OBJECTIVE To analyze the current status and challenges in importing rare disease drugs in China， providing references for optimizing the import process and improving relevant policies. METHODS Questionnaires and interviews were conducted with stakeholders involved in rare disease drug importation， including government departments， multinational pharmaceutical enterprises， healthcare institutions， and patient organizations. This explored the current situation and challenges encountered by each party. Expert opinions were synthesized to propose improvement suggestions. RESULTS A questionnaire survey of representatives from 25 multinational pharmaceutical companies in the rare disease field revealed that these companies had a strong willingness to import rare disease drugs， with 58.33% of them practicing diverse import models. However， significant challenges hindered this process， including unclear regulations （54.17%）， complex approval procedures （45.83%）， and excessively long approval cycles （41.67%）， negatively impacting their motivation. Meanwhile， interviews with 13 experts from government departments， healthcare institutions， pharmaceutical enterprises， and patient organizations identified deficiencies in policy design， approval processes， sampling inspection costs， and communication efficiency with regulators. Additionally， the drug import model in special medical zones also required improvement. CONCLUSIONS The importation of rare disease drugs in China faces challenges such as incomplete policies， inflexible regulatory mechanisms， and insufficient communication channels. It is recommended to enhance the rare disease definition criteria， optimize import incentive policies， and refine regulatory models， so as to further optimize the import process of rare disease drugs and improve relevant policies.

ObjectiveTo investigate the alleviating effect of calcium cyanamide （CaCN₂） soil fumigation on replanting problems of Rehmannia glutinosa. MethodsNewly soil （NP） was used as the control group， while three treatment groups were established： replanted soil （RP）， newly soil treated with CaCN₂ （120 g·m²， tillage depth 25 cm） （NPCC）， and replanted soil treated with CaCN₂ （RPCC）. R. glutinosa was cultivated in all groups. At harvest， the tuber agronomic traits （number of enlarged roots， maximum root diameter， fresh weight， dry weight） were measured. The content of catalpol and rehmannioside D was quantified by ultra-high-performance liquid chromatography （UPLC） to evaluate medicinal quality. Rhizosphere soil available nutrients and enzyme activities were analyzed by assay kits. The community structure and composition of fungi and bacteria in rhizosphere soil were assessed via internal transcribed spacer 2 （ITS2） sequencing and 16S rDNA sequencing， respectively. ResultsCompared with NP， the RP group showed obviously reduced in tuber agronomic traits and quality indicators （P0.05）. However， the RPCC group showed significant improvement in agronomic traits and a notable increase in rehmannioside D content compared to RP （P0.05）. The contents of available phosphorus and potassium in RPCC and NP groups were obviously lower than those in RP （P0.05）. The polyphenol oxidase soil （S-PPO） activity in RP was obviously lower than in NP （P0.05）， while sucrose soil （S-SC）， acid phosphatase soil （S-ACP）， and S-PPO activities in RPCC were obviously higher than in RP （P0.05）. Microbial richness and diversity in RP were obviously higher than in NP （P0.05）， whereas no significant differences were observed between the RPCC and NP. The relative abundances of fungal genera Nectria， Myrothecium， Tomentella， and bacterial genus Skermanella were obviousl lower in RPCC and NP than in RP （P0.05）. Correlation analysis that S-ACP activity was positively correlated with the content of rehmannioside D （P0.05）. Fungal genera Engyodontium and Alternaria， and bacterial genera Pir4 lineage， Pirellula， Methyloversatilis， Brevundimonas， Ralstonia， and Acidibacter were obviously positively correlated with tuber dry weight （P0.05）. Conversely， fungal genera Pseudaleuria， Nectria， Haematonectria， Ceratobasidium， and bacterial genera Streptomyces， Skermanella， RB41， Gemmatimonas， and Bacillus were obviously negatively correlated with dry weight （P0.05）. The fungal genus Alternaria and bacterial genera Brevundimonas， Ralstonia， Acidibacter， and Dongia showed positive correlations with medicinal quality of R.glutinosa tuber， while fungal genera Pseudaleuria， Nectria， Stachybotrys， Fusarium， Gibberella， Ceratobasidium， and bacterial genera Sphingomonas， Skermanella， RB41， Gemmatimonas， and Bacillus were obviously negatively correlated （P0.05）. ConclusionCaCN₂ soil fumigation can significantly improve enzyme activities in replanted Rehmannia rhizosphere soil， enhance the utilization of available nutrients， reshape microbial community structure of replanted R.glutinosa at the family and genus level， and notably improve tuber agronomic traits and medicinal quality. This study provides a novel approach to alleviating replanting problems and offers insights for the integrated development of standardized cultivation techniques， including soil disinfection， nutrient-targeted regulation， and microbial inoculant application.

