Cleaning process validation is an important guarantee for implantable medical devices to ensure product cleanliness. In the manufacturing process, implantable devices usually need to control pollution through cleaning process to achieve a certain cleanliness to ensure the effectiveness of sterilization and product safety. This paper discusses the cleaning process validation of the manufacturing process of the implantable devices based on relevant regulations and technical standards, and proposes the influencing factors and principles to be considered in the cleaning process validation, so as to provide technical reference for the design of the cleaning process validation.
Prostheses and Implants ; Sterilization ; Equipment and Supplies

Objective To explore the traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.

Objective Compare the depression phenotypes of a breast cancer tumor-bearing mouse model constructed using two different method and a mouse model of breast cancer depression with clinical manifestations,as well as assess their suitability for basic research.Methods We constructed a tumor model with 4T1 breast cancer cells alone(4T1 group)and a tumor-depression composite model given chronic unpredictable mild(CUMS)(4T1+CUMS group).The experimental period was 42 d,and the body mass,tumor volume,and survival time of the mice were monitored throughout the whole process.Two depressive behavioral tests(of sucrose preference test,open field test,tail suspension test,and elevated plus maze)were performed on the 15th and 29th days,respectively.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of hippocampal neurons in brain tissue sections.Results(1)Body mass:The body mass of the 4T1 group and 4T1+CUMS group began to decrease from 29 d,and the body mass of the 4T1+CUMS group was significantly lower than that of the 4T1 group and Control group at the end of the experiment(P<0.001).(2)Tumor volume:There was no significant difference in the growth rate of tumors between the two model groups throughout the experiment(P>0.05).(3)Survival time:The survival rates of the 4T1 group and 4T1+CUMS group were 100％and 60％,and the first death of mice in the 4T1+CUMS group was on the 36th day.(4)Behavior test of depression:There was no significant difference between the three groups in the first depressive behavior tests(P>0.05),and the two groups showed obvious depressive phenotypes in the second behavioral tests.The sucrose preference index and activity distance in the central area were significantly decreased in the two model groups(P<0.001),and the immobility time was significantly increased(P<0.001).(5)Pathological section of brain tissue:On pathological examination of brain tissue,we observed a reduced number of neuronal cells in the hippocampus of the 4T1 group and 4T1+CUMS group,their morphology was irregular,the arrangement between the cells was disordered and the gap was unclear,and some nucleoli were blurred.Conclusions Although the tumor-only method and the tumor with compound stress stimulation method can both be used to prepare breast cancer depression models,the tumor-only modeling method is simpler and the mortality rate after successful modeling is higher.The long window of time is convenient for subsequent drug administration and detection,and the causes of the depression phenotype are more in line with the clinical causes and manifestations.Therefore,the 4T1 model can provide a reference model for future animal experiments on breast cancer tumor-related depression.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Objective To investigate the correlation between different TCM syndrome types and RNF180/Septin9 gene methylation in patients with chronic gastritis.Methods Hospitalized cases diagnosed with chronic gastritis from March 2022 to July 2024 were retrieved through the information system of Wangjing Hospital,China Academy of Medical Sciences.Information such as general conditions,pathological findings and RNF180/Septin9 gene methylation detection results were collected.A total of 441 patients with chronic gastritis were finally collected according to the attrition criteria,and were divided into 5 types:liver-stomach disharmony syndrome,spleen-stomach damp-heat syndrome,spleen-stomach weakness syndrome,stomach-collateral stasis syndrome and stomach-yin deficiency syndrome.SPSS 25.0 was used to analyze the correlation between TCM syndrome types of chronic gastritis and methylation of RNF180/Septin9 gene.Results The majority of 441 patients with chronic gastritis were spleen-stomach damp-heat syndrome.The results of statistical analysis showed that there were differences in gender,smoking and drinking history and age distribution among different TCM syndrome types(P<0.05).The positive rate of RNF180/Septin9 gene methylation in stomach-collateral stasis syndrome was significantly higher than that in other syndrome types(P<0.01).Correlation analysis further showed that spleen-stomach damp-heat syndrome and stomach-collateral stasis syndrome were positively correlated with RNF180/Septin9 gene methylation(P<0.05),and the correlation of stomach-collateral stasis syndrome was particularly significant(P<0.01).Conclusion Spleen-stomach damp-heat syndrome and stomach-collateral stasis syndrome are positively correlated with RNF180/Septin9 gene methylation in patients with chronic gastritis.Pathological products such as blood stasis and damp-pathogenic bacteria can increase the risk of"inflammatory-cancer"transformation,and its prognosis is worse than other syndrome types.Timely intervention and regular examination should be conducted to achieve early diagnosis and treatment.

