As a mercury-containing elixir， Hongshengdan has been known as a sacred medicine for surgery by ancient medical practitioners because of its precise curative effects. It originated from Yizong Shuoyue in the Qing dynasty， Qing dynasty and modern medical practitioners have adapted and modified its formula for clinical application. Employing bibliometric methods， the authors systematically organized relevant ancient literature of the Qing dynasty and modern literature， and analyzed the composition and dosage， preparation method， and clinical application. Among the 25 ancient books concerning Hongshengdan， a total of 12 medicinal formulas， 15 refining methods and 9 clinical applications were obtained. Research confirms that Hongshengdan consisted of mercury， saltpeter， alum， soap alum， cinnabar and realgar. Using measurement conversion standards of Qing dynasty， the modern single-batch formulation comprised 37.30 g of mercury， 149.20 g of saltpeter， 37.30 g of alum， 22.38 g of soap alum， 18.65 g of cinnabar， and 18.65 g of realgar. In modern refining of Hongshengdan， most medical practitioners take the core medicines， with dosages approximately 30 g of mercury， 30 g of saltpeter， and 30 g of alum. Refining method involves pretreatment stewing the materials during preparation， and alum， soap alum， and saltpeter are first ground together， then combined with mercury， cinnabar， and realgar for grinding until mercury and other drugs grind to the degree of no star points. The mixture is then placed in a pot or vessel by cold-forming method. After covering， the opening is sealed using either raw gypsum salt mud or honey-dipped cotton paper strips. Sand is packed around the vessel and then pressurized. During the calcination process， begin with a low flame（30 min）， then increase to a medium flame（30 min）， followed by a high flame（30 min）， after removing fire toxins， collect the final product. Hongshengdan has the efficacy of lifting the poison， removing the corrosion， producing muscle and dispersing， and is often used in the treatment of surgical sore and carbuncle type of diseases. Modern research indicates that Hongshengdan is commonly used to treat skin system diseases such as ulcers and herpes. The aforementioned findings provide a reference basis for the subsequent refining method and clinical application of Hongshengdan.

Hongsheng Dan, historically referred to as the "surgical sacred medicine", is at risk of losing its refining technology in contemporary times. This study aimed to preserve and innovate this traditional non-heritage refining technology. By utilizing the analytic hierarchy process(AHP) combined with the entropy weight method, this study established the hierarchical structure model of refining process of Hongsheng Dan and conducted a single factor experiment and an L_9(3~4) orthogonal experiment to optimize the refining method of Hongsheng Dan. Additionally, the study employed infrared thermal imaging to monitor temperature variations of Hongsheng Dan during the refining process. The optimized refining parameters for Hongsheng Dan were established as follows: a slow fire temperature of 175 ℃ with a duration of 30 minutes, a strong fire temperature of 270 ℃ with a duration of 60 minutes, and a tail fire temperature of 180 ℃ with a duration of 15 minutes. The stability and feasibility of this optimized process were confirmed through validation tests. The research focused on the material transformation of Hongsheng Dan, starting from the material changes during the refining process of Hongsheng Dan and the synthesis of mercuric oxide from nitric acid. The study investigated elemental transformations, physical phase changes, and alterations in thermal properties. 78.98% of the mercury in Hongsheng Dan and 80.21% of the mercury in mercuric oxide from nitric acid were retained. The diffraction peak intensity of the(011) crystal plane of Hongsheng Dan was highest at approximately 30.07°, indicating that the(011) crystal plane had a preferred crystalline orientation. Furthermore, the temperature range for the alteration in thermal properties during the refining process of Hongsheng Dan was found to be between 80 ℃ and 130 ℃. This research not only optimized the refining technology of Hongsheng Dan but also pioneered the application of infrared thermal imaging to study temperature changes throughout the refining process. By exploring the material transformation patterns of Hongsheng Dan and the synthesis of mercuric oxide from nitric acid, the study provided technical support for the preservation and innovation of Hongsheng Dan.
