Zhishi Shaoyaosan is the 34^th prescription in the Catalogue of Ancient Classic Formulas （Second Batch） published by the National Administration of Traditional Chinese Medicine in 2023. It is widely used in clinical practice and has a definite curative effect. However， there is currently a lack of its ancient literature analysis and textual research， and there is no corresponding Chinese patent medicine preparation. By consulting and combing the relevant ancient books of traditional Chinese medicine， this paper analyzes and conducts textual research of the origin， composition， measurement， administration， and efficacy of Zhishi Shaoyaosan. The results show that Zhishi Shaoyaosan is derived from Essentials from the Golden Cabinet written by Zhang Zhongjing in the Eastern Han Dynasty. It is mainly recorded in the name of Zhishi Shaoyaosan in the literature of the past dynasties. The prescription is composed of Aurantii Fructus Immaturus and Paeoniae Radix Alba. The processing method is stir-frying Aurantii Fructus Immaturus to scorch and using raw Paeoniae Radix Alba. The dose of the prescription recorded in the ancient books is mainly an equal amount of Aurantii Fructus Immaturus and Paeoniae Radix Alba in one square-cun spoon， taken three times a day， which is converted into a modern dose of 1.5 g each time （0.75 g Aurantii Fructus Immaturus and 0.75 g Paeoniae Radix Alba each time）. The components of the prescription are ground into powder and taken with barley porridge， three times a day. The efficacy is to break stagnated Qi， harmonize blood， and relieve restlessness and pain. It is mainly used to treat postpartum abdominal pain， acute pelvic inflammatory disease， acute cholecystitis and intestinal diseases， stroke sequelae， and other diseases. This study combs and analyzes the ancient literature recording Zhishi Shaoyaosan and clarifies the key information of the prescription， which provides a basis for promoting the research and development of its patent medicine.

Objective: To explore the relationship of physical activity (PA) and sedentary behavior (SB) with cardiorespiratory fitness (CRF) among middle schoold students in Tibet, so as to provide empirical references for improving the cardiorespiratory fitness and health levels of adolescents in Tibet. Methods: From August to December 2020, 1 225 junior and senior high school students were selected from 2 middle schools in Lhasa, Tibet Autonomous Region, using the stratified cluster random sampling method. Triaxial accelerometers were used to evaluate PA and SB behaviors, and the 20 meter shuttle run was employed to assess CRF among the middle school students. Isochronous substitution modeling was used to analyze the associations of SB, low intensity physical activity (LPA), and moderate vigorous physical activity (MVPA) with CRF, and the saturation threshold effect in the dose response relationship between MVPA and CRF was analyzed through restricted cubic spline and two stage linear regression. Results: After adjusting for covariates such as gender, body mass index and sleep quality score, isotemporal substitution analysis showed that among junior high school students aged 13-15, replacing 30 minutes of SB ( B =1.73) or LPA ( B =2.38) with MVPA were positively associated with CRF (both P <0.05). Among senior high school students aged 16-18, replacing SB ( B =0.99) or LPA ( B =1.38) with MVPA were also positively associated with CRF (both P <0.05). Restricted cubic spline and two piecewise linear regression analyses indicated that only middle school girls aged 13-18 exhibited a saturation threshold effect between MVPA and CRF (logarithmic likelihood ratio test=0.03), with the optimal CRF improvement observed at 60 minutes of MVPA per day ( B=0.13, P ＜ 0.01). Conclusions Reducing SB and LPA while increasing MVPA can improve CRF in Tibetan middle school students. To maximize CRF improvement, middle school girls should engage in at least 60 minutes of MVPA daily.

