Background: We investigated osteoporosis management strategies and clinical outcomes following the occurrence of medicationrelated osteonecrosis of the jaw (MRONJ). Methods: We retrospectively studied individuals diagnosed with MRONJ during osteoporosis treatment who were managed in the Osteoporosis Center or the Oral Maxillofacial Surgery & Dental Unit at Queen Mary Hospital in Hong Kong between 2010 and 2022. We examined subsequent osteoporosis management plans, fracture events, and bone mineral density (BMD). Results: Thirty-six individuals were included (mean age, 78.5 years; 94.4% women). The estimated prevalence of MRONJ was 0.26%. All patients had been exposed to bisphosphonates, and seven had also received denosumab before MRONJ. Following MRONJ, only 14 individuals continued anti-osteoporosis treatment, a decision influenced by a higher fracture probability at MRONJ onset. The most common regimen was a teriparatide-raloxifene sequence (n=8): three patients achieved stable BMD, four achieved improving BMD, and one exhibited a mixed response. The patient with a mixed BMD response had also been treated with denosumab. Six patients sustained incident fractures after MRONJ, and these patients had lower BMD T-scores than their counterparts. Two patients experienced MRONJ recurrence, which was associated with the resumption of bisphosphonate or denosumab therapy after MRONJ. These patients had higher BMD T-scores than those who did not experience MRONJ recurrence. Conclusion MRONJ is challenging because high fracture risk necessitates discontinuation of antiresorptive agents. Teriparatide followed by raloxifene may be a reasonable regimen. Individualised decisions in osteoporosis management after MRONJ are required to balance fracture risk reduction with minimising MRONJ recurrence.

The classical famous prescription Dajianzhong Decoction is recorded in Synopsis of the Golden Chamber written by Zhang Zhongjing in the Eastern Han Dynasty. It has a long history and definite clinical effects, while this prescription has not been manufactured into Chinese patent medicine preparation. We collected many ancient books of traditional Chinese medicine(TCM) by using the method of bibliometrics and got 211 valid data terms which involved 67 ancient books. The history, main treated syndromes, formulation principle, origins and processiong of medicinal materials, and decoction method of Dajianzhong Decoction were analyzed. Despite the different views of various generations of medical experts toward the composition of this prescription, the compatibility ratio of Ginseng Radix et Rhizoma to Zingiberis Rhizoma Recens is constant. Furthermore, we explored the origins of synonyms of Dajianzhong Decoction. On the basis of this study, we hope to gain an insight into the research and development of the compound preparations of Dajianzhong Decoction and provide reference for the heritage and innovation of other classical prescriptions.
Drugs, Chinese Herbal ; Medicine, Chinese Traditional ; Prescriptions ; Rhizome

Objective: To explore the safety and feasibility of stereotactic radiation therapy (SBRT) strategy for irradiating porcine ventricular septum, see if can provide a preliminary experimental evidence for clinical SBRT in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: Five male pigs (39-49 kg, 6 months old) were used in this study. Pigs were irradiated at doses of 25 Gy (n=2) or 40 Gy (n=3). Delineation of the target volume was achieved under the guidance of 3-dimensional CT image reconstruction, and SBRT was then performed on defined target volume of porcine ventricular septum. Blood biomarkers, electrocardiogram and echocardiography parameters were monitored before and after SBRT. Pathological examination (HE staining, Masson staining) was performed on the target and non-target myocardium at 6 months post SBRT. Results: SBRT was successful and all animals survived to the designed study endpoint (6 months) after SBRT. Serum cardiac troponin T (cTnT) level was significantly higher than the baseline level at 1 day post SBRT, and reduced at 1 week after SBRT, but was still higher than the baseline level(P<0.05). Serum N-terminal pro-B type natriuretic peptide (NT-proBNP) was also significantly increased at 1 day post SBRT (P<0.05) and returned to baseline level at 1 week post SBRT. The serum NT-proBNP level was (249±78), (594±37) and (234±46) pg/ml, respectively, and the cTnT was (14±7), (240±40) and (46±34) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 40 Gy dose group. The serum NT-proBNP level was (184±20), (451±49) and (209±36) pg/ml, respectively, the cTnT values ​​were (9±1), (176±29) and (89±27) pg/ml, respectively at baseline, 1 day and 1 week after SBRT in the 25 Gy dose group. Both NT-proBNP and cTnT values tended to be higher post SBRT in the 40 Gy dose group as compared with the 25 Gy dose group, but the difference was not statistically significant (P>0.05). The left ventricular ejection fraction and the left ventricular end-diastolic diameter remained unchanged before and after SBRT (P>0.05). The interventricular septum thickness showed a decreasing trend at 6 months after SBRT, but the difference was not statistically significant ((9.54±0.24) mm vs. (9.82±8.00) mm, P>0.05). The flow velocity of the left ventricular outflow tract, and the valve function and morphology were not affected by SBRT. At 6 months after SBRT, HE staining revealed necrosis in the irradiated target area of ​​the myocardium in the 40 Gy dose group and the 25 Gy dose group, and the degree of necrosis in the irradiated interventricular septum was more obvious in the 40 Gy dose group as compared with the 25 Gy group. The combined histological analysis of the two groups showed that the necrotic area of ​​the irradiated target area accounted for (26±9)% of the entire interventricular septum area, which was higher than that of the non-irradiated area (0) (P<0.05). There was no damage or necrosis of myocardial tissue outside the target irradiation area in both groups. The results of Masson staining showed that the percentage area of myocardial fibrosis was significantly higher in the irradiated target area than non-irradiated area ((12.6±5.3)% vs. (2.5±0.8)%, P<0.05). Conclusion: SBRT is safe and feasible for irradiating porcine ventricular septum.
Animals ; Feasibility Studies ; Male ; Necrosis ; Radiosurgery/methods* ; Stroke Volume ; Swine ; Ventricular Function, Left ; Ventricular Septum