Drugs, Chinese Herbal/standards* ; Temperature

BACKGROUND: Poly adenosine-diphosphate-ribose polymerase (PARP) inhibitors (PARPi) have been approved to act as first-line maintenance (FL-M) therapy and as platinum-sensitive recurrent maintenance (PSR-M) therapy for ovarian cancer in China for >5 years. Herein, we have analyzed the clinical-application characteristics of olaparib and niraparib in ovarian cancer-maintenance therapy in a real-world setting to strengthen our understanding and promote their rational usage. METHODS: A retrospective chart review identified patients with newly diagnosed or platinum-sensitive recurrent ovarian cancer, who received olaparib or niraparib as maintenance therapy at Sichuan Cancer Hospital between August 1, 2018, and December 31, 2021. Patient medical records were reviewed. We grouped and analyzed patients based on the type of PARPi they used (the olaparib group and the niraparib group) and the line of PARPi maintenance therapy (the FL-M setting and the PSR-M setting). The primary endpoint was the 24-month progression-free survival (PFS) rate. RESULTS: In total, 131 patients (olaparib: n = 67, 51.1%; niraparib: n = 64, 48.9%) were enrolled. Breast cancer susceptibility genes ( BRCA ) mutations ( BRCA m) were significantly less common in the niraparib group than in the olaparib group [9.4% (6/64) vs . 62.7% (42/67), P <0.001], especially in the FL-M setting [10.4% (5/48) vs . 91.4% (32/35), P <0.001]. The 24-month progression-free survival (PFS) rates in the FL-M and PSR-M settings were 60.4% and 45.7%, respectively. In patients with BRCA m, the 24-month PFS rates in the FL-M and PSR-M settings were 62.2% and 72.7%, respectively. CONCLUSIONS Olaparib and niraparib were effective in patients with ovarian cancer without any new safety signals except for skin pigmentation. In patients with BRCA m, the 24-month PFS of the PARPi used in the PSR-M setting was even higher than that used in the FL-M setting.
Humans ; Female ; Ovarian Neoplasms/drug therapy* ; Piperazines/therapeutic use* ; Middle Aged ; Retrospective Studies ; Phthalazines/therapeutic use* ; Piperidines/therapeutic use* ; Indazoles/therapeutic use* ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use* ; Adult ; Aged ; China ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival

Objective:To establish a microfluidic chip-based digital PCR (cdPCR) method for detecting hepatitis B virus (HBV) RNA and evaluate its application in patients with chronic HBV infection.Methods:A total of 135 patients with chronic HBV infection were recruited from the First Affiliated Hospital of Fujian Medical University and stratified into two groups based on HBV DNA levels: HBV DNA>100 IU/ml ( n=85) and HBV DNA≤100 IU/ml ( n=50). Additionally, healthy individuals and subjects infected with other viruses ( n=15) served as controls. Primers and probes targeting the HBV pre-C/C region were designed to optimize the microfluidic cdPCR method, and its linear range, limit of detection (LOD), specificity, and precision were assessed. Serum HBV RNA levels were measured using the self-developed method and two commercial kits. Pearson correlation was applied to evaluate the relationships between HBV RNA and other HBV markers. Results:The optimized microfluidic cdPCR method featured a denaturation time of 10 seconds, an annealing/extension temperature of 62 ℃, and primer and probe concentrations of 0.3 μmol/L and 0.2 μmol/L, respectively. The method demonstrated a linear range of 103-10? copies/ml and an LOD of 102 copies/ml. The intra-assay coefficient of variation ( CV) for plasmid standards at 10? and 10? copies/ml were 1.06% and 0.82%, respectively, while the inter-assay CVs were 0.75% and 0.44%. Specificity analysis confirmed the absence of positive signals in sera from healthy controls and subjects infected with other pathogens. In the HBV DNA>100 IU/ml group, the detection rate of the self-developed cdPCR method was 81.18% (69/85), significantly higher than the 64.71% (55/85) achieved by commercial kit B ( P<0.016 7). However, in the HBV DNA≤100 IU/ml group, no significant differences were observed among the three methods ( P>0.05). HBV RNA levels were positively correlated with HBV DNA ( r=0.67), hepatitis B surface antigen ( r=0.53), and hepatitis B e antigen ( r=0.44) (all P<0.001). Conclusion:A microfluidic cdPCR assay for the quantitative detection of HBV RNA has been successfully developed. This assay demonstrates high sensitivity, specificity, and robust detection capability, even for low HBV DNA-concentration samples.

