Objective To investigate the influence of plasma infusion during orthotopic liver transplantation on the incidence of acute kidney injury (AKI) in recipients. Methods Cinical data of 473 liver transplant recipients who underwent orthotopic liver transplantation at Beijing Chaoyang Hospital Affiliated to Capital Medical University from January 2016 to December 2020 were retrospectively collected. The study included 354 recipients who received plasma infusion during the operation (plasma group) and 119 recipients who did not receive plasma infusion during the operation (control group). Preoperative conditions, donor conditions, intraoperative conditions, main outcome indicators and secondary outcome indicators of the two groups were analyzed and compared. Receiver operating characteristic curve was drawn to calculate the maximum cut-off value of intraoperative plasma infusion volume that affected the occurrence of AKI within 7 days after surgery. Logistic regression analysis was performed to analyze the correlation between intraoperative plasma infusion volume and the incidence of AKI within 7 days after surgery. Results Before propensity score matching, the incidence of AKI within 7 days after surgery and the incidence of grade Ⅲ AKI in the plasma group were higher than those in the control group (both P<0.05). After propensity score matching, 62 recipients were included in each group. There was no statistically significant difference in the incidence of AKI within 7 days after surgery between the plasma group and the control group, but the incidence of grade Ⅲ AKI within 7 days after surgery in the plasma group was higher than that in the control group (P=0.041). Logistic regression analysis showed that intraoperative plasma infusion volume >900 mL was a potential risk factor for AKI within 7 days after surgery (odds ratio=1.936, 95% confidence interval 1.193-3.142, P=0.007). There were no statistically significant differences in the incidence of 365-day postoperative fatality, reperfusion syndrome, and postoperative 30-day complications between the two groups before and after propensity score matching. In addition, the postoperative albumin, fibrinogen levels, and international normalized ratio in the plasma group were better than those in the control group before and after matching (all P<0.05). Conclusions Large amount of intraoperative plasma infusion is associated with an increased risk of grade Ⅲ AKI after orthotopic liver transplantation. Intraoperative plasma infusion volume >900 mL may increase the risk of AKI within 7 days after surgery.

ObjectiveTo evaluate the effects of Qingre Huoxue prescription combined with methotrexate （MTX） and folic acid （FA） on homocysteine （Hcy） levels and disease activity in patients with rheumatoid arthritis （RA） complicated by hyperhomocysteinemia （HHcy）. MethodsOn the basis of a multicenter real-world cohort from the China Registry of Traditional Chinese Medicine for Rheumatism （CERTAIN） platform，408 patients with RA complicated by HHcy were selected and included in this study. Treatment with Qingre Huoxue prescription was used as the exposure factor. According to whether Qingre Huoxue prescription was combined with MTX and FA，patients were assigned into an exposure group of 281 cases and a control group of 127 cases. Follow-ups were conducted every three months，with the primary outcome indicator being the achievement rate of target Hcy level. A generalized estimating equation model was adopted to analyze the dynamic changes in Hcy level under different medication regimens. Kaplan-Meier analysis was performed to evaluate the cumulative achievement rate of target Hcy level in the two groups，and Cox regression analysis was conducted to explore the predictive factors affecting the achievement rate of target Hcy level. Changes in erythrocyte sedimentation rate （ESR），C-reactive protein （CRP），28-joint disease activity score （DAS 28），and Health Assessment Questionnaire-Disability Index （HAQ-DI） scores before and after the first combined treatment with Qingre Huoxue prescription were compared between the two groups. ResultsThe Hcy level in the exposure group showed a gradual decreasing trend over time，while the decrease in Hcy level was not significant in the control group. At the 12-month follow-up，the achievement rate of target Hcy level in the exposure group （124/281，44.13%） was higher than that in the control group （23/127，18.11%，P<0.01）. Multivariable Cox regression analysis showed that treatment with Qingre Huoxue prescription ［hazard ratio（HR）=3.013，95% confidence interval （CI） 2.188-4.149， P<0.001］， absence of comorbidities （HR=2.035， 95%CI 1.352-3.061， P<0.001）， and baseline Hcy <15 μmol·L^-1 （HR=1.810， 95%CI 1.390-2.357， P<0.001） were significantly associated with an increased likelihood of achieving target Hcy levels within 6 months. In contrast， higher PGA scores were associated with a reduced likelihood of achieving target Hcy levels （HR=0.991， 95% CI 0.986-0.997， P=0.003）. After treatment，the exposure group demonstrated reductions in ESR，CRP，and DAS 28 scores （P<0.05） and had lower ESR，CRP and DAS 28 scores than the control group （P<0.05）. ConclusionEven after taking FA supplements，some RA patients undergoing MTX treatment still have high Hcy levels. When being used in conjunction with MTX and FA，Qingre Huoxue prescription can effectively lower the Hcy level and disease activity in RA patients with HHcy，outperforming Western treatment alone.