OBJECTIVE To observe the clinical efficacy of Yijinjing in the treatment of elderly sarcopenia and its effect on chro-nic inflammatory response in patients,and to explore the Yijinjing exercise prescription suitable for elderly patients with sarcopenia.METHODS A total of 120 elderly patients with sarcopenia admitted to the Department of Rehabilitation Medicine,Suzhou Hospital of Traditional Chinese Medicine from September 2022 to September 2024 were selected and randomly divided into a control group and a Yijinjing group,with 60 cases in each group.The control group received health education and dietary guidance,and the Yijinjing group received Yijinjing exercises on the basis of the intervention of the control group.The changes in skeletal muscle mass,upper and lower limb muscle strength,muscle thickness,muscle cross-sectional area,physical fitness and chronic inflammation level were observed in the two groups before and after the intervention.RESULTS After intervention,the skeletal muscle mass,grip strength,30 s sit-stand test times,rectus femoris thickness and cross-sectional area,vastus intermedius thickness,and physical fit-ness assessment of the patients in the Yijinjing group were significantly increased compared with those before treatment(P<0.05),and the indicators after intervention were higher than those in the control group(P<0.05);the serum TNF-α and IL-18 levels in the Yi-jinjing group were significantly decreased compared with those before treatment(P<0.05),and the indicators after intervention were lower than those in the control group(P<0.05);there was no statistically significant change in the biceps brachii thickness and serum IL-6 level in the Yijinjing group compared with those before treatment(P>0.05);there was no significant correlation between the bi-ceps brachii thickness and grip strength after Yijinjing intervention,r=0.139 8,P>0.05;there was a significant negative correlation between the TNF-α level and grip strength after Yijinjing intervention,r=-0.313 8,P<0.05.CONCLUSION Yijinjing exercises can improve muscle mass and strength in elderly patients with sarcopenia,and improve the physical fitness of patients,which may be related to improving the chronic inflammatory state of the body.

Objective:To evaluate the effects of low level laser therapy(LLLT)on accelerating tooth movement and reducing pain during orthodontic treatment.Methods:26 patients with malocclusion of class Ⅱ,division 1 were included.Maxillary teeth on left and right sides were selected randomly as the experimental side and control side.Dental arches of experimental side received the irra-diation of LLLT with 7.5 J/cm2 for each point,10 points for each tooth,and the control side received placebo treatment,with the la-ser light off.The pain and the rate of teeth movement on experimental and control sides were compared.Results:The mean score of pain at the control side was significantly higher than that of the experimental side in the 7 days(P＜0.001).The average movement rate of the experimental group was higher than that of the control group(P＜0.05).Conclusion:LLLT is effective in accelerating tooth movement and reducing the related pain.

Objective To introduce the fundamental principles of the multivariate functional mixed model(MFMM)and provide a methodological basis for interpreting the principal components derived from dimension reduction of multivariate functional data.Methods The MFMM models the mean function,auto-covariance function,and cross-covariance function within functions non-parametrically,clearly separating the shared latent processes common to all indicators from the specific latent processes unique to each indicator.In the case study,data from colorectal cancer patients at the Yunnan Cancer Hospital are used to extract the common and specific principal components of longitudinal carcinoembryonic antigen(CEA)and carbohydrate antigen 125(CA125)within 12 months post-surgery using MFMM,coupled with interpretation through a random survival forest prediction model.Results The MFMM identified 2 shared principal components for CEA and CA125,5 specific components for CEA,and 5 specific components for CA125.The random survival forest prediction model constructed based on these extracted components showed higher prediction accuracy than the baseline model.Furthermore,variable importance analysis revealed that the first specific component of CEA was the most important predictive variable after clinical baseline variables,while the importance of CA125 specific components was lower than that of CEA,consistent with the current consensus on colorectal cancer.Conclusion MFMM effectively manages the correlations among multiple longitudinal indicators and their changes over time,capturing the shared and specific processes of multiple longitudinal measurement indicators as they evolve.This enhances the model's interpretability and offers theoretical and practical advantages.