Objective:To investigate the laboratory diagnostic value of 5 new blood routine indexes in chronic hepatitis B (CHB), liver cirrhosis and hepatocellular carcinoma (HCC).Methods:The retrospective study included 65 patients with chronic HBV infection, 72 patients with liver cirrhosis and 163 patients with HCC recruited at Liver Disease Center in First Affiliated Hospital of Fujian Medical University, as well as 52 healthy controls recruited from the Physical Examination Center of the First Affiliated Hospital of Fujian Medical University from October 2022 to April 2023. Five new parameters [early granulated cell percent (EGC%), early granulated cell absolute count (EGC#), microcytic anemia factor (MAF), leukocyte estimate(corrected)from the DIFF optical channel (WDOP) and leukocyte estimate(corrected)from the NRBC optical channel (WNOP)] were detected by UniCel DxH 900 blood cell analyzer. Univariate analysis of the expression levels of the 5 new parameterswere compared among CHB, liver cirrhosis and HCC groups. Pearson correlation analysis was used to explore the correlation between the 5 new parameters and HBV-related markers in CHB and Child-Pugh score in liver cirrhosis. Receiver operating characteristic (ROC) curve and AUC were used to estimate the diagnostic capacity of the 5 new blood routine indexes in CHB, liver cirrhosis and HCC.Results:In patients with CHB, the levels of EGC% ( Z=4.613, P<0.001) and EGC# ( Z=4.220, P<0.001) were higher than those of healthy controls; EGC# was positively correlated with HBsAg and HBeAg (both P<0.05). In patients with cirrhosis, the level of MAF ( Z=-4.928, P<0.001) was lower than that of healthy controls, and Child-Pugh score was found to be negatively correlated with MAF ( r=-0.349, P<0.05). In HCC patients, WDOP ( Z=2.45, P=0.017) and WNOP ( Z=2.90, P=0.017) levels were higher in patients with tumor volume>3 cm 3 than those in patients with volume ≤3 cm 3. The AUCs of combination of 5 new parameters to diagnose CHB, liver cirrhosis and HCC were 0.901 (95% CI 0.830-0.973, P<0.001), 0.946 (95% CI 0.909-0.984, P<0.001), and 0.904 (95% CI 0.858-0.950, P<0.001). Conclusions:The 5 new parameters based on peripheral blood cell analysis have good clinical value in the diagnosis of CHB, liver cirrhosis and HCC diseases.

