Bioengineering breakthroughs:The impact of stem cell models on advanced therapy medicinal product development

The burgeoning field of bioengineering has witnessed significant strides due to the advent of stem cell models,particularly in their application in advanced therapy medicinal products(ATMPs).In this review,we examine the multifaceted impact of these developments,emphasizing the potential of stem cell models to enhance the sophistication of ATMPs and to offer alternatives to animal testing.Stem cell-derived tissues are particularly promising because they can reshape the preclinical landscape by providing more physiologically relevant and ethically sound platforms for drug screening and disease modelling.We also discuss the critical challenges of reproducibility and accuracy in measurements to ensure the integrity and utility of stem cell models in research and application.Moreover,this review highlights the imperative of stem cell models to align with regulatory standards,ensuring using stem cells in ATMPs translates into safe and effective clinical therapies.With regulatory approval serving as a gateway to clinical adoption,the collaborative efforts between scientists and regulators are vital for the progression of stem cell applications from bench to bedside.We advocate for a balanced approach that nurtures innovation within the framework of rigorous validation and regulatory compliance,ensuring that stem cell-base solutions are maximized to promote public trust and patient health in ATMPs.

MEDICINAL VESICULATION THERAPY AND ITS CLINICAL APPLICATION

In this paper, the authors introduce medicinal vesiculation therapy from its origin, points for attention in clinical application, and their individual experiences. In clinical application, the authors advocate: ① avoid using drugs that are over-irritating in the property, and strictly controlling the dose of drugs and the duration of application, ② in selection of drugs, some factors as patients’ conditions, the season, the geographic location, etc. should be taken into account. In the present paper, 3 typical cases of bronchial asthma, tonsil swelling and facial paralysis treated with medicinal vesiculation therapy are introduced. Clinical practice demonstrates that this therapy is economical, simple and convenient and fairly effective in treatment of some chronic diseases.

New era of personalized medicine:Advanced therapy medicinal products in Europe

Advanced therapy medicinal products are human medical therapies based on genes,cells,or tissues,and due to their characteristics,they offer new innovative opportunities for the treatment of diseases and injuries,especially for diseases beyond the reach of traditional approaches.These therapies are at the forefront of innovation and have historically been very controversial,although in the last decade they have gained prominence while the number of new advanced therapies has increased every year.In this regard,despite the controversy they may generate,they are expected to dominate the market in the coming decades.Technologies based on advanced therapies are the present and future of medicine and bring us closer to the long-awaited precision medicine.Here we review the field as it stands today,with a focus on the molecular mechanisms that guided the different advanced therapies approved by the European Medicines Agency,their current status,and their legal approval.

Observation on Therapeutic Effect of Lotus Needle Cupping Therapy for Removing Blood Stasis in Zhuang Medicine on PHN and Its Influ-ence on Inflammatory Mediators

[Objectives]To observe the clinical effect of the lotus needle cupping therapy for removing blood stasis in Zhuang medicine in treating PHNand its influence on inflammatory factors.[Methods]96 patients with PHN were randomly divided into three groups:lotus nee-dle cupping therapy group,TCM surrounding acupuncture group and gabapentin group.Venous blood and acupoint blood were collected at 0,21 and 42 d of treatment,and the expression levels of 5-HT,SP and CGRPinflammatory mediators were detected before and after treatment.The changes of VAS scores before,during and after treatment and the clinical efficacy were observed.[Results]The total effective rate of the lotus needle cupping group was 87.50%,which was better than that of the TCM acupuncture group(81.25%)and the gabapentin group(62.50%);after treatment,the VAS scores and the expression of inflammatory mediators in the three groups of patients were lower than those before treatment,and the decrease was more significant in the treatment group(P<0.05).[Conclusions]The lotus needle cupping therapy for removing blood stasis in Zhuang medicine is effective in treating PHN,and its mechanism is to reduce the release of inflammatory media-tors,reduce hyperalgesia,relieve pain and improve the quality of life of patients.

