Neuronal reprogramming is an innovative technique for converting non-neuronal somatic cells into neurons that can be used to replace lost or damaged neurons, providing a potential effective therapeutic strategy for central nervous system (CNS) injuries or diseases. Transcription factors have been used to induce neuronal reprogramming, while their reprogramming efficiency is relatively low, and the introduction of exogenous genes may result in host gene instability or induce gene mutation. Therefore, their future clinical application may be hindered by these safety concerns. Compared with transcription factors, small-molecule compounds have unique advantages in the field of neuronal reprogramming, which can overcome many limitations of traditional transcription factor-induced neuronal reprogramming. Here, we review the recent progress in the research of small-molecule compound-mediated neuronal reprogramming and its application in CNS regeneration and repair.
Humans ; Cellular Reprogramming/drug effects* ; Neurons/cytology* ; Animals ; Transcription Factors ; Small Molecule Libraries/pharmacology* ; Nerve Regeneration

OBJECTIVE: To explore clinical efficacy of vancomycin-loaded antibiotic bone cement combined with induced membrane grafting for the treatment of diabetic foot ulcers(DFU). METHODS: Totally 68 DFU patients treated with bone cement combined with induced membrane grafting from November 2019 to November 2021 were retrospectively analyzed, including 37 males and 31 females, aged from 51 to 79 years old with an average of (63.63±7.85) years old;47 patients on the right side and 21 patients on the left side;28 patients with grade 2, 31 patients with were grade 3, and 9 patients with grade 4 according to Wagner's grades;the diameter of the wound ranged from 20.40 to 96.99 mm with an average of (59.67±23.26) mm. The time of wound healing, the number of operations, the survival of postoperative skin grafting, the number of postoperative recurrence and the rate of amputation were observed. RESULTS: All 68 patients were followed up for 12 to 18 months with an average of (15.06±2.12) months. The wound healing time ranged from 42 to 65 d with an average of (51.50±7.24) d, the numbers of operation ranged from 2 to 3 with an average of (2.25±0.44) times. All skin grafts were survived well after operation, without recurrence and amputation cases. CONCLUSION Vancomycin-containing antibiotic bone cement combined with induced membrane grafting is effective in treating DFU, and the operation is simple and reliable.
Humans ; Male ; Female ; Middle Aged ; Vancomycin/therapeutic use* ; Bone Cements/therapeutic use* ; Aged ; Diabetic Foot/therapy* ; Skin Transplantation ; Anti-Bacterial Agents/therapeutic use* ; Retrospective Studies ; Wound Healing/drug effects*

The increasing prevalence of chronic kidney disease (CKD) is a major global public health concern. Despite the complicated pathogenesis of CKD, renal fibrosis represents the most common pathological condition, comprised of progressive accumulation of extracellular matrix in the diseased kidney. Over the last several decades, tremendous progress in understanding the mechanism of renal fibrosis has been achieved, and corresponding potential therapeutic strategies targeting fibrosis-related signaling pathways are emerging. Importantly, extracellular vesicles (EVs) contribute significantly to renal inflammation and fibrosis by mediating cellular communication. Increasing evidence suggests the potential of EV-based therapy in renal inflammation and fibrosis, which may represent a future direction for CKD therapy.

