1.Interpretation of Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines
Wenxi PENG ; Meng QIAO ; Lianxin WANG ; Yuanyuan LI ; Xiuhui LI ; Xin CUI ; Zijia CHEN ; Xinyi CHEN ; Yi DENG ; Yanming XIE ; Zhifei WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):152-160
The Pharmacovigilance Guidelines for Clinical Application of Oral Chinese Patent Medicines (hereinafter referred to as the Guidelines) is first specialized in the field of drug safety for oral Chinese patent medicines (OCPMs) in China. Rooted in China's healthcare context, the Guidelines address the unique usage patterns and risk characteristics of OCPMs, filling a regulatory gap in the pharmacovigilance framework specific to this category. To facilitate accurate understanding and effective implementation of the Guidelines, and to promote the standardized development of pharmacovigilance practices for OCPMs, this study offered a systematic interpretation based on its three core components. In the domain of risk monitoring and reporting, the paper analyzed the rationale for multi-source information integration and clarified the criteria for identifying key products and target populations for intensive monitoring. Regarding risk assessment, the Guidelines were examined from three dimensions of formulation components, medication behaviors, and population to address complex safety issues arising from medicinal constituents, irrational use, and individual susceptibility. In the area of risk control, the analysis focused on context-based interventions and dynamic closed-loop management strategies, exploring practical pathways to shift from passive response to proactive risk mitigation. Furthermore, this paper evaluated the applied value of the Guidelines and identified implementation challenges, such as insufficient capacity at the primary-care level and limited digital infrastructure. In response, the study proposed optimization strategies including establishing a dynamic updating mechanism, strengthening training at the grassroots level, and incorporating artificial intelligence to enhance pharmacovigilance capacity. This interpretation aims to provide actionable insights for marketing authorization holders (including manufacturers), pharmaceutical distributors, healthcare institutions, and research organizations, ultimately supporting the establishment and refinement of a full lifecycle pharmacovigilance system for OCPMs.
2.Correlation of Symptom Burden and Nutritional Status of Patients with Cancer in Chemotherapy Stage Under Guidance of TCM Constitution
Bailu SUI ; Yuhang FANG ; Yi XIE ; Yan WANG ; Ying ZHANG
Cancer Research on Prevention and Treatment 2026;53(2):127-132
Objective To investigate the relationship between symptom burden and nutritional status under Traditional Chinese Medicine (TCM) constitution classification in patients undergoing chemotherapy. Methods Data on the physical constitution, symptom burden, and nutritional status of 640 patients with malignant tumors within the 21st–28th days of chemotherapy treatment were collected and analyzed. Results Symptom burden was found to have a positive correlation with nutritional risk and TCM bias (except for idiosyncrasies), suggesting that constitution bias may be an important internal factor for the aggravation of clinical symptoms and malnutrition in patients with cancer. Conclusion The relationship between symptom burden and nutritional status in chemotherapy under the guidance of TCM constitution can be studied to predict the nutritional status and symptom burden of patients after chemotherapy to guide the symptom and nutritional management of patients with cancer in the chemotherapy stage.
3.Zishen Huoxue Prescription Alleviates Endoplasmic Reticulum Stress in Hippocampal Neurons of 2-VO Rats via GRP78/PERK/ATF4 Signaling Pathway
Yao SU ; Feng QIU ; Tao YI ; Hanquan LI ; Le XIE ; Xiuli ZHANG ; Dahua WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):93-102
ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription (ZSHXP) ameliorates cognitive dysfunction in rats with vascular dementia (VD) induced by the bilateral common carotid artery ligation (2-VO model rats) through regulating the glucose-regulated protein 78 (GRP78)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley (SD) rats were randomly divided into six groups: Sham group, Model group, donepezil hydrochloride group (0.45 mg·kg-1), and ZSHXP groups at low (8.90 g·kg-1), medium (17.80 g·kg-1), and high (35.60 g·kg-1) doses,with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats, and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin (HE) and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen (NeuN) with GRP78 and βⅢ Tubulin with gasdermin D (GSDMD) in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress (ERS)-related proteins including GRP78, PERK, ATF4, phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), C/EBP homologous protein (CHOP), NOD-like receptor protein 3 (NLRP3), Caspase-1 and GSDMD. ResultsCompared with the sham operation group, the model group showed a significantly prolonged escape latency (P<0.01), a significant decrease in the number of platform crossings and the residence time in the target quadrant (P<0.01), and a markedly reduced recognition index (P<0.01). Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity, deformed and shrunken cell bodies, and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously, accompanied by abnormal dilation and swelling, and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78, p-PERK/PERK, ATF4, CHOP, NLRP3, GSDMD and Caspase-1 in the model group were significantly elevated (P<0.01). Compared with the model group, the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency (P<0.01) and an increased number of platform crossings (P<0.05, P<0.01). The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups (P<0.05, P<0.01), with a significantly improved recognition index (P<0.01). In the donepezil hydrochloride group and all ZSHXP groups, the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group, the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group, the protein expressions of GRP78, ATF4 and CHOP were increased (P<0.01), while the expression of p-PERK/PERK was decreased (P<0.05). In the ZSHXP low-dose group, the expressions of GRP78, p-PERK/PERK and CHOP were elevated (P<0.05, P<0.01). The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK, ATF4 and CHOP (P<0.01), and the high-dose group had a markedly reduced GRP78 protein expression (P<0.01). In the donepezil hydrochloride group, the Caspase-1 protein expression was increased (P<0.01) and the NLRP3 protein expression was decreased (P<0.01). In the ZSHXP low-dose group, the GSDMD expression was elevated (P<0.01) while the NLRP3 protein expression was reduced (P<0.01). After treatment with medium and high doses of ZSHXP, the protein expression levels of NLRP3, GSDMD and Caspase-1 were significantly decreased (P<0.01). ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway, which ameliorates ERS and inhibits neuronal pyroptosis.
4.Zishen Huoxue Prescription Alleviates Endoplasmic Reticulum Stress in Hippocampal Neurons of 2-VO Rats via GRP78/PERK/ATF4 Signaling Pathway
Yao SU ; Feng QIU ; Tao YI ; Hanquan LI ; Le XIE ; Xiuli ZHANG ; Dahua WU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):93-102
ObjectiveTo investigate the mechanism by which the Zishen Huoxue prescription (ZSHXP) ameliorates cognitive dysfunction in rats with vascular dementia (VD) induced by the bilateral common carotid artery ligation (2-VO model rats) through regulating the glucose-regulated protein 78 (GRP78)/protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4) signaling pathway. MethodsA VD rat model was established via the 2-VO method. A total of 72 male Sprague-Dawley (SD) rats were randomly divided into six groups: Sham group, Model group, donepezil hydrochloride group (0.45 mg·kg-1), and ZSHXP groups at low (8.90 g·kg-1), medium (17.80 g·kg-1), and high (35.60 g·kg-1) doses,with 12 rats in each group. The Morris Water Maze test was utilized to assess spatial learning and memory abilities of rats, and the Novel Object Recognition test was used to evaluate cognitive performance. Hematoxylin-eosin (HE) and Nissl staining were applied to observe the histological and morphological changes in hippocampal tissues. Transmission electron microscopy (TEM) was used to observe the morphological changes of endoplasmic reticulum in rat hippocampal neurons. Immunofluorescence staining was adopted to detect the colocalization of neuronal nuclei antigen (NeuN) with GRP78 and βⅢ Tubulin with gasdermin D (GSDMD) in hippocampal neurons. Western blot was used to detect the expression levels of endoplasmic reticulum stress (ERS)-related proteins including GRP78, PERK, ATF4, phosphorylated protein kinase R-like endoplasmic reticulum kinase (p-PERK), C/EBP homologous protein (CHOP), NOD-like receptor protein 3 (NLRP3), Caspase-1 and GSDMD. ResultsCompared with the sham operation group, the model group showed a significantly prolonged escape latency (P<0.01), a significant decrease in the number of platform crossings and the residence time in the target quadrant (P<0.01), and a markedly reduced recognition index (P<0.01). Histological observations revealed that the hippocampal neurons in the model group were disorderly arranged with reduced quantity, deformed and shrunken cell bodies, and pyknotic and hyperchromatic nuclei. The number of Nissl bodies decreased significantly. The number of endoplasmic reticula reduced obviously, accompanied by abnormal dilation and swelling, and the loss of normal folding structure. