Melatonin (Mel) has been shown to have cardioprotective effects, but its action on ion channels is unclear. In this experiment, we investigated the inhibitory effect of Mel on late sodium currents (I_Na.L) in mouse ventricular myocytes and the anti-arrhythmic effect at the organ level as well as its mechanism. The whole-cell patch clamp technique was applied to record the ionic currents and action potential (AP) in mouse ventricular myocytes while the electrocardiogram (ECG) and monophasic action potential (MAP) were recorded simultaneously in mouse hearts using a multichannel acquisition and analysis system. The results demonstrated that the half maximal inhibitory concentration (IC₅₀) values of Mel on transient sodium current (I_Na.T) and specific I_Na.L opener 2 nmol·L^-1 sea anemone toxins II (ATX II) increased I_Na.L were 686.615 and 7.37 μmol·L^-1, respectively. Mel did not affect L-type calcium current (I_Ca.L), transient outward current (I_to), and AP. In addition, 16 μmol·L^-1 Mel shortened ATX II-prolonged action potential duration (APD), suppressed ATX II-induced early afterdepolarizations (EADs), and significantly reduced the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) in Langendorff-perfused mouse hearts. In conclusion, Mel exerted its antiarrhythmic effects principally by blocking I_Na.L, thus providing a significant theoretical basis for new clinical applications of Mel. Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Wuhan University of Science and Technology (2023130).

As a new transdermal drug delivery system, microneedles can significantly improve skin permeability, enhance drug transdermal delivery, and demonstrate unique advantages in breaking stratum corneum barrier of skin. This feature enables microneedles to demonstrate enormous potential in delivering biotechnology drugs. The traditional delivery method for biotechnology drugs is mainly injection, which brings problems such as pain and skin redness to patients, leading to poor patient compliance. In addition, the production, transportation, and storage of biotechnology drugs require strict low-temperature conditions to maintain their activity and increase cost output. Microneedles, by contrast, have many benefits, providing new avenues and solutions for biomolecular delivery. Accordingly, this review introduced the microneedle drug delivery system for delivery biotechnology drugs, and summarized the research progress of microneedle systems in biotechnology drugs.

Traditional decoction pieces have low efficiency, poor batch-to-batch consistency, and irregular physical form, making it difficult to meet the demands of modern automated production and precise and rapid clinical blending. Therefore, this study aims to develop a new type of granular drinking tablet to meet the demand for high-quality development in the traditional Chinese medicine industry. In the current study, the differences and similarities between the new Lonicerae Japonicae Flos (LJF) granular drinking tablets and the traditional ones were evaluated based on the flowability, the paste rate of the standard soup, the characterization fingerprint, the degree of pasting, the content of active ingredients, the transfer rate, and its traditional antipyretic and anti-inflammatory efficacy, using the traditional LJF decoction piece as a reference. The flowability experiments showed that the flowability of medium-sized granules (10-24 mesh) was significantly better than that of traditional drinking tablets (P < 0.01); the results of the paste rate showed that there was no significant difference between the different particle sizes and the original decoction pieces (P > 0.05), but the small particle sizes (24-65 mesh) had poor decoction clarity and gelatinization; the transfer rate was calculated as chlorogenic acid and luteoloside, and there was no significant difference in the transfer rate between traditional slices and different particle sizes (P > 0.05); the pharmacological results showed that the contents of rat tumor necrosis factor-α (TNF-α), rat interleukin-1β (IL-1β) and rat prostaglandin E₂ (PGE₂), xylene ear swelling inhibition rate and granuloma inhibition rate showed that there was no significant difference between the traditional and new granule decoction pieces (P > 0.05). In this study, by examining the fluidity, paste rate, paste degree, and antipyretic and anti-inflammatory effects of the new granular decoction piece of LJF, it was initially revealed that the new granular drinking tablets of LJF were consistent with the basic properties and pharmacological effects of the commercially available traditional drinking tablets. Still, the new granular tablets were characterized by high utilization rate, homogeneous quality, and ease of clinical transfer, which had a good prospect for application. The animal experiment was approved by the Ethics Committee of the China Academy of Chinese Medical Sciences (approval number. 2022B214).

