AIM: To investigate the effects of Conbercept on various optical coherence tomography(OCT)biomarkers in patients with retinal vein occlusion-related macular edema(RVO-ME), and to analyze the correlation of these biomarker changes with visual prognosis.METHODS: Retrospective study. A total of 57 patients(57 eyes)with RVO-ME, including 25 patients(25 eyes)with central retinal vein occlusion(CRVO)and 32 patients(32 eyes)with branch retinal vein occlusion(BRVO), were enrolled in this study. All the patients received intravitreal injection of conbercept once a month, three times in total. The preoperative and postoperative best-corrected visual acuity(BCVA), and changes in OCT biomarkers, including central macular thickness(CMT), the length of disorganization of the retinal inner layers(DRIL), the number of hyperreflective dots(HRD), the area of intraretinal fluid(IRF), the area of subretinal fluid(SRF), and the length of ellipsoid zone(EZ)disruption were compared. Furthermore, the relationship of these changes with BCVA was analyzed.RESULTS:Compared with the baseline, at 3 mo post-treatment, BCVA(LogMAR)was improved, CMT was decreased, the length of DRIL was shortened, the number of HRD was reduced, the area of IRF was decreased, the area of SRF was reduced, and the length of EZ disruption was shortened(all P<0.05). Spearman correlation analysis showed that there was no correlation between the changes in CMT, the length of DRIL, the number of HRD, the area of IRF, the area of SRF and the change in BCVA before and after treatment(P>0.05). However, the change in the length of EZ disruption was positively correlated with the change in BCVA(rs=0.34, P=0.011), and the R2 value of the fitting curve between the change in the length of EZ disruption and the change in BCVA was 0.113(P=0.011). When comparing the pre- and post-treatment changes in BCVA, the length of DRIL, the number of HRD, the area of IRF, the area of SRF, and the length of EZ disruption between patients in the CRVO group and BRVO group, no significant differences were observed(all P>0.05). In contrast, a significant difference was found in the change in CMT between the two groups(P=0.002).CONCLUSION:Conbercept effectively improves multiple OCT biomarkers in patients with RVO-ME. Repair of EZ disruption is a key driver of visual recovery, and its stability may serve as a novel indicator for personalized decision-making in anti-vascular endothelial growth factor therapy.

OBJECTIVE To design and synthesize rifamycin S derivatives and load them into milk exosomes to evaluate their in vitro antimicrobial activity.METHODS Rifamycin S derivatives were synthe-sized and characterized by mass spectrometry and NMR.Using the dilution assay method,the inhibitory activity of each rifamycin S derivatives molecule against Staphylococcus aureus and Pseudomonas aerugi-nosa was determined,and the IC50 was calculated.Derivatives molecules with excellent antimicrobial activity were selected and loaded into milk exosomes using the ultrasonication method,resulting in the preparation of milk exosome-loaded rifamycin S derivatives.The antimicrobial activity against Staphylo-coccus aureus was determined using the dilution assay method.The inhibitory effect of the exosome-loaded rifamycin S derivatives on Staphylococcus aureus residing within macrophages was detected using the plate colony counting method.RESULTS Three rifamycin S derivatives were successfully designed and synthesized,which demonstrated superior antimicrobial activity against Staphylococcus aureus(the parent compound's antimicrobial activity is merely from 1/20 to 1/80 of that of the three rifamycin S derivatives)and Pseudomonas aeruginosa(the parent compound's antimicrobial activity is only 1/14 and 1/9 of that of compound 1 and compound 3)compared to the parent compound.The loading of milk exosomes with the rifamycin S derivatives compound 3 was successfully achieved,with a loading efficiency of 10.9％.The antimicrobial activity of the compound after exosome loading was significantly enhanced against Staphylococcus aureus in vitro and against Staphylococcus aureus residing within macrophages(P＜0.01).CONCLUSION The designed and synthesized derivatives of rifamycin S possess stronger anti-microbial activity,and their antibacterial efficacy against both extracellular and intracellular bacteria can be further enhanced after loading into exosomes.