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly increased in the model group. The protein expression levels of GRP78, p-PERK/PERK, ATF4, CHOP, NLRP3, GSDMD and Caspase-1 in the model group were significantly elevated (P<0.01). Compared with the model group, the donepezil hydrochloride group and the ZSHXP medium- and high-dose groups had a significantly shortened escape latency (P<0.01) and an increased number of platform crossings (P<0.05, P<0.01). The residence time in the target quadrant was increased in the donepezil hydrochloride group and all ZSHXP groups (P<0.05, P<0.01), with a significantly improved recognition index (P<0.01). In the donepezil hydrochloride group and all ZSHXP groups, the number of hippocampal neurons increased with a more compact arrangement and reduced nuclear hyperchromasia. The number of Nissl bodies increased with morphological structures tending to be normal. In the ZSHXP high-dose group, the number of endoplasmic reticula increased and the folding structure was restored. The fluorescence colocalization of NeuN with GRP78 and βⅢ Tubulin with GSDMD in the hippocampus was significantly weakened in the treatment groups. In the donepezil hydrochloride group, the protein expressions of GRP78, ATF4 and CHOP were increased (P<0.01), while the expression of p-PERK/PERK was decreased (P<0.05). In the ZSHXP low-dose group, the expressions of GRP78, p-PERK/PERK and CHOP were elevated (P<0.05, P<0.01). The ZSHXP medium- and high-dose groups showed a significant decrease in the protein expressions of p-PERK/PERK, ATF4 and CHOP (P<0.01), and the high-dose group had a markedly reduced GRP78 protein expression (P<0.01). In the donepezil hydrochloride group, the Caspase-1 protein expression was increased (P<0.01) and the NLRP3 protein expression was decreased (P<0.01). In the ZSHXP low-dose group, the GSDMD expression was elevated (P<0.01) while the NLRP3 protein expression was reduced (P<0.01). After treatment with medium and high doses of ZSHXP, the protein expression levels of NLRP3, GSDMD and Caspase-1 were significantly decreased (P<0.01). ConclusionThe ameliorative effect of ZSHXP on cognitive function in 2-VO model rats may be associated with its regulation of the GRP78/PERK/ATF4 signaling pathway, which ameliorates ERS and inhibits neuronal pyroptosis.
5.Development of a Diagnostic Scale for Qi-Yin Deficiency with Blood Stasis Syndrome in Diabetic Macrovascular Disease
Qingzhi LIANG ; Ting LUO ; Yi SU ; Xiaoqin LIU ; Hong GAO ; Hongyan XIE ; Chunguang XIE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):225-234
ObjectiveTo construct a standardized diagnostic scale for Qi-Yin deficiency with blood stasis syndrome in diabetic macrovascular disease. MethodsLiterature related to Qi-Yin deficiency with blood stasis syndrome in diabetic macrovascular disease was retrieved from CNKI, VIP, and Wanfang databases. Diagnostic information from four diagnostic methods was extracted and standardized, with items having a frequency of ≥15 included in the item pool. A three-round Delphi expert consultation was conducted, screening items using support degree, mean score, rank sum, and coefficient of variation. Item weights were determined using analytic hierarchy process (AHP), gactor analysis (FA), and combined weighting method (CWM). The optimal weighting method was selected by comparing the area under the receiver operating characteristic (ROC) curve (AUC). The Youden index was calculated to establish the diagnostic cutoff value, which was proportionally scaled. ResultsA total of 102 studies were included. Thirty-five items were incorporated into the item pool. The authority coefficients for the three Delphi rounds were 0.82, 0.85, and 0.86, with coordination coefficients of 0.648, 0.538, and 0.506, respectively. Fifteen items were retained after screening. ROC curve analysis showed the AUC ranking as FA > CWM > AHP. The maximum Youden index was 0.814, corresponding to a diagnostic cutoff of 8.361 (scaled to 40 points). The final scale adopted a structured diagnostic framework: the symptom dimension requires at least 2 items, and the tongue or pulse dimension requires at least 1 category. ConclusionThis study developed a standardized diagnostic scale for Qi-Yin deficiency with blood stasis syndrome in diabetic macrovascular disease. Core items were screened via the Delphi method, with factor analysis identified as the optimal weighting method through AUC comparison. The diagnostic threshold (40 points) and structured diagnostic framework provide a quantitatively clear, clinically practical tool.
6.Olfactory Receptors Expressed in The Intestine and Their Functions
Pei-Wen YANG ; Meng-Meng YUAN ; Ying ZHOU ; Peng LI ; Gui-Hong QI ; Ying YANG ; Zhong-Yi MAO ; Meng-Sha ZHOU ; Xiao-Shuang MAO ; Jian-Ping XIE ; Yi-Nan YANG ; Shi-Hao SUN
Progress in Biochemistry and Biophysics 2026;53(3):534-549
Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.
