OBJECTIVE To systematically evaluate the effects of C3435T polymorphism in ABCB1 gene on lipid-lowering efficacy of statins. METHODS Retrieved from PubMed， Web of Science， the Cochrane Library， CNKI and VIP， the cohort studies on the use of statins were collected from the inception to November 1， 2023. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.4 software. RESULTS A total of 11 literature involving 1 575 patients were included. The results showed that under the dominant genetic model， the reduction of low-density lipoprotein cholesterol （LDL-C） [MD＝－1.87， 95%CI （－3.62， －0.13）， P＝0.04]， total cholesterol （TC） [MD＝－1.42， 95%CI （－2.80， －0.04）， P＝0.04] in patients with CT+TT genotype was significantly higher than CC genotype. There was no significant difference in the increase of high-density lipoprotein cholesterol （HDL-C） [MD＝－0.65， 95%CI （－2.48， 1.18）， P＝0.49] or the decrease of triglyceride （TG） [MD＝－0.05， 95%CI （－2.94， 2.84）， P＝0.97] between patients with CT+TT genotype and CC genotype. Under the recessive genetic model， the reduction of TC [MD＝2.26， 95%CI （0.97， 3.56）， P＝0.000 6] and the increase of HDL-C [MD＝2.38， 95%CI （0.42， 4.35）， P＝0.02] in patients with TT genotype were significantly higher than CC+ CT genotype. There was no significant difference in the reduction of LDL-C [MD＝1.53， 95%CI （－0.10， 3.15）， P＝0.07] or TG [MD＝0.06， 95%CI （－2.98， 3.10）， P＝0.97] between CC+CT genotype and TT genotype. Under the additive genetic model， the reduction of TC [MD＝2.98， 95%CI （1.27， 4.69）， P＝0.000 6] and LDL-C [MD＝2.84， 95%CI （0.67， 5.01）， P＝0.01] in patients with TT genotype were significantly higher than CC genotype. There was no significant difference in the increase of HDL-C [MD＝2.40， 95%CI （－0.17， 4.97）， P＝0.07] or the decrease of TG [MD＝0.97， 95%CI 　　 （－2.93， 4.87）， P＝0.63] between patients with TT genotype and CC genotype. CONCLUSIONS The reduction of LDL-C and TC in patients with dyslipidemia treated with statins may be related to the heterozygous and homozygous mutation of C3435T in ABCB1 gene， and the reduction of LDL-C and TC in patients with CT or TT genotype is more obvious， compared with patients with CC genotype. The elevation of HDL-C may be related to homozygous mutation， and the effect of HDL-C elevation may be more obvious in patients with TT genotype， compared with CC+CT genotype. However， the change of TG may not be related to the C3435T polymorphism in ABCB1 gene.

Objective To compare the efficacy and safety between hypofractionated radiotherapy(HyRt)and conventional radiotherapy after breast-conserving surgery.Methods This study was a single-center,prospective,randomized controlled study.Eighty-three patients with pTis-T2N0M0 breast cancer admitted to Tangshan People's Hospital from May 2017 to May 2019 were included.The patients received breast-conserving surgery+sentinel lymph node biopsy(SLNB).After surgery,they were treated with intensity modulated radiation therapy(IMRT).According to random table method,patients were divided into HyRt group(n=41)and conventional radiotherapy group(n=42).The dose of organs at risk,treatment efficacy,treatment failure modes,and radiotherapy related adverse reactions were analyzed in the two groups.The radiotherapy-related adverse reactions were evaluated according to NCI CTC AE Version 3.0,including radiation dermatitis,radiation pneumonia,breast/skin fibrosis,pulmonary fibrosis,etc.Results Eighty-three patients with breast cancer were included,with a median age of 44(26-67)years.There was no statistically significant difference in clinical parameters such as age(P=0.443),TNM stage(P=0.335),molecular typing(P=0.333),degree of differentiation(P=0.617),and pathological type(P=0.127)between the two groups of patients.Compared with conventional radiotherapy group,the V5(25.6％vs.33.8％,P=0.015),V20(13.3％vs.17.2％,P=0.042),and the mean radiation dose(MLD;7.4 Gy vs.10.4 Gy,P=0.020)of the affected lung of HyRt group significantly decreased.Only 3 patients in this study experienced distant metastasis,and no regional lymph node metastasis or local recurrence was observed.There was no significant difference in PFS rate at 2 years between HyRt group and conventional radiotherapy group(94.4％vs.85.2％,P=0.818).Compared with conventional radiotherapy group,the incidence of≥grade Ⅱ irradiation dermatitis in HyRt group was significantly reduced(2.4％vs.21.4％,P=0.015).There was no difference in the incidence of grade Ⅰ breast/skin fibrosis(19.5％vs.14.3％,P=0.570)between the two groups,and no grade Ⅲ radiotherapy-related side effects were observed in the two groups.Conclusions Compared with conventional radiotherapy with simultaneously integrated boosting-intensity modulated radiotherapy,the patients who received HyRt after breast-conserving surgery for early-stage breast cancer have good tolerance and low incidence of adverse reactions.HyRt can be used as the first option of radiation therapy.