BACKGROUND:Bone microenvironment is also rich in various immune cells and cytokines,which are closely related to bone cells and form an interactive network.Therefore,bone aging is not only caused by the senescence of osteocytes,but also accelerated by age-related changes in the immune system.OBJECTIVE:To review the age-related changes of bone marrow mesenchymal stem cells,osteoblasts,osteoclasts,and immune cells in the bone microenvironment,emphasize the key role of the immune microenvironment in bone aging,and the potential of immunotherapy in the treatment of bone aging.METHODS:We searched PubMed and China National Knowledge Infrastructure for articles on the interaction between bone cell senescence and immune cell senescence using"osteocytes,bone aging,immune microenvironment,immune cells,cytokines,immunosenescence,immunotherapy"as Chinese and English search terms.According to the inclusion and exclusion criteria,128 articles were finally included in the review.RESULTS AND CONCLUSION:Bone aging is a common pathological condition in the elderly,characterized by the interaction of multiple biological processes,among which immune factors play a key role.The cells,molecules,and signaling pathways in the immune microenvironment together constitute a complex network,and the imbalance of this network will accelerate the process of bone aging.The combination of anti-cellular aging and immunotherapy may bring new methods for the treatment of bone aging diseases,including the removal of senescent cells,targeted drugs for senescence-related secretory phenotypes,targeted therapy of inflammatory cytokines,immune cell regulation therapy,stem cell therapy,and molecular therapy.To more effectively and reasonably remove senescent cells,a deeper understanding of the mechanism of senescent cells is needed,which will help to identify senescent cells more accurately.Immunotherapy shows great potential and prospects in the treatment of bone aging,but there are some potential risks.It is believed that with the advancement of science and technology,people can more accurately understand the genetic information and immune status of the human body and develop more personalized immunotherapy plans.

Objective To observe the clinical efficacy and safety of recombinant human growth hormone injection(rhGH)in the treatment of children with idiopathic short stature(ISS)and its influence on levels of insulin-like growth factor 1(IGF-1),alkaline phosphatase(AKP)and insulin-like growth factor binding protein 3(IGFBP-3).Methods Children with ISS were randomized into control group and treatment group.The control group was subcutaneously injected with 0.15 U·kg-1 of rhGH injection,while the treatment group was given subcutaneous injection of 0.20 U·kg-1 of rhGH injection,and both groups were continuously treated for 6 months.The clinical efficacy,growth status[growth velocity,height standard deviation score(HtSDS),predicted adult height(PAH)],bone metabolism indicators { AKP,osteocalcin(OC),25-hydroxyvitamin D[25(OH)D]} and serum IGF-1 and IGFBP3 levels were compared,and the safety was assessed.Results In the treatment group,46 cases were enrolled,6 cases were lost,and 40 cases were finally included in the statistical analysis.In the control group,46 cases were enrolled,1 case was lost,and 45 cases were finally included in the statistical analysis.The total effective rates in treatment group and control group after 6 months treatment were 85.00％(34 cases/40 cases)and 64.44％(29 cases/45 cases),respectively,with a statistical significance(P＜0.05).After 6 months treatment,the growth rates in treatment group and control group were(7.96±1.62)and(6.84±1.56)cm·year-1;HtSDS values were-2.38±0.24 and-2.61±0.28;PAH values were(156.86±4.18)and(155.02±4.25)cm;serum AKP levels were(278.42±47.46)and(257.14±42.79)U·L-1;OC levels were(76.92±10.17)and(72.43±10.32)μg·L-1;25(OH)D levels were(59.96±4.74)and(55.52±4.69)nmol·L-1;serum IGF-1 levels were(296.77±28.32)and(251.47±24.96)ng·mL-1;serum IGFBP3 levels were(5.76±1.22)and(4.86±0.89)μg·mL-1,respectively.Compared with the control group,the above indexes in the treatment group were statistically significant(all P＜0.05).The adverse drug reactions in treatment and control group were mainly headache,rash and joint pain,rash and joint pain.The incidence rates of adverse reactions in treatment group and control group were 12.50％(5 cases/40 cases)and 6.67％(3 cases/45 cases),without significant difference(P＞0.05).Conclusion The clinical efficacy of rhGH injection in the treatment of children with ISS is definite;and the improvement of IGF-1,AKP and IGFBP3 levels by 0.20 U·kg-1 rhGH is significantly better than that by 0.15 U·kg-1 rhGH,which is more conducive to promoting bone development and accelerating growth without increasing the incidence of adverse drug reactions.