Objective:To explore the efficacy and safety of embolization of anterior cranial fossa dural arteriovenous fistula (ACF-DAVF) via different arterial approaches, and provide evidence for individualized treatment of ACF-DAVF. Methods:A retrospective study was performed; 25 patients with ACF-DAVF admitted to Department of Cerebrovascular Surgery, Neurosurgery Center, Zhujiang Hospital, Southern Medical University from January 2020 to December 2023 were enrolled. Vascular approaches, including the anterior cerebral artery ( n=7), facial artery ( n=3), middle meningeal artery ( n=8), ophthalmic artery ( n=6), and vein ( n=1), were selected based on angioarchitectural features and microcatheter accessibility. Fistula and proximal draining vein occlusions were confirmed by immediate post-embolization digital subtraction angiography (DSA), and perioperative complications were recorded. At a 6-month follow-up, prognoses were assessed by modified Rankin Scale (mRS), and DSA or MRA was performed to detect the recurrence of ACF-DAVF. Results:Six patients had complete embolization and 2 patients had near-total embolization of the fistula and proximal draining vein immediately after embolization via middle meningeal artery approach; 4 patients achieved complete embolization and 2 patients achieved near-total embolization via ophthalmic artery approach; 6 patients achieved complete embolization and one patient achieved near-total embolization via anterior cerebral artery approach; 3 patients achieved complete embolization via facial artery approach; one patient achieved complete embolization via venous approach. No perioperative intracranial hemorrhage or central retinal artery occlusion was noted. Follow-up for 6 months was performed in 25 patients: mRS score was 0 in 19 patients, 1 in 2 patients, and 2 in 4 patients; DSA in 19 patients and MRA in 6 patients indicated no ACF-DAVF recurrence. Conclusion:Based on the angioarchitectural features and microcatheter accessibility, individualized selection of vascular approaches for ACF-DAVF embolization can achieve better efficacy and safety.

BACKGROUND:Cartilaginous endplate stromal homeostasis is closely related to intervertebral disc degeneration.Acupotomy that releases posterior wall ligamentum flavum of the interforaminal orifice can improve the symptoms of patients with lumbar disc degeneration.Whether the mechanism of action is related to the regulation of cartilaginous endplate stromal homeostasis remains to be clarified.OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife relaxation of the internal orifice of the rabbit L7/S1 intervertebral foramina on the matrix homeostasis of the rabbit cartilage endplate.METHODS:A total of 24 male New Zealand rabbits were randomly divided into a control group(n=6)and a modeling group(n=18).Lumbar disc degeneration modeling was performed by intermittent standing after transection of the supraspinous interspinous ligament for 12 weeks.After modeling,the modeling group was randomly divided into model group,needle-knife group and fake needle knife group,with 6 rabbits in each group.In the needle-knife group,the ultrasound-guided needle-knife released the ligamentum flavum posterior wall of the right intervertebral foramina,while in the fake needle-knife group,the needle-knife only reached the surface of the posterior wall ligamentum flavum of the intervertebral foramina,with a total of four interventions,each time at an interval of 1 week.No intervention was performed in the control and model groups.Thirty days after the intervention,the disc degeneration was observed by MRI.The morphology of L7/S1 intervertebral disc cartilaginous endplate,nucleus pulposus and annulus fibrosus were observed with hematoxylin-eosin and safranin O-fast green staining and was then scored.The expressions of type II collagen,proteoglycan and matrix metalloproteinase-13 in nucleus pulposus and cartilage endplate of L7/S1 intervertebral disc were detected by immunohistochemistry.RESULTS AND CONCLUSION:MRI results showed that the relative gray value of L7/S1 nucleus pulposus was significantly lower in the model group than in the control group(P<0.01),and higher in the needle-knife group than in the model group and the fake needle-knife group(P<0.05).Hematoxylin-eosin and safranin O-fast green staining showed obvious degeneration of the nucleus pulposus and annulus fibrosus,thinning of the cartilaginous endplate,and obvious calcification at the junction with bone endplate in the model group.The morphology of the cartilaginous endplate and degeneration of the nucleus pulposus were improved in the needle-knife group compared with the model group.The morphological scores of the model group,needle-knife group and fake needle-knife group were significantly higher than those of control group(P<0.01).The morphological score of the needle-knife group was significantly lower than that of the model group and fake needle-knife group(P<0.01).Immunohistochemistry results showed that compared with the control group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate in the model group and fake needle-knife group were significantly decreased(P<0.01),while the expression of matrix metalloproteinase-13 was significantly increased(P<0.01).Compared with the model group and fake needle-knife group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate were increased in the needle-knife group(P<0.05),while the expression of matrix metalloproteinase-13 was decreased significantly(P<0.01).In conclusion,the relaxation of the interforaminal orifice by needle knife can regulate the matrix homeostasis of the rabbit cartilage endplate and improve the degeneration of the intervertebral disc.

