ObjectiveTo investigate the effect of Yaoshu Zhuyu Fang on the regulation of the microRNA-17-5P (miR-17-5P)/murine double minute 2 (MDM2)/p53 axis in the proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells, and its potential molecular mechanism. MethodsIntervertebral disc annulus fibrosus tissues were obtained from 8-week-old SPF-grade male SD rats, and annulus fibrosus cells were isolated and obtained by enzyme digestion and mechanical dispersion. Annulus fibrosus cells were divided into 6 groups: Group C was the blank control group, in which annulus fibrosus cells were not treated with interleukin-1β (IL-1β) but were cultured in RPMI 1640 complete medium. Group β was the degeneration model group constructed by treating annulus fibrosus cells with 10 ng/mL IL-1β for 24 h. Group β+B was the IL-1β + blank serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% blank serum for 24 h. Group β+W was the IL-1β + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. Group β+I was the IL-1β + miR-17-5P inhibitor group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor. Group β+I+W was the IL-1β + miR-17-5P inhibitor + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor, and finally treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. CCK-8 assay was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the expression levels of miR-17-5P, MDM2 mRNA, and p53 mRNA in cells. Western blotting was used to detect the protein expression levels of MDM2 and p53 in cells. Dual-luciferase reporter system was used to analyze the targeting relationship between miR-17-5P and MDM2. ResultsCompared with Group C, Group β showed a significant decrease in cell survival rate (P<0.001), a significant increase in cell apoptosis rate (P<0.001), significantly increased expression of miR-17-5P, p53 mRNA, and p53 protein (P<0.001), and significantly decreased expression of MDM2 mRNA and protein (P<0.001). Compared with Group β, Group β+W, Group β+I, and Group β+I+W showed significantly increased cell survival rate, significantly decreased apoptosis rate, significantly decreased expression of miR-17-5P, p53 mRNA, and p53 protein, and significantly increased expression of MDM2 mRNA and protein (P<0.001). Moreover, changes in the above indicators were greater in Group β+I+W (P<0.001). Circular RNA Interactome predicted that miR-17-5P had specific binding sites with the 3' untranslated region (3'UTR) of MDM2. Transfection of miR-17-5P mimic significantly reduced the luciferase expression level of co-transfected luciferase reporter plasmid containing wild-type MDM2 3'UTR (P<0.05), but had no significant effect on luciferase expression in cells co-transfected with luciferase reporter plasmid containing mutant MDM2 3'UTR (P>0.05). ConclusionYaoshu Zhuyu Fang down-regulates the expression of miR-17-5P, promotes the synthesis of MDM2 protein, thereby down-regulates p53, promotes proliferation, and inhibits the apoptosis of rat intervertebral disc annulus fibrosus cells.

Background: The tight junction protein claudin18.2 (CLDN18.2) has been implicated in poor prognosis and suboptimal immunotherapy response in gastric cancer (GC). This study investigates the clinicopathological relevance of CLDN18.2 expression and its association with molecular subtypes in GC patients from a high-incidence region, combining transcriptomic and proteomic approaches to explore how CLDN18.2 contributes to progression and metastasis. Methods: A retrospective cohort of 494 GC patients (2019–2024) underwent immunohistochemical analysis for CLDN18.2, Epstein-Barr virus (Epstein–Barr virus–encoded RNA), p53, human epidermal growth factor receptor 2 (HER2), and mismatch repair proteins (MLH1, MSH2, PMS2, and MSH6). CLDN18.2 positivity was defined as moderate to strong (2+/3+) membranous staining in ≥75% of tumor cells. Clinicopathological correlations, biomarker associations, and survival outcomes were evaluated. Transcriptomic and proteomic sequencing was performed to explore molecular mechanisms. Results: CLDN18.2 positivity was observed in 26.9% (133/494) of gastric adenocarcinomas. CLDN18.2-positive tumors correlated with TNM stage (p = .003) and shorter overall survival (p = .018). No associations were identified with age, sex, HER2 status, microsatellite instability, or Epstein-Barr virus infection. Transcriptomic profiling revealed CLDN18.2-high tumors enriched in pathways involving cell junction disruption, signaling regulation, and immune modulation. Proteomic profiling showed that tumors with high CLDN18.2 were enriched in multiple mechanism-related pathways such as integrated metabolic reprogramming, cytoskeletal recombination, immune microenvironment dysregulation, and pro-survival signaling. These mechanisms may collectively contribute to tumor progression and metastasis. Conclusions CLDN18.2 overexpression is associated with poor prognosis in GC patients. Transcriptomic and proteomic analyses demonstrate that CLDN18.2 promotes tumor progression and metastasis, underscoring its potential as an independent prognostic factor in regions with a high incidence of GC.