Objective:To describes the probability and rate of native liver survival (NLS) in biliary atresia (BA) patients after Kasai portoenterostomy (KPE)over various time periods and analyzes the perioperative factors associated with liver transplantation or death.Methods:A retrospective case-summary.BA patients administrated at the Department of Fetal and Neonatal Surgery in Hunan Children′s Hospital between January 2015 and December 2021.Probability and rate of NLS were calculated by life table.Cox proportional hazards regression model and Logistic model was applied to explore the perioperative factors related to post-Kasai liver transplantation/death.Results:The median age at Kasai surgery was 62 days.The rate of jaundice clearance (JC) was 64.5% within 3 months after Kasai, and 58.3% of the patients had cholangitis.The probability of NLS reached its lowest point in the first 1 year after Kasai (76.2%) and ranged from 93.2% to 98.0% in years 2-8 after Kasai.The rates of NLS in 2 years, 5 years and 8 years were 71.1%, 62.8% and 56.0%, respectively.Cytomegalovirus (CMV) infection before or on the day of Kasai without antiviral treatment can increase the risk of liver transplantation or death[ HR(95% CI): 1.628 (1.081-2.452), P=0.020].Preoperative gamma-glutamyl transferase increased the risk of liver transplantation/death within 1 year after Kasai[ OR(95% CI): 1.001 (1.000-1.001), P=0.021], and early cholangitis was a risk factor for liver transplantation/death within 5 years after Kasai[ OR(95% CI): 1.934 (1.004-3.726), P=0.048].JC within 3 months post-KPE was a protective factor of NLS. Conclusions:The first year after Kasai was the highest risk period for liver transplantation/death, which should be the focus of follow-up management.JC within 3 months after surgery is the protective factor for overall NLS, 1-year NLS and 5-year NLS.

Objective To explore the functions of β-glucan-induced extracellular vesicles(EVs)released from J774A.1 cells.Methods EVs were extracted from the culture supernatant of J774A.1 cells,which were cultured with or without β-glucan,using differential centrifugation.The phenotype of extracellular vesicles was identified by transmission electron microscopy(TEM),nano-particle tracking analysis(NTA)and Western blotting(WB).The peritoneal macrophages(PMs)were harvested from C57BL/6J mice,and incubated with the control EVs(C-EVs)and theβ-glucan-induced EVs(G-EVs).Total RNA was extracted from the PMs and reversely transcribed to cDNA.The expression levels of the macrophage polarization-related genes were detected through real-time fluorescence quantitative PCR(qRT-PCR).Meanwhile,the culture supernatant of the PMs was collected and assayed by enzyme-linked immunosorbent assay(ELISA)to detect the expression levels of proinflammatory cytokines tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6).Results EVs of the control(C-EVs)and those from the β-glucan-induced(G-EVs)were isolated from J774A.1 cell culture medium.The results of TEM analysis showed that EVs had a membrane wrapped structure and the particle diameters ranged from 100 to 1000 nm.The NTA results showed that the average particle sizes were 162.4 and 175.6 nm respectively.The results of WB assay showed the expressions of characterized marker molecules such as CD81,CD9,CD63 and TSG101 were detected.qRT-PCR results showed that the expression levels of M1 polarization related genes such as Tnfa and inos were significantly increased in PM cells of the C-EVs treatment group,but those in the G-EVs treatment group were significantly lower than in the C-EVs treatment group.Meanwhile,the expression levels of M2 polarization indicators Cd206 and Arg-1 in the C-EVs treatment group were significantly decreased,while those in the G-EVs treatment group were significantly higher than those in C-EVs treatment group.Accordingly,the results of ELISA showed that the expression levels of TNF-α and IL-6 in the conditioned medium of the C-EVs treatment group were significantly increased,while those in the G-EVs treatment group were significantly lower than in the C-EVs treatment group.Conclusion Compared with the natural EVs from J774A.1 cells,the ability of β-glucan-induced EVs to drive M1 polarization of macrophages isdramatically compromised,with much fewer proinflammatory cytokines released,suggesting that β-glucan might contribute to immune regulation through EVs.