Objective:To observe effect of Zeqi Tang in intervening mice with orthotopic lung cancer model, in order to observe its anti-tumor mechanism. Method:An in situ mouse model of non-small cell lung cancer was established through intrapulmonary injection with 1×10⁵ LLC-luc cells. The model mice were intragastrically administered with Zeqi Tang(0.171 g·mL^-1) or normal saline for 35 days. Appearance (spirit, hair, appetite, sleep), survival period and Zeqi Tang anti-tumor effect were observed, weekly vital imaging was performed to detect the fluorescence signal in the lungs of mice. Flow cytometry was used to detect the NK cell content in the spleen of the model mice. CD107α was used to detect the degranulation of NK cells in the spleen of mice after administration of Zeqi Tang. Kromasil 100 5 C₁₈ column was used and eluted with acetonitrile-0.025%phosphoric acid in a gradient mode, with flow rate at 1.0 mL·min^-1, column temperature at 35℃ and detection wavelength of 265 nm, as to establish the fingerprint of Zeqi Tang. The fingerprints of 10 batches of samples was evaluated by using the Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System Software (2012 Edition) recommended by the Chinese Pharmacopoeia Commission, in order to complete the quality control of Zeqi Tang. Result:Zeqi Tang could significantly inhibit the lung fluorescence signal of lung cancer in situ model mice and prolong the survival of mice(P<0.05, P<0.01). After the intervention with Zeqi Tang, the NK cells in the tumors increased significantly(P<0.01), and the degranulation of CD107α also increased significantly(P<0.01). Moreover, the HPLC-DAD fingerprint of Zeqi Tang showed a significant increase in the fingerprint similarity of 10 batches of lacquer soup aqueous extract. Moreover, the HPLC-DAD fingerprint of Zeqi Tang showed that the fingerprint similarity of 10 batches of lacquer soup aqueous extract was ≥ 0.9, indicating that small differences between the batches. Conclusion:Zeqi Tang may enhance the tumor growth and prolong the survival period of mice by up-regulating the number of NK cells in mice and enhancing their degranulation function. The evaluation of similarity of HPLC fingerprint of Zeqi Tang reflects the quality of lacquer soup to a certain extent, and can provide reference for further study.

