ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

OBJECTIVES: To evaluate the value of ⁶⁸Ga-DOTATATE and ¹⁸F-FDG PET/CT imaging in staging and treatment decision for gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). METHODS: This retrospective analysis was conducted in 49 patients with GEP-NEN undergoing ¹⁸F-FDG and ⁶⁸Ga-DOTATATE PET/CT imaging at our hospital from August, 2020 to March, 2023, including 34 newly diagnosed patients and 15 patients with recurrence or metastasis after treatment. GEP-NEN were classified into G1, G2, and G3 neuroendocrine tumors (NET) and neuroendocrine carcinomas (NEC) based on pathological typing. The detection efficiency were classified into 4 patterns based on the number of positive tumor lesions detected by the two tracers: ⁶⁸Ga-DOTATATE>¹⁸F-FDG (A); ⁶⁸Ga-DOTATATE=¹⁸F-FDG (B); ⁶⁸Ga-DOTATATE<¹⁸F-FDG (C); and complementation (D). The value of dual-modality imaging in staging and treatment decision were evaluated by visual analysis. RESULTS: In the 49 patients with GEP-NEN, ⁶⁸Ga-DOTATATE PET/CT was superior to ¹⁸F-FDG PET/CT for detecting systemic tumor lesions (P<0.001) and more sensitive for detecting primary/recurrent lesions, lymph node metastasis, liver metastasis, and bone metastasis (P<0.05), while ¹⁸F-FDG PET/CT had higher detection rates for lung metastasis and peritoneal metastasis (P<0.05). In terms of the detection efficiency, Pattern A was found in 46.9% (23/49) patients, Pattern B in 38.8% (19/49), Pattern C in 12.2% (6/49), and Pattern D in 2.0% (1/49). The complementary value of ¹⁸F-FDG PET/CT to ⁶⁸Ga-DOTATATE PET/CT was 0% in G1 NET patients (0/13), 8.3% in G2 NET patients (2/24), 50% in G3 NET patients (3/6), and 33.3% in NEC patients (2/6). 12.2% (6/49) of the patients had their staging confirmed or changed due to additional lesions detected by ¹⁸F-FDG PET/CT imaging, resulting subsequently in establishment or adjustment of their treatment plans. CONCLUSIONS ⁶⁸Ga-DOTATATE PET/CT imaging should be the primary choice for GEP-NEN patients. Additional ¹⁸F-FDG PET/CT imaging can potentially improve precision of staging and treatment decision-making for G2, G3 and NEC patients but provides virtually no clinical benefits for G1 NET patients.
Humans ; Positron Emission Tomography Computed Tomography/methods* ; Neuroendocrine Tumors/therapy* ; Pancreatic Neoplasms/therapy* ; Retrospective Studies ; Organometallic Compounds ; Stomach Neoplasms/therapy* ; Neoplasm Staging ; Fluorodeoxyglucose F18 ; Intestinal Neoplasms/therapy* ; Female ; Male ; Middle Aged ; Aged ; Adult

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Numerous c-mesenchymal-epithelial transition (c-MET) inhibitors have been reported as potential anticancer agents. However, most fail to enter clinical trials owing to poor efficacy or drug resistance. To date, the scaffold-based chemical space of small-molecule c-MET inhibitors has not been analyzed. In this study, we constructed the largest c-MET dataset, which included 2,278 molecules with different structures, by inhibiting the half maximal inhibitory concentration (IC₅₀) of kinase activity. No significant differences in drug-like properties were observed between active molecules (1,228) and inactive molecules (1,050), including chemical space coverage, physicochemical properties, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles. The higher chemical diversity of the active molecules was downscaled using t-distributed stochastic neighbor embedding (t-SNE) high-dimensional data. Further clustering and chemical space networks (CSNs) analyses revealed commonly used scaffolds for c-MET inhibitors, such as M5, M7, and M8. Activity cliffs and structural alerts were used to reveal "dead ends" and "safe bets" for c-MET, as well as dominant structural fragments consisting of pyridazinones, triazoles, and pyrazines. Finally, the decision tree model precisely indicated the key structural features required to constitute active c-MET inhibitor molecules, including at least three aromatic heterocycles, five aromatic nitrogen atoms, and eight nitrogen-oxygen atoms. Overall, our analyses revealed potential structure-activity relationship (SAR) patterns for c-MET inhibitors, which can inform the screening of new compounds and guide future optimization efforts.