Background/Aims: Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. Methods: We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. Results: The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. Conclusions Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.

Objective:To anatomically study the external bone graft axis from the pedicle (canal) to the endplate designed for compression healing fractures of the anterior vertebral column in freshly dried vertebral specimens from T10 to L5.Methods:Eight groups of freshly dried vertebral specimens from T10 to L5 (128 vertebral bodies and 256 lateral pedicles and lateral vertebral bodies) were used to observe the vertebral axis of the pedicle (canal), the internal sagittal diameter of the pedicle (canal), and the sagittal diameter of the vertebral body, and the position of vertebral pedicle (canal) axis (f-angle) before design of the external bone graft axis from the pedicle (canal) to the endplate of the compression healing vertebral body. (1) The internal sagittal diameter of the pedicle (canal) was divided into 3 segments. The lateral segment of the vertebral plate was wide, the middle segment of the isthmus of the vertebral arch was narrow and the medial segment of the terminal segment of the vertebral arch was wide. The narrow isthmus of the middle arch (canal) was used as a transposition axis in the design of the axis of the bone graft from the vertebral arch (canal) to the endplate of the compression healing vertebral body. (2) The axis of the vertebral body of the pedicle (canal) was located medial to the transposition axis, parallel to the f-angle at 0° as described by Saillant G. (3) The compression degree of the vertebral body was measured at the outer edge of the lateral anterior column, with Ⅰ° for less than 1/4 compression of the anterior column of the vertebral body, Ⅱ° for 1/4 to 2/4, Ⅲ° for 2/4 to 3/4 and Ⅳ° for more than 3/4 of the compression. (4) The f-angle described by Salliant G at the entry end which was corresponding to the endplate of the compression healing vertebral body was used to design the pedicle (canal) to the outer implant axis of the endplate of the compression healing vertebral body.Results:At an f-angle of 8° to 10°, the bone graft axis was aligned with the Ⅱ° compression healing vertebral endplate on the superior endplate side of the vertebral body axis of the arch; at an f-angle of 16° to 18°, the bone graft axis corresponded to the superior endplate of the Ⅰ° compression healing vertebral body. At an f-angle of -10°~-8°, the bone graft axis corresponded to the Ⅲ° compression healing vertebral endplate on the inferior endplate side of the vertebral body axis of the arch; at an f-angle of -18°~-16°, the bone graft axis corresponded to the inferior endplate of the Ⅳ° compression healing vertebral body.Conclusions:The external axis from the pedicle (canal) to the endplate designed in the present anatomic study for compression healing fractures of the anterior vertebral column allows for safe and easy granular bone implantation due to the toughness of the cortical bone around the arch root (canal) in addition to the precise design of the bone graft axis from the pedicle to the endplate from T10 to L5.

Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.
Humans ; Gastrointestinal Microbiome ; Medicine, Chinese Traditional ; Renal Insufficiency, Chronic/drug therapy*

Background: and Purpose This study aimed to construct an optimal dynamic nomogram for predicting malignant brain edema (MBE) in acute ischemic stroke (AIS) patients after endovascular thrombectomy (ET). Methods: We enrolled AIS patients after ET from May 2017 to April 2021. MBE was defined as a midline shift of >5 mm at the septum pellucidum or pineal gland based on follow-up computed tomography within 5 days after ET. Multivariate logistic regression and LASSO (least absolute shrinkage and selection operator) regression were used to construct the nomogram. The area under the receiver operating characteristic curve (AUC) and decisioncurve analysis were used to compare our nomogram with two previous risk models for predicting brain edema after ET. Results: MBE developed in 72 (21.9%) of the 329 eligible patients. Our dynamic web-based nomogram (https://successful.shinyapps.io/DynNomapp/) consisted of five parameters: basal cistern effacement, postoperative National Institutes of Health Stroke Scale (NIHSS) score, brain atrophy, hypoattenuation area, and stroke etiology. The nomogram showed good discrimination ability, with a C-index (Harrell’s concordance index) of 0.925 (95% confidence interval=0.890–0.961), and good calibration (Hosmer-Lemeshow test, p=0.386). All variables had variance inflation factors of <1.5 and tolerances of >0.7, suggesting no significant collinearity among them. The AUC of our nomogram (0.925) was superior to those of Xiang-liang Chen and colleagues (0.843) and Ming-yang Du and colleagues (0.728). Conclusions Our web-based dynamic nomogram reliably predicted the risk of MBE in AIS patients after ET, and hence is worthy of further evaluation.