7.Establishment and Evaluation of Diabetic Macrovascular Atherosclerosis Model with Qi and Yin Deficiency Syndrome
Ting LUO ; Qingzhi LIANG ; Xi PENG ; Yi SU ; Hongyan XIE ; Chunguang XIE
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(13):86-98
ObjectiveTo explore the establishment of a rat model of diabetic macrovascular atherosclerosis (DMA) with Qi and Yin deficiency syndrome induced by high-fat diet, streptozotocin (STZ), and Yin-depleting herbs, and to evaluate its biological characteristics. MethodsForty SD rats were randomly divided into a blank group (n=10) and a modeling group (n=30). Except for the blank group, rats in the model group were fed a high-fat diet for 4 weeks, followed by intraperitoneal injection of STZ (30 mg·kg-1) to establish a diabetic model. Twenty-four successfully modeled diabetic rats were randomly divided into a model group (n=7), a Qi and Yin deficiency syndrome group (n=8), and a counter-syndrome group (n=9). Except for the model group, rats received intragastric administration of Yin-depleting herbs (1.2 g·kg-1) for 8 weeks. The counter-syndrome group was further treated with Shenqi compound formula (1.69 g·kg-1) for an additional 8 weeks. General condition and body weight were recorded, and syndrome-related indicators were assessed, including precordial temperature, skin moisture content, grip strength, open-field test performance, and tongue appearance. Serum levels of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), vascular cell adhesion molecule-1 (VCAM-1), insulin-like growth factor-1 (IGF-1), and monocyte chemotactic protein-1 (MCP-1) were measured by enzyme-linked immunosorbent assay (ELISA). Fasting blood glucose, blood lipids, hemorheological parameters, and coagulation function were analyzed using an automatic biochemical analyzer. Vascular ultrasound and hematoxylin-eosin (HE) staining were used to evaluate vascular lesions. ResultsIn terms of syndrome manifestations, compared with the blank group, body weight increased rapidly during the first 5 weeks in the model, Qi and Yin deficiency, and counter-syndrome groups. After STZ injection combined with Yin-depleting herbal administration at week 5, body weight decreased significantly (P<0.01) and continued to decline until the end of the experiment. Rats exhibited decreased activity, irritability, coarse and yellowish fur with obvious shedding, polydipsia, polyphagia, frequent urination, and dry stools, which were most pronounced in the Qi and Yin deficiency group. Grip strength decreased, peak activity time occurred earlier, total distance in the open-field test was reduced, and residence time was prolonged. Precordial temperature decreased (P<0.01), while paw temperature increased (P<0.05), and skin moisture and oil content were reduced (P<0.05, P<0.01). In terms of disease-related indicators, compared with the blank group, fasting blood glucose was significantly increased (>16.7 mmol·L-1) in the model and Qi and Yin deficiency groups, and blood lipid levels were significantly elevated (P<0.05). Vascular-related factors ET-1, MCP-1, VCAM-1, and VEGF were significantly increased (P<0.05,P<0.01), while IGF-1 was significantly decreased (P<0.01). Pathological examination of the aortic valve showed valvular thickening and structural disorganization. Carotid artery examination revealed discontinuity of the intima, foam cell accumulation beneath the intima, disordered smooth muscle arrangement, and widened intercellular spaces. Compared with the model group, ET-1, MCP-1, and VEGF levels were significantly decreased in both the Qi and Yin deficiency group and the counter-syndrome group. The reductions in ET-1 and MCP-1 were more pronounced in the Qi and Yin deficiency group (P<0.01), while the decrease in VCAM-1 was more significant in the counter-syndrome group (P<0.05). Compared with the blank group, the Qi and Yin deficiency group showed significantly prolonged activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT) (P<0.01). The erythrocyte deformability index (TK), erythrocyte sedimentation rate, erythrocyte electrophoresis index, and whole blood low-shear viscosity all showed increasing trends. Vascular ultrasound revealed reduced arterial blood flow velocity, increased vascular resistance, and intimal thickening without plaque formation. The aortic intima showed no obvious overall thickening, with only occasional localized thickening and foam cell presence, and carotid artery injury was observed. ConclusionA rat model of DMA with Qi and Yin deficiency syndrome was successfully established using high-fat diet feeding combined with STZ injection and Yin-depleting herbal administration. Shenqi compound formula effectively alleviated Qi and Yin deficiency syndrome, regulated glucose and lipid metabolism, improved hemorheological and coagulation function, reduced vascular lesion severity, and demonstrated potential for early prevention and treatment of DMA.