ObjectiveTo evaluate the effects of Qingre Huoxue prescription combined with methotrexate （MTX） and folic acid （FA） on homocysteine （Hcy） levels and disease activity in patients with rheumatoid arthritis （RA） complicated by hyperhomocysteinemia （HHcy）. MethodsOn the basis of a multicenter real-world cohort from the China Registry of Traditional Chinese Medicine for Rheumatism （CERTAIN） platform，408 patients with RA complicated by HHcy were selected and included in this study. Treatment with Qingre Huoxue prescription was used as the exposure factor. According to whether Qingre Huoxue prescription was combined with MTX and FA，patients were assigned into an exposure group of 281 cases and a control group of 127 cases. Follow-ups were conducted every three months，with the primary outcome indicator being the achievement rate of target Hcy level. A generalized estimating equation model was adopted to analyze the dynamic changes in Hcy level under different medication regimens. Kaplan-Meier analysis was performed to evaluate the cumulative achievement rate of target Hcy level in the two groups，and Cox regression analysis was conducted to explore the predictive factors affecting the achievement rate of target Hcy level. Changes in erythrocyte sedimentation rate （ESR），C-reactive protein （CRP），28-joint disease activity score （DAS 28），and Health Assessment Questionnaire-Disability Index （HAQ-DI） scores before and after the first combined treatment with Qingre Huoxue prescription were compared between the two groups. ResultsThe Hcy level in the exposure group showed a gradual decreasing trend over time，while the decrease in Hcy level was not significant in the control group. At the 12-month follow-up，the achievement rate of target Hcy level in the exposure group （124/281，44.13%） was higher than that in the control group （23/127，18.11%，P<0.01）. Multivariable Cox regression analysis showed that treatment with Qingre Huoxue prescription ［hazard ratio（HR）=3.013，95% confidence interval （CI） 2.188-4.149， P<0.001］， absence of comorbidities （HR=2.035， 95%CI 1.352-3.061， P<0.001）， and baseline Hcy <15 μmol·L^-1 （HR=1.810， 95%CI 1.390-2.357， P<0.001） were significantly associated with an increased likelihood of achieving target Hcy levels within 6 months. In contrast， higher PGA scores were associated with a reduced likelihood of achieving target Hcy levels （HR=0.991， 95% CI 0.986-0.997， P=0.003）. After treatment，the exposure group demonstrated reductions in ESR，CRP，and DAS 28 scores （P<0.05） and had lower ESR，CRP and DAS 28 scores than the control group （P<0.05）. ConclusionEven after taking FA supplements，some RA patients undergoing MTX treatment still have high Hcy levels. When being used in conjunction with MTX and FA，Qingre Huoxue prescription can effectively lower the Hcy level and disease activity in RA patients with HHcy，outperforming Western treatment alone.

OBJECTIVE To construct and evaluate nomogram prediction model for refractory chemotherapy-induced nausea and vomiting （CINV）. METHODS The data of malignant tumor patients who received chemotherapy at the Third People’s Hospital of Zhengzhou from January 2017 to December 2023 were collected. These patients were categorized into the occurrence group and the non-occurrence group according to the occurrence of refractory CINV. Multivariate Logistic regression analysis was employed to screen predictive factors for refractory CINV and constructing a nomogram prediction model. Model performance was assessed via receiver operating characteristic curve analysis. Model calibration was evaluated using Bootstrap resampling. Decision curve analysis （DCA） was used to determine the clinical net benefit of three strategies under different risk thresholds. Clinical impact curves were utilized to assess the clinical value of the model at different risk thresholds. Shapley additive explanations （SHAP） analysis was performed to evaluate individual factor contributions to the predictive model. RESULTS A total of 388 patients were included， with 219 experiencing refractory CINV. Multivariate Logistic regression identified 11 predictive factors for refractory CINV， including gastrointestinal disease history， anticipated nausea and vomiting， chemotherapy-induced emetic risk classification， and electrolyte levels， etc. The model’s area under the curve was 0.80 [95% confidence interval （0.76， 0.84）]， with a mean error of 0.036. DCA demonstrated the prediction model had higher clinical net benefit when the risk threshold was between 0.05 and 0.85. SHAP analysis revealed the top three predictive factors as gastrointestinal disease history （0.924）， chemotherapy- induced emetic risk classification （0.866）， and electrolyte levels （0.581）. CONCLUSIONS Eleven factors， including gastrointestinal disease history， anticipated nausea and vomiting， chemotherapy-induced emetic risk classification， and electrolyte levels， are identified as predictors of refractory CINV. The model based on these factors has good predictive ability， which can be used to predict the risk of refractory CINV.

