylococcus lugdunensis Cas9 (SlugCas9-HF) genes, and the LacO operator sequence was used as the aptamer and linked to the dsDNA donor template by PCR. The Cas9 nuclease activity after the fusion and the homology-directed repair (HDR) efficiency of the LacO-linked dsDNA template were firstly examined using surrogate reporter assays with the corresponding reporter vectors. The CRISPR/Cas9-hLacI DASs mediated genome precise editing were further checked, and we achieved a high efficiency up to 30.5% of precise editing at the VEGFA locus in HEK293T cells by using the CRISPR/SlugCas9-hLacI DAS. In summary, we developed a novel CRISPR/Cas9-hLacI DAS for dsDNA-templated gene editing, which enriches the CRISPR/Cas9-derived gene editing techniques and provides a novel tool for animal molecular design breeding researches.
Humans ; Animals ; Gene Editing ; CRISPR-Cas Systems/genetics* ; HEK293 Cells ; Homologous Recombination ; DNA