BACKGROUND:At present,modern medical treatment has certain limitations on the treatment of knee osteoarthritis.Traditional Chinese medicine alkaloids can effectively prevent and treat knee osteoarthritis through various mechanisms. OBJECTIVE:To review the mechanism of alkaloids in traditional Chinese medicine in the prevention and treatment of knee osteoarthritis,providing a scientific basis for the clinical development of drugs for the treatment of knee osteoarthritis. METHODS:CNKI,WanFang,PubMed,Web of Science and Google Scholar were retrieved for relevant literature published from database inception to May 2024.The key words were"knee osteoarthritis""osteoarthritis""osteoclast""chondrocyte""alkaloids"in Chinese and English.Duplicates and obsolete non-referenced literature were excluded,and a total of 68 eligible papers were included for further review. RESULTS AND CONCLUSION:Although traditional Chinese medicine has a long history of treating knee osteoarthritis,only a small number of natural compounds are in the preclinical stage of research against knee osteoarthritis.Alkaloids have a greater potential for the prevention and treatment of knee osteoarthritis,among which,sophocarpidine,oxymatrine,sinomenine,and betaine have been shown to be effective in the prevention and treatment of knee osteoarthritis by modulating multiple signaling pathways.Alkaloids can delay the progression of knee osteoarthritis by inhibiting inflammatory response,exerting antioxidant response,inhibiting chondrocyte apoptosis,promoting chondrocyte proliferation,and inhibiting osteoclast formation and differentiation.

BACKGROUND:With the variation of disease treatment modes and the in-depth research on senile osteoporosis in recent years,increasing studies have confirmed that traditional Chinese medicine has a significant effect on the prevention and treatment of senile osteoporosis. OBJECTIVE:To investigate the effect of Yishen Gushu Formula on bone metabolic markers in patients with osteoporosis of kidney deficiency and blood stasis type. METHODS:102 patients with senile osteoporosis of kidney deficiency and blood stasis type who were treated at Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2020 to March 2022 were enrolled,including 32 males and 70 females,aged 71-93 years.All patients were randomly divided into two groups,with 51 patients in each group.The control group was treated with calcium carbonate D3 granules and sodium alendronate tablets,while the treatment group was treated with Yishen Gushu Formula beyond the control group.Treatments in each group lasted 3 months.Bone mineral density of the L1-4 lumbar vertebrae and left femoral neck,visual analog scale score,and serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were measured before and 3 months after treatment.Traditional Chinese medicine syndrome score and therapeutic efficiency were also assessed. RESULTS AND CONCLUSION:After 3 months of treatment,the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly increased in both two groups(P<0.05),and the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly higher in the treatment group than the control group(P<0.05).The visual analog scale scores of both groups after 3 months of treatment were lower than those before treatment(P<0.05),and the visual analog scores of the treatment group after 3 months of treatment were lower than those of the control group(P<0.05).After 3 months of treatment,the serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly improved in both two groups,while compared with the control group,the serum levels of osteocalcin and osteopontin were significantly higher(P<0.05)and the serum levels of type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly lower in the treatment group(P<0.05).After 3 months of treatment,the Traditional Chinese medicine syndrome scores were decreased in both two groups,while the Traditional Chinese medicine syndrome scores in the treatment group were lower than those in the control group.After 3 months of treatment,no significant adverse reactions occurred in both groups.The total effective rate was 88.2%and 70.6%in the treatment and control groups respectively,and there was a significant difference between the two groups(P<0.05).To conclude,Yishen Gushu Formula combined with anti-osteoporosis drugs can significantly improve the clinical symptoms of patients with senile osteoporosis of kidney deficiency and blood stasis type and prevent disease progression by regulating bone metabolism,increasing bone mineral density,and relieving pain.

Sex difference has shown in the arthritis diseases in human population and animal models. We investigate how the sex and symmetry vary among mouse models with different genomic backgrounds. Disease data of sex and limbs accumulated in the past more than two decades from four unique populations of murine arthritis models were analyzed. They are (1) interleukin-1 receptor antagonist (IL-1ra) deficient mice under Balb/c background (Balb/c KO); (2) Mice with collagen II induced arthritis under DBA/1 background; (3) Mice with collagen II induced arthritis under C57BL/6 (B6) background and (4) A F2 generation population created by Balb/c KO X DBA/1 KO.Our data shows that there is a great variation in sexual dimorphism for arthritis incidence and severity of arthritis in mice harboring specific genetic modifications. For a F2 population, the incidence of arthritis was 57.1% in female mice and 75.6% in male mice. There was a difference in severity related to sex in two populations: B6.DR1/ B6.DR4 (P < 0.001) and F2 (P = 0.023) There was no difference Balb/c parental strain or in collagen-induced arthritis (CIA) in DBA/1 mice. Among these populations, the right hindlimbs are significantly higher than the scores for the left hindlimbs in males (P < 0.05). However, when examining disease expression using the collagen induced arthritis model with DBA/1 mice, sex-dimorphism did not reach statistical significance, while left hindlimbs showed a tendency toward greater disease expression over the right. Sexual dimorphism in disease expression in mouse models is strain and genomic background dependent. It sets an alarm that potential variation in sexual dimorphism among different racial and ethnic groups in human populations may exist. It is important to not only include both sexes and but also pay attention to possible variations caused by disease expression and response to treatment in all the studies of arthritis in animal models and human populations.