Objective To evaluate the effects of anterior cruciate ligament (ACL) reconstruction timing on the motor performance and proprioception by clinical evaluation as well as proprioception and motor performance tests on the patients more than 2 years after ACL reconstruction. Methods The patients who underwent ACL reconstruction in the National Institute of Sports Medicine,General Administration of Sport of China from January 2015 to January 2021 and met the inclusion criteria were followed up,and the postoperative data were collected retrospectively.Fifty-six patients who met the inclusion criteria were included in this study and categorized into two groups:early surgery (n=28,who underwent ACL reconstruction ≤3 weeks after injury) and delayed surgery (n=28,who underwent ACL reconstruction >3 weeks after injury).The basic information,clinical evaluation results,proprioception,and motor performance were compared between the two groups. Results The ACL return to sport after injury scale (ACL-RSI) score in the early surgery group was higher than that in the delayed surgery group [(68.68±22.04)scores vs. (55.82±24.87)scores,P=0.045].There was no difference in the range of motion of the knee joint,the positive rate of pivot shift test,or the scores of Tegner,Marx,Lysholm,knee injury and osteoarthritis outcome score (KOOS),and international knee documentation committee (IKDC) between the two groups (all P>0.05).Although there was no significant difference in range of motion of the knee joint between the two groups,the proportion of knee flexion and extension affected in the early surgery group was smaller than that in the delayed surgery group.Neither motor performance (isokinetic strength test,Y-balance test,and single-leg jump test) nor proprioception had difference between the two groups (all P>0.05). Conclusions Early ACL reconstruction outperformed delayed ACL reconstruction in improving the psychological health,emotions,and confidence in returning to sport,accelerating functional recovery of the patients.The timing of ACL reconstruction has no significant effect on the short-term postoperative knee stability,knee function,motor performance,or proprioceptive recovery of the patients.Early ACL reconstruction is recommended for improving the clinical outcomes.
Humans ; Anterior Cruciate Ligament Reconstruction/methods* ; Proprioception/physiology* ; Retrospective Studies ; Male ; Female ; Range of Motion, Articular ; Anterior Cruciate Ligament Injuries/physiopathology* ; Adult ; Postoperative Period ; Time Factors ; Return to Sport ; Recovery of Function ; Knee Joint/physiopathology* ; Young Adult

Objective To evaluate the effects of knee flexor and extensor strength on the subjective function and motor performance of knees after anterior cruciate ligament reconstruction. Methods A total of 53 patients who underwent anterior cruciate ligament reconstruction in the National Institute of Sports Medicine,General Administration of Sport of China from June 2015 to June 2021 and met the inclusion criteria were enrolled in this study.The patients were followed up time for at least 2 years.An isometric muscle strength test system was used to measure the strength of bilateral quadriceps and hamstring muscles.The patients were grouped according to whether the limb symmetry index (LSI) of peak torque of quadriceps and hamstring muscle reached 85% at an angular velocity of 60°/s.Specifically,26 patients were classified into group A (LSI≥85%) and 27 patients were classified into group B (LSI<85%).The subjective function and motor performance of knees were compared between the two groups. Results In terms of subjective function of knees,the international knee documentation committee (IKDC) score (88.76±9.93 vs. 81.08±12.57,P=0.017) and knee injury and osteoarthritis outcome score (KOOS) (86.27±8.96 vs. 80.22±11.31,P=0.036) were different between groups A and B.There was no significant difference in Lysholm score [95.0 (79.8,100.00) vs. 86.00 (66.00,100.00),P=0.238],ACL return to sports after injury scale score (66.08±22.25 vs. 61.12±23.53,P=0.434),Marx score [6.00 (4.75,7.00) vs. 6.00 (4.00,7.00),P=0.805] or Tegner activity score [8.00 (4.00,12.00) vs. 4.00 (2.00,12.00),P=0.566] between the two groups.In terms of motor performance,the single-leg triple hop LSI (0.92±0.13 vs. 0.81±0.18,P=0.016) and single-leg crossover hop LSI (0.96±0.12 vs. 0.84±0.22,P=0.021) showed significant differences between groups A and B,while there was no significant difference in single-leg hop LSI (0.90±0.18 vs. 0.79±0.25,P=0.116) between the two groups.In addition,there was no statistical significance in proprioception [30°:8.83±4.66 vs. 10.73±4.63,P=0.143;45°:6.94±3.82 vs. 7.66±3.93,P=0.504;60°:4.10 (3.20,4.72) vs. 3.90 (2.30,5.20),P=0.493] or Y-balance test results [anterior LSI:0.98 (0.84,1.02) vs. 0.94 (0.86,0.98),P=0.328;posterolateral LSI:1.00±0.08 vs. 0.97±0.07,P=0.249;posteromedial LSI:1.00 (0.97,1.03) vs. 0.96 (0.93,1.03),P=0.179] between groups A and B. Conclusion The patients with good symmetry of quadriceps and hamstring muscle strength after anterior cruciate ligament reconstruction had better subjective function and movement performance of knees than the patients with poor symmetry,which was mainly reflected in the IKDC score,KOOS,single-leg triple hop,and single-leg crossover hop.
Humans ; Anterior Cruciate Ligament Reconstruction ; Muscle Strength/physiology* ; Male ; Quadriceps Muscle/physiology* ; Female ; Adult ; Anterior Cruciate Ligament Injuries/physiopathology* ; Hamstring Muscles/physiopathology* ; Knee Joint/physiopathology* ; Anterior Cruciate Ligament/physiopathology* ; Torque ; Knee/physiopathology*