Objective To compare the efficacy and safety of transurethral blue laser vaporization of the prostate, transurethral resection of the prostate (TURP) or plasmakinetic resection of the prostate in the treatment of benign prostatic hyperplasia (BPH). Methods The domestic and foreign clinical studies on transurethral blue laser vaporization of the prostate (observation group), TURP or plasmakinetic resection of the prostate (control group) in the treatment of BPH during Jan. 2015 and Mar. 2025 were retrieved. The data were extracted with Cochrane systematic review method. The operation time, decrease in hemoglobin, bladder irrigation time, catheter indwelling time, total complication rate, retrograde ejaculation rate and urinary incontinence rate of the two groups were compared with RevMan 5.3.0 statistical software. Results A total of 5 Chinese studies involving 491 patients (248 in the observation group and 243 in the control group) were included in the Meta-analysis. Compared with the control group, the observation group had shorter operation time [MD=-20.80, 95%CI:-26.88—-14.72, P＜0.00001], less decrease in hemoglobin [MD=-10.61, 95%CI: -20.21—-1.01, P=0.03], shorter bladder irrigation time [MD=-17.85, 95%CI: -32.62—-3.09, P=0.002], shorter catheter indwelling time [MD=-1.71, 95%CI: -2.81—- 0.62, P=0.002], lower total complication rate [OR=0.11, 95%CI: 0.06—0.21, P＜0.00001], lower retrograde ejaculation rate [OR=0.05, 95%CI: 0.02—0.16, P＜0.00001] and lower urinary incontinence rate [OR=0.24, 95%CI: 0.07—0.79, P=0.02]. There were no significant differences in other complications between the two groups (P＞0.05). The international erectile function score (IIEF-5) of the observation group was significantly higher than that of the control group [MD=1.87, 95%CI:1.16—2.57, P＜0.00001]. There were no significant differences in international prostate symptom score (IPSS), maximum urinary flow rate (Qmax) and post-voiding residual (PVR) between the two groups (P＞0.05). Conclusion All three surgical procedures can effectively improve the lower urinary tract symptoms of BPH patients. Compared with TURP or plasmakinetic resection of the prostate, transurethral blue laser vaporization of the prostate has obvious advantages in terms of perioperative recovery, reduction of total complications, urinary incontinence and retrograde ejaculation rates, and preservation of sexual function.

Puerariae Lobatae Radix and Puerariae Thomsonii Radix are the dried roots of Pueraria lobata and Pueraria thomsonii of the Leguminosae family， respectively. Since their separate inclusion in the 2005 edition of Pharmacopoeia of the People's Republic of China， the two herbs have been individually recorded. Although they share the same functions and indications， the required content of puerarin differs by a factor of up to eightfold between them. The current quality standard relies solely on a single indicator， puerarin， which fails to reflect the correlation between chemical constituents and core therapeutic effects. This has resulted in prominent issues of mixed use in clinical practice and production， thereby constraining the high-quality development of the industry. Modern research has demonstrated that Puerariae Lobatae Radix contains a comprehensive range and higher content of isoflavonoid constituents， while Puerariae Thomsonii Radix is rich in starch and polysaccharides. Puerariae Lobatae Radix exhibits stronger effects in antipyresis， cardiovascular and cerebrovascular protection， and central analgesia， while Puerariae Thomsonii Radix demonstrates greater advantages in anti-inflammation， hypoglycemia， and peripheral analgesia. Based on this， the chemical material bases of Puerariae Lobatae Radix and Puerariae Thomsonii Radix at both the macromolecule and micromolecule levels were systematically reviewed and compared. The pharmacodynamic material bases and mechanisms of action underlying their three core therapeutic effects， namely "relieving exterior syndrome and clearing heat"， "promoting fluid production to quench thirst"， and "dredging channels and activating collaterals"， were summarized. The most highly correlated common metabolic pathway shared by both herbs for these three therapeutic effects is the arachidonic acid metabolic pathway， and their common core target is prostaglandin-endoperoxide synthase 2 （PTGS2）. This review provided clinical application recommendations based on the therapeutic differences between the two herbs， elucidated the scientific connotation of their "same origin but different effects"， and， grounded in the quality marker （Q-Marker）， proposed the concept of efficacy-related Q-Marker based on "substance-efficacy-syndrome" association， as well as a novel strategy for efficacy-oriented quality evaluation. Preliminary screening of quality markers associated with different therapeutic effects was also conducted. This study aims to provide critical scientific evidence for the precise clinical application of Puerariae Lobatae Radix and Puerariae Thomsonii Radix， the improvement of quality standards， and the high-quality development of the industry.