OBJECTIVE To observe the clinical efficacy of Yijinjing in the treatment of elderly sarcopenia and its effect on chro-nic inflammatory response in patients,and to explore the Yijinjing exercise prescription suitable for elderly patients with sarcopenia.METHODS A total of 120 elderly patients with sarcopenia admitted to the Department of Rehabilitation Medicine,Suzhou Hospital of Traditional Chinese Medicine from September 2022 to September 2024 were selected and randomly divided into a control group and a Yijinjing group,with 60 cases in each group.The control group received health education and dietary guidance,and the Yijinjing group received Yijinjing exercises on the basis of the intervention of the control group.The changes in skeletal muscle mass,upper and lower limb muscle strength,muscle thickness,muscle cross-sectional area,physical fitness and chronic inflammation level were observed in the two groups before and after the intervention.RESULTS After intervention,the skeletal muscle mass,grip strength,30 s sit-stand test times,rectus femoris thickness and cross-sectional area,vastus intermedius thickness,and physical fit-ness assessment of the patients in the Yijinjing group were significantly increased compared with those before treatment(P<0.05),and the indicators after intervention were higher than those in the control group(P<0.05);the serum TNF-α and IL-18 levels in the Yi-jinjing group were significantly decreased compared with those before treatment(P<0.05),and the indicators after intervention were lower than those in the control group(P<0.05);there was no statistically significant change in the biceps brachii thickness and serum IL-6 level in the Yijinjing group compared with those before treatment(P>0.05);there was no significant correlation between the bi-ceps brachii thickness and grip strength after Yijinjing intervention,r=0.139 8,P>0.05;there was a significant negative correlation between the TNF-α level and grip strength after Yijinjing intervention,r=-0.313 8,P<0.05.CONCLUSION Yijinjing exercises can improve muscle mass and strength in elderly patients with sarcopenia,and improve the physical fitness of patients,which may be related to improving the chronic inflammatory state of the body.

Objective:To evaluate the effects of low level laser therapy(LLLT)on accelerating tooth movement and reducing pain during orthodontic treatment.Methods:26 patients with malocclusion of class Ⅱ,division 1 were included.Maxillary teeth on left and right sides were selected randomly as the experimental side and control side.Dental arches of experimental side received the irra-diation of LLLT with 7.5 J/cm2 for each point,10 points for each tooth,and the control side received placebo treatment,with the la-ser light off.The pain and the rate of teeth movement on experimental and control sides were compared.Results:The mean score of pain at the control side was significantly higher than that of the experimental side in the 7 days(P＜0.001).The average movement rate of the experimental group was higher than that of the control group(P＜0.05).Conclusion:LLLT is effective in accelerating tooth movement and reducing the related pain.

This article reports a case of an elderly female patient with osteoporotic vertebral fractures who experienced recurrent fractures within a short period after percutaneous vertebroplasty. The case highlights the necessity and importance of implementing anti-osteoporosis interventions to prevent subsequent fractures, in addition to performing appropriate orthopedic management for the initial fracture.