Objective Compare the depression phenotypes of a breast cancer tumor-bearing mouse model constructed using two different method and a mouse model of breast cancer depression with clinical manifestations,as well as assess their suitability for basic research.Methods We constructed a tumor model with 4T1 breast cancer cells alone(4T1 group)and a tumor-depression composite model given chronic unpredictable mild(CUMS)(4T1+CUMS group).The experimental period was 42 d,and the body mass,tumor volume,and survival time of the mice were monitored throughout the whole process.Two depressive behavioral tests(of sucrose preference test,open field test,tail suspension test,and elevated plus maze)were performed on the 15th and 29th days,respectively.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of hippocampal neurons in brain tissue sections.Results(1)Body mass:The body mass of the 4T1 group and 4T1+CUMS group began to decrease from 29 d,and the body mass of the 4T1+CUMS group was significantly lower than that of the 4T1 group and Control group at the end of the experiment(P<0.001).(2)Tumor volume:There was no significant difference in the growth rate of tumors between the two model groups throughout the experiment(P>0.05).(3)Survival time:The survival rates of the 4T1 group and 4T1+CUMS group were 100％and 60％,and the first death of mice in the 4T1+CUMS group was on the 36th day.(4)Behavior test of depression:There was no significant difference between the three groups in the first depressive behavior tests(P>0.05),and the two groups showed obvious depressive phenotypes in the second behavioral tests.The sucrose preference index and activity distance in the central area were significantly decreased in the two model groups(P<0.001),and the immobility time was significantly increased(P<0.001).(5)Pathological section of brain tissue:On pathological examination of brain tissue,we observed a reduced number of neuronal cells in the hippocampus of the 4T1 group and 4T1+CUMS group,their morphology was irregular,the arrangement between the cells was disordered and the gap was unclear,and some nucleoli were blurred.Conclusions Although the tumor-only method and the tumor with compound stress stimulation method can both be used to prepare breast cancer depression models,the tumor-only modeling method is simpler and the mortality rate after successful modeling is higher.The long window of time is convenient for subsequent drug administration and detection,and the causes of the depression phenotype are more in line with the clinical causes and manifestations.Therefore,the 4T1 model can provide a reference model for future animal experiments on breast cancer tumor-related depression.

