AIM: To assess the clinical efficacy and safety of epithelial-off accelerated corneal collagen cross-linking(CXL)in the management of progressive keratoconus over 1 a period.METHODS:A retrospective pre-post self-controlled study. Data were collected from complete cases of 63 patients(84 eyes)with progressive keratoconus who underwent epithelial-off accelerated CXL between August 2018 and September 2021. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), refraction, corneal transparency, maximum keratometry(Kmax)of the anterior corneal surface, minimum corneal thickness, endothelial cell counts, and intraocular pressure(IOP)were analyzed preoperatively and at 1, 3, 6, and 12 mo postoperatively.RESULTS:No significant differences were observed in UCVA and spherical power before and after surgery(all P>0.05). However, there were significant differences in BCVA, cylinder power, Kmax, minimum corneal thickness, and IOP(all P<0.05). At 12 mo postoperatively, there were no significant differences in BCVA, cylinder power, minimum corneal thickness, and IOP compared with preoperative values(all P>0.05), while Kmax was decreased compared with preoperative value(P<0.05). At 1 mo postoperatively, the corneal endothelial cell count(2519.87±345.28 cells/mm2)was decreased compared with preoperative value(2693.63±313.39 cells/mm2; P<0.001). At 1 wk postoperatively, 22 eyes developed corneal haze(grade 0.5 to 1), and 15 eyes presented with linear corneal stromal opacity at 1 mo postoperatively. In 7 eyes, corneal opacity subsided within 3 to 6 mo after the operation, however, 5 eyes still exhibited corneal nebula or macula without affecting visual acuity.CONCLUSION: After epithelial-off accelerated CXL, the UCVA, BCVA and spherical diopter of patients remained stable over time. The astigmatism and corneal curvature temporarily increased and then gradually decreased. The cornea minimum thickness decreased initially but subsequently returned to preoperative levels. The corneal curvature at 6 and 12 mo after surgery was significantly lower than that before surgery, which could effectively prevent the progression of keratoconus. Despite potential localized corneal opacity and macular complications, as well as a possible decrease in corneal endothelial cell count, BCVA remained unaffected, demonstrating favorable safety outcomes.

AIM: To assess the clinical efficacy and safety of epithelial-off accelerated corneal collagen cross-linking(CXL)in the management of progressive keratoconus over 1 a period.METHODS:A retrospective pre-post self-controlled study. Data were collected from complete cases of 63 patients(84 eyes)with progressive keratoconus who underwent epithelial-off accelerated CXL between August 2018 and September 2021. Uncorrected visual acuity(UCVA), best corrected visual acuity(BCVA), refraction, corneal transparency, maximum keratometry(Kmax)of the anterior corneal surface, minimum corneal thickness, endothelial cell counts, and intraocular pressure(IOP)were analyzed preoperatively and at 1, 3, 6, and 12 mo postoperatively.RESULTS:No significant differences were observed in UCVA and spherical power before and after surgery(all P>0.05). However, there were significant differences in BCVA, cylinder power, Kmax, minimum corneal thickness, and IOP(all P<0.05). At 12 mo postoperatively, there were no significant differences in BCVA, cylinder power, minimum corneal thickness, and IOP compared with preoperative values(all P>0.05), while Kmax was decreased compared with preoperative value(P<0.05). At 1 mo postoperatively, the corneal endothelial cell count(2519.87±345.28 cells/mm2)was decreased compared with preoperative value(2693.63±313.39 cells/mm2; P<0.001). At 1 wk postoperatively, 22 eyes developed corneal haze(grade 0.5 to 1), and 15 eyes presented with linear corneal stromal opacity at 1 mo postoperatively. In 7 eyes, corneal opacity subsided within 3 to 6 mo after the operation, however, 5 eyes still exhibited corneal nebula or macula without affecting visual acuity.CONCLUSION: After epithelial-off accelerated CXL, the UCVA, BCVA and spherical diopter of patients remained stable over time. The astigmatism and corneal curvature temporarily increased and then gradually decreased. The cornea minimum thickness decreased initially but subsequently returned to preoperative levels. The corneal curvature at 6 and 12 mo after surgery was significantly lower than that before surgery, which could effectively prevent the progression of keratoconus. Despite potential localized corneal opacity and macular complications, as well as a possible decrease in corneal endothelial cell count, BCVA remained unaffected, demonstrating favorable safety outcomes.