Objective:To observe and analyze the pathogenic genes and clinical phenotype characteristics of retinitis pigmentosa sinepigmento(RPSP).Methods:A retrospective clinical study. Two patients (proband) and five family members from two RPSP families admitted to Xiamen Eye Center of Xiamen University in December 2022 and Shenzhen Eye Hospital in July 2023 were included in the study. Two families have no blood relationship and were both Han Chinese. Detailed ocular and systemic medical history and specialized examinations were performed for all members, including color fundus photography, fundus autofluorescence (FAF), and full field electroretinogram (ff-ERG) examination. The peripheral venous blood of all members was collected, and genomic DNA was extracted. Pathogenic genes and their loci were screened using whole exome high-throughput sequencing technology. Sanger sequencing was used to verify the pathogenic genes in the two pedigrees. The pathogenicity of candidate variants was evaluated according to the American Society for American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants.Results:The two probands were male, aged 9 and 7 years, respectively. The main complaint was poor binocular vision for 6 and 3 years and poor treatment effect of amblyopia. The proband (Ⅱ2) in family 1 had a pale red color on the optic disc, with leopard-like changes in the posterior pole and thinner retinal arteries. FAF showed mottled fluorescence attenuation outside the macular vascular arch. There was no significant waveform in both bright and dark visual responses of ff-ERG. He also had 6-toed deformity of both feet, renal cysts, and a slightly overweight body. The clinical diagnosis was non-pigmentary retinitis pigmentosa. The proband of family 2 (Ⅱ1) had poor binocular vision in a dark environment and had atrophy lesions on the nasal side of the optic disc and leopard print like changes in the fundus. FAF showed uneven enhancement in the fovea. ff-ERG showed severe abnormalities in dark and light response, with significant decrease and delay in b-wave amplitude and latency. He had no other systemic abnormalities. The clinical diagnosis was binocular RPSP. There were no abnormal ocular and systemic manifestations in the two family members. Gene sequencing revealed a homozygous mutation (c.534+1G>T) of BBS2 gene, which was inherited from the mother and father respectively. Based on clinical manifestations and genetic testing results, the final diagnosis was Bardet Biedl syndrome. The genetic sequencing results confirmed a novel compound heterozygous mutation (c.950T>G: p. Leu317Arg missense mutation and c.849+1G>C splicing mutation) of BBS7 gene. His father (Ⅰ1) and mother (Ⅰ2) carried M1 heterozygous variants. Combined with the clinical manifestations and genetic testing results, the final diagnosis was Bardet-Biedl syndrome (BBS). Family 2 proband (Ⅱ1) carried the BBS7 gene C.950T>G (p.Leu317Arg) (M2) missense variation and C.849 +1G>C (M3) splice site variation. His father (Ⅰ1) and mother (Ⅰ2) carried M3 shear site variation and M2 missense variation, respectively. The two families all fit the autosomal recessive inheritance pattern, and the genotype and clinical phenotype were coseparated. According to ACMG guidelines, M1, M2 and M3 were all identified as possible pathogenic variants. Conclusions:BBS2 gene M1 homozygous variation and BBS7 gene M2, M3 complex heterozygous variation are the possible pathogenic genes in family 1 and family 2, respectively. Two families are affected by BBS and RPSP, respectively.

Objective To introduce the fundamental principles of the multivariate functional mixed model(MFMM)and provide a methodological basis for interpreting the principal components derived from dimension reduction of multivariate functional data.Methods The MFMM models the mean function,auto-covariance function,and cross-covariance function within functions non-parametrically,clearly separating the shared latent processes common to all indicators from the specific latent processes unique to each indicator.In the case study,data from colorectal cancer patients at the Yunnan Cancer Hospital are used to extract the common and specific principal components of longitudinal carcinoembryonic antigen(CEA)and carbohydrate antigen 125(CA125)within 12 months post-surgery using MFMM,coupled with interpretation through a random survival forest prediction model.Results The MFMM identified 2 shared principal components for CEA and CA125,5 specific components for CEA,and 5 specific components for CA125.The random survival forest prediction model constructed based on these extracted components showed higher prediction accuracy than the baseline model.Furthermore,variable importance analysis revealed that the first specific component of CEA was the most important predictive variable after clinical baseline variables,while the importance of CA125 specific components was lower than that of CEA,consistent with the current consensus on colorectal cancer.Conclusion MFMM effectively manages the correlations among multiple longitudinal indicators and their changes over time,capturing the shared and specific processes of multiple longitudinal measurement indicators as they evolve.This enhances the model's interpretability and offers theoretical and practical advantages.