Comprehensive Rehabilitation Therapy of Traditional Chinese Medicine Combined with Modern Rehabilitation Training Improves the Spasticity and Motor Function of Hemiplegia after Stroke

Objective:To analyze the impact of comprehensive rehabilitation therapy of traditional Chinese medicine(TCM)(based on modern rehabilitation training)on the spasticity and motor function in stroke patients with hemiplegia.Methods:Seventy-nine stroke and hemiplegia patients admitted to the hospital from June 2021 to June 2023 were selected and randomly divided into a control group(39 cases)using modern rehabilitation training,and an observation group combined with comprehensive TCM rehabilitation therapy(40 cases),over 1 month.The clinical index data of the two groups were compared.Results:There were differences in the clinical index data between the two groups.The total effective rate after 2 treatment in the observation group(92.50%)was higher than that of the control group(74.36%)(χ^(2)=4.727,P<0.05).All central sensitization inventory(CSI)and stroke quality of life(PRO)scores in both groups were lower after treatment,with the observation group having lower scores as compared to the control group(P<0.05).The scores of FMA(upper limbs,lower limbs),Barthel index scores,and Functional Ambulation Categories(FAC)scores of both groups increased after treatment,with the observation group having higher scores as compared to the control group(P<0.05).Conclusion:Comprehensive TCM rehabilitation therapy had a significant therapeutic effect on patients with hemiplegia after stroke.It improved the patient’s spasticity,limb movement,and walking function.Their daily living abilities and quality of life were also enhanced.

Study on Treatment of Polycystic Ovarian Syndrome with Infertility by Combined Therapy of Chinese Herbal Medicine and Compound Cyproterone Acetate

Objective: To evaluate the effect of combined therapy of Chinese herbal medicine and compound cyproterone acetate (CPA) in treating non-obesity polycystic ovarian syndrome (PCOS) and to explore its mechanism in improving withdrawal ovulation. Methods: Eighty-six patients of non-obesity P-COS, typed as Shen-deficiency with blood stasis Syndrome or Shen-deficiency with Phlegm-Dampness Syndrome by Syndrome Differentiation in traditional Chines medicine, were randomly divided into three groups: (1) The TCM group (n = 26) was treated with Chinese drugs for 6 menstrual cycles; (2) The western medicine (WM) group (n=30) was treated with 1 tablet of CPA for 21 days, with the treatment beginning from the 5th day of menstruation. The treatment was given for 3 menstrual cycles by repetitious medication, which stopped and restarted on the 5th day of withdrawal bleeding. Then the ovulation promoting therapy was applied by using clomifene citrate and human chorionic gonadotropin (CC/hCG) for 3 menstrual cycles; (3) The TCM-WM group (n=30) was treated with the medications used for the above two groups. The menstrual cycle, the volume and duration of the menstruation, as well as the improvement of acne and pilosis [Ferriman-Gallway (F-G) scoring] were observed after 3 cycles ended. Moreover, condition of ovulation was monitored by B-ultrasonography at the 4th- 6th cycle and status of pregnancy was observed. Results: Compared with before treatment, the blood level of luteinizing hormone (LH) and testosterone (T) in all 3 groups after treatment significantly decreased (P<0. 05), with its ratio to follicle-stimulating hormone (LH/FSH) recovered to normal, but without markedly change in levels of FSH, estradiol (E2) and prolactin (PRL). The menstrual cycle in most patients got regular and acne significantly alleviated (P<0. 05), and the improvement of infrequent menstruation and acne was better in the WM group and the TCM-WM group than that in the TCM group, but pilosis showed no significant improvement in all three groups. The periodical ovulation rate in the TCM-WM group (73. 1%) and the WM group (68. 3%) was significantly higher than that in the TCM group (40%). The pregnancy rate in the TCM-WM group (53. 8%) was significantly higher than that in the other two groups (26.1% and 25% respectively, all P<0.05). Conclusion: Using combined therapy of TCM and composite CPA followed by o-vulation promoting agents of TCM and WM to treat patients of non-obesity PCOS could relieve the clinical symptoms, improve the abnormal blood level of sex hormones and significantly elevate the pregnancy rate.