Objective To investigate the prevalence of osteoarthrosis and the association between hot spring bathing and osteoarthrosis among local adults in typical hot spring areas of Guizhou Province. Methods A face-to-face questionnaire survey was conducted among residents aged from 30 to 65 in five typical hot spring areas, including Xifeng(Xifeng County, Guiyang), Jianhe(Jianhe County, Qiandongnan), Fodingshan(Shiqian County, Tongren), Guiyu(Wudang District, Guiyang)and Huishangu(Suiyang County, Zunyi). Residents' basic information, bone and joint diseases prevalence, hot spring bathing, and other health-related behaviors were investigated in this study. The prevalence of local bone and joint diseases was analyzed, and binary logistic regression was used to calculate OR(95%CI)to analyze the association between hot spring bathing and bone and joint diseases. Results A total of 3 708 adults(1 648 males and 2 060 females)were included as the statistical analysis survey subjects, and 794 people reported bone and joint diseases, accounting for a prevalence rate of 21.41%, 95% CI: 0.201-0.227. The prevalence of females(24.56%)was higher than that of males(17.48%)(P < 0.001). The prevalence rates of diseases increased with age(χ_trend²=130.265, P < 0.001). There were also statistically significant differences in the prevalence rate of bone and joint diseases among different genders, age groups, occupations, education levels, and smoking behaviors(P < 0.05). After gender, age, occupation, education and smoking were adjusted for, compared with the group who never took hot spring baths, participants who took hot spring baths occasionally(OR=0.793, 95%CI: 0.631-0.996)and frequently(OR=0.713, 95%CI: 0.536-0.948)were associated with a lower risk of bone and joint diseases. Conclusion The prevalence of osteoarthrosis is 21.41% in the typical hot spring areas of Guizhou Province. Older or females have a higher risk of prevalence of bone and joint diseases. Hot spring bathing may be associated with a lower risk of bone and joint diseases.

Drynariae Rhizoma is warm in nature and bitter in taste, mainly acting on liver and kidney systems. It is a common Chinese herbal medicine for the treatment of fracture and bone injury. The chemical compositions of Drynariae Rhizoma mainly include flavonoids, triterpenoids, phenylpropanoids and lignans. At present, modern pharmacological and clinical studies have shown that Drynariae Rhizoma has the effects of anti osteoporosis, promoting fracture healing, kidney protection, anti-inflammatory, promoting tooth growth, preventing and treating aminoglycoside ototoxicity and lowering blood lipid. In addition, the toxicity evaluation experiment of Drynariae Rhizoma has also shown that it has no obvious toxic and side effects. Naringin is a kind of dihydroflavone in Drynariae Rhizoma. Many studies have shown that naringin and other total flavonoids play an important role in anti-osteoporosis, promoting fracture healing, anti-inflammation, promoting tooth growth and lowering blood lipid. In this study, the research progresses on chemical consti-tuents and pharmacological activities of Drynariae Rhizoma in recent years were reviewed, and some mechanisms of action were summarized, to provide references for the further research and development of Drynariae Rhizoma.
Drugs, Chinese Herbal/pharmacology* ; Flavonoids ; Humans ; Osteoporosis/drug therapy* ; Polypodiaceae ; Rhizome

Background: Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans. Methods: We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Jin Yin-tan Hospital, Wuhan, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed. Results: Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8–99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6–87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor. Conclusion: A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.

Objective To explore the associations of body mass index (BMI), waist circumference (WC), waist height ratio (WHtR) and the prevalence of hypertension in elderly residents over 60 years in Baodi district, Tianjin. Methods Residents over 60 who underwent medical examinations in the Koudong Health Center, Baodi district, Tianjin, were all invited to participate in the study from April to May, 2018. Participants were asked to fill out structured questionnaires and undergo physical examinations. Stratified analysis and logistic regression analysis were applied to examine joint effects and interactions of BMI and WC (or WHtR) on the risk of hypertension. Results A total of 1 417 residents (83.75%) out of 1 692 residents participated in the study. The prevalence of hypertension in the participants was 46.36%. 66.50% of the participants were BMI overweight or obese. Participants with central obesity accounted for 74.66% (measured by the WC) and 75.38% (by the WHtR). Compared to the normal weight measured by the BMI or the WC, BMI overweight (OR=1.65, 95%CI: 1.19-2.30) or obesity (OR=3.41, 95%CI: 2.23-5.20) and WC central obesity (OR: 1.49, 95%CI: 1.00-2.23) were associated with increased risk of hypertension. The joint effects of BMI and WC (OR=2.49, 95%CI: 1.78-3.46), or BMI and WHtR (WHtR overweight: OR=2.05, 95%CI: 1.41-2.99; WHtR obesity: OR=2.37, 95%CI: 1.50-3.76) were greater than the single effect of the latter (WC overweight/obesity: OR=1.39, 95%CI: 0.90-2.15; WHtR overweight: OR=1.02, 95%CI: 0.62-1.66; WHtR obesity: OR=1.44, 95%CI：0.55-3.81). Conclusions Of the three indices, BMI is strongly correlated with the risk of hypertension. BMI overweight or obesity has enhanced the association of WC or WHtR and the risk of hypertension, suggesting that weight control in the normal range, especially measured by the BMI index, may prevent and control hypertension.