Currently, researchers have identified several mutated genes associated with hereditary eye diseases; however, effective therapeutic options remain scarce. The emergence of clustered regularly interspaced short palindromic repeats(CRISPR)and its associated proteins(CRISPR-associated proteins, Cas)offers a promising approach for treating these diseases. CRISPR/Cas9 enables precise targeting and modification of specific genetic sequences, allowing for the correction of mutated genes, as well as knockout or replacement of pathogenic genes to achieve therapeutic effects. In ophthalmology, CRISPR/Cas9 has been applied to various hereditary eye disorders, including corneal dystrophy, congenital cataracts, glaucoma, and retinitis pigmentosa. Additionally, significant progress has been made to utilize CRISPR/Cas9 to develop disease models. Therefore, it has great potential for clinical applications. However, challenges such as delivery efficiency and off-target effects remain. This review summarizes the mechanism of CRISPR/Cas9, its applications in genetic eye diseases and disease models, as well as the existing challenges, aiming to provide new insights for treatment.

Continuous manufacturing, as an innovative pharmaceutical production model, offers advantages such as high production efficiency and ease of control compared to traditional batch production, aligning with the future trend of drug production moving toward greater efficiency and intelligence. However, the development of continuous manufacturing technology in wet granulation has been slow. On one hand, this is closely related to its high technical complexity, substantial equipment investment costs, and stringent process control requirements. On the other hand, the long-term use of the traditional batch production model has created strong path dependence, and the lack of mature standardized processes further increases the difficulty of technological transformation. To promote the deep integration of wet granulation technology with continuous manufacturing, this review systematically outlines the current application of wet granulation in continuous manufacturing. It focuses on the development of key technologies such as online detection, process modeling, and process scale-up, with the aim of providing a reference for process innovation and application in wet granulation.
Drug Compounding/instrumentation* ; Technology, Pharmaceutical/methods* ; Drugs, Chinese Herbal/chemistry* ; Models, Theoretical

This study explored the efficacy and mechanisms of Shenqi Buqi Granules in treating chronic heart failure(CHF) of Qi deficiency using proteomics and bioinformatics methods. A total of 18 healthy participants(health group) and 19 patients with Qi deficiency-type CHF(experimental group) were enrolled and treated with Shenqi Buqi Granules for 12 weeks. Clinical indicators, including Qi deficiency scores, complete blood count, biochemical parameters, lipid profiles, and cardiac function, were collected from pre-and post-experimental groups. Serum proteomics analysis was performed. Differential proteins were screened through differential analysis and K-means clustering. Further analyses, including subcellular localization, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and protein-protein interaction(PPI) network construction, were conducted to identify pathways and proteins associated with Shenqi Buqi Granules treatment. Spearman correlation analysis focused on proteins most correlated with the core phenotype of CHF of Qi deficiency. The results show that Shenqi Buqi Granules treatment reduced Qi deficiency scores and brain natriuretic peptide levels of pre-experimental group. A total of 1 594 proteins were quantified in the proteomics analysis, with 98 proteins showing differential expression between healthy group and experimental group before and after treatment. Subcellular localization analysis revealed 6 protein sources, while KEGG pathway enrichment highlighted biological processes including angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. Core genes identified included CD34, CSF1, CALM1, CALML3, PPP1CA, PFN1, and 3 ribosomal large subunit proteins. Correlation analysis between core proteins and Qi deficiency scores revealed that CD34(r=-0.67, P<0.05) and PPP1CA(r=0.62, P<0.01) were most strongly associated with Qi deficiency scores. This study suggests that Shenqi Buqi Granules improves Qi deficiency scores and CHF symptoms by regulating angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. CD34 and PPP1CA are identified as core proteins involved in the therapeutic effects of Shenqi Buqi Granules on Qi deficiency.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Heart Failure/metabolism* ; Male ; Female ; Proteomics ; Middle Aged ; Qi ; Aged ; Protein Interaction Maps/drug effects* ; Adult ; Chronic Disease