Objective: To investigate the expressions of tissue factor (TF) and vascular endothelial growth factor (VEGF) in diffuse large B-cell lymphoma (DLBCL) and their clinical significances. Methods: The clinical data of 80 cases of DLBCL diagnosed at the Second People's Hospital of Lianyungang from January 2010 to December 2017 were collected, and 30 cases of reactive hyperplasia of lymph node (RLN) were selected as the controls. The expressions of TF and VEGF in the two groups were detected by using immunohistochemical staining. Results: The positive rate of TF and VEGF in the DLBCL group was higher than that in the RLN group [TF: 86.3% (69/80) vs. 50.0% (15/30) ; VEGF: 90.0% (72/80) vs. 53.3% (16/30) ; both P < 0.01]. And there was a positive correlation between the expression of TF and VEGF (r = 0.704, P < 0.05). There was no significant difference in the positive rates of TF and VEGF among the patients with different gender, age and Hans subtypes in DLBCL group (all P > 0.05). The positive rate of TF in DLBCL patients with B symptom, increased LDH, physical status grade ≥2, and extranodal lesion number >1 was higher (all P < 0.05). The positive rate of VEGF in patients with Ann Arbor stage Ⅲ-Ⅳ, B symptom, increased LDH, and extranodal lesion number >1 was higher (all P < 0.05). The positive rate of TF in international prognostic index (IPI) high-risk group was higher than that in low-risk group (P < 0.01); the positive rate of VEGF in IPI high-risk group and middle-high-risk group was higher than that in low-risk group (all P < 0.01). The expressions of TF (r = 0.491, P < 0.01) and VEGF (r = 0.529, P < 0.01) were positively correlated with IPI. The overall survival rates of TF and VEGF low-expression group were higher than those of TF and VEGF high-expression group (both P < 0.05). Conclusion The expressions of TF and VEGF are highly expressed in DLBCL, which is associated with the IPI. It can provide a reference value in evaluating prognosis of DLBCL.

Objective To analyze some related causes of hypocytosis or hematocytosis with bone marrow dry pumping. Methods Bone marrow histology, reticular fiber staining and selective immunohistochemical staining were performed in 34 bone marrow dry pumping patients with hypocytosis or hematocytosis in the Second People's Hospital of Lianyungang from January 2012 to August 2017. Results All the patients showed dizziness, fatigue, splenomegaly, night sweats and bleeding, including primary myelofibrosis (17 cases, 50.0 %), chronic myelocytic leukemia (4 cases, 11.8 %), acute myelocytic leukemia (2 cases, 5.9 %), acute lymphoblastic leukemia (1 case, 2.9 %), myelodysplastic syndrome (2 cases, 5.9 %), multiple myeloma (2 cases, 5.9 %), non-Hodgkin lymphoma with bone marrow infiltration (2 cases, 5.9 %), polycythemia vera (1 case, 2.9 %) and bone marrow metastatic tumor (3 cases, 8.8 %). The bone marrow proliferative degree in primary myelofibrosis group was mainly "grade Ⅱ" to "grade Ⅳ", and the non primary myelofibrosis group was mainly "grade Ⅲ" to "grade Ⅴ", and the differences of proliferative degree component between them were statically significant (χ2＝ 12.900, P＝ 0.004). The fibrosis level in primary myelofibrosis group was mainly "grade 2" to "grade 3", and the non primary myelofibrosis group was mainly "grade 1" to "grade 2", and the differences of myelofibrosis degree component between them were also statistically significant (χ2＝ 12.692, P＝ 0.003). Conclusions Hematological malignancies, especially primary myelofibrosis, are the common causes of bone marrow "dry pumping". Bone marrow histology, reticular fiber staining and selective immunohistochemical staining are of great significance in the etiological diagnosis.