Changing paradigm of cancer therapy：precision medicine by next-generation sequencing

Precision medicine aims to identify the right drug, for the right patient, at the right dose, at the right time, which is particularly important in cancer therapy. Problems such as the variability of treatment response and resistance to medication have been longstanding challenges in oncology, especially for development of new medications. Solid tumors, unlike hematologic malignancies or brain tumors, are remarkably diverse in their cellular origins and developmental timing. The ability of next-generation sequencing(NGS) to analyze the comprehensive landscape of genetic alterations brings promises to diseases that have a highly complex and heterogeneous genetic composition such as cancer. Here we provide an overview of how NGS is able to facilitate precision medicine and change the paradigm of cancer therapy, especially for solid tumors, through technical advancements, molecular diagnosis, response monitoring and clinical trials.

Comprehensive Therapy of Pancreatic Cancer by Integrative Traditional and Western Medicine

In recent 20 years, there has been an increasing trend in the incidence of pancreatic cancer both at home and abroad. An estimated 31 860 new cases and 31 270 deaths are expected to occur in the United States in 2004 due to this disease, the 4th and 5th leading cause of cancer death for men and women respectively. In China, new cases of pancreatic cancer continue to increase and are 6

Changing the paradigm：the potential for targeted therapy in laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma(LSCC) remains a highly morbid and fatal disease. Historically, it has been a model example for organ preservation and treatment stratification paradigms. Unfortunately, survival for LSCC has stagnated over the past few decades. As the era of next-generation sequencing and personalized treatment for cancer approaches, LSCC may be an ideal disease for consideration of further treatment stratification and personalization. Here, we will discuss the important history of LSCC as a model system for organ preservation, unique and potentially targetable genetic signatures of LSCC, and methods for bringing stratified, personalized treatment strategies to the 21^(st) century.

Study on the Key to Massage Therapy of Traditional Chinese Medicine

ＳｔｕｄｙｏｎｔｈｅＫｅｙｔｏＭａｓｓａｇｅＴｈｅｒａｐｙｏｆＴｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ￥ＷｕＫａｎｙａｎｇ（ＳｈｅｎｚｈｅｎＬｕｏｈｕＤｉｓｔｒｉｃｔＨｏｓｐｉｔａｌｏｆＴｒａｄｉｔｉｏｎａｌＣｈｉｎｅｓｅＭｅｄｉｃｉｎｅ...

Meta Analysis of the Efficacy of Nonpharmaceutical Chinese Medicine Therapy in the Treatment of Obese Polycystic Ovary Syndrome

Objective:To systematically evaluate the effects of acupuncture,auricular point sticking,acupoint catgut embedding,cupping and other non-pharmaceutical Chinese medicine therapies on sex hormone as well as glucose and lipid metabolism in patients with obese polycystic ovary syndrome.Method:The databases such as China National Knowledge Infrastructure were searched by computer to collect the literature on the treatment of obese polycystic by non-pharmaceutical Chinese medicine therapy combined with western medicine or lifestyle change,and the literature quality of the included literature was evaluated,and finally the data were analyzed.A total of 15 randomized controlled trial(RCT)literature were included in this study,with a total of 1263 patients.Results:Non-pharmaceutical Chinese medicine therapy combined with metformin or lifestyle can reduce body mass index,insulin resistance index,fasting plasma insulin,fasting blood glucose,luteinizing hormone,ratio of luteinizing hormone to follicle stimulating hormone,testosterone,but it has no obvious advantage over follicle stimulating hormone(FSH).Conclusion:Compared with simple application of metformin or lifestyle change,traditional Chinese medicine non drug therapy combined with metformin or lifestyle change can better improve sex hormone and blood glucose metabolism in obese PCOS patients.