Objective To explore the traditional Chinese medicine(TCM)syndrome characteristics of patients with Chikungunya hemorrhagic fever and to provide empirical data to support the application of TCM in diagnosing and treating Chikungunya hemorrhagic fever.Methods A cross-sectional survey was conducted to collect clinical data(sex,age,days since onset,and comorbidity underlying disease conditions)and TCM with four-examination information(symptoms,tongue manifestations,and pulse manifestations)from 255 patients with Chikungunya hemorrhagic fever who visited Lecong Hospital of Shunde,Foshan,the Third People's Hospital of Shunde District of Foshan,Shunde Hospital of Southern Medical University Affiliated Chencun Hospital between July 23 and July 29,2025.Factor and cluster analyses were used to summarize TCM syndrome characteristics and analyze core pathogenesis in conjunction with clinical features.Results Among the 255 patients with Chikungunya hemorrhagic fever,131 were male and 124 were female,with a age of(49.05±17.93)years and a disease duration of(3.26±1.78)days.Among the four types of examination information in TCM,35 items exhibited a frequency exceeding 10%.The most prevalent symptoms were arthralgia(180 patients,70.59%),exanthem(153 patients,60.00%),fatigue(99 patients,38.82%),anhidrosis(98 patients,38.43%),pruritus(96 patients,37.65%),and fever(92 patients,36.08%).Tongue and pulse manifestations were primarily white fur(155 patients,60.78%),pink tongue(111 patients,43.53%),slippery pulse(143 patients,56.08%),and greasy fur(134 patients,52.53%).Patients with disease onset≤3 d had a higher incidence of arthralgia,fatigue,fever,aversion to cold,generalized muscle pain,aversion to wind,insomnia,headache,sweating,low-grade fever,poor appetite,loose stool,hyperhidrosis,and red tongue than those with disease onset≥4 d(P<0.05).Patients with disease onset≥4 d had a higher incidence of pink tongue and thick fur than those with disease onset≤3 d(P<0.05).The syndrome elements in patients with Chikungunya hemorrhagic fever predominantly manifested on the defensive exterior,with involvement of the sinew-bone joints,skin-muscle,and spleen.Pathogenic factors were primarily characterized by external winds,dampness,and heat.Factor and cluster analysis result indicated three TCM pathogenesis progression patterns:imbalance of the defensive exterior with wind-dampness conflict and heat transformation;dampness-heat flowing into muscles and meridians causing joint obstruction and qi blood stasis;and dampness-heat congelation resulting in qi mechanism obstruction,consumption of body fluids,and infiltration of the skin.Conclusion Patients with Chikungunya hemorrhagic fever primarily present with fever,joint pain,and rashes.In TCM,this condition falls under the category of"dampness-warmth"syndrome.Its etiology is attributed to pathogens,with transmission occurring through mosquito bites.The core pathogenesis of TCM is the invasion of the defensive exterior and dampness-toxic heat accumulation.The therapeutic principles focus on clearing heat pathogens,resolving dampness pathogens,dispersing wind pathogens,and promoting the resolution of rashes.

Objective To investigate the correlation between different TCM syndrome types and RNF180/Septin9 gene methylation in patients with chronic gastritis.Methods Hospitalized cases diagnosed with chronic gastritis from March 2022 to July 2024 were retrieved through the information system of Wangjing Hospital,China Academy of Medical Sciences.Information such as general conditions,pathological findings and RNF180/Septin9 gene methylation detection results were collected.A total of 441 patients with chronic gastritis were finally collected according to the attrition criteria,and were divided into 5 types:liver-stomach disharmony syndrome,spleen-stomach damp-heat syndrome,spleen-stomach weakness syndrome,stomach-collateral stasis syndrome and stomach-yin deficiency syndrome.SPSS 25.0 was used to analyze the correlation between TCM syndrome types of chronic gastritis and methylation of RNF180/Septin9 gene.Results The majority of 441 patients with chronic gastritis were spleen-stomach damp-heat syndrome.The results of statistical analysis showed that there were differences in gender,smoking and drinking history and age distribution among different TCM syndrome types(P<0.05).The positive rate of RNF180/Septin9 gene methylation in stomach-collateral stasis syndrome was significantly higher than that in other syndrome types(P<0.01).Correlation analysis further showed that spleen-stomach damp-heat syndrome and stomach-collateral stasis syndrome were positively correlated with RNF180/Septin9 gene methylation(P<0.05),and the correlation of stomach-collateral stasis syndrome was particularly significant(P<0.01).Conclusion Spleen-stomach damp-heat syndrome and stomach-collateral stasis syndrome are positively correlated with RNF180/Septin9 gene methylation in patients with chronic gastritis.Pathological products such as blood stasis and damp-pathogenic bacteria can increase the risk of"inflammatory-cancer"transformation,and its prognosis is worse than other syndrome types.Timely intervention and regular examination should be conducted to achieve early diagnosis and treatment.