OBJECTIVE: To evaluate the clinical efficacy of modified high tibial osteotomy combined with platelet-rich plasma in the treatment of moderate to severe knee osteoarthritis. METHODS: From January 2021 to March 2022, the clinical data of 60 patients with moderate to severe knee osteoarthritis admitted to the Third Affiliated Hospital of Beijing University of Chinese Medicine were analyzed. Among them, 30 patients were treated with modified tibia high osteotomy combined with platelet-rich plasma as the observation group, including 12 males and 18 females, aged from 51 to 74 years old, with an average age of (64.37±5.72) years old. The course of disease ranged from 1 to 7 years with an average of(3.43±1.41) years. Thirty patients were treated with modified high tibial osteotomy combined with sodium hyaluronate as control group, including 10 males and 20 females, aged from 50 to 78 years, with an average age of (64.33±8.18) years. The course of disease was 1 to 7 years with an average of(3.30±1.39) years. Knee X-rays were taken before surgery and at the last follow-up, and the changes of lower limb bearing-line ratio (WBLR), proximal medial tibial Angle (MPTA), femoro-tibial angle (FTA) and posterior tibial slope (PTS) were compared between the two times. Visual analogue scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and Lysholm score were used to evaluate knee pain and functional changes before surgery and at 1, 3, and 6 months after surgery. RESULTS: The wounds of all patients healed in stage I after surgery. All 60 patients completed treatment and follow-up, with an average follow-up duration of (8.08±1.75) months, ranged from 6 to 12 months. No serious adverse events or complications occurred. At the last follow-up, WBLR, MPTA and FTA were significantly improved in both groups (P<0.05). At the last follow-up, there was no significant difference in PTS between the two groups compared with pre-operation(P>0.05). At the last follow-up, there were no significant differences in WBLR, MPTA, FTA and PTS between the observation group and the control group (P>0.05). The VAS scores, WOMAC scores and Lysholm scores of both groups were significantly Modified with time after operation (P<0.05). At 1, 3 and 6 months after operation, VAS score, WOMAC score and Lysholm score of the observation group were significantly better than those of the control group, with statistical significance (P<0.05). CONCLUSION For patients with moderate and severe knee osteoarthritis, modified high tibial osteotomy can significantly correct lower limb alignment, and combined with platelet-rich plasma therapy can further significantly relieve knee pain and improve knee function, the effect is better than combined with sodium hyaluronate.
Humans ; Male ; Female ; Osteoarthritis, Knee/physiopathology* ; Middle Aged ; Osteotomy/methods* ; Platelet-Rich Plasma ; Aged ; Tibia/surgery*

OBJECTIVE: To compare clinical efficacy of tibial transverse transport (TTT) microcirculation reconstruction and periosteal distraction in treating patients with early diabetic foot(DF). METHODS: From June 2021 to June 2024, 60 patients with DF were admitted and divided into bone transport group and stretch group according to different treatment methods. There were 30 patients in bone transport group, including 16 males and 14 females;aged from 48 to 65 years old with an average of (55.59±3.78) years old;the course of disease ranged from 2 to 9 months with an average of(5.95±1.32) months;TTT microcirculation reconstruction surgery was performed. There were 30 patients in distraction group, including 17 males and 13 females;aged from 47 to 67 years old with an average of (55.24±3.81) years old;the course of disease ranged from 2 to 10 months with an average of (5.68±1.54) months;periosteal distraction surgery was performed. The skin temperature of the affected feet, the time of getting out of bed and walking after operation, the time of full weight-bearing, the wound healing time and complications were compared between two groups;the pain was evaluated by visual analogue scale (VAS) before operation and one month after operation respectively;the changes of blood flow velocity of dorsal foot arteries, ankle brachial index(ABI), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF) before and after operation at 3 months were compared between two groups. RESULTS: All patients were followed up for 3 to 4 months with an average of (3.52±0.12) months. There were no statistically significant differences in comparison of foot skin temperature, postoperative walking time, full weight-bearing time and complications between two groups (P>0.05). The wound healing time of bone transport group (61.26±7.31) days was shorter than that of distraction group (70.17±7.15) days, and the difference was statistically significant (P<0.05). Postoperative VAS at 1 month of bone transport group (2.19±0.21) was lower than that of distraction group (2.55±0.20), and the difference was statistically significant (P<0.05). At 3 months after operation, the blood flow velocity of dorsal foot artery, ankle-brachial index, EGF and bFGF in bone transport group were(34.73±4.18) cm·s^-1, (0.95±0.13), (716.61±71.13) pg·ml^-1 and (175.69±31.28) pg·ml^-1, respectively;which were higher than that of distraction group (31.86±3.23) cm·s^-1, (0.84±0.11), (677.37±70.21) pg·ml^-1, (149.26±30.13) pg·ml^-1, and the differences were statistically significant (P<0.05). There was no recurrence of ulcers in situ or at other sites in both groups during follow-up. CONCLUSION Compared with periosteal distraction, TTT microcirculation reconstruction surgery has a definite effect in the treatment of early DF. It could effectively reduce pain level, improve blood flow indicators and vascular endothelial function of the foot, and has a relatively high safety.
Humans ; Male ; Female ; Middle Aged ; Aged ; Tibia/blood supply* ; Diabetic Foot/physiopathology* ; Microcirculation ; Periosteum/surgery* ; Plastic Surgery Procedures/methods* ; Osteogenesis, Distraction

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

OBJECTIVE: This study aimed to reexplore minimum iodine excretion and to build a dietary iodine recommendation for Chinese adults using the obligatory iodine loss hypothesis. METHODS: Data from 171 Chinese adults (19-21 years old) were collected and analyzed based on three balance studies in Shenzhen, Yinchuan, and Changzhi. The single exponential equation was accordingly used to simulate the trajectory of 24 h urinary iodine excretion as the low iodine experimental diets offered (iodine intake: 11-26 μg/day) and to further deduce the dietary reference intakes (DRIs) for iodine, including estimated average requirement (EAR) and recommended nutrient intake (RNI). RESULTS: The minimum iodine excretion was estimated as 57, 58, and 51 μg/day in three balance studies, respectively. Moreover, it was further suggested as 57, 58, and 51 μg/day for iodine EAR, and 80, 81, and 71 μg/day for iodine RNI or expressed as 1.42, 1.41, and 1.20 μg/(day·kg) of body weight. CONCLUSION The iodine DRIs for Chinese adults were established based on the obligatory iodine loss hypothesis, which provides scientific support for the amendment of nutrient requirements.
Humans ; Iodine/administration & dosage* ; Male ; Female ; China ; Young Adult ; Diet ; Adult ; Nutritional Requirements ; East Asian People