ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

ObjectiveTo investigate the effects of Tongxinluo capsules on traditional Chinese medicine （TCM） syndrome elements and major adverse cardiovascular events （MACEs） in patients with chronic coronary syndrome of Qi deficiency and blood stasis type. MethodsA multicenter and prospective cohort study was conducted. The intervention of Tongxinluo Capsules was used as the exposure factor， and the patients were divided into an exposure group （integrated traditional Chinese and western medicine treatment group） and a non-exposure group （western medicine treatment group）. The patients were followed up for one year. The TCM syndrome element scores were assessed by using a syndrome element diagnosis scale on the day of enrollment and in the third， sixth， and twelfth months， and the incidence of MACE within one year was recorded. ResultsA total of 186 patients were included， with 128 patients in the exposure group and 58 patients in the non-exposure group. There was no significant difference in baseline data between the two groups. Compared with those in the pretreatment period for each group， the Qi deficiency and blood stasis syndrome scores in the treatment and follow-up period were significantly improved （P<0.05）. Compared with the non-exposure group， the exposure group exhibited significantly decreased Qi deficiency syndrome scores in the treatment and follow-up period （P<0.01） and significantly reduced blood stasis syndrome scores in the sixth month （P<0.05）. In the remaining follow-up period， there was no statistically significant difference between the two groups. Compared with that of the non-exposure group， during the treatment period （the third month）， the difference in Qi deficiency and blood stasis syndrome scores of the exposure group was statistically significant （P<0.05， P<0.01）. At the end of the follow-up period， patients in the non-exposure group had a MACE probability of 6.90% （4/58）， higher than 3.13% in the exposure group （4/58）. Compared with patients with angina pectoris who used conventional medicine， patients administered with Tongxinluo Capsules had a relative risk（RR） of 0.45 ［95%confidence interval（95%CI） 0.12-1.75， P=0.26］. There was no significant difference in the incidence of MACE within one year between the two groups. ConclusionTongxinluo capsules can improve the degree of Qi deficiency in patients with chronic coronary syndrome in the short term， and the improvement effect of blood stasis syndrome appears in the medium and long term. They can better improve the Qi deficiency syndrome in the long term. Within one year， the incidence of MACE in the exposure group was lower than that in the non-exposure group.

Objective To investigate the role of hydrogen therapy in reducing radiation-induced lung injury and the specific mechanism. Methods Forty C57BL/6 mice were randomly divided into four groups: normal control group, model group, hydrogen therapy group I, and hydrogen therapy group II. A mouse model of radiation-induced lung injury was established. The pathological changes in the lung tissue of the mice were examined with HE staining. Immunofluorescence staining was used to detect the expression of surface markers of M1 and M2 macrophages to observe macrophage polarization. The expression of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-10 in the lung tissue was measured by immunohistochemistry. The expression of nuclear factor-kappa B (NF-κB) p65 and phosphorylated NF-κB (P-NF-κB) p65 was measured by Western blot. Results HE staining showed that compared with the control group, the model group exhibited alveolar septal swelling and thickening, vascular dilatation and congestion, and inflammatory cell infiltration in the lung tissue; the hydrogen groups had significantly reduced pathological damage and inflammatory response than the model group, with more improvements in hydrogen group II than in hydrogen group I. Immunohistochemical results showed that compared with those in the control group, the levels of the inflammatory cytokines IL-6 and TNF-α were significantly increased in the model group; the hydrogen groups showed significantly decreased IL-6 and TNF-α levels and a significantly increased level of the anti-inflammatory factor IL-10 than the model group, which were more marked in hydrogen group II than in hydrogen group I. Immunofluorescence results showed that compared with the control group, the expression of the surface marker of M1 macrophages in the model group was significantly upregulated; the hydrogen groups showed significantly downregulated M1 marker and significantly upregulated M2 marker, and hydrogen group II showed significantly increased M2 marker compared with hydrogen group I. Western blot results showed that compared with that in the control group, the ratio of P-NF-κB p65/NF-κB p65 in the model group was significantly increased; the P-NF-κB p65/NF-κB p65 ratio was significantly reduced in the hydrogen groups than in the model group, and was significantly lower in hydrogen group II than in hydrogen group I. Conclusion Hydrogen inhalation therapy may reduce the inflammatory response of radiation-induced lung injury by inhibiting the NF-κB signaling pathway to promote the polarization of the macrophage M1 subtype to the M2 subtype.