ObjectiveTo observe the clinical efficacy and safety of Zhinao capsules in the treatment of mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. MethodsA randomized， double-blind， placebo， controlled clinical trial design was adopted， and 60 Alzheimer's disease patients aged 50-85 years with mild and moderate sleep disorders due to spleen-kidney deficiency and combined phlegm and stasis were included. According to the randomized numble table method， the patients were assigned into a treatment group and a control group （30 in each group， with 29 patients in the treatment group and 28 patients in the control group finally completing the trial）. The treatment group was treated with donepezil hydrochloride tablets combined with Zhinao capsules， and the control group was treated with donepezil hydrochloride tablets combined with the simulant of Zhinao capsules for 12 weeks. The Pittsburgh sleep quality index （PSQI）， smart bracelet sleep monitoring， epworth sleeping scale （ESS）， Mini-Mental State Examination （MMSE）， Activities of Daily Living （ADL）， and traditional Chinese medicine symptoms were scored. Furthermore， the brain-derived neurotrophic factor （BDNF） and gamma-aminobutyric acid （GABA） levels were measured. ResultsAfter 12 weeks of treatment， the total response rate of clinical efficacy assessment in the treatment group reached 89.7%， which was significantly higher than that （21.4%） in the control group （Z=-5.14， P<0.01）. After treatment， the TCM symptom scores declined in both groups （P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.01）. After treatment， the treatment group showed decreased total score and seven component scores of the PSQI scale （P<0.05， P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.05， P<0.01）. After treatment， the treatment group showed increases in the duration of deep sleep， light sleep， rapid eye movement sleep， and total sleep at night and decreases in the time to fall asleep， the number of awakenings from sleep at night， and the time for sporadic daytime naps （P<0.01）. The control group did not show significant changes in the duration of light sleep， time to fall asleep， and number of awakenings from sleep at night. Moreover， the treatment group outperformed the control group in terms of the indicators above （P<0.05， P<0.01）. After treatment， the treatment group showed decreased scores of ESS， ADL and its subscales physical self-maintenance scale （PSMS）， and Instrumental Activities of daily living scale （IADLs） and increased score of MMSE and levels of BDNF and GABA （P<0.05， P<0.01）. There was no significant difference in PSMS between the two groups， and the treatment group was significantly better than the control group in terms of the rest of the above indicators （P<0.05， P<0.01）. Patients in neither groups complained of uncomfortable symptoms. ConclusionZhinao capsules have significant clinical efficacy in treating patients with mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. Zhinao capsules can significantly reduce PSQI， ESS， and ADL scores， increase the MMSE score and the expression of BDNF and GABA， effectively optimize the structure of sleep， improve the intelligence， and enhance the ability of daily life， without causing uncomfortable symptoms. The mechanism may be related to the increase in the expression of sleep/wake-related neurotransmitters.