OBJECTIVE: To assess the effectiveness of bone acupuncture in improving pain and function in degenerative lumbar spinal stenosis (DLSS) and compare it with Jiaji acupuncture. METHODS: From January to December 2023, 80 DLSS patients were treated with acupuncture and divided into bone acupuncture and Jiaji acupuncture groups. Among them, 40 patients in the bone acupuncture group included 15 males and 25 females, with a mean age of (60.60±6.98) years old;anthor 40 patients in the Jiaji acupuncture group included 16 males and 24 females, with a mean age of (61.48±9.55) years old. The Roland Morris disability questionnaire(RMDQ), walking distance, visual analogue scale(VAS), and the MOS item short from health survey(SF-36) of two groups at baseline, 2 weeks, 4 weeks, and 12 weeks post-treatment were compared. RESULTS: Eighty patients were followed up for 3 to 5 months with an average of (3.62±0.59) months. There was no significant differences in general data and the scores before treatment between two groups(P>0.05). The RMDQ scores in both groups decreased significantly at 2, 4 and 12 weeks after treatment compared with before treatment(P<0.05), at each time point after treatment, the decrease was more significant in the bone acupuncture group than in the Jiaji acupuncture group(P<0.05). The VAS of waist and leg in both groups was significantly lower at 2, 4 and 12 weeks after treatment that before treatment(P<0.05). At all time points after treatment, the waist VAS in the bone acupuncture group was reduced more significant than in the Jiaji acupuncture group(P<0.05);there was no significant difference in leg VAS at 2 and 12 weeks after treatment between two groups(P>0.05), the improvement was more significant in the bone acupuncture group in the 4 weeks after treatment than in the Jiaji acupuncture group. The SF-36 scores in both groups were significantly higher at 2, 4, and 12 weeks after treatment than before treatment(P<0.05);the SF-36 score raised more significant in the bone acupuncture group than in the Jiaji acupunture group(P<0.05). No significant difference in the walking distance between two groups at 2 weeks after treatment(P>0.05);the walking distance in the bone acupuncture group was significantly higher than that in the Jiaji acupuncture group at 4 and 12 weeks after treatment(P<0.05). CONCLUSION Bone-penetrating acupuncture moderately improves functional impairment, pain, and quality of life in patients with DLSS, showing better efficacy than Jiaji acupuncture.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/methods* ; Spinal Stenosis/physiopathology* ; Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management

We propose a strategy to reduce unnecessary prostate biopsies in Chinese patients with total prostate-specific antigen (tPSA) >10 ng ml -1 and Prostate Imaging Reporting and Data System (PI-RADS) scores between 1 and 3. Clinical data derived from 517 patients of The First Affiliated Hospital of USTC (Hefei, China) from January 2020 to December 2023 who met the screening criteria for the study were retrospectively collected. Independent predictors were identified via univariate and multivariate logistic regression analysis. The diagnostic capacity of clinical variables was evaluated using the receiver operating characteristic (ROC) curves and area under the curve (AUC). A prostate biopsy strategy was developed via risk stratification. Of the 517 patients, 17/348 (4.9%) with PI-RADS 1-2 were diagnosed with clinically significant prostate cancer (csPCa), and 27/169 (16.0%) patients with PI-RADS 3 were diagnosed with csPCa. The appropriate prostate-specific antigen density (PSAD) cut-off values were 0.45 ng ml -2 for PI-RADS 1-2 patients and 0.3 ng ml -2 for PI-RADS 3 patients. The appropriate prostate volume (PV) cut-off values were 40 ml for PI-RADS 1-2 patients and 50 ml for PI-RADS 3 patients. The prostate biopsy strategy based on PSAD and PV developed in this study can reduce unnecessary prostate biopsies in patients with tPSA >10 ng ml -1 and PI-RADS 1-3. In the study, 66.5% (344/517) patients did not need to undergo prostate biopsy, at the expense of missing only 1.7% (6/344) patients with csPCa.
Humans ; Male ; Prostatic Neoplasms/diagnostic imaging* ; Prostate-Specific Antigen/blood* ; Aged ; Middle Aged ; Retrospective Studies ; Prostate/diagnostic imaging* ; Unnecessary Procedures/statistics & numerical data* ; Biopsy/statistics & numerical data* ; China ; ROC Curve