Meta-analysis of traditional Chinese medicine Jiedu therapy in the treatment of psoriasis vulgaris

Objective:To evaluate the clinical efficacy of traditional Chinese medicine Jiedu therapy in treatment of psoriasis.Methods: CNKI, Wanfang knowledge service platform, VIP journal database, Chinese biomedical literature database ( CBM), PubMed, the Cochrane Library and EMbase database from the establishment of the database to March 2020 were searched for the randomized controlled trials (Rcts) on traditional Chinese medicine Jiedu therapy in treatment of psoriasis. Literature selection and information extraction was completed and screened by two independent reviewers, and then the Cochrane recommended bias risk assessment method was used to evaluate the bias risk, and Review Manager5.3 was used for the data analysis. Totally 17clinical Rcts were included in this study, involving 1376 patients.Results:Analysis results showed that traditional Chinese medicine Jiedu therapy had higher clinical effective rate, with statistically significant difference ( OR= 4.53, 95% CI[3.17,6.46], Z =8.32, P<0. 00001);the improvement of score was more evident, PASI score (WMD =-2.21, 95%CI[-2.77, -1.64], Z = 7.60, P<0. 00001);and trial-related adverse events were reported in 6RCTs. Conclusion: Studies have shown that traditional Chinese medicine Jiedu therapy had higher clinical efficacy.

CLINICAL OBSERVATION ON THE ACUPOINT INTRADERMAL EMBEDDING OF RINGHEADED THUMBTACK-NEEDLE THERAPY FOR HYPERPLASIA OF MAMMARY GLANDS

In the present paper, the author used acupoint intradermal embedding of ringheaded thumbtack-needle therapy combined with herbal medicine therapy to treat 110 cases of hyperplasia of mammary glands, and compared its therapeutic effect with that of herbal therapy alone. The observed indexes of the treatment were pain relief degree, the size of hyperplasic glands and the time of occurrence of marked effect. Following 3 courses of treatment,the results showed the therapeutic effect of the ringheaded thumbtack-needle needle plus herbal medicine therapy was superior to that of herbal medicine therapy alone in the above-mentioned 3 indexes (P ＜ 0.01 ).

Clinical Observation on the Effect of Chinese Medicine Five-Color Therapy on the Treatment of Children with Chronic Urticaria

Objective:To analyze the clinical treatment effect of traditional Chinese medicine five-color therapy on chronic urticaria in children.Methods:The income data target of this article is 80 children with chronic urticaria.The grouping method is a randomized method with 40 children in each group.The experimental group was treated with five-color treatment of traditional Chinese medicine,and the control group was treated with western medicine.The incidence,treatment and recurrence of adverse reactions in children with chronic urticaria were compared between the two groups.Results:Showed total effective rate of children with chronic urticaria in the experimental group was compared with the control group,P<0.05,the data showed statistical significance.Conclusion:Stated use of TCM five-color therapy in the treatment of children with chronic urticaria can significantly improve safety.

Application regularity of medicinal and dietary substances for patients during COVID-19 rehabilitation