OBJECTIVES: To investigate the targets and mechanisms of 7-hydroxyethyl chrysin (7-HEC) in prevention and treatment of high-altitude cerebral edema (HACE) in rats. METHODS: Fifty-four male Wistar rats were randomly divided into normal control group, HACE model group, and 7-HEC-treated group (18 rats in each group). Except for the normal control group, rats in the two other groups were exposed to a hypobaric hypoxic chamber simulating a 7000 m altitude for 72 h to establish the HACE model. The 7-HEC-treated group was intraperitoneally injected with 7-HEC (150 mg·kg^－¹·d^－¹) for 3 consecutive days before modeling, while the model group received equivalent isotonic sodium chloride solution. Tandem Mass Tag (TMT) proteomics technology was used to detect differentially expressed proteins (DEPs) with screening criteria set at a fold change >1.2 and P<0.05. Western blotting was used to verify the expression levels of target proteins. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed. RESULTS: Compared with the normal control group, 256 DEPs were identified in the HACE model group. Compared with the HACE model group, 87 DEPs were identified in the 7-HEC-treated group. Among them, 19 DEPs that were dysregulated in the HACE model group were restored after 7-HEC intervention, of which seven (HSPA4, Arhgap20, SERT, HACL1, CCDC43, POLR3A, and PCBD1) were confirmed by Western blotting. GO enrichment analysis of the DEPs between the HACE model and 7-HEC-treated groups revealed their involvement in 13 biological processes, five cellular components, and two molecular functions. KEGG pathway analysis indicated associations with the mRNA surveillance pathway, Th17 cell differentiation, serotonergic synapse, RNA polymerase, protein processing in the endoplasmic reticulum, peroxisome, neuroactive ligand-receptor interaction, folate biosynthesis. PPI network analysis demonstrated that HSPA4, POLR3A, and HACL1, which were validated by Western blotting, interacted with multiple signaling pathways and ranked among the top 20 hub proteins by degree value, suggesting their potential role as core regulatory factors. Arhgap20, SERT and PCBD1 also exhibited interactions with several proteins, suggesting their potential as key regulatory proteins, whereas no interactions for CCDC43 were identified. CONCLUSIONS This study applied TMT proteomics to identify seven potential therapeutic targets of 7-HEC for the prevention and treatment of HACE. These targets may be involved in the pathogenesis of HACE through multiple pathways, including maintaining cellular homeostasis, ameliorating oxidative stress, regulating energy metabolism, and reducing vascular permeability.
Animals ; Male ; Proteomics/methods* ; Rats, Wistar ; Flavonoids/therapeutic use* ; Rats ; Brain Edema/etiology* ; Altitude Sickness/metabolism* ; Protein Interaction Maps

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

This study employed ultrahigh-performance liquid chromatograph-hybrid quadrupole orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) to detect the chemical constituents of traditional Chinese medicine in Sizi Dingchuan granules. Network pharmacology and molecular docking techniques were then utilized to predict the effects of Sizi Dingchuan granules on bronchial asthma, along with its target molecules and signaling pathways. UHPLC analysis identified 172 compounds, including 84 flavonoids, 38 organic acids and their derivatives, 22 phenylpropanoids, 16 organic oxygen compounds, 3 phenolic compounds, 2 terpenoids, 2 sugars and glycosides, and 5 other compounds. Typical compound fragmentation patterns were documented. Using network pharmacology methods, 117 compounds were ultimately selected for target prediction, establishing a “drug-component-target-disease” network, which revealed that quercetin, schisandrin A, baicalin, gomisin H, and baicalin exhibit multiple targets related to bronchial asthma, suggesting that they may be the active components responsible for the compound’s efficacy in treating this condition. Protein-protein interaction analysis identified core targets including TNF, IL-6, JAK2, STAT3, BCL2, CASP3, and EGFR, primarily clustered within the JAK-STAT signaling pathway. This suggests that the main components of Sizi Dingchuan granules may regulate the balance between Th17 and Treg cells, as well as Th1 and Th2 cell differentiation, by modulating the JAK-STAT signaling pathway, thereby exerting a positive therapeutic effect on bronchial asthma.

Objective:To compare the results of invasive prenatal diagnosis and preimplantation genetic testing (PGT) and explore the underlying mechanism.Methods:Clinical data of pregnant women undergoing PGT and invasive prenatal diagnosis at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to December 2022 were collected. The results of PGT and invasive prenatal diagnosis were compared, and the outcomes of pregnancies were followed up. This study has been approved by the Medical Ethics Committee of the the Sixth Affiliated Hospital of Sun Yat-sen University (No. 2022SLYEC-491).Results:A total of 172 couples were included in this study, and 26 non-targeted variants were discovered upon prenatal diagnosis, including 10 cases (38.5%) by chromosomal karyotyping, 15 (57.7%) by chromosomal microarray analysis (CMA), and 1 (3.8%) by whole exome sequencing. The 10 karyotypic anomalies had included 6 chromosomal polymorphisms, 2 chromosomal mosaicisms, 1 paternally derived translocation, and 1 missed maternal chromosomal inversion. CMA has identified 15 copy number variations (CNVs), which included 11 microdeletions and microduplications, 3 loss of heterozygosity, and 1 low-level mosaicism of paternal uniparental disomy. One CNV was classified as pathogenic, and another one was likely pathogenic, whilst the remaining 13 were classified as variants of uncertain significance. Therefore, 8.7% of CNVs was detected by invasive prenatal diagnosis after PGT. 92.3% (24/26) of the non-targeted variants have been due to technological limitations of next-generation sequencing (NGS).Conclusion:Invasive prenatal diagnosis after PGT can detect non-targeted variants, which may further reduce the incidence of birth defects.