In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

The phase changes and quantity-quality transfer of 17 batches of Ostreae Concha(Ostrea rivularis) during the raw material-calcined decoction pieces-standard decoction process were analyzed. The content of calcium carbonate(CaCO_3), the main component, was determined by chemical titration, and the extract yield and transfer rate were calculated. The CaCO_3 content in the raw material, calcined decoction pieces, and standard decoction was 94.39%-98.80%, 95.03%-99.22%, and 84.58%-90.47%, respectively. The process of raw material to calcined decoction pieces showed the yield range of 96.85% to 98.55% and the CaCO_3 transfer rate range of 96.92% to 99.27%. The process of calcined decoction pieces to standard decoction showed the extract yield range of 2.86% to 5.48% and the CaCO_3 transfer rate range of 2.59% to 5.13%. The results of X-ray fluorescence(XRF) assay showed that the raw material, calcined decoction pieces, and standard decoction mainly contained Ca, Na, Mg, Si, Br, Cl, Al, Fe, Cr, Mn, and K. The chemometric results showed an increase in the relative content of Cr, Fe, and Si from raw material to calcined decoction pieces and an increase in the relative content of Mg, Al, Br, K, Cl, and Na from calcined decoction pieces to standard decoction. X-ray diffraction(XRD) was employed to establish XRD characteristic patterns of the raw material, calcined decoction pieces, and standard decoction. The XRD results showed that the main phase of all three was calcite, and no transformation of crystalline form or generation of new phase was observed. Fourier transform infrared spectroscopy(FTIR) was employed to establish the FTIR characteristic spectra of the raw material, calcined decoction pieces, and standard decoction. The FTIR results showed that the raw material had internal vibrations of O-H, C-H, C=O, C-O, and CO■ groups. Due to the loss of organic matter components after calcination, no information about the vibrations of C-H, C=O, and C-O groups was observed in the spectra of calcined decoction pieces and standard decoction. In summary, this study elucidated the quantity-quality transfer and phase changes in the raw material-calcined decoction pieces-standard decoction process by determining the CaCO_3 content, calculating the extract yield and transfer rate, and comparing the element changes, FTIR characteristic spectra, and XRD characteristic pattern. The results were reasonable and reliable, laying a foundation for the subsequent process research and quality control of the formula granules of calcined Ostreae Concha(O. rivularis Gould), and providing ideas and methods for the quality control of the whole process of raw material-decoction pieces-standard decoction-formula granules of Ostreae Concha and other testacean traditional Chinese medicine.
Drugs, Chinese Herbal/isolation & purification* ; Calcium Carbonate/analysis* ; Quality Control

OBJECTIVES: To study clinical manifestations and gene mutation features of neonates with centronuclear myopathy. METHODS: A retrospective analysis was conducted on the medical data of 5 neonates with centronuclear myopathy diagnosed in the Neonatal Intensive Care Unit of Children's Hospital, Zhejiang University School of Medicine from January 2020 to August 2024. The data included gender, gestational age, birth weight, Apgar score, clinical manifestations, creatine kinase level, electromyography, genetic testing results and the outcomes of the infants. RESULTS: All 5 male neonates had a history of postpartum asphyxia and resuscitation. They all presented with hypotonia, myasthenia, and respiratory failure; two neonates also had swallowing dysfunction. Of the five neonates, three had normal creatine kinase levels, while two had slightly elevated levels. Electromyography was performed for three neonates, among whom two had myogenic damage. MTM1 gene mutations were identified by genetic testing in all five neonates, including two nonsense mutations and three missense mutations, among which one variant had not been previously reported. Four mutations were inherited from the mother, and the other one was a de novo mutation. The five neonates showed no clinical improvement following treatment, failed weaning from mechanical ventilation, and ultimately died after withdrawal of life-sustaining therapy. CONCLUSIONS Centronuclear myopathy caused by MTM1 gene mutation often has a severe phenotype and a poor prognosis, and it should be considered for neonates with hypotonia and myasthenia after birth. Genetic testing should be performed as soon as possible.
Humans ; Myopathies, Structural, Congenital/genetics* ; Male ; Infant, Newborn ; Retrospective Studies ; Mutation ; Female ; Protein Tyrosine Phosphatases, Non-Receptor/genetics*