8.Application research of linear calibration using two reference substances in the establishment of qualitative standards for multi-component analysis of Saposhnikovia divaricata
YAN Jingyi ; ZHOU Hongxu ; TAO Muke ; XIE LinJuan ; JU Miao ; ZHANG Yi
Drug Standards of China 2026;27(1):0092-0099
Objective: Establishment of a HPLC method for six chemical components in Saposhnikovia divaricata (prim-O-glucosylcimifugin, cimifugin, 5-O-methylvisamminoside, sec-O-glucosylhamaudol, psoralen, and imperatorin), comparison of the advantages and disadvantages of the dual-standard linear calibration method and the relative retention time method, and investigation of the feasibility of the linear calibration using two reference substances for qualitative analysis of multiple components in Saposhnikovia divaricata.
Methods: A HPLC method was employed, using 21 different brands and models of C18 columns. The mobile phase consisted of acetonitrile (A) and 0.02% phosphoric acid aqueous solution (B), with gradient elution (0-20 min, 18%A; 20-45 min, 18%A-50%A; 45-60 min, 50%A). The column temperature was set at 30 ℃, the flow rate was 1 mL·min-1, and the detection wavelength was 254 nm.
Results: The results predicted by the linear calibration using two reference substances were accurate and superior to those of the relative retention time method, and the six components exhibited good linear relationships within their respective ranges.
Conclusion: The established linear calibration using two reference substances accurately predicts the retention times of the target components. This method is stable and reliable, providing a reference for the establishment of digital standards in traditional Chinese medicine.
9.Key Challenges and Mitigation Strategies for Animal Pregnancy in Non-clinical Reproductive Toxicity Testing of Drugs
Kun LIU ; Qing LAN ; Bing YI ; Xiaojie XIE
Laboratory Animal and Comparative Medicine 2025;45(4):449-456
Non-clinical reproductive toxicity studies typically employ mammals like rats, rabbits, and cynomolgus monkeys, with animal pregnancy being a key challenge in such testing. This article focuses on the difficulties encountered in the animal pregnancy process and potential countermeasures. Rats can be used for fertility and early embryonic development toxicity studies (Segment Ⅰ), embryo-fetal development toxicity studies (Segment Ⅱ), and perinatal toxicity studies (Segment Ⅲ). The estrous cycle of female rats can be determined by vaginal smear, and mating behavior is confirmed through copulatory plug checks the following day after pairing one female with one male in the same cage. Rabbits are commonly used in embryo-fetal development toxicity studies (Segment Ⅱ). Mating behavior between male rabbits and estrous females is observed to determine the time of conception. However, challenges such as atypical estrus of female rabbits, large variations in estrus between batches, and mating failure often occur in reproductive toxicity testing, which may be addressed through prolonged light exposure, increased protein supplementation, optimized mating strategies, and environmental modifications like female and male rabbits are raised adjacent to each other. Non-human primates (NHPs) are typically employed in perinatal toxicity studies (Segment Ⅲ), where one of the key challenges lies in accurately determining sexual maturity in males - a critical factor for reproductive toxicity testing, which can be assessed through comprehensive evaluation of age, body weight, and testicular volume. Generally, male macaques are considered sexually mature when they meet the following criteria: age >4.5 years, body weight >4.5 kg, single testis volume >10 mL, and combined testicular volume >20 mL. For pregnancy confirmation, ultrasound examination demonstrating visible gestational sacs is required, though this necessitates experienced veterinary clinicians to establish standardized ultrasound examination protocols. In conclusion, reproductive toxicity studies should employ species-appropriate detection methods and evaluation criteria based on anatomical characteristics of the reproductive system to ensure successful mating and proper study execution.
10.Association between household solid fuel use for cooking and depressive symptoms among middle-aged and elderly adults in rural China: Evidence from the China Family Panel Studies Database
Ting YANG ; Yong LIU ; Xufeng LI ; Yun GAI ; Zhihao XIE ; Junkui WANG ; Yong YU ; Jingxuan WANG
Journal of Environmental and Occupational Medicine 2025;42(8):926-931
Background Although current evidence suggests a link between outdoor air pollution and depressive symptoms, the effect of solid fuel use (a significant indoor air pollutant) on depressive symptoms in China's rural middle-aged and elderly population remains poorly understood. Objective To explore the association between solid fuel use for cooking and depressive symptoms among middle-aged and elderly people in rural areas of China, and to provide a basis for the prevention and control of depressive symptoms among residents in rural areas. Methods Data were obtained from the 2020 China Family Panel Studies (CFPS), depressive symptoms were assessed using 8-item Center for Epidemiologic Studies Depression Scale (CES-D), and cooking fuel type was self-reported. Subsequently, two-level binary unconditional logistic regression models were fitted to assess the impact of solid fuel use for cooking on depressive symptoms. Results A total of

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