BACKGROUND:Cartilaginous endplate stromal homeostasis is closely related to intervertebral disc degeneration.Acupotomy that releases posterior wall ligamentum flavum of the interforaminal orifice can improve the symptoms of patients with lumbar disc degeneration.Whether the mechanism of action is related to the regulation of cartilaginous endplate stromal homeostasis remains to be clarified.OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife relaxation of the internal orifice of the rabbit L7/S1 intervertebral foramina on the matrix homeostasis of the rabbit cartilage endplate.METHODS:A total of 24 male New Zealand rabbits were randomly divided into a control group(n=6)and a modeling group(n=18).Lumbar disc degeneration modeling was performed by intermittent standing after transection of the supraspinous interspinous ligament for 12 weeks.After modeling,the modeling group was randomly divided into model group,needle-knife group and fake needle knife group,with 6 rabbits in each group.In the needle-knife group,the ultrasound-guided needle-knife released the ligamentum flavum posterior wall of the right intervertebral foramina,while in the fake needle-knife group,the needle-knife only reached the surface of the posterior wall ligamentum flavum of the intervertebral foramina,with a total of four interventions,each time at an interval of 1 week.No intervention was performed in the control and model groups.Thirty days after the intervention,the disc degeneration was observed by MRI.The morphology of L7/S1 intervertebral disc cartilaginous endplate,nucleus pulposus and annulus fibrosus were observed with hematoxylin-eosin and safranin O-fast green staining and was then scored.The expressions of type II collagen,proteoglycan and matrix metalloproteinase-13 in nucleus pulposus and cartilage endplate of L7/S1 intervertebral disc were detected by immunohistochemistry.RESULTS AND CONCLUSION:MRI results showed that the relative gray value of L7/S1 nucleus pulposus was significantly lower in the model group than in the control group(P<0.01),and higher in the needle-knife group than in the model group and the fake needle-knife group(P<0.05).Hematoxylin-eosin and safranin O-fast green staining showed obvious degeneration of the nucleus pulposus and annulus fibrosus,thinning of the cartilaginous endplate,and obvious calcification at the junction with bone endplate in the model group.The morphology of the cartilaginous endplate and degeneration of the nucleus pulposus were improved in the needle-knife group compared with the model group.The morphological scores of the model group,needle-knife group and fake needle-knife group were significantly higher than those of control group(P<0.01).The morphological score of the needle-knife group was significantly lower than that of the model group and fake needle-knife group(P<0.01).Immunohistochemistry results showed that compared with the control group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate in the model group and fake needle-knife group were significantly decreased(P<0.01),while the expression of matrix metalloproteinase-13 was significantly increased(P<0.01).Compared with the model group and fake needle-knife group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate were increased in the needle-knife group(P<0.05),while the expression of matrix metalloproteinase-13 was decreased significantly(P<0.01).In conclusion,the relaxation of the interforaminal orifice by needle knife can regulate the matrix homeostasis of the rabbit cartilage endplate and improve the degeneration of the intervertebral disc.