Objective To design and synthesize novel triazole antifungal derivatives with 1 ,3 ,4-oxadiazole side chain for the study of antifungal activities. Methods Fourteen title compounds were synthesized via acylation ,aminolysis reaction ,cy-clization ,nucleophilic substitution ,etc. All the compounds were characterized by 1 H NMR ,MS spectra. The in vitro antifun-gal activities were evaluated against six human pathogenic fungi through the micro-broth dilution method. Results The title compounds exhibited strong antifungal activities against all the tested fungi ,especially against Candida albicans. Compounds 10d ,10i , 10l , and 10n were found to be the most effective , with a minimum inhibitory concentration (MIC80 ) of 0.003 9 μg/ml .They are 16-fold more potent than ICZ ( MIC80 0.062 5 μg/ml) and 64-fold more potent than FCZ (MIC80 0.25 μg/ml) .Conclusion The 1 ,3 ,4-oxadiazole side chain could affect the antifungal activities. That could be due to the prop-er incorporation between the 1 ,3 ,4-oxadiazole substituted phenyl ring with the target enzyme.

OBJECTIVE:To study the effect and its mechanism of Fuzheng Jiedu Quyu formula(short forFuzheng formula) combined with oxaliplatin (L-OHP) on human colon cancer HT-29 cell proliferation and apoptosis. METHODS:HT-29 cells were divided into blank control group(without drugs),Fuzheng formula group(1000 mg/L),L-OHP group(31.25 mg/L)and combi-nation group (1000 mg/L Fuzheng formula+31.25 mg/L L-OHP). After cultured with corresponding drug for 48 h,MTT method was used to detect the cell proliferation;the changes of cellular morphology were observed by invert microscope;flow cytometry was used to detect the cell cycle and apoptosis rate. Proapoptotic gene Bax,apoptotic gene Bcl-2 mRNA expressions were deter-mined by real-time fluorescence quantitative polymerase chain reaction method;Bax,Bcl-2 protein expressions were assayed by Western blot. RESULTS:Compared with blank control group,cell proliferation was inhibited in L-OHP group and combination group;cell proportion was increased in S stage,G2/M stage and decreased in G0/G1 stage(P<0.05). Cell apoptosis rate in L-OHP group,Fuzheng formula group and combination group was increased;Bax mRNA and protein expression were up-regulated,Bcl-2 mRNA expression was downregulated(P<0.05);and combination group changed more obviously than the single drug groups(P<0.05). CONCLUSIONS:Fuzheng formula combined with L-OHP can inhibit HT-29 cell proliferation and promote its apoptosis, showing better effects than either of the two drugs alone. The mechanism may be associated with up-regulation of Bax gene and pro-tein expressions and down-regulation of Bcl-2 gene expressions in cells.

Objective To investigate the clinical and laboratory features of IgG-2κ light chain multiple myeloma. Methods The clinical data and laboratory results of 2 multiple myeloma (MM) patients with IgG-2κ light chain were analyzed and the related literatures were reviewed. Results Two male and 1 female patients were 50-82 years old and mainly suffered with backache, infection, anemia and renal dysfunction. Multiple osteolytic bone destruction was detected in X-ray as well as magnetic resonance imaging (MRI). The level of serum IgG was normal, slight or obviously increased, but the levels of IgA and IgM were decreased. The levels of κ light chain in serum and urine were both increased significantly, and Bence-Jones protein was positive. Double M protein peaks of serum in γ area were detected by protein electrophoresis in 2 patients. A single band of IgG and double bands of light chain κ were revealed by immunofixation electrophoresis. Bone marrow smear showed that abnormal plasma cells were increased obviously. One patient gave up chemotherapy because of lung infection, acute left heart failure and acute renal failure, the others 2 patients achieved partial remission and stable disease by receiving DVD and VAD chemotherapy. Conclusions IgG-2κ light chain MM lacks typical clinical presentation, but some laboratory characteristics may be different from those of IgG-κ light chain. Further researches are needed to confirm whether or not it belongs to biclonal MM.

Breast cancer has become the main malignant tumors which pose a serious threat to women's health .Selective estrogen receptor modulators ,which served as the effective drug treatment ,have been attracting more attention .Present re‐search progress on the selective estrogen receptor modulators was summarized in this paper .

Objective To optimize novel triazole antifungal compounds synthesis of key intermediates.Methods The or-thogonal experimental design is used,emphasizing on four factors including the reaction temperature,the weight ratio of mate-rial,reaction time and solvent on the yield.Results The effect of reaction temperature on the reaction yield is the most signifi-cant,followed by reaction time ;the weight ratio of material and solvent on the yield impact is not obvious.Conclusion The new technology has several advantages and yields up to about 50%,less reactive impurities,easy post processing.