This study applied the grading of recommendations assessment, development and evaluation(GRADE) system and the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(Eff-iEC) to evaluate the evidence for 12 commonly used Chinese patent medicines for the treatment of osteoporosis, which are frequently recommended in guidelines or expert consensuses. The results showed that Xianling Gubao Capsules/Tablets were rated as C(low-level evidence) according to the GRADE system, and as BA~+B~+(intermediate evidence) according to the Eff-iEC system. Jintiange Capsules were rated as C(low-level evidence) by the GRADE system, and as AA~+B(high-level evidence) by the Eff-iEC system. Gushukang Granules/Capsules were rated as C(low-level evidence) by GRADE system, and as BA~+B~+(intermediate evidence) by Eff-iEC system. Zuogui Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Qianggu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B~+(high-level evidence) by Eff-iEC system. Zhuanggu Zhitong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BA~+B(intermediate evidence) by Eff-iEC system. Jingui Shenqi Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~+B(high-level evidence) by Eff-iEC system. Quanduzhong Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AD~+B~+(low-level evidence) by Eff-iEC system. Epimedium Total Flavones Capsules were rated as D(extremely low-level evidence) by GRADE system, and as AAB~+(high-level evidence) by Eff-iEC system. Yougui Pills were rated as D(extremely low-level evidence) by GRADE system, and as AA~(++)B~(+ )(high-level evidence) by Eff-iEC system. Qigu Capsules were rated as D(extremely low-level evidence) by GRADE system, and as BB~+B(intermediate evidence) by Eff-iEC system. Liuwei Dihuang Pills were rated as C(low-level evidence) by GRADE system, and as AA~(++)B~+(high-level evidence) by Eff-iEC system. Overall, the Eff-iEC system provides a more comprehensive assessment of the effectiveness evidence for traditional Chinese medicine(TCM) than the GRADE system. However, it still has certain limitations that hinder its wider promotion and application. In terms of clinical evidence evaluation, both the Eff-iEC and GRADE systems reflect that the current clinical research quality on Chinese patent medicines for the treatment of osteoporosis is generally low. High-quality clinical trials are still needed in the future to further validate clinical efficacy.
Drugs, Chinese Herbal/therapeutic use* ; Osteoporosis/drug therapy* ; Humans ; Nonprescription Drugs/therapeutic use* ; Evidence-Based Medicine ; Medicine, Chinese Traditional

Taxifolin (TAX) is a natural compound known for its liver protection effect, but the mechanism remains unknown. Phosphorylated proteomics analyses discovered that the phosphorylation level of NDRG1 at T328 was a key event of TAX-improved liver fibrosis. We established models with NDRG1 knockout (KO) in vivo and in vitro, demonstrating that NDRG1 KO attenuated the development of hepatocyte injury, and combining NDRG1 KO and TAX administration did not result in a reduction in protection against liver injury. Cellular thermal shift assay and surface plasma resonance analysis showed that TAX directly binds to NDRG1 rather than its upstream kinase, subsequently demonstrating that TAX regulated phosphorylation of NDRG1 at T328 through binding to its C289 site. NDRG1 T328A (phosphorylated mutation) and T328E (mimic phosphorylation) in vivo and in vitro confirmed that pNDRG1_T328 exacerbates hepatocyte injury along with DNA damage, inflammatory response, and apoptosis, thereby contributing to hepatic stellate cells (HSCs) activation. In contrast, TAX can inhibit the above pathological abnormalities and block hepatocyte injury-triggered HSCs activation and fibrosis. Overall, TAX is a potent liver protection drug primarily targeting NDRG1 and inhibiting pNDRG1_T328 in hepatocytes.

Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To analyze the characteristics and possible influencing factors of cognitive impairment in patients with CSF1R related diseases (CRD), and provide a basis for the diagnosis, evaluation, treatment, and prognosis of CRD.Methods:A retrospective analysis was conducted on CRD patients diagnosed at the Shanghai Sixth People′s Hospital from April 1, 2018 to May 1, 2024. Information such as gender, age of onset, family history, Montreal Cognitive Assessment (MoCA) score, Mini Mental State Examination (MMSE) score, imaging features, and CSF1R gene mutations were collected to analyze the phenotypic characteristics of CRD patients with different cognitive levels. Multiple linear regression was used to identify factors that may be related to CRD cognitive dysfunction.Results:A total of 40 patients were collected, including 22 males and 18 females. 42.5%(17/40) of the patients had a family history, with an onset age of (39.6±7.9)years and an overall median disease duration of 1.25(1.00, 2.00)years. The MMSE score was (17.90±7.89)points and the MoCA score was (15.16±7.76)points. All patients had frontal leukoencephalopathies and no cerebellar involvement. The cognitive impairment of patients was multidimensional, mainly characterized by orientation disorders, structural barriers attention and calculation disorders, visual spatial and executive dysfunction, delayed recall disorders, and language dysfunction. Patients with onset age ≥40 years old had poorer abstract ability. In addition, patients with a positive family history had poorer immediate memory and naming abilities, while those with ventricular dilation had poorer scores in MMSE total score, MoCA total score, orientation, delayed recall ability, and naming ability.Conclusions:CRD patients generally exhibit significant impairment in multiple cognitive domains, mainly characterized by deficits in orientation, structure attention, and computational abilities. Patients with early onset, long course of illness, positive family history, and ventricular enlargement are more likely to experience partial cognitive decline.

AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of gallic acid,protocatechuic acid,neomangiferin,catechin,caffeic acid,mangiferin,isomangiferin,albiflorin,paeoniflorin,vitexin,liquiritin,scutellarin,baicalin,liquiritigenin,timosaponin BⅡ,quercetin,wogonoside,benzoylpaeoniflorin,isoliquiritigenin,honokiol,magnolol,norarecaidine,arecaidine,arecoline,epicatechin,baicalein,glycyrrhizinate and wogonin in Dayuan Drink.METHODS The analysis was performed on a 35℃thermostatic Syncronis C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of 0.1%formic acid-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with select reaction monitoring mode.RESULTS Twenty-eight constituents showed good linear relationships within their own ranges(R2≥0.991 0),whose average recoveries were 95.60%-103.53%with the RSDs of 0.60%-5.45%.CONCLUSION This rapid,simple,selective,accurate and reliable method can be used for the quality control of Dayuan Drink.

As one of the imaging features of cerebral small vessel disease, white matter hyperintensity (WMH) of presumed vascular origin is quite common in the elderly. The burden of WMH is thought to progress slowly over time and is significantly associated with cognitive decline. However, the pathogenesis of WMH remains unclear and there is no effective treatment available. Recent studies have reported that some WMH lesions can regress during follow-up, along with progression and regression occurring alternately, suggesting that longitudinal changes in WMH are not unidirectional. This article presents a systematic review of current neuroimaging studies on WMH regression to enhance the understanding of dynamic changes in WMH and to provide new theoretical evidence for WMH intervention.

Objective:To investigate the efficacy and safety of different treatment duration of dual therapy including vonoprazan and low-dose amoxicillin in Helicobacter pylori ( H. pylori) eradication. Methods:From December 1, 2022 to November 30, 2023, a total of 150 H. pylori-infected patients who underwent primary treatment in the Affiliated Changzhou No.2 People′s Hospital of Nanjing Medical University were recruited. The patients were divided into 10-day treatment group and 14-day treatment group with 75 patients in each group by random number table method. Patients of both groups were treated with vonoprazan (20 mg each time, twice per day) combined with amoxicillin (0.75 g each time, 3 times per day), and the treatment duration was 10 and 14 days, respectively. Intention-to-treat (ITT) and per-protocol (PP) analyses were used to evaluate the eradication efficacy of H. pylori of the 10-day treatment group and 14-day treatment group. PP analysis was used to compare the incidence of adverse events between the 2 groups. Cost-effectiveness analysis was performed to evaluate the economic efficiency of the 2 treatment regimens. Identified factors affecting the eradication rate in the 10-day treatment group based on the PP. Independent sample t-test and chi-square test were used for statistical analysis. Results:In ITT and PP analysis, a total of 75, 75 patients and 70, 72 patients were included in the 10-day treatment group and 14-day treatment group, respectively. The results of ITT analysis showed that the eradication rates of 10-day treatment group and 14-day treatment group were 86.7% (65/75) and 90.7% (68/75), respectively. The results of PP analysis showed that the eradication rates of the 2 groups were 92.9% (65/70) and 94.4% (68/72), respectively, and the differences were not statistically significant (both P>0.05). The results of PP analysis showed that the incidences of adverse events of the 10-day treatment group and 14-day treatment group were 12.9% (9/70) and 9.7% (7/72), respectively, and the difference was not statistically significant( P>0.05). The cost-effectiveness ratios of the 10-day treatment group and 14-day treatment group were 3.29 and 4.19 yuan/%, respectively. The optimal cut-off values were 63.5 kg for body weight and 1.73 m 2 for body surface area to affect the H. pylori eradication rate. The H. pylori eradication rate of patients with body weight ≤ 63.5 kg was higher than that of patients with body weight >63.5 kg (100.0%, 42/42 vs. 82.1%, 23/28), and the H. pylori eradication rate of the patients with body surface area≤1.73 m 2 was higher than that of patients with body surface area>1.73 m 2 (100.0%, 45/45 vs. 80.3%, 20/25), and the differences were statistically significant ( χ2=5.61 and 6.91, P=0.018 and 0.009). Conclusions:The 10-day combination therapy of vonoprazan and low-dose amoxicillin is a safe and effective primary treatment regimen for H. pylori eradication. Body weight and body surface area are influencing factors of the eradication rate.

The methanol extract of Huperzia serrata was separated and purified by ODS, AB-8 macroporous adsorption resin, dextran gel Sephadex LH-20 and silica gel column chromatography combined with the semi-pre HPLC. The chemical structures of the isolated compounds were identified by MS, IR, NMR, etc. Four compounds were isolated from Huperzia serrata and identified, named as serratinine C (1), lycobeline C (2), diphaladin A (3) and crenatine (4). Compound 1 is a new alkaloid, compounds 2-4 were isolated for the first time. In vitro biological activity experiments showed that compound 1 could significantly reduce the levels of nitric oxide and reactive oxygen species in glial cells induced by lipopolysaccharide and had significant antioxidant biological activity.