Objective:To establish a microfluidic chip-based digital PCR (cdPCR) method for detecting hepatitis B virus (HBV) RNA and evaluate its application in patients with chronic HBV infection.Methods:A total of 135 patients with chronic HBV infection were recruited from the First Affiliated Hospital of Fujian Medical University and stratified into two groups based on HBV DNA levels: HBV DNA>100 IU/ml ( n=85) and HBV DNA≤100 IU/ml ( n=50). Additionally, healthy individuals and subjects infected with other viruses ( n=15) served as controls. Primers and probes targeting the HBV pre-C/C region were designed to optimize the microfluidic cdPCR method, and its linear range, limit of detection (LOD), specificity, and precision were assessed. Serum HBV RNA levels were measured using the self-developed method and two commercial kits. Pearson correlation was applied to evaluate the relationships between HBV RNA and other HBV markers. Results:The optimized microfluidic cdPCR method featured a denaturation time of 10 seconds, an annealing/extension temperature of 62 ℃, and primer and probe concentrations of 0.3 μmol/L and 0.2 μmol/L, respectively. The method demonstrated a linear range of 103-10? copies/ml and an LOD of 102 copies/ml. The intra-assay coefficient of variation ( CV) for plasmid standards at 10? and 10? copies/ml were 1.06% and 0.82%, respectively, while the inter-assay CVs were 0.75% and 0.44%. Specificity analysis confirmed the absence of positive signals in sera from healthy controls and subjects infected with other pathogens. In the HBV DNA>100 IU/ml group, the detection rate of the self-developed cdPCR method was 81.18% (69/85), significantly higher than the 64.71% (55/85) achieved by commercial kit B ( P<0.016 7). However, in the HBV DNA≤100 IU/ml group, no significant differences were observed among the three methods ( P>0.05). HBV RNA levels were positively correlated with HBV DNA ( r=0.67), hepatitis B surface antigen ( r=0.53), and hepatitis B e antigen ( r=0.44) (all P<0.001). Conclusion:A microfluidic cdPCR assay for the quantitative detection of HBV RNA has been successfully developed. This assay demonstrates high sensitivity, specificity, and robust detection capability, even for low HBV DNA-concentration samples.

Objective:To investigate the laboratory diagnostic value of 5 new blood routine indexes in chronic hepatitis B (CHB), liver cirrhosis and hepatocellular carcinoma (HCC).Methods:The retrospective study included 65 patients with chronic HBV infection, 72 patients with liver cirrhosis and 163 patients with HCC recruited at Liver Disease Center in First Affiliated Hospital of Fujian Medical University, as well as 52 healthy controls recruited from the Physical Examination Center of the First Affiliated Hospital of Fujian Medical University from October 2022 to April 2023. Five new parameters [early granulated cell percent (EGC%), early granulated cell absolute count (EGC#), microcytic anemia factor (MAF), leukocyte estimate(corrected)from the DIFF optical channel (WDOP) and leukocyte estimate(corrected)from the NRBC optical channel (WNOP)] were detected by UniCel DxH 900 blood cell analyzer. Univariate analysis of the expression levels of the 5 new parameterswere compared among CHB, liver cirrhosis and HCC groups. Pearson correlation analysis was used to explore the correlation between the 5 new parameters and HBV-related markers in CHB and Child-Pugh score in liver cirrhosis. Receiver operating characteristic (ROC) curve and AUC were used to estimate the diagnostic capacity of the 5 new blood routine indexes in CHB, liver cirrhosis and HCC.Results:In patients with CHB, the levels of EGC% ( Z=4.613, P<0.001) and EGC# ( Z=4.220, P<0.001) were higher than those of healthy controls; EGC# was positively correlated with HBsAg and HBeAg (both P<0.05). In patients with cirrhosis, the level of MAF ( Z=-4.928, P<0.001) was lower than that of healthy controls, and Child-Pugh score was found to be negatively correlated with MAF ( r=-0.349, P<0.05). In HCC patients, WDOP ( Z=2.45, P=0.017) and WNOP ( Z=2.90, P=0.017) levels were higher in patients with tumor volume>3 cm 3 than those in patients with volume ≤3 cm 3. The AUCs of combination of 5 new parameters to diagnose CHB, liver cirrhosis and HCC were 0.901 (95% CI 0.830-0.973, P<0.001), 0.946 (95% CI 0.909-0.984, P<0.001), and 0.904 (95% CI 0.858-0.950, P<0.001). Conclusions:The 5 new parameters based on peripheral blood cell analysis have good clinical value in the diagnosis of CHB, liver cirrhosis and HCC diseases.