Objective: To understand the knowledge, attitude, and current status of vaccination of herpes zoster vaccination among urban residents aged 25 years and above in China. Methods: In August to October 2022, a convenience sampling method was used to survey residents aged 25 years and above at 36 community centers in 9 cities across China. Questionnaires were used to collect basic information, knowledge, and attitude toward herpes zoster and its vaccination, as well as vaccination status and reasons for non-vaccination among residents. Results: A total of 2 864 urban residents were included in the study. The total score of residents' cognition of herpes zoster and its vaccine was 3.01±2.08, and the total score of their attitude was 18.25±2.76. Factors such as being male (β=-0.45, P<0.001), older than 40-59 years (β=-0.34, P=0.023) or ≥60 years (β=-0.68, P<0.001), married (β=-0.69, P=0.002) were negatively associated with knowledge score. The educational level of high school or secondary school (β=0.44, P=0.036), college (β=0.65, P=0.006), bachelor's degree and above (β=1.20, P<0.001), annual net household income ≥120 000 Yuan in 2021 (β=0.42, P=0.020), having urban employee medical insurance (β=0.62, P=0.030), having public or commercial medical insurance (β=0.65, P=0.033), and having a history of chickenpox (β=0.29, P=0.025) were positively associated with knowledge scores. Being male (β=-0.38, P=0.008) and not remembering a history of chickenpox (β=-0.49, P=0.012) were negatively associated with attitude scores. Annual net household income in 2021 was between 40 000-80 000 Yuan (β=0.44, P=0.032) or between 80 000-120 000 Yuan (β=0.62, P=0.002) or ≥120 000 Yuan (β=0.93, P<0.001), and a history of herpes zoster (β=0.59, P=0.004) were positively associated with attitude scores. Of the 2 864 residents surveyed, only 29 (1.01%) had received the herpes zoster vaccine, with a vaccination rate of 1.70% for those aged 50 years and above, with the main reason for non-vaccination being lack of knowledge about the herpes zoster vaccine, followed by the high price. 42.67% of the population said they would consider getting the herpes zoster vaccine in the future. Conclusion: Low knowledge of herpes zoster and its vaccine, positive attitudes towards the preventive effects of herpes zoster and its vaccine, and extremely low vaccination rates among the urban population in China call for multiple measures to strengthen health education and vaccination recommendations for residents, especially for the elderly, low-education and low-income populations.
Aged ; Male ; Humans ; Female ; Herpes Zoster Vaccine ; Chickenpox ; Health Knowledge, Attitudes, Practice ; Urban Population ; Herpes Zoster/prevention & control* ; China

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.
Administration, Cutaneous ; Skin Absorption ; Chromatography, Liquid ; Oils, Volatile ; Viscosity

An ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method was established to investigate the pharmacokinetic behaviors of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone in rat plasma after oral administration of Bufei Huoxue Capsules. After SD rats were administered with Bufei Huoxue Capsules suspension by gavage, blood samples were collected from the inner canthus at different time points. After protein precipitation, plasma samples were separated on ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm). The mobile phase consisted of acetonitrile(A) and water(B) containing 0.1% formic acid in gradient elution. The positive and negative ions were measured simultaneously in the multi-reaction monitoring(MRM) mode. The pharmacokinetic parameters were calculated and fitted by DAS 3.2.8. Psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, psoralen, isopsoralen, methylnissolin, and neobavaisoflavone were detected in the rat plasma after drug administration, with AUC_(0-t) of(3 357±1 348),(3 555±1 696),(3.03±0.88),(2.21±0.33),(1 787±522),(2 295±539),(5.69±1.41) and(3.40±0.75) μg·L~(-1)·h, and T_(max) of(1.56±0.62),(1.40±0.70),(0.21±0.05),(0.25±0.12),(0.26±0.11),(0.34±0.29),(0.74±0.59), and 0.25 h. The method is proved specific and repeatable and is suitable for the determination of psoralenoside, isopsoralenoside, calycosin-7-glucoside, ononin, pso-ralen, isopsoralen, methylnissolin, and neobavaisoflavone in the rat plasma, which can be applied to pharmacokinetic study.
Animals ; Capsules ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/pharmacokinetics* ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Tandem Mass Spectrometry/methods*

Obvious epigenetic differentiation occurred on Lycium barbarum in different cultivation areas in China. To investigate the difference and change rule of DNA methylation level and pattern of L. barbarum from different cultivation areas in China, the present study employed fluorescence-assisted methylation-sensitive amplified polymorphism(MSAP) to analyze the methylation level and polymorphism of 53 genomic DNA samples from Yinchuan Plain in Ningxia, Bayannur city in Inner Mongolia, Jingyuan county and Yumen city in Gansu, Delingha city in Qinghai, and Jinghe county in Xinjiang. The MSAP technical system suitable for the methylation analysis of L. barbarum genomic DNA was established and ten pairs of selective primers were selected. Among amplified 5'-CCGG-3' methylated sites, there were 35.85% full-methylated sites and 39.88% hemi-methylated sites, showing a high degree of epigenetic differentiation. Stoichiometric analysis showed that the ecological environment was the main factor affecting the epigenetic characteristics of L. barbarum, followed by cultivated varieties. Precipitation, air temperature, and soil pH were the main ecological factors affecting DNA methylation in different areas. This study provided a theoretical basis for the analysis of the epigenetic mechanism of L. barbarum to adapt to the diffe-rent ecological environments and research ideas for the introduction, cultivation, and germplasm traceability of L. barbarum.
China ; DNA Methylation ; DNA Primers ; Epigenesis, Genetic ; Lycium/genetics*

