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

PURPOSE: Intertrochanteric fracture (ITF) classification is crucial for surgical decision-making. However, orthopedic trauma surgeons have shown lower accuracy in ITF classification than expected. The objective of this study was to utilize an artificial intelligence (AI) method to improve the accuracy of ITF classification. METHODS: We trained a network called YOLOX-SwinT, which is based on the You Only Look Once X (YOLOX) object detection network with Swin Transformer (SwinT) as the backbone architecture, using 762 radiographic ITF examinations as the training set. Subsequently, we recruited 5 senior orthopedic trauma surgeons (SOTS) and 5 junior orthopedic trauma surgeons (JOTS) to classify the 85 original images in the test set, as well as the images with the prediction results of the network model in sequence. Statistical analysis was performed using the SPSS 20.0 (IBM Corp., Armonk, NY, USA) to compare the differences among the SOTS, JOTS, SOTS + AI, JOTS + AI, SOTS + JOTS, and SOTS + JOTS + AI groups. All images were classified according to the AO/OTA 2018 classification system by 2 experienced trauma surgeons and verified by another expert in this field. Based on the actual clinical needs, after discussion, we integrated 8 subgroups into 5 new subgroups, and the dataset was divided into training, validation, and test sets by the ratio of 8:1:1. RESULTS: The mean average precision at the intersection over union (IoU) of 0.5 (mAP50) for subgroup detection reached 90.29%. The classification accuracy values of SOTS, JOTS, SOTS + AI, and JOTS + AI groups were 56.24% ± 4.02%, 35.29% ± 18.07%, 79.53% ± 7.14%, and 71.53% ± 5.22%, respectively. The paired t-test results showed that the difference between the SOTS and SOTS + AI groups was statistically significant, as well as the difference between the JOTS and JOTS + AI groups, and the SOTS + JOTS and SOTS + JOTS + AI groups. Moreover, the difference between the SOTS + JOTS and SOTS + JOTS + AI groups in each subgroup was statistically significant, with all p < 0.05. The independent samples t-test results showed that the difference between the SOTS and JOTS groups was statistically significant, while the difference between the SOTS + AI and JOTS + AI groups was not statistically significant. With the assistance of AI, the subgroup classification accuracy of both SOTS and JOTS was significantly improved, and JOTS achieved the same level as SOTS. CONCLUSION In conclusion, the YOLOX-SwinT network algorithm enhances the accuracy of AO/OTA subgroups classification of ITF by orthopedic trauma surgeons.
Humans ; Hip Fractures/diagnostic imaging* ; Orthopedic Surgeons ; Algorithms ; Artificial Intelligence

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Objective To investigate the osteogenic properties of a methacrylated gelatin(GelMA)/bone marrow mesenchymal stem cells(BMSCs)composite hydrogel applied to the skull defect area of rats and to provide an experi-mental basis for the development of bone regeneration biomaterials.Methods This study was approved by the Animal Ethics Committee of Nanjing University.A novel photocurable composite biohydrogel was developed by constructing photoinitiators[lthium phenyl(2,4,6-trimethylbenzoyl)phosphinate,LAP],GelMA,and BMSCs.The surface morphology and elemental composition of the gel were examined using scanning electron microscopy(SEM)and energy-dispersive X-ray spectroscopy(EDX).The compressive strength of the gel was evaluated using an electronic universal testing ma-chine.After in vitro culture for 1,2,and 5 days,the proliferation of the BMSCs in the hydrogels was assessed using a CCK-8 assay,and their survival and morphology were examined through confocal microscopy.A 5 mm critical bone de-ficiency model was generated in a rat skull.The group receiving composite hydrogel treatment was referred to as the Gel-MA/BMSCs group,whereas the untreated group served as the control group.At the 4th and 8th weeks,micro-CT scans were taken to measure the bone defect area and new bone index,while at the 8th week,skull samples from the defect ar-ea were subjected to H&E staining,van Gieson staining,and Goldner staining to evaluate the quality of bone regenera-tion and new bone formation.Results SEM observed that the solidified GelMA showed a 3D spongy gel network with uniform morphology,the porosity of GelMA was 73.41％and the pore size of GelMA was(28.75±7.13)μm.EDX results showed that C and O were evenly distributed in the network macroporous structure of hydrogel.The hydrogel compres-sion strength was 152 kPa.On the 5th day of GelMA/BMSCs culture,the cellular morphology transitioned from oval to spindle shaped under microscopic observation,accompanied by a significant increase in cell proliferation(159.4％,as determined by the CCK-8 assay).At 4 weeks after surgery,a 3D reconstructed micro-CT image revealed a minimal re-duction in bone defect size within the control group and abundant new bone formation in the GelMA/BMSCs group.At 8 weeks after surgery,no significant changes were observed in the control group's bone defect area,with only limited evi-dence of new bone growth;however,substantial healing of skull defects was evident in the GelMA/BMSCs group.Quan-titative analysis at both the 4-and 8-week examinations indicated significant improvements in the new bone volume(BV),new bone volume/total bone volume(BV/TV),bone surface(BS),and bone surface/total bone volume(BS/TV)in the GelMA/BMSCs group compared to those in the control group(P＜0.05).Histological staining showed continuous and dense formation of bone tissue within the defects in the GelMA/BMSCs group and only sporadic formation of new bone,primarily consisting of fibrous connective tissue,at the defect edge in the control group.Conclusion Photocur-ing hydrogel-based stem cell therapy exhibits favorable biosafety profiles and has potential for clinical application by inducing new bone formation and promoting maturation within rat skull defects.