Objective This study focused on the application regularity of medicinal and dietary sub-stances(MDS)of traditional Chinese medicine(TCM)diet therapy during rehabilitation,in order to help patients with Corona Virus Disease 2019(COVID-19)reduce sequelae and improve their life quality.Methods The official websites of the national and provincial health committees,the website of the National Administration of Traditional Chinese Medicine,the China BioMedical Literature Database(CBM),China National Knowledge Infrastructure(CNKI),China Science and Technology Journal Database(VIP),and Wanfang Database were used to search the keywords,such as“coronavirus”“novel coronavirus pneumonia”“COVID-19”“protocol”“guideline”“consensus”and“rehabilitation period”.The search time was from the establishment of databases to July 31,2022.The prevention and control protocols of various provinces and cities were manually supplemented and screened out.The information on the frequency,property,flavor,meridian tropism,and efficacy of MDS was collected for association rule analysis through the Apriori algorithm.Hierarchical cluster analysis was performed using the Euclidean distance and longest distance.Results A total of 18 protocols were screened out,including 56 lists of TCM diet therapy,and 47 kinds of MDS with a frequency of 132 times during the rehabilitation of COVID-19.Among them,six lists of diet therapy were collected from national websites,26 from local government websites,and 24 from social and academic institution websites.The intended population can be divided into seven categories including normal recovery,lung-spleen Qi deficiency,deficiency of both Qi and Yin,spleen-stomach weakness,deficiency of Yang Qi,kidney Qi deficiency,and blood deficiency.Shanyao(Dioscoreae Rhizoma)and Lianzi(Nelumbinis Semen),followed by Dazao(Jujubae Fructus)were used most commonly in MDS,with mainly flat property,sweet flavor,and spleen and lung meridians in meridian tropism.Besides,deficiency-tonifying drugs were commonly used in MDS.Through association rule analysis,12 groups of association MDS pairs were obtained.The pair of Yiyiren(Coicis Semen)and Chenpi(Citri Reticulatae Pericarpium)had the highest Lift value,and Yiyiren(Coicis Semen)was used most frequently in the MDS category for eliminating pathogenic factors.The results of complex network analysis showed that the core MDS were Yiyiren(Coicis Semen),Shanyao(Dioscoreae Rhizoma),Huangqi(Astragali Radix),Fuling(Poria),and Dazao(Jujubae Fructus).Three core categories were classified by cluster analysis,including the category of strengthening spleen,nourishing kidney,and grasping Qi,the category of removing phlegm,abating panting,and regulating Qi,and the category of strengthening the middle-energizer and reinforcing Qi.Conclusion Based on the TCM theory,most patients during the rehabilitation of COVID-19 are in a state of lingering pathogens due to deficient vital Qi.TCM diet therapy is based on the principle of“giving both reinforcing and reducing treatment”,and the MDS combinations focus on both reinforcing the health Qi and eliminating pathogenic factors.The diet therapy mainly uses the MDS with flat property and sweet flavor,which belongs to deficiency-tonifying drugs,adding suitable MDS of pathogen-eliminating drugs according to different situations.The ultimate goal is to promote lung inflammation absorption,improve pulmonary fibrosis,increase immunity,reduce the occurrence of sequelae,and improve life quality.

COMBINED TREATMENT OF 200 CASES OF PERIPHERY FACIAL PARALYSIS WITH ACUPUNCTURE AND CHINESE MEDICINAL HERBS

In the present study, 200 cases of periphery facial paralysis were treated with combined therapies of handle needle, electroacupuncture (EA), electronic moxibustion and oral administration of Supplemented Qianzheng San. After treatment, of the 200 cases, 176 were cured, 15 had marked improvement and 9 had improvement. Two groups of acupoints were chosen and used alternately for keeping the excitement of acupoints, preventing acupoint fatigue and raising the therapeutic effect. In the acute stage of periphery facial palsy, acupuncture treatment was performed using shallow needling, mild manipulation and no needling penetration. In the convalescence stage and sequela stage, penetration needling was adopted and stronger stimulation given. During acute period and when facial muscular spasm appeared, EA stimulation was not suitable for facial acupoints. Over use of vision should be avoided.

Study of the Effect of Zhuang Medicine Aponeurotic System Triple Therapy on Lumbar Disc Herniation and Alpha-1 Acid Glycoprotein Level

Objective:To analyze the application effect of Zhuang medicine aponeurotic system triple therapy in the treatment of lumbar disc herniation and its effect on the level of alpha-1 acid glycoprotein(alpha-1 AGP).Methods:200 patients with lumbar disc herniation were selected and randomly divided into a treatment group and a control group,100 cases in each group.The control group was given conventional acupuncture,and the treatment group was treated with manipulation+fire needling+cupping.The alpha-1-AGP levels before and after treatment,as well as the lumbar spine function and pain scores before and after treatment,and the adverse reactions occurred during treatment between the two groups were compared.Results:Before treatment,there was no significant difference in alpha-1 AGP levels,lumbar function,and pain scores between the two groups(P>0.05).After treatment,the lumbar function scores of the two groups were significantly increased,with the treatment group having higher scores than the control group(P<0.05);the incidence of adverse reactions in the treatment group was 2.00%,which was much lower than the control group(P>0.05).Conclusion:Appropriate application of Zhuang medicine aponeurotic system triple therapy in the clinical treatment of lumbar disc herniation can promote the improvement of alpha-1 AGP index level,reduce the pain degree of patients,and improve their lumbar spine function.At the same time,Zhuang medicine also has significant advantages in terms of safety,while ensuring the efficacy and safety of the treatment.

