To gain an in-depth understanding of the clinical application of Rehmanniae Radix during the Qing Dynasty and to clarify its specifications and corresponding therapeutic effects， this study took Rehmanniae Radix in the prescriptions documented in Research on Medical Cases of the Qing Imperial Court as the research subject. According to historical medical literature， a comprehensive investigation was conducted on the specifications， therapeutic efficacy， frequency of use， dosage， and seasonal patterns of Rehmanniae Radix employed by imperial physicians. The findings revealed that Rehmanniae Radix in the medical cases of the Qing court was primarily classified into three categories： Xiaoshengdi， Zhongshengdi， and Dashengdi. Xiaoshengdi was also referred to as Xishengdi or Cishengdi， all denoting dried Rehmanniae Radix. The term Xishengdi was inconsistently defined in the literature. It should refer to the slender variant of dried Rehmanniae Radix and was utilized as a specific specification in the medical cases of the Qing court. In contrast， the wild fresh roots of Rehmanniae Radix， described as "as slender as fingers"， were commonly documented as fresh Rehmanniae Radix in these medical cases. There were variations in Rehmanniae Radix size and grading between historical and contemporary standards. Furthermore， therapeutic differences were observed among Rehmanniae Radix specifications in the medical cases of the Qing court. Xiaoshengdi and Zhongshengdi exhibited slightly stronger blood-cooling and heat-clearing effects while maintaining a non-cloying Yin-nourishing property. In contrast， Dashengdi demonstrated a greater emphasis on Yin supplementation with relatively milder heat-clearing activity. In the medical cases of the Qing court， the dosage of Rehmanniae Radix in different specifications was usually 11.2-18.7 g per dose， typically administered twice daily. Rehmanniae Radix in different specifications exhibits variations in efficacy， which can provide evidence-based insights for precise clinical application.

To gain an in-depth understanding of the clinical application of Rehmanniae Radix during the Qing Dynasty and to clarify its specifications and corresponding therapeutic effects， this study took Rehmanniae Radix in the prescriptions documented in Research on Medical Cases of the Qing Imperial Court as the research subject. According to historical medical literature， a comprehensive investigation was conducted on the specifications， therapeutic efficacy， frequency of use， dosage， and seasonal patterns of Rehmanniae Radix employed by imperial physicians. The findings revealed that Rehmanniae Radix in the medical cases of the Qing court was primarily classified into three categories： Xiaoshengdi， Zhongshengdi， and Dashengdi. Xiaoshengdi was also referred to as Xishengdi or Cishengdi， all denoting dried Rehmanniae Radix. The term Xishengdi was inconsistently defined in the literature. It should refer to the slender variant of dried Rehmanniae Radix and was utilized as a specific specification in the medical cases of the Qing court. In contrast， the wild fresh roots of Rehmanniae Radix， described as "as slender as fingers"， were commonly documented as fresh Rehmanniae Radix in these medical cases. There were variations in Rehmanniae Radix size and grading between historical and contemporary standards. Furthermore， therapeutic differences were observed among Rehmanniae Radix specifications in the medical cases of the Qing court. Xiaoshengdi and Zhongshengdi exhibited slightly stronger blood-cooling and heat-clearing effects while maintaining a non-cloying Yin-nourishing property. In contrast， Dashengdi demonstrated a greater emphasis on Yin supplementation with relatively milder heat-clearing activity. In the medical cases of the Qing court， the dosage of Rehmanniae Radix in different specifications was usually 11.2-18.7 g per dose， typically administered twice daily. Rehmanniae Radix in different specifications exhibits variations in efficacy， which can provide evidence-based insights for precise clinical application.

Background: Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice. Methods: We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years. Results: Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi. Conclusion ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

Background: Antithyroid drug (ATD) treatment is the preferred initial treatment for Graves’ disease (GD) in South Korea, despite higher treatment failure rates than radioactive iodine (RAI) therapy or thyroidectomy. This study aimed to evaluate the incidence of treatment failure associated with the primary modalities for GD treatment in real-world practice. Methods: We included 452,001 patients diagnosed with GD between 2004 and 2020 from the Korean National Health Insurance Service-National Health Information Database. Treatment failure was defined as switching from ATD, RAI, or thyroidectomy treatments, and for ATD specifically, inability to discontinue medication for over 2 years. Results: Mean age was 46.2 years, with females constituting 70.8%. Initial treatments for GD included ATDs (98.0%), thyroidectomy (1.3%), and RAI (0.7%), with a noted increment in ATD application from 96.2% in 2004 to 98.8% in 2020. During a median follow- up of 8.5 years, the treatment failure rates were 58.5% for ATDs, 21.3% for RAI, and 2.1% for thyroidectomy. Multivariate analysis indicated that the hazard ratio for treatment failure with ATD was 2.81 times higher than RAI. RAI treatments ≥10 mCi had 37% lower failure rates than doses <10 mCi. Conclusion ATDs are the most commonly used for GD in South Korea, followed by thyroidectomy and RAI. Although the risk of treatment failure for ATD is higher than that of RAI therapy, initial RAI treatment in South Korea is relatively limited compared to that in Western countries. Further studies are required to evaluate the cause of low initial RAI treatment rates in South Korea.