ObjectiveTo investigate the effect of Tongxinluo capsules on the use of anti-ischemic drugs in patients with chronic coronary syndrome （CCS） of Qi deficiency and blood stasis. MethodA multicenter，prospective cohort study was conducted，with Tongxinluo capsules intervention as the exposure factor. Patients were divided into an exposed group （combination of traditional Chinese and western medicine） and a non-exposed group （western medicine alone），and followed up for one year. The use of anti-ischemic drugs was observed on the day of enrollment and at 3，6，12 months. ResultA total of 186 patients were enrolled，with 128 in the exposed group and 58 in the non-exposed group. There were no statistically significant differences in baseline characteristics between the two groups. At the 3-month follow-up，the types of first-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01），and this difference remained statistically significant at 6 months （P<0.05） but was no longer significant at 12 months. At the 3- and 6-month follow-ups，there were no significant differences between the two groups in the types of second-line anti-ischemic drugs used. However，at the 12-month follow-up，the types of second-line anti-ischemic drugs used in the exposed group were significantly fewer than those in the non-exposed group （P<0.01）. At the 3-month follow-up，both groups showed a reduction in the types of first-line anti-ischemic drugs used compared to baseline （P<0.05），with a more pronounced reduction in the exposed group （P<0.05）. At the 6-month follow-up，the exposed group showed a significant reduction in the types of second-line anti-ischemic drugs used compared to baseline （P<0.05），while no significant changes were observed in the non-exposed group. At the 12-month follow-up，the difference in the types of second-line anti-ischemic drugs between the exposed and non-exposed groups was statistically significant （P<0.05），while there was no significant difference in the types of first-line anti-ischemic drugs. ConclusionTongxinluo capsules can effectively reduce the use of anti-ischemic drugs in patients with CCS of Qi deficiency and blood stasis.

Objective To investigate the effect of calcium ions on the expression of kallikrein-4(KLK4)and cell growth of ameloblast,and to provide an experimental basis for calcium ion promoting normal mineralization of enamel.Methods ALC cells were treated with 0,2.0,2.5,3.0,and 3.5 mmol/L CaCl2 for 24 and 48 h.KLK4 expression was analyzed by qRT-PCR and Western blot analysis.The viability of ALC cells was determined by using CCK-8.Annex-inV-FITC/PI dual staining combined with flow cytometry and Hoechst 33342 staining were used to detect the ALC cell cycle and cell apoptosis.The protein expression level of glucose-regulated protein 78(GRP78)was measured by West-ern blot analysis.Results After 24 h of treatment with 2.5,3.0,and 3.5 mmol/L CaCl2,the expression of KLK4 mRNA was increased(P＜0.05),and after 24 h of treatment with 2.0,2.5,3.0,and 3.5 mmol/L CaCl2,the expression of KLK4 protein was increased(P＜0.05).After 48 h of treatment with 3.0 mmol/L and 3.5 mmol/L CaCl2,the expression of KLK4 mRNA and protein was increased(P＜0.05).Compared with the control group,the viability of ALC cells was in-creased after 24 and 48 h of treatment with 2.0,2.5,and 3.0 mmol/L CaCl2(P＜0.05),and the highest cell viability was observed with 2.5 mmol/L CaCl2.Hoechst 33342 staining results showed that 3.0 mmol/L and 3.5 mmol/L CaCl2 may promote apoptosis in ALC cells.Flow cytometry showed that the proportion of G2/M phase cells and the apoptosis rate increased after 3.5 mmol/L CaCl2 treatment for 24 h(P＜0.05),compared with the 0,2.0,2.5,and 3.0 mmol/L CaCl2 groups.After 24 h of treatment with 3.0 mmol/L and 3.5 mmol/L CaCl2,the expression of GRP78 protein was re-duced(P＜0.05),and after 48 h of treatment with 2.5 mmol/L CaCl2,the expression of GRP78 protein was reduced(P＜0.05).Conclusion Calcium ions can promote the increase of KLK4 expression and cell viability in ALC cells,but a higher concentration of calcium ions can block the G2/M phase of ALC cells,thus inducing apoptosis of ALC cells and reducing the expression of apoptosation-related protein GRP78.

[Objective] To investigate the effects of fluoride on kallikrein-4 (KLK4) and cell apoptosis as well as the possible mechanisms in ALC cells. [Methods] ALC cells were treated with different concentrations of fluoride for 24 and 48 hours. The effects on cell viability, cell cycle and cell apoptosis were detected using CCK-8, flow cytometry and hoechst 33342, respectively. KLK4 expression was detected by qRT-PCR and Western blotting, and the protein expressions of glucose-regulated protein 78 (GRP78), p-eukaryotic initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) were detected by Western blotting. [Results] The results showed that the expression of KLK4 was significantly reduced after treatment with 1.0 and 2.0 mmol/L NaF for 24 and 48 hours (P<0.05). The difference was statistically significant in cell activity between 2.0 mmol/L NaF treatment group and the control group (P<0.05). The G0/G1 phase cells significantly reduced and the S phase cells significantly increased after treatment with 0.1 and 1.0 mmol/L NaF for 24 hours (P<0.05), while the G0/G1 phase cells significantly increased and the S phase cells significantly reduced in the 2.0 mmol/L NaF treatment cells (P<0.05). The G0/G1 phase cells significantly increased and G2/M phase cells significantly reduced after treatment with 2.0 mmol/L NaF for 48 hours (P<0.05). With the increase of NaF treatment concentration, the number of bright blue cells gradually increased, and the percentage of apoptosis also increased successively. Except for the cells treated with 0.1 mmol/L NaF for 24 hours, the apoptosis rate of the other fluoride treatment groups was statistically significant compared with the control group (P<0.05). The expressions of GRP78 and p-eIF2α were significantly increased after treatment with 0.1, 1.0, and 2.0 mmol/L NaF for 24 hours (P<0.05). The expressions of ATF4 and CHOP were significantly increased after treatment with 1.0 and 2.0 mmol/L NaF for 24 hours (P<0.05). The expressions of ATF4 and CHOP were significantly increased after treatment with 0.1, 1.0, and 2.0 mmol/L NaF for 48 hours (P<0.05). [Conclusion] Sodium fluoride may result in inhibition of KLK4 expression and abnormal cell growth, possibly by inducing GRP78 expression and activating eIF2α/ATF4/CHOP signaling pathway in ALC ameloblasts.