ObjectiveTo observe the clinical efficacy and safety of Zhinao capsules in the treatment of mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. MethodsA randomized， double-blind， placebo， controlled clinical trial design was adopted， and 60 Alzheimer's disease patients aged 50-85 years with mild and moderate sleep disorders due to spleen-kidney deficiency and combined phlegm and stasis were included. According to the randomized numble table method， the patients were assigned into a treatment group and a control group （30 in each group， with 29 patients in the treatment group and 28 patients in the control group finally completing the trial）. The treatment group was treated with donepezil hydrochloride tablets combined with Zhinao capsules， and the control group was treated with donepezil hydrochloride tablets combined with the simulant of Zhinao capsules for 12 weeks. The Pittsburgh sleep quality index （PSQI）， smart bracelet sleep monitoring， epworth sleeping scale （ESS）， Mini-Mental State Examination （MMSE）， Activities of Daily Living （ADL）， and traditional Chinese medicine symptoms were scored. Furthermore， the brain-derived neurotrophic factor （BDNF） and gamma-aminobutyric acid （GABA） levels were measured. ResultsAfter 12 weeks of treatment， the total response rate of clinical efficacy assessment in the treatment group reached 89.7%， which was significantly higher than that （21.4%） in the control group （Z=-5.14， P<0.01）. After treatment， the TCM symptom scores declined in both groups （P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.01）. After treatment， the treatment group showed decreased total score and seven component scores of the PSQI scale （P<0.05， P<0.01）， and the scores in the treatment group were lower than those in the control group （P<0.05， P<0.01）. After treatment， the treatment group showed increases in the duration of deep sleep， light sleep， rapid eye movement sleep， and total sleep at night and decreases in the time to fall asleep， the number of awakenings from sleep at night， and the time for sporadic daytime naps （P<0.01）. The control group did not show significant changes in the duration of light sleep， time to fall asleep， and number of awakenings from sleep at night. Moreover， the treatment group outperformed the control group in terms of the indicators above （P<0.05， P<0.01）. After treatment， the treatment group showed decreased scores of ESS， ADL and its subscales physical self-maintenance scale （PSMS）， and Instrumental Activities of daily living scale （IADLs） and increased score of MMSE and levels of BDNF and GABA （P<0.05， P<0.01）. There was no significant difference in PSMS between the two groups， and the treatment group was significantly better than the control group in terms of the rest of the above indicators （P<0.05， P<0.01）. Patients in neither groups complained of uncomfortable symptoms. ConclusionZhinao capsules have significant clinical efficacy in treating patients with mild and moderate sleep disorders in Alzheimer's disease patients with the syndrome of spleen-kidney deficiency and combined phlegm and stasis. Zhinao capsules can significantly reduce PSQI， ESS， and ADL scores， increase the MMSE score and the expression of BDNF and GABA， effectively optimize the structure of sleep， improve the intelligence， and enhance the ability of daily life， without causing uncomfortable symptoms. The mechanism may be related to the increase in the expression of sleep/wake-related neurotransmitters.

Objective: Randomized controlled trials (RCTs) of Chinese patent medicines and classic traditional Chinese medicine prescriptions were systematically reviewed from both Chinese and English journals published in 2023. A preliminary summary and evaluation were conducted on the generation and translation of clinical evidence for these treatments. This analysis aims to inform future research on clinical efficacy evaluation and guide the rational application of evidence. Methods: RCTs of Chinese patent medicines and classic traditional Chinese prescriptions published in 2023 were comprehensively retrieved from the Artificial Intelligence Clinical Evidence Database for Chinese Patent Medicine (AICED-CPM), with supplementary searches conducted in China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Science and Technology Journal Database (VIP), Chinese Biomedical Literature Database (SinoMed), Cochrane Library, PubMed, Embase, and Web of Science. The study characteristics and methodological quality of these RCTs were systematically analyzed and evaluated. Results: A total of 1 443 RCTs of Chinese patent medicines were included, comprising 1 399 Chinese articles and 44 English articles. Additionally, 334 RCTs of classic traditional Chinese medicine prescriptions were found, with 331 published in Chinese and 3 in English. 196 567 participants were included, covering 585 types of Chinese patent medicines (487 oral, 61 injectable, and 37 topical) and 179 classic traditional Chinese medicine prescriptions. The involved studies encompassed 22 types of diseases, with research primarily focusing on diseases of the circulatory system, the respiratory system, and the genitourinary system. The sample sizes ranged from 18 to 3 777 participants, and most studies were conducted at a single center. Methodologically, the implementation of allocation concealment and blinding remained insufficiently emphasized. Conclusion Overall, compared with 2022, both the number of RCT publications and their methodological quality have improved in 2023, with heightened attention to research on diseases of the genitourinary system. However, quality control and standardized management in the design and implementation processes still require enhancement to produce more high-quality clinical evidence and accelerate the translation and application of this evidence.

Autism Spectrum Disorder (ASD) is marked by early-onset neurodevelopmental anomalies, yet the temporal dynamics of genetic contributions to these processes remain insufficiently understood. This study aimed to elucidate the role of the Shank3 gene, known to be associated with monogenic causes of autism, in early developmental processes to inform the timing and mechanisms for potential interventions for ASD. Utilizing the Shank3B knockout (KO) mouse model, we examined Shank3 expression and its impact on neuronal maturation through Golgi staining for dendritic morphology and electrophysiological recordings to measure synaptic function in the anterior cingulate cortex (ACC) across different postnatal stages. Our longitudinal analysis revealed that, while Shank3B KO mice displayed normal neuronal morphology at one week postnatal, significant impairments in dendritic growth and synaptic activity emerged by two to three weeks. These findings highlight the critical developmental window during which Shank3 is essential for neuronal and synaptic maturation in the ACC.
Animals ; Nerve Tissue Proteins/metabolism* ; Mice, Knockout ; Dendrites/metabolism* ; Mice ; Synapses/metabolism* ; Gyrus Cinguli/metabolism* ; Male ; Mice, Inbred C57BL ; Autism Spectrum Disorder/genetics* ; Microfilament Proteins