The "theory of Zangqi method" in Huangdi Neijing the "Tangye Jingfa picture" in Dunhuang's posthumous book Fuxingjue both contain the relationship between the five medicinal tastes and the reinforcing-reducing treatment of the five Zang organs. This article made a systematic comparative analysis of the two methods from the aspects of narrative methods， specific content， mathematical logic， clinical experience， and real treatment effect. From the perspective of narrative methods， they both adopted the expression structure of three medicinal tastes corresponding to one organ， which were respectively described as tonic， laxative， and urgent tastes， with the same way of thinking and the narrative frame shared. From the perspective of reinforcing-reducing content， out of a total of 15 attributes related to the corresponding tonic， laxative， and urgent tastes of the five organs involved in the two methods， there were seven inconsistencies between the two methods. In terms of medicinal taste distribution， the "Tangye Jingfa Tu" presented the order of "liver， heart， spleen， lung， and kidney"， Whether tonic， laxative， or transforming tastes， they were all pungent， salty， sweet， sour， or bitter. However， the "theory of Zangqi method" showed no such pattern. From the perspective of mathematical modeling analysis， the distribution of medicinal tastes in the "Tangye Jingfa Tu" conformed to the mathematical logic of the outer product of a five-dimensional space vector， while the "theory of Zangqi method" had no such law. From the perspective of clinical experience， the effect of removing the heart-fire with a bitter taste in the "Tangye Jingfa Tu" was more consistent with the clinical cognition of clearing heat and detoxification effects of traditional Chinese medicine （TCM） with a sweet taste in the "theory of Zangqi method". From the perspective of understanding prescriptions and solving prescriptions， the combination and compatibility principle of 160 common classical prescriptions in the Formulas of Traditional Chinese Medicine can be analyzed by using the "Tangye Jingfa Tu". Therefore， the authors believed that the relationship between the five medicinal tastes and the reinforcing-reducing treatment of the five zang organs in the Fuxingjue was more rigorous and logical， in line with clinical empirical cognition than the relevant records in the Yellow Emperor's Canon of Medicine.

The "theory of Zangqi method" in Huangdi Neijing the "Tangye Jingfa picture" in Dunhuang's posthumous book Fuxingjue both contain the relationship between the five medicinal tastes and the reinforcing-reducing treatment of the five Zang organs. This article made a systematic comparative analysis of the two methods from the aspects of narrative methods， specific content， mathematical logic， clinical experience， and real treatment effect. From the perspective of narrative methods， they both adopted the expression structure of three medicinal tastes corresponding to one organ， which were respectively described as tonic， laxative， and urgent tastes， with the same way of thinking and the narrative frame shared. From the perspective of reinforcing-reducing content， out of a total of 15 attributes related to the corresponding tonic， laxative， and urgent tastes of the five organs involved in the two methods， there were seven inconsistencies between the two methods. In terms of medicinal taste distribution， the "Tangye Jingfa Tu" presented the order of "liver， heart， spleen， lung， and kidney"， Whether tonic， laxative， or transforming tastes， they were all pungent， salty， sweet， sour， or bitter. However， the "theory of Zangqi method" showed no such pattern. From the perspective of mathematical modeling analysis， the distribution of medicinal tastes in the "Tangye Jingfa Tu" conformed to the mathematical logic of the outer product of a five-dimensional space vector， while the "theory of Zangqi method" had no such law. From the perspective of clinical experience， the effect of removing the heart-fire with a bitter taste in the "Tangye Jingfa Tu" was more consistent with the clinical cognition of clearing heat and detoxification effects of traditional Chinese medicine （TCM） with a sweet taste in the "theory of Zangqi method". From the perspective of understanding prescriptions and solving prescriptions， the combination and compatibility principle of 160 common classical prescriptions in the Formulas of Traditional Chinese Medicine can be analyzed by using the "Tangye Jingfa Tu". Therefore， the authors believed that the relationship between the five medicinal tastes and the reinforcing-reducing treatment of the five zang organs in the Fuxingjue was more rigorous and logical， in line with clinical empirical cognition than the relevant records in the Yellow Emperor's Canon of Medicine.