In recent years, the incidence of cancer in China has been increasing steadily. Advancing primary prevention measures for cancers could be an effective strategy to curb this trend. Diet has been considered a modifiable and shared risk factor for various cancers. Studying dietary patterns, with consideration of the interactions between foods and nutrients, has a practical implication for cancer prevention. This study provided an overview of dietary pattern extraction methods, summarized the research findings on the association between dietary patterns and cancers in the digestive system, respiratory system, and genitourinary system, and elucidated the potential mechanisms underlying these associations, in order to provide scientific references for future research in this field.

Objective:To seek the optimal melanin-removal method for hematoxylin and eosin (HE) staining, immunohistochemistry and molecular detection.Methods:Thirty-eight paraffin tissue samples of malignant melanoma diagnosed at the Fujian Cancer Hospital, Fuzhou, China between January 2018 and March 2022 were collected and used to make a tissue microarray. Melanin in these cases was removed using warm hydrogen peroxide, double oxidation depigmentation, modified potassium permanganate-oxalic acid or trichloroisocyanuric acid, followed by HE staining. The cases were divided into two cohorts: one was subject to the one of the above four methods to remove melanin first, followed by immunohistochemistry (SOX-10, Ki-67, HMB45 and Melan A), while the other was subject to immunohistochemical staining first and then a melanin removal. Following that, seventeen melanin-rich paraffin tissue samples were collected and depigmented using the methods described above. DNA extraction was then done, followed by assessments of DNA content and quality. Moreover, the completeness of melanin removal, the effect on HE and immunohistochemical staining, and the quality of DNA were compared between the depigmented methods.Results:Regarding the effectiveness of melanin removal, the modified potassium permanganate-oxalic acid and the warm hydrogen peroxide methods were the most effective, and both showed residual melanin in only 5.26% (2/38) of the cases. The trichloroisocyanuric acid method showed residual melanin in 10.53% (4/38) of the cases. The worst was the double oxidation depigmentation method, which showed pigment residue in 15.79% (6/38) of the cases. For HE staining, the percentage of good staining with the warm hydrogen peroxide method was 92.11%, higher than the other three methods. For immunohistochemical staining, the mean staining scores of immunohistochemistry first followed by melanin removal with modified potassium permanganate-oxalic acid, double oxidation and trichloroisocyanuric acid were 20.84, 26.63 and 35.02, respectively. These immunohistochemical staining scores were higher than those of melanin removal first followed by immunohistochemistry (8.70, 15.41 and 21.22, respectively). The mean staining score of melanin removal by warm hydrogen peroxide method followed by immunohistochemistry was 33.57, superior to that of immunohistochemistry followed by the melanin removal (19.96). Moreover, the staining scores of HMB45, MelanA and Ki-67 with immunohistochemical staining followed by trichloroisocyanuric acid method were 36.45, 33.79, and 36.24, respectively, while the staining score of SOX10 with melanin removal by warm hydrogen peroxide followed by immunohistochemistry was 34.39. The DNA was significantly degraded by modified potassium permanganate-oxalic acid, double oxidation depigmentation and trichloroisocyanuric acid, whereas the mean concentration of DNA extracted after melanin removal by hydrogen peroxide method was 59.59 μg/L, substantially higher than that of DNA extracted without melanin removal (30.3 μg/L, P=0.001). The A260/ A280 of DNA extracted after melanin removal by hydrogen peroxide was between 1.8 and 2.0 in all cases, and the A260/ A230 was above 2.0 in sixteen cases, suggesting high purity of DNA. However, the DNA extracted without removing the melanin showed poor purity, with A260/ A280 below 1.8 in eight cases and A260/ A230 below 2.0 in sixteen cases. Conclusions:Warm hydrogen peroxide showed the least melanin residue, superior HE staining and a minimal effect on DNA purity/quality compared to the other three methods. It thus appears most suitable for PCR, NGS and other molecular detection. Melanin removal with trichloroisocyanuric acid after immunohistochemical staining has the least melanin residual, and thus could be the most convenient and efficient. However, it is noted that the efficacy of the same depigmentation method varies with different antibodies. Therefore, the optimal depigmentation method should be selected based on the specific markers of interest.