OBJECTIVE: To explore and evaluate the efficacy and safety of a modified thiotepa-based conditioning regimen combined with autologous hematopoietic stem cell transplantation (ASCT) for the treatment of primary central nervous system lymphoma (PCNSL). METHODS: In a retrospective, single center, single arm study, we collected data of 28 patients with PCNSL who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDC-ASCT) at our center from March 2021 to December 2024. The clinical characteristics of the patients, the conditioning regimen details, treatment-related toxicities and adverse reactions, post-transplant disease remission status, and survival outcomes were analyzed. RESULTS: A total of 28 patients were included. Among them, 19 patients received ASCT as first-line consolidation therapy in complete response (CR) or partial response (PR) status, and 9 patients with relapsed/refractory disease underwent salvage ASCT. The median time to neutrophil engraftment was 9 days (range: 5-11 days), and the median time to platelet engraftment was 10 days (range: 6-13 days). All patients achieved CR at the initial efficacy evaluation post-ASCT. The main complications during the transplantation period were febrile neutropenia (26 cases) and grade 3 diarrhea (9 cases). No transplantation-related mortality occurred. Post-ASCT, 19 patients received maintenance therapy, which was demonstrated to be safe and effective. Three patients relapse, and one patient died. The median progression-free survival (PFS) and overall survival (OS) of patients were not reached. The estimated 1-year and 2-year cumulative PFS rates were 88.4% and 66.3%, respectively, while the 1-year and 2-year OS rates were both 94.1%. CONCLUSION The modified thiotepa-based conditioning regimen combined with ASCT is safe and effective for the treatment of PCNSL.
Humans ; Thiotepa/therapeutic use* ; Retrospective Studies ; Transplantation, Autologous ; Transplantation Conditioning/methods* ; Central Nervous System Neoplasms/therapy* ; Hematopoietic Stem Cell Transplantation ; Female ; Male ; Middle Aged ; Adult ; Lymphoma/therapy* ; Treatment Outcome ; Aged

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

Kidney fibrosis is the final common pathway of virtually all chronic kidney disease (CKD). However, despite great progress in recent years, no targeted antifibrotic therapies have been approved. Epidemiologic, clinical, and molecular evidence suggest that aging is a major contributor to the increasing incidence of CKD. Senescent renal tubular cells, fibroblasts, endothelial cells, and podocytes have been detected in the kidneys of patients with CKD and animal models. Nonetheless, although accumulated evidence supports the essential role of cellular senescence in CKD, the mechanisms that promote cell senescence and how senescent cells contribute to CKD remain largely unknown. In this review, we summarize the features of the cellular senescence of the kidney and discuss the possible functions of senescent cells in the pathogenesis of kidney fibrosis. We also address whether pharmacological approaches targeting senescent cells can be used to retard the the progression of kidney fibrosis.
Humans ; Cellular Senescence/physiology* ; Fibrosis ; Renal Insufficiency, Chronic/pathology* ; Kidney/pathology* ; Animals

BACKGROUND: China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy. OBJECTIVE: This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment. MAIN OUTCOME MEASURES: The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12. RESULTS: Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ² = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05). CONCLUSION: Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL. TRIAL REGISTRATION Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans ; Male ; Female ; Middle Aged ; Acupuncture Points ; Upper Extremity/physiopathology* ; Biomechanical Phenomena ; Single-Blind Method ; Aged ; Stroke/therapy* ; Acupuncture Therapy/methods* ; Stroke Rehabilitation/methods* ; Adult ; Muscle Spasticity/therapy* ; Paresis/physiopathology* ; Treatment Outcome