Objective:To evaluate the perioperative application effect of enhanced recovery after surgery (ERAS) clinical pathway in percutaneous vertebro plasty (PVP).Methods:The clinical data of 274 patients who underwent PVP treatment for osteoporotic vertebral compression fracture (OVCF) in Beijing Friendship Hospital, Capital Medical University from May 2023 to August 2024 were retrospectively analyzed. The patients were divided into two groups according to the different numbers of surgical segments: the single-segment group ( n=211) and the multisegment group ( n=63). Patients in the single-segment group underwent single-segment surgery, while patients in the multisegment group underwent surgery on ≥2 segments. The core points of the ERAS clinical pathway adopted in this study include perioperative education, pain management, early mobilization, application of "outfast", and joint guidance from the departments of nutrition and rehabilitation. Comparison was made between the two groups of patients in terms of visual analog scale (VAS) scores for low back pain at preoperative, 2 h, 6 h, 24 h postoperatively, and on the day of discharge; Oswestry disability index (ODI) scores preoperatively and on the day of discharge; time to first ambulation postoperatively, total length of hospital stay, postoperative length of stay, perioperative complications, and perioperative application of Opioid consumption. Measurement data were expressed as mean±standard deviation ( ± s), and the independent sample t-test was used for comparison between groups; count data were expressed as cases and percentage, and the Chi-square test was used for comparison between groups. The VAS pain scores at each stage of the perioperative period were evaluated using repeated measures analysis of variance or generalized estimating equations. Results:Compared with that before the operation [(6.17±0.93) points, (6.29±0.83) points], the VAS scores of low back pain of patients in the single-segment group and the multisegment group at 2 hours after surgery [(3.09±0.82) points, (3.27±0.65) points], 6 hours after surgery [(2.60±0.79) points, (2.62±0.55) points], and 24 hours after surgery [(1.89±0.77) points, (1.97±0.72) points] and on the day of discharge [(1.72±0.71) points, (1.81±0.64) points] were significantly decreased, and the differences were statistically significant ( P<0.05). At the same stage, the VAS scores of low back pain in both groups were not statistically significant ( P>0.05). The ODI scores of patients in the single-segment group and the multisegment group on the day of discharge [(24.21±2.35) points, (24.63±3.31) points] were significantly lower than those before the operation [(64.50±4.81) points, (65.52±4.08) points], and the differences were statistically significant ( P<0.05). There were no statistically significant differences in perioperative complications and the proportion of Opioid drug application between the two groups of patients ( P>0.05). Conclusion:For patients with single-segment or multisegment OVCF, PVP surgical treatment under ERAS clinical pathway management can achieve immediate pain relief, early ambulation exercise, and satisfactory perioperative efficacy.

Background and aims:Liver fibrosis is a prevalent pathological stage of various chronic liver diseases and has the potential to progress to liver cirrhosis and hepatocellular carcinoma.However,experimental models for in vivo research are limited.Unexpectedly,increased liver inflammation and fibrosis were previously observed in mice treated with aluminum adjuvant(commercial Imject Alum,a mixture of Al(OH)3 and Mg(OH)2).Our study aimed to reveal the pathogenesis and pathological features of Imject Alum-induced liver injury and evaluate its potential as an experimental model of fibrotic liver disease.Methods and materials:C57BL/6J mice were randomly divided into the following four groups:(ⅰ)control group,which received phosphate-buffered saline injections on days 1,12,26,40,and 54;(ⅱ)Imject Alum(Al(OH)3 160 mg/kg)D26 group,which was administered with Imject Alum(Al(OH)3 160 mg/kg)on days 1,12,and 26;(ⅲ)Imject Alum(Al(OH)3 80 mg/kg)D54;and(ⅳ)Imject Alum(Al(OH)3 160 mg/kg)D54 groups,which were treated with 80 mg/kg and 160 mg/kg of Imject Alum(Al(OH)3),respectively,on days 1,12,26,40,and 54.All reagents were delivered by intraperitoneal injection.Serum biochemical pa-rameters,liver pathology,and expression of genes related to inflammation and fibrogenesis were eval-uated.Transcriptome sequencing was performed.The genetic characteristics of the Imject Alum-induced liver lesions in the existing fibrosis model and patients with cirrhosis were determined.Results:Administration of Imject Alum(Al(OH)3 160 mg/kg)at certain points for 54 days led to extensive hepatic inflammation and fibrosis,accompanied by disturbed bile acid metabolism in mice.Moreover,Imject Alum aggravated liver inflammation and injury by activating the pyroptosis-related inflamma-some pathway.Transcriptome analysis revealed that Imject Alum-induced liver lesions had differentially expressed genes that were significantly enriched in pathways related to inflammation,fibrogenesis,and multiple metabolic processes.Moreover,Imject Alum-induced liver lesions exhibited gene signatures similar to those of existing fibrosis models and patients with cirrhosis.Conclusions:Aluminum adjuvant(Imject Alum;Al(OH)3 160 mg/kg)administration at certain points for 54 days resulted in notable liver injury,inflammation,and fibrosis.This model had similar gene expression characteristics with existing fibrosis models and liver samples from patients with cirrhosis.Overall,aluminum adjuvant(Imject Alum)-induced mouse model may be a novel approach for estab-lishing a liver fibrosis animal model.