Effect of Stereoscopic Comprehensive Therapy of Zhuang Medicine on Inflammatory Factor IL-6 in Patients with Rheumatoid Arthritis

Objective:To study the effect of Stereoscopic Comprehensive of Therapy Zhuang Medicine on IL-6 in serum of patients with rheumatoid arthritis.Methods:Sixty rheumatoid arthritis patients who met the inclusion criteria were selected and randomly divided into a control group and a treatment group using a random number table.Among them,30 cases in the control group were treated with Western medicine,and 30 cases in the treatment group were treated with Western medical and Stereoscopic Comprehensive Therapy of Zhuang Medicine.The observation period was 8 weeks.Results:After 8 weeks of treatment,the level of IL-6 in the treatment group and the control group decreased,and the treatment group was better than the control group(P<0.05).Conclusion:The Stereoscopic Comprehensive of Zhuang Medicine can reduce the level of IL-6 in the serum of patients with rheumatoid arthritis,and has a good regulating effect on the inflammation of rheumatoid arthritis.

Research Progress on Prevention and Treatment of Diabetes with Traditional Chinese Medicine Based on Intestinal Flora

In recent years,the World Health Organization has proposed the concept that only intes‐tinal health can lead to longevity.It can be seen that gut microbiota plays an important role in maintaining human health,and gut microbiota has become a hot topic in medical research.With the change of Chinese residents'lifestyle,the incidence rate of diabetes is increasing rapidly.Research shows that the incidence of diabetes is closely related to intestinal flora imbalance.Traditional Chinese medicine can reduce blood sugar and improve clinical symptoms by regulating intestinal flora.Based on the theory of tradi‐tional Chinese medicine,this paper discusses the etiology and pathogenesis of intestinal flora imbalance,and provides a theoretical basis for traditional Chinese medicine to regu‐late intestinal flora to prevent and treat diabetes.Intestinal flora is a complex ecosystem,which plays an important role in maintaining human health.The imbalance of intestinal flora may lead to the occurrence of diabetes.The dynamic balance of gut microbiota is closely related to the kidneys,spleen,liver,and lungs.Traditional Chinese medicine monomer and compound can prevent and cure diabetes by regulating intestinal flora.

AN OBSERVATION OF THE THERAPEUTIC EFFECT OF WARMING NEEDLING TECHNIQUE ON JIAJI POINTS FOR THE TREATMENT OF DEPRESSION AND ITS INFLUENCE ON EEG-α WAVE IN PATIENTS

Objective To discuss the therapeutic effect and mechanism of warming needling technique for the treatment of depression. Methods A total of 60 patients with depression were randomly divided into treatment group and control group with 30 cases each. The treatment group was treated with warming needle technique on the Jiaji points of the heart, lung, liver, spleen and kidney, control group with Amitriptyline, HAMD scale and the qualitative change of EEG-α wave were observed before and after the treatment. Results The total effective rate of treatment group was 100%, much better than that of the control group with 80% (P<0.05); the HAMD scale of treatment group was better than that of control group (P<0.05); the comparison of the improvement of somatic symptoms between treatment group and control group was significant (P<0.05); the comparison of frequency and amplitude of EEG-α wave was significant (P<0.05), there was no toxic and side effect in the treatment group. Conclusion Warming needling technique for depression has better effect than Amitriptyline, and there was no toxic and side effect in the treatment group. Warming needle technique can effectively regulate the frequency and amplitude EEG-α wave, and acts to improve depressive condition.