Sophorae Flavescentis Radix is one of the commonly used traditional Chinese medicine in China, and a large amount of pharmaceutical residue generated during its processing and production is discarded as waste, which not only wastes resources but also pollutes the environment. Therefore, elucidating the chemical composition of the residue of Sophorae Flavescentis Radix and the differences between the residue and Sophorae Flavescentis Radix itself is of great significance for the comprehensive utilization of the residue. This study, based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) technology combined with multivariate statistical methods, provides a thorough characterization, identification, and differential analysis of the overall components of Sophorae Flavescentis Radix and its residue. Firstly, 61 compounds in Sophorae Flavescentis Radix were rapidly identified based on their precise molecular weight, fragment ions, and compound abundance, using a self-constructed compound database. Among them, 41 compounds were found in the residue, mainly alkaloids and flavonoids. Secondly, through principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA), 15 key compounds differentiating Sophorae Flavescentis Radix from its residue were identified. These included highly polar alkaloids, such as oxymatrine and oxysophocarpine, which showed significantly reduced content in the residue, and less polar flavonoids, such as kurarinone and kuraridin, which were more abundant in the residue. In summary, this paper clarifies the overall composition, structure, and content differences between Sophorae Flavescentis Radix and its residue, suggesting that the residue of Sophorae Flavescentis Radix can be used as a raw material for the extraction of its high-activity components, with promising potential for development and application in cosmetics and daily care. This research provides a scientific basis for the future comprehensive utilization of Sophorae Flavescentis Radix and its residue.
Drugs, Chinese Herbal/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Mass Spectrometry/methods* ; Sophora/chemistry* ; Flavonoids/chemistry* ; Alkaloids/chemistry*

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

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

BACKGROUND: The choice of unicompartmental knee arthroplasty (UKA) vs . total knee arthroplasty (TKA) in the surgical treatment of knee osteoarthritis (KOA) remains controversial. This study aimed to perform a systematic review and meta-analysis of randomized controlled trials (RCTs) to compare the clinical results of UKA and TKA for treating unicompartmental KOA. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched for articles published up to January 2, 2023. The literature was rigorously screened to include only RCTs comparing UKA and TKA for unicompartmental KOA. A systematic review and meta-analysis were performed to calculate the mean difference (MD), relative risk (RR), and 95% confidence interval (CI) according to the Cochrane standards. RESULTS: Thirteen publications involving 683 UKAs and 683 TKAs were analyzed. Except for one study with a follow-up period of 15 years, all outcome measures reported were within 5 years of follow-up. Meta-analysis showed better knee recovery (MD: 1.23; 95% CI: 1.01-1.45; P  <0.001), greater knee function (MD: 1.78; 95% CI: 0.34-3.22; P  = 0.020), less pain (MD: 0.75; 95% CI: 0.43-1.06; P  <0.001), and better health status (MD: 3.75; 95% CI: 0.81-6.69; P  = 0.010) after UKA than TKA. However, considering the minimal clinically important difference values for these variables, the findings were not clinically relevant. Moreover, UKA patients had fewer complications (RR: 0.59; 95% CI: 0.45-0.78; P  <0.001) and shorter hospital stays (MD: -0.89; 95% CI: -1.57 to -0.22; P  = 0.009) than did TKA patients. There were no statistically significant differences in terms of postoperative range of movement, revision, failure, operation time, and patient satisfaction. CONCLUSIONS In terms of clinical efficacy, there was no obvious advantage of UKA over TKA in the surgical treatment of knee OA when considering the minimal clinically important difference. The main advantage of UKA over TKA is that it leads to fewer complications and a shorter length of hospital stay. It is ideal to perform prospective studies with longer follow-up periods to fully evaluate the long-term efficacy and safety of the two procedures in the future.
Humans ; Arthroplasty, Replacement, Knee/methods* ; Osteoarthritis, Knee/surgery* ; Randomized Controlled Trials as Topic ; Treatment Outcome