Objective:To study the mechanism of aloesin in inducing apoptosis in human non-small cell lung cancer (NSCLC) A549 cells, so as to inhibit its proliferation. Method:A549 cells in logarithmic growth phase were collected, and cell counting kit-8 (CCK-8) was used to detect the effect of different concentrations of aloesin (2, 4, 8, 16, 32, 64, 128 μmol·L^-1) on the proliferation of A549. Effect of aloesin (0, 16 μmol·L^-1) on the number of clones formed in A549 cells and the size of clone formation was determined by crystal violet staining. effect of aloesin on apoptosis of A549 cells was detected by annexin V/propidium iodide(PI)apoptosis kit staining. Hoechst staining was used to detect the phenomenon of apoptotic nuclear pyknosis. Western blot was used to detect aloesin's effect on death-related protein expressions of Bcl-xl/Bcl-2 associated death promoter (Bad), cleaved-Caspase-3,cl-Caspase-3(Asp175), Caspase-3, cleaved poly ADP-ribose polymerase (cl-PARP), poly ADP-ribose polymerase (PARP) in A549 cells. In vivo, 5-week-old nude mice were subcutaneously inoculated with 2×10⁶ A549 cells, and randomly divided into the medication group and the blank group. aloesin or normal saline was intraperitoneally injected for 4 weeks, and the tumor volume of nude mice was measured weekly. The body weight of the mice was observed, and the appearance of the nude mice was observed. Result:Aloesin inhibited the proliferation and cloning of A549 cells in a concentration-dependent manner (P<0.05). After treatment with aloesin, the number of apoptosis and the phenomenon of nuclear pyknosis in A549 cells increased significantly (P<0.01). At the same time, aloesin significantly down-regulated the expression of apoptosis-related protein Bcl-xl (P<0.05), and increased the expression of Bad protein (P<0.01). The expression levels of cl-PARP (P<0.01) and cl-Caspase-3 (P<0.05) were also significantly increased. In addition, in vivo, aloesin significantly shrank the volume of subcutaneous tumors in mice, reduced tumor weight, with a better appearance than that of the control group. Conclusion:Aloesin may inhibit the expression of NSCLC by inducing apoptosis of A549 cells, and is safe to use, with no inhibitory effect on the body weight of mice.

Objective:To investigate the effect of astragaloside on the macrophage polarization and the possible anti-tumor immunity mechanism of astragaloside. Method:The cytotoxic effect of different concentrations of astragaloside at different time points on macrophage was measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT), in order to choose the suitable concentration of astragaloside, macrophages were co-cultured with tumor cells at the ratio 1:1, and the effect of astragaloside on macrophage-mediated lysis of tumor cells was performed by biophotonic cytotoxicity assay after the mixed cells were effected with 0.1 mg·L^-1 astragaloside for 24 h. Macrophages were dealt with 0.1 mg·L^-1 astragaloside for 24h, the expressions of CD16/32 and CD206 in macrophages were performed by flow cytometry, the mRNA expressions of macrophage inducible nitric oxide synthase (iNOS), Arginine-1 (Arg-1), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-12 (IL-12), interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) were measured by Real-time PCR, the protein expressions of macrophage signal transducers and activators of transcription 1 (STAT1) and phosphorylation signal transducers and activators of transcription 1 (p-STAT1) were determined by Western blot. Result:Astragaloside had no effect on the viability of macrophages with 0.1 mg·L^-1. Compared with control group, astragaloside obviously enhanced the macrophage-mediated lysis of tumor cells according to the biophotonic cytotoxicity assay, induced the M1 macrophage marker CD16/32 expression according to flow cytometry, increased the mRNA expressions of iNOS, IL-1β, TNF-α and IL-12 according to the Real-time PCR, and promoted the phosphorylation of STAT1 in macrophages on the basis of Western blot. Conclusion:Astragaloside could induce M1 macrophage polarization by increasing the phosphorylation of STAT1, and initiate macrophage-related anti-tumor immunity response.

Early diagnoses and treatment methods are being constantly improved, but cancer metastasis remains a main cause of mortality in malignant tumor patients. Lung is thought to be the organ most prone to distal metastasis among malignant tumors due to its unique physiological and pathological character. Tumor lung metastasis is unpredictable and may result in irreversible damages. Presently, no exact mechanism or specific targeting therapies are found. Depending on the unique theory system-treatment based on symptom differentiation, traditional Chinese medicine has made significant progress on controlling tumor lung metastasis, but its application methods and mechanism still need further study and exploration. More appropriate and idealized animal models are required as a studying medium. Therefore, the establishment of animal models to simulate lung metastasis of cancer patients has become the key to the study of tumor lung metastasis. In order to produce a better platform for investigating the pathogenesis, underlying mechanism, early diagnosis and therapeutics for tumor lung metastasis, and to provide reference for the selection and establishment of mouse lung metastasis model, this article would introduce the implementation, application and estimation of several common methods (tail vein injection, mammary fat pad orthotopic injection, tibia injection, tissue orthotopic implantation, transgenic mice and so on). Meanwhile, the development of mouse lung metastasis model still needs expanding of thoughts, rational and flexible utilization of existing models, and interdisciplinary cooperation to establish preferable animal models and make results more reliable.