Objective·To summarize the clinical features,imaging features,and diagnosis and treatment experience of primary mediastinal yolk sac tumor(YST).Methods·Data of 29 patients with primary mediastinal YST,who attended Shanghai Chest Hospital,Shanghai Jiao Tong University School of Medicine from September 2016 to May 2023,were collected and comprehensively analyzed,including imaging examination results,serum indicators,pathology reports and treatment methods.Results·There were 22 cases of pure YST and 7 cases of mixed YST comprising 28 males and 1 female.The mean age of onset was(24.5±5.9)years.The initial symptoms were chest tightness(34.5%),chest pain(27.8%),cough(34.5%),expectoration(34.5%)and no specific symptoms(24.1%).Chest computerized tomography(CT)enhancement showed that all the 29 lesions were located in the anterior mediastinum.The maximum diameter of the lesions ranged from 5.6 cm to 18.2 cm.The lesions were irregular in shape,uneven in density,partially cystic and solid in density.The enhancement scan showed the solid part was slightly and moderately enhanced,and the low-density area was not enhanced.Tumor boundary was not clear because tumors often compressed and invaded surrounding tissues.Among the 29 newly diagnosed patients,serum alpha-fetoprotein(AFP)was significantly increased in 28 cases(1 case was not tested).Patients received multidisciplinary comprehensive treatment,including chemotherapy(25/29),surgery(26/29),and radiotherapy(8/29).Seven patients directly received surgery after diagnosis.Nineteen patients received chemotherapy first and then surgery;16(84.2%)cases were evaluated as lesion shrinkage after chemotherapy.After surgery,73.1%(19/26)patients had a significant decrease in serum AFP.After chemotherapy,56.0%(14/25)patients had decreased serum AFP.Conclusion·Primary mediastinal YST usually occurs in middle-aged and young men,with certain clinical and radiographic features and elevated serum AFP,which requires multidisciplinary comprehensive treatment.

Objective:To investigate the efficacy and safety of tenofovir amibufenamide in patients over 65 years old with chronic hepatitis B and liver cirrhosis.Methods:We recruited 45 patients in Linyi People's Hospital with chronic hepatitis B and liver cirrhosis who were treated with TMF antiviral therapy for 48 weeks, compared the virologic response rate and HBV DNA decrease level at 12, 24 and 48 weeks, and the changes in hepatitis B surface antigen, alanine aminotransferase, glomerular filtration rate, creatinine, triglycerides, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum phosphorus and blood lipids, and the changes in ALT normalization rate at 48 weeks. P<0.05 was statistically significant. Results:The age of the enrolled patients was 69.0 (67.0, 72.5) years. At 12, 24, and 48 weeks of treatment, the complete virological response rates were 32.4% (12/37), 70.0% (28/40), and 84.6% (33/39) respectively, and the level of HBV DNA decreased from baseline ( P＜0.05). After 48 weeks of treatment, the level of HBsAg decreased ( P<0.05), and there was no negative HBsAg conversion and seroconversion. After 48 weeks of treatment, the level of ALT decreased ( P<0.05). At 48 weeks of treatment, the rates of ALT reverted to normality were 88.9% (16/18) and 70.4% (19/27), respectively. There was no significant difference in the levels of glomerular filtration rate, creatinine, phosphorus, triglycerides, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol estimated at baseline before and after treatment ( P＞0.05), and no serious adverse events were observed. Conclusions:For patients over 65 years old with chronic hepatitis B and liver cirrhosis, TMF can significantly inhibit HBV DNA replication, and the ALT normalization rate is high and well tolerated.

Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.

Ascites is the most common complication in patients with decompensated cirrhosis. This condition results in a severely impaired quality of life, excessive healthcare use, recurrent hospitalizations and significant morbidity and mortality. While loop diuretics and mineralocorticoid receptor antagonists are commonly employed for symptom relief, our understanding of their impact on survival remains limited. A comprehensive understanding of the underlying pathophysiological mechanism of ascites is crucial for its optimal management. The renin-angiotensin-aldosterone system (RAAS) is increasingly believed to play a pivotal role in the formation of cirrhotic ascites, as RAAS overactivation leads to a reduction in urine sodium excretion then a decrease in the ability of the kidneys to excrete water. In this review, the authors provide an overview of the pathogenesis of cirrhotic ascites, the challenges associated with current pharmacologic treatments, and the previous attempts to modulate the RAAS, followed by a description of some emerging targeted RAAS agents with the potential to be used to treat ascites.