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective: To explore the diagnosis, surgical management and outcome of jugular foramen chondrosarcoma (CSA). Methods: Fifteen patients with jugular foramen CSA hospitalized in the Department of Otorhinolaryngology Head and Neck Surgery of Chinese PLA General Hospital from December 2002 to February 2020 were retrospectively collected,of whom 2 were male and 13 were female, aging from 22 to 61 years old. The clinical symptoms and signs, imaging features, differential diagnosis, surgical approaches, function of facial nerve and cranial nerves IX to XII, and surgical outcomes were analyzed. Results: Patients with jugular foramen CSA mainly presented with facial paralysis, hearing loss, hoarseness, cough, tinnitus and local mass. Computed tomography (CT) and magnetic resonance (MR) could provide important information for diagnosis. CT showed irregular destruction on bone margin of the jugular foramen. MR demonstrated iso or hypointense on T1WI, hyperintense on T2WI and heterogeneous contrast-enhancement. Surgical approaches were chosen upon the sizes and scopes of the tumors. Inferior temporal fossa A approach was adopted in 12 cases, inferior temporal fossa B approach in 2 cases and mastoid combined parotid approach in 1 case. Five patients with facial nerve involved received great auricular nerve graft. The House Brackmann (H-B) grading scale was used to evaluate the facial nerve function. Preoperative facial nerve function ranked grade Ⅴ in 4 cases and grade Ⅵ in 1 case. Postoperative facial nerve function improved to grade Ⅲ in 2 cases and grade Ⅵ in 3 cases. Five patients presented with cranial nerves Ⅸ and Ⅹ palsies. Hoarseness and cough of 2 cases improved after operation, while the other 3 cases did not. All the patients were diagnosed CSA by histopathology and immunohistochemistry, with immunohistochemical staining showing vimentin and S-100 positive, but cytokeratin negative in tumor cells. All patients survived during 28 to 234 months' follow-up. Two patients suffered from tumor recurrence 7 years after surgery and received revision surgery. No complications such as cerebrospinal fluid leakage and intracranial infection occurred after operation. Conclusions: Jugular foramen CSA lacks characteristic symptoms or signs. Imaging is helpful to differential diagnosis. Surgery is the primary treatment of jugular foramen CSA. Patients with facial paralysis should receive surgery in time as to restore the facial nerve. Long-term follow-up is necessary after surgery in case of recurrence.
Humans ; Male ; Female ; Young Adult ; Adult ; Middle Aged ; Facial Paralysis/etiology* ; Diagnosis, Differential ; Jugular Foramina ; Retrospective Studies ; Cough ; Hoarseness ; Neoplasm Recurrence, Local ; Chondrosarcoma/surgery*

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.
Medicine, Chinese Traditional ; Nonprescription Drugs ; Consensus ; China ; Reference Standards ; Drugs, Chinese Herbal

Objective:To investigate genetic characteristics of human rhinovirus (HRV) in adult inpatients with pneumonia in autumn and winter in Bengbu, Anhui province, 2021.Methods:The pharyngeal swabs of inpatients with pneumonia in Bengbu were collected for the detection of 14 common respiratory pathogens by Real-time PCR during September to December 2021. VP4/VP2 coding regions of HRV positive samples were amplified by nested PCR and phylogenetic tree was constructed using MEGA7.0.Results:A total of 146 samples were collected from inpatients with pneumonia; 35.62% (52/146) samples were positive with at least one pathogen. The four viruses with high detection rate were HRV, adenovirus, human coronavirus OC43 and influenza B virus. HRV positive samples accounted for 44.23% (23/52) of the positive samples, among which 9 cases (39.13%, 9/23) co-infected with HRV. Phylogenetic analysis found that HRV infection were dominated by HRV-A and HRV-B groups. The analysis based on clinical syndrome found that the white blood cells count and the proportion neutrophils of patients with HRV co-infection were higher that of HRV single infection. The proportion of patients with hypertension, diabetes, mechanical ventilation and poor prognosis in the HRV co-infection group were higher than that of HRV single infection group ( P<0.05). Conclusions:HRV is the predominant pathogen among the adult inpatients with pneumonia in Bengbu. HRV-A and HRV-B groups are common. Patients accompanied by hypertension, diabetes were easily co-infected with HRV. Patients coinfeted with HRV are more likely to be mechanical ventilation and poor prognosis.

Based on the difference between disease and syndrome differentiation of acupuncture and moxibustion and each department of TCM, i.e. internal medicine, external medicine, gynecology and pediatrics, it is believed that "differentiation of disease location" is the key of disease and syndrome differentiation of acupuncture and moxibustion. According to the disease location, in the section "treatment" of Science of Acupuncture and Moxibustion, the disorders/illness are classified as zangfu disorder, disorders of limbs and meridians, dermatological disorder, ophthalmological and otorhinolaryngological disorder, gynecological disorder, as well as qi, blood and body fluid disorder. Besides, the rules of disease and syndrome differentiation, as well as treatment characteristics of each category are explained separately. It is considered that the clinical diagnosis and treatment system of acupuncture and moxibustion should be constructed by focusing on "differentiation of disease location".
Acupuncture ; Acupuncture Therapy ; Child ; Humans ; Meridians ; Moxibustion ; Syndrome