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health worldwide.The complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory damage.Nuclear factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated injury.Therefore,Nrf2-targeting therapies hold promise for preventing and treating NCDs.Quercetin(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory properties.It modulates the Nrf2 signaling pathway to ameliorate oxidative stress and inflammation.Que modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against NCDs.Here,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone damage.Furthermore,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applica-tions of Que in treating NCDs.In addition,we focused on the challenges and prospects for its clinical use.Que represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

Newborn screening (NBS) plays a significant role in reducing the risk of birth defects. NBS in China began in the early 1980s. Under the protection of laws and regulations and the leadership of the national health administration, approved screening centers in public hospitals took the responsibility for publicity, screening, diagnosis, treatment, follow-up and management of birth defects. As of 2022, 31 provinces (autonomous regions and municipalities directly under the central government) have carried out NBS for phenylketonuria, congenital hypothyroidism, and hearing loss, 23 provinces have carried out screening for glucose-6-phosphate dehydrogenase (with a screening rate of 89.24%), and 24 provinces have carried out screening for congenital adrenal cortical hyperplasia (91.45% screening rate). Over the past four decades, screening techniques have evolved from bacterial inhibition, fluorescence analysis, and tandem mass spectrometry for the detection of biochemical markers to genetic testing, which has greatly contributed to the expansion of the types of diseases screened for. The combined use of metabolomics and genomics is currently being explored. Effective management and rigorous quality control of NBS are prerequisites for improving the quality and ensuring the accuracy of screening. The Quality Management System for Newborn Screening System Network (QMS-NBS), established by the National Center for Clinical Laboratories, covers all screening centers and related blood collection agencies. The operation of the QMS-NBS allows the quality and performance of screening to be transparent and measurable, ensuring the quality and efficiency of screening. This article provides an overview of the history of NBS, especially the evolution of policies for the NBS in China, the construction of screening institutions, the number of newborns screened, the incidence rates of screened diseases, the changes in screening technology, the expansion of new diseases screened for, and the quality control of NBS. Overall, the progress in NBS in China has not only benefited from the development and standardization at the technological level, but also benefited from the construction of policies, regulations and ethics.
Infant, Newborn ; Humans ; Neonatal Screening ; Phenylketonurias ; Genetic Testing ; Congenital Hypothyroidism ; China

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.
Female ; Humans ; Male ; Bilirubin ; Esophageal and Gastric Varices ; Gastrointestinal Hemorrhage/surgery* ; Portasystemic Shunt, Transjugular Intrahepatic ; Postoperative Period ; Retrospective Studies ; Treatment Outcome ; Adult ; Middle Aged ; Glucuronosyltransferase/genetics*

Humans ; Diabetes Mellitus, Type 2/epidemiology* ; Air Pollution/adverse effects* ; Air Pollutants/toxicity* ; Risk Assessment ; Particulate Matter ; Environmental Exposure