This study aims to investigate the anti-tumor effect and mechanism of Guiqi Yiyuan Ointment combined with cisplatin on Lewis lung carcinoma-bearing mice via the protein kinase RNA-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2α(eIF2α)/activated transcription factor 4(ATF4)/C/EBP homologous protein(CHOP) signaling pathway. Sixty SPF-grade male C57BL/6 mice were selected and assigned into a blank group and a modeling group by the random number table method. After modeling of the Lewis lung carcinoma, the mice in the modeling group were randomized into model, cisplatin(5 mg·kg~(-1), once a week), and low-, medium-, and high-dose(1.7, 3.5, and 7.05 g·kg~(-1), respectively, once a day) Guiqi Yiyuan Ointment+cisplatin(5 mg·kg~(-1)) groups(n=10). After 14 days of continuous intervention, the spleen, thymus, and tumor samples of the mice were collected, weighed, and recorded, and the spleen index, thymus index, and tumor suppression rate were calculated. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes in the tumor tissue. The morphological changes of the endoplasmic reticulum of tumor cells were observed by transmission electron microscopy. The positive expression of phosphorylated eIF2α(p-eIF2α) and ATF4 in the tumor tissue was detected by immunofluorescence. Western blot was employed to determine the protein levels of phosphorylated PERK(p-PERK), p-eIF2α, ATF4, CHOP, B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), cyclin-dependent kinase inhibitor 1A(p21), and cyclinD1 in the tumor tissue. Real-time fluorescent quantitative PCR was employed to determine the mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, Bcl-2, p21, and cyclinD1 in the tumor tissue. Compared with the blank group, the model group showed decreases in spleen index and thymus index(P<0.05). Compared with the model group, the cisplatin group showed decreases in spleen index and thymus index(P<0.05), and the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups presented increases in spleen index and thymus index(P<0.05). In addition, the treatment groups all showed decreased tumor mass(P<0.05), increased tumor cell lysis and nuclear rupture, widened gap between rough endoplasmic reticulum, enhanced average fluorescence intensity of p-eIF2α and ATF4(P<0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P<0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P<0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P<0.05). Compared with the cisplatin group, the combination groups showed increases in spleen index and thymus index(P<0.05) as well as mean optical density(P<0.05), and the high-dose Guiqi Yiyuan Ointment+cisplatin group showed decreased tumor mass(P<0.05). In addition, the medium-and high-dose Guiqi Yiyuan Ointment+cisplatin groups showcased enhanced average fluorescence intensity of p-eIF2α and ATF4(P<0.05), up-regulated protein levels of p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, Bax, and p21(P<0.05), down-regulated protein and mRNA levels of Bcl-2 and cyclinD1(P<0.05), and up-regulated mRNA levels of PERK, eIF2α, ATF4, CHOP, Bax, and p21(P<0.05). In conclusion, Guiqi Yiyuan Ointment combined with cisplatin can effectively inhibit the growth of Lewis lung carcinoma in mice by regulating the expression of proteins related to the PERK/eIF2α/ATF4/CHOP signaling pathway and promoting cell cycle arrest and apoptosis.
Animals ; Cisplatin/administration & dosage* ; Activating Transcription Factor 4/genetics* ; Eukaryotic Initiation Factor-2/genetics* ; eIF-2 Kinase/genetics* ; Carcinoma, Lewis Lung/pathology* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Mice ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Transcription Factor CHOP/genetics* ; Ointments/administration & dosage* ; Humans ; Cell Proliferation/drug effects* ; Antineoplastic Agents/administration & dosage*