OBJECTIVE: To summarize research progress on enhanced recovery after posterior cruciate ligament (PCL) reconstruction, clarify the core contradictions, effective intervention methods, and evaluation shortcomings in current clinical practice, and provide theoretical support for optimizing clinical rehabilitation strategies. METHODS: Relevant domestic and international literature in recent years was systematically searched. The key technologies and challenges for enhanced recovery after PCL reconstruction were analyzed from three aspects: the core issues of enhanced recovery after PCL reconstruction, treatment strategies, and the post-reconstruction effectiveness evaluation system. RESULTS: Enhanced recovery after PCL reconstruction mainly faces two core problems. First, there is a balance dilemma between graft tendon protection and knee joint function recovery: the tensile capacity of the graft tendon is weak in the early postoperative period, so excessive weight-bearing easily leads to relaxation, while overly conservative immobilization causes muscle atrophy and joint adhesion. Second, the return-to-sport rate is significantly affected by injury type and treatment method: patients with combined multiple ligament or meniscus injuries have a much lower return-to-sport rate than those with isolated PCL injury, and the risk of return-to-sport failure is higher. Current research mainly promotes rehabilitation from two aspects: physical therapy and surgical technology. Physical therapy runs through the perioperative period: preoperatively, muscle strength training, swelling control, and maintenance of joint range of motion are used to optimize surgical conditions; postoperatively, phased intervention is implemented. Surgical technology focuses on minimally invasive and anatomical approaches: arthroscopic surgery reduces injury, double-bundle reconstruction and internal tension-relief technology improve stability, and modified tunnel positioning and special surgical methods avoid the risk of "Killer Turn". Postoperative functional evaluation adopts multi-dimensional indicators: subjective evaluation relies on scales such as Lysholm and International Knee Documentation Committee (IKDC); objective evaluation assesses stability through Telos stress test and posterior drawer test; imaging evaluation takes MRI as the core; psychological evaluation is assisted by the Tampa scale of kinesiophobia-11 (TSK-11). However, there are obvious shortcomings, such as the lack of PCL-specific evaluation tools. CONCLUSION Enhanced recovery after PCL reconstruction requires the integration of precise surgery, individualized rehabilitation, and comprehensive subjective and objective evaluation. In the future, biomaterials and digital technologies should be integrated to optimize the full-cycle management of PCL reconstruction, thereby improving functional recovery and the effect of return to sports.
Humans ; Posterior Cruciate Ligament Reconstruction/rehabilitation* ; Posterior Cruciate Ligament/injuries* ; Recovery of Function ; Knee Joint/physiopathology* ; Knee Injuries/rehabilitation* ; Return to Sport ; Enhanced Recovery After Surgery ; Tendons/transplantation* ; Arthroscopy

Objective To investigate the effect of lung lobe surface projection localization combined with lung segment drainage sputum technique on airway clearance in patients with aspiration pneumonia,providing a reference for clinical nursing practice.Methods A convenience sampling method was used to select 62 patients with perioperative aspiration pneumonia secondary to brain diseases admitted to a tertiary A hospital in Beijing from May 2022 to October 2024 as the research subjects.A total of 31 patients admitted from August 2023 to October 2024 were assigned to a control group,and 31 patients admitted from May 2022 to July 2023 were assigned to an experimental group.The experimental group received lung lobe surface projection positioning combined with lung segment drainage sputum technique on top of conventional back percussion sputum clearance technique,while the control group received conventional back percussion sputum clearance technique.After the intervention,the differences in oxygenation state,inflammatory test indicators,treatment efficiency,vital signs and frequency of suction coughing between 2 groups were compared.Results After the intervention,the experimental group showed better oxygenation index,frequency of suction coughing,white blood cell count,percentage of neutrophils,procalcitonin levels,interleukin-6 levels,and treatment efficiency compared to those in the control group(P＜0.05).There was no statistically significant difference in heart rate,respiratory rate,and C-reactive protein levels between 2 groups(P＞0.05).Conclusion Lung lobe surface projection positioning combined can effectively promote the patients with aspiration pneumonia of loosening of sputum in the lungs,improve airway clearance efficiency,enhance the patient's pulmonary ventilation and gas exchange capacity,improve oxygenation levels,and reduce systemic inflammatory levels.