Objective: To identify the risk factors related to perinatal complications in patients with pulmonary hypertension underwent cesarean section. Methods: We retrospectively analyzed the medical records of all pregnant women with pulmonary hypertension hospitalized in 4 different hospitals in Shandong province and underwent cesarean section between May 2010 and May 2020. Patients were divided into perinatal complication group and control group according to the presence or absence of perinatal complications. Perinatal complications included aggravated heart function, new onset arrythmias, sudden cardiac arrest, all-cause death within 42 days post cesarean section, postpartum bleeding and thrombotic events. Risk factors of perinatal complications were analyzed. Results: A total of 167 patients (47 cases in the perinatal complication group and 120 cases in the control group) were included in this study. The average age of this cohort was 28(24, 32) years, and 75(44.9%) patients suffered newly diagnosed pulmonary hypertension during pregnancy. The main cause of pulmonary hypertension was congenital heart disease (137(82.0%)). Age, pregnant weeks, percent of primipara, intra-cardiac shunt, and receiving targeted medication therapy, cardiac dimensions were similar between the two groups. A total of 62 complications were recorded in the complication group including 28 cases of aggravated heart function, 4 cases of new onset arrythmias, 2 cases of cardiac arrest, 11 cases of bleeding or thrombotic events and 17 patients were dead. Prevalence of idiopathic pulmonary hypertension and general anesthesia was significantly higher, functional capacity was significantly lower in perinatal complication group than in control group (all P<0.05). The estimated systolic pulmonary artery pressure, serum N-terminal pro-B type natriuretic peptide and total bilirubin (TBIL) levels were significantly higher in perinatal complication group than in control group (all P<0.05). Logistic analysis demonstrated WHO Function Class(FC) Ⅲ/Ⅳ (OR=2.416,95%CI 1.016-5.743, P=0.046) and TBIL level (OR=6.874,95%CI 1.643-28.757, P=0.008) were the independent risk factors of perinatal complications. Conclusion: TBIL and WHO FC are independent risk factors of perinatal complications in pregnant women with pulmonary hypertension underwent cesarean section.
Cesarean Section/adverse effects* ; China/epidemiology* ; Female ; Humans ; Hypertension, Pulmonary/epidemiology* ; Pregnancy ; Pregnancy Outcome ; Retrospective Studies ; Risk Factors

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

Herbal pair is formed based on the experience summary of doctors' deep understanding and perception of the medicinal nature in long-term clinical practice. It gradually becomes the exquisite structural unit for preparing traditional Chinese medicine(TCM) prescriptions, and often plays a core bridge role in the prescription combination. Frankincense and myrrh are raw resin materials of incense abroad, which are subsequently included as Chinese medicinal herbs and endowed with rich medicinal connotation. With the functions of relaxing Zang-fu organs, activating blood and relieving pain, they have definite clinical efficacy. From the perspective of herbal description and clinical application, this study systematically analyzed the combination of frankincense and myrrh as well as their combination proportion, efficacy characterization, diseases and syndromes, effective components and action mechanism. On this basis, the focus of in-depth research of frankincense-myrrh and the application prospects were proposed, in order to further reveal the potential meditation law of this herbal pair, thus contributing to clinical practice and drug innovation of traditional Chinese medicine, and providing reference for understanding of TCM medicinal nature and research of herbal pairs.
Humans ; Frankincense/chemistry* ; Commiphora ; Resins, Plant/chemistry* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use*