Objective:To explore the treatment methods and clinical efficacy of penetrating high-voltage electric burns to thoracoabdominal wall.Methods:This study was a retrospective observational study. From March 2020 to March 2023, six male patients with penetrating high-voltage electric burns to thoracoabdominal wall who met the inclusion criteria were hospitalized at West China Hospital of Sichuan University, aged 42 to 57 years. Among them, one patient had thoracoabdominal wall defects with perforation and necrosis of the gastric wall and diaphragm, two patients had thoracoabdominal wall defects with perforation and necrosis of the gastric wall alone, and three patients had abdominal wall defects with perforation and necrosis of the small intestine. In the emergency department, aesthetic plastic and burn surgery, general surgery, and/or thoracic surgery doctors jointly formulated an emergency surgery plan for the patients. Three patients with perforation and necrosis of the gastric wall underwent subtotal gastrectomy and anastomosis. One of them, who also had diaphragmatic perforation and necrosis, underwent resection of the necrotic diaphragm and repair. The other three patients with perforation and necrosis of the small intestine underwent resection and anastomosis of the necrotic intestinal segment. After debriding the thoracoabdominal wall wounds conservatively in stage Ⅰ and repairing the abdominal wall defects with greater omentum coverage, the thoracoabdominal wall wounds were treated with vacuum sealing drainage (VSD). Seven days later, a stage Ⅱ thorough debridement of the thoracoabdominal wall wounds was performed, and bovine acellular dermal matrix was transplanted onto the surface of the greater omentum and the surrounding skin wounds without skin coverage, and the VSD treatment of the thoracoabdominal wall wounds was continued. After 7 days, the VSD treatment was stopped, and after the fresh granulation tissue well developed in the wounds, a stage Ⅲ transplantation of meshed split-thickness skin graft from the lateral femur was performed to close the thoracoabdominal wall wounds, followed by continuing VSD treatment for another 7 days. Data were recorded including the status of patients' enteral nutrition recovery and occurrence of complications such as abdominal infection after stage Ⅰ surgery, the time from starting moist dressing change to the wound being ready for skin grafting after stage Ⅱ surgery, the microbiological culture of wound exudate samples and conditions of wound surrounding areas from starting moist dressing change to wound healing after stage Ⅱ surgery, skin graft survival, and wound healing time. Follow-up was carried out to observe the occurrence of gastrointestinal symptoms, abdominal wall hernia, scars, and functional disorders, etc.Results:All six patients resumed enteral nutrition on day 2 to 4 after stage Ⅰ surgery, with no occurrence of intestinal obstruction, anastomotic leakage, or abdominal infection. The time from starting moist dressing change to the wound being ready for skin grafting after stage Ⅱ surgery was 8 (6, 12) days. During the period from starting moist dressing change to wound healing after stage Ⅱ surgery, microbiological culture of wound exudate sample showed Enterobacter cloacae in one patient and Pseudomonas aeruginosa in another patient, while the remaining four patients had negative cultures; no patient developed wound edge inflammation. All grafted skin survived, and the wound healing time was 38 (30, 46) days. During follow-up from 12 to 36 months after stage Ⅲ surgery, patients had no intractable constipation or intestinal obstruction symptoms, no obvious local tissue herniation requiring surgical treatment, no scar ulceration, and no functional disorders. Conclusions:For penetrating high-voltage electric burns to thoracoabdominal wall, a sequential three-stage surgical treatment plan under a multidisciplinary team collaboration model can effectively protect organ function and control wound infection. Long-term follow-up shows good gastrointestinal function and thoracoabdominal wall appearance. This method is highly reproducible and effective, which is suitable for clinical promotion and use.