Lung cancer is a common malignancy with a high morbidity and high mortality. Although chemoradiotherapy is still the main therapy, the side effects caused by radiotherapy and chemotherapy cannot be ignored. There is an urgent need to find a targeted anti-cancer compound with a low toxicity and strong effect. Therefore, a large number of natural product-derived compounds have received increasing attention for their anti-cancer effect. They are diverse in structure, rich in variety but simpler in composition than natural plants, with a clear efficacy. This facilitates research, and the enriched ingredients have stronger pharmacological effect and clinical efficacy than natural plants. Quinonoids are natural bioactive molecules that widely exist in more than 100 species of higher and lower plants, including naphthoquinones, phenanthrenequinones, benzoquinones and pyrenes. Most of them have anti-tumor effect. They are applied and studied in many cancers, especially lung cancer; and the mechanism of action involves multiple pathways, which play a role in promoting apoptosis, inhibiting proliferation, inducing autophagy, inhibiting angiogenesis and cell invasion and migration. When they are used in combination with other drugs, there is also an anti-tumor effect. With the development of researches, many synthetic quinonoid derivatives with similar structures also increase the diversity of anti-cancer steroids, and quinonoids have broad application prospects in lung cancer. On the basis of a large amount of literature, this article reviews current studies on the molecular mechanisms of antitumor activity of quinonoids, summarizes the common research targets with different effect, and analyzes the relationship between the pharmacological effects and anti-lung cancer effects of quinonoids, and proposes the direction of further research, so as to provide the reference for the follow-up research and development of other quinonoids.

The diagnosis and treatment methods for cancer are being improved continually, but the mortality of cancer still remains high. At present, the academic circle has realized deficiency of existing treatment ideas, and the concept of cancer cells has been gradually changed from "extremely extinct" to "peaceful coexistence". The concept of "survival with tumors" is universally accepted in the cancer academia. The tumor microenvironment is the place where tumor cells survive and develop. Therefore, regulation of the tumor microenvironment has become an important new strategy for tumor treatment. Myeloid-derived suppressor cells (MDSCs) are a group of heterogeneous cells that have immunosuppressive properties on T cells in the tumor microenvironment and play an important role in tumor immune escape. Now, therapy with MDSCs in the tumor microenvironment as the treatment targets also provides new ideas for the tumor treatment. As MDSCs subpopulations are similar with neutrophils and monocytes, they can be divided into two major subtypes:granulocyte-like myeloid-derived suppressor cells (G-MDSCs) and monocyte-myeloid-derived suppressor cells(M-MDSCs). But how to differ these two subtypes from neutrophils and monocytes. What are the differences in the functional characteristics of different subtypes of MDSCs. How do they accumulate, differentiate, and exert immunosuppressive effects through different pathways. Traditional Chinese medicine(TCM) has always been good at modulating the body's microenvironment. More and more researches have shown that, the recruitment, amplification and activation of MDSCs can be effectively inhibited by TCM compound and its active ingredients, providing scientific basis for Chinese medicine targeting MDSCs in the tumor microenvironment. However, which specific pathways could regulate G-MDSCs or M-MDSCs is still in need of further studies. Most previous literature focus on the overall level of MDSCs, while the this paper would be based on the specific subpopulations of MDSCs to clarify the biological characteristics of these two subtypes of MDSCs, so as to achieve more precise targeted therapy in the tumor microenvironment.

The Chinese medicine master Qiu Peiran, good at the treatment of liver cirrhosis, believes that the etiology of liver cirrhosis covers exogenous pathogenic factors, infection of parasite, excess alcohol and food, emotional depression, deficiency of vital qi, and its primary pathogenesis is the deficiency of vital qi and lingering of evil qi, including coexistence of yin deficiency and heat-dampness, blood heat and blood stasis, and disease in liver and spleen.The diagnosis and treatment strategy of liver cirrhosis is summed up according to the clinical experience of Prof.Qiu, involving applicable diseases, basis of syndrome differentiation, therapeutic principle and method, prescription and evaluation index of efficacy, etc.