OBJECTIVE: To summarize the clinical characteristics, differential diagnosis, and treatment methods of finger flexion contracture caused by three kinds of forearm flexor diseases. METHODS: Between December 2008 and August 2021, 17 patients with finger flexion contracture were treated, including 8 males and 9 females, aged 5-42 years, with a median of 16 years. The disease duration ranged from 1.5 months to 30 years, with a median of 13 years. The etiology included 6 cases of Volkmann's contracture, all of which were flexion deformity of the 2nd to 5th fingers, accompanied by limitation of thumb dorsiflexion in 3 cases and limitation of wrist dorsiflexion in 3 cases; 3 cases of pseudo-Volkmann's contracture, including 2 cases of flexion deformity of middle, ring, and little fingers, and 1 case of flexion deformity of ring and little fingers; 8 cases of ulnar finger flexion contracture caused by forearm flexor disease or anatomical variations, all of which were flexion deformity of middle, ring, and little fingers. Operations such as slide of flexor and pronator teres origin, excision of abnormal fibrous cord and bony prominence, and release of entrapped muscle (tendon) were performed. Hand function was evaluated according to WANG Haihua's hand function rating standard or modified Buck-Gramcko classification standard, and muscle strength was evaluated according to British Medical Research Council (MRC) muscle strength rating standard. RESULTS: All patients were followed up 1-10 years (median, 1.5 years). At last follow-up, 8 patients with contracture caused by forearm flexor disease or anatomical variations and 3 patients with pseudo-Volkmann's contracture achieved excellent hand function, with muscle strength of grade M5 in 6 cases and grade M4 in 5 cases. One patient with mild Volkmann's contracture and 3 patients with moderate Volkmann's contracture without severe nerve damage had excellent hand function in 2 cases and good in 2 cases, with muscle strength of grade M5 in 1 case and grade M4 in 3 cases. Two patients with moderate or severe Volkmann's contracture had poor hand function, with 1 case of muscle strength of grade M3 and 1 case of grade M2, which improved when compared with those before operation. The overall excellent and good rate of hand function and the proportion of patients with muscle strength of grade M4 and above were 88.2% (15/17), respectively. CONCLUSION The finger flexion contracture caused by different etiology can be differentiated by analyzing the history, physical examination, radiographs, and intraoperative findings. After different surgical treatments, such as resection of contracture band, release of compressed muscle (tendon), and downward movement of flexor origin, most patients have a good outcome.
Male ; Female ; Humans ; Forearm/surgery* ; Contracture/surgery* ; Ischemic Contracture/surgery* ; Fingers/surgery* ; Muscle, Skeletal/surgery*

Objective:To explore the clinical efficacy of double traction-assisted reduction internal fixation and open reduction internal fixation in treating tibial plateau fractures.Methods:Data of patients with tibial plateau fracture admitted to West China Hospital of Sichuan University from January 2016 to December 2021 were retrospectively analyzed, and patients were divided into two groups according to treatment method: double traction-closed reduction internal fixation group (referred to as double traction group) and open reduction internal fixation group (referred to as open group). The double traction group included 21 patients, with 15 male and 6 female patients, with a mean age of 56.14±9.24 years (range, 45-72 years). Schatzker classification of fractures: 1 type I, 2 type II, 2 type III, 5 type IV, 6 type V, and 5 type VI. The open group included 29 patients, with 20 male and 9 female patients, with a mean age of 58.97±4.84 years (range, 47-70 years). Schatzker classification of fractures: 2 type I, 4 type II, 8 type III, 4 type IV, 5 type V, and 6 type VI. The surgical time, incision length, intraoperative blood loss, length of hospital stays, fracture healing time, postoperative time to full weight bearing, Rasmussen score, Hospital for Special Surgery (HSS) knee score, and complications were compared between the two groups of patients.Results:Both groups were followed up for 24 to 36 months, with an average of 30 months. There were significant differences in the operation time (92.61±6.22 min vs. 47.92±9.53 min), incision length (4.54±0.56 cm vs. 6.26±0.51 cm), and intraoperative blood loss (47.05±9.72 ml vs. 156.82±4.62 ml) between the group treated with closed reduction and double traction and the group treated with open reduction, with statistical significance ( t=18.83, 10.78, 53.24, P<0.001). There were also significant differences in the hospitalization time (5.35±0.41 d vs. 5.84±0.78 d), fracture healing time (3.72±0.74 months vs. 4.22±0.42 months), and time to full weight-bearing after surgery (11.29±1.10 weeks vs. 15.07±1.96 weeks) between the two groups, with statistical significance ( t=2.30, P=0.026; t=3.38, P<0.001; t=7.96, P<0.001). The HSS score at 6 months after surgery in the group treated with closed reduction and double traction was 81.61±2.32 points, which was higher than the score in the group treated with open reduction (77.66±4.01 points), with statistical significance ( t=4.07, P<0.001); at 12 months after surgery, the Rasmussen score in the group treated with closed reduction and double traction was 16.71±1.00 points, which was higher than the score in the group treated with open reduction (13.79±1.42 points), with statistical significance ( t=8.05, P<0.001). There was no fracture malunion or compartment syndrome occurred in both groups. The incidence of complications was 5% (1/21) in the group treated with closed reduction and double traction, and 10% (3/29) in the group treated with open reduction, with statistical significance (χ 2=0.52, P=0.473). Conclusion:The advantages of double traction-assisted reduction and internal fixation for tibial plateau fractures include minimal trauma, minimal bleeding, early mobilization, and shorter fracture healing time. It is a safe and reliable treatment method.