Knee osteoarthritis (KOA) is a prevalent degenerative joint disease characterized by synovial inflammation, cartilage loss. Often manifesting as joint pain and limited mobility, it severely affects the quality of life of patients. Traditional treatment methods such as pharmacological injections and surgical interventions primarily aim to alleviate symptoms but have limited effects on cartilage repair. Human umbilical cord mesenchymal stem cells (hUC-MSCs), due to their anti-inflammatory and chondrogenic capabilities, is considered a new hope for the treatment of KOA. This article synthesizes the latest research findings from both domestic and international sources to discuss the theoretical basis for the clinical application of hUC-MSCs in treating KOA, clinical study design, and efficacy evaluation. It also addresses the challenges in the clinical application of hUC-MSCs and explores future directions, in the hope of providing feasible theoretical support for the treatment of KOA with hUC-MSCs.

Tangye Jingfa Tu is an important content in the ancient book Fuxingjue from Dunhuang， implying the fundamental principles of formula compatibility in traditional Chinese medicine （TCM）. Our research group has delved into nearly 200 formulas （both classical and contemporary formulas） recorded in the Fangjixue under the theoretical framework of the deficiency or excess syndrome of five Zang-organs together with the reinforcing and reducing effects of Chinese medicinal materials of five flavors. We have initially elucidated the essential principles of the correspondence between formulas and syndromes， revealing the deep-level logic of medicinal material selection and compatibility， thus enriching the understanding about the core characteristics and essence of the diseases and syndromes targeted by formulas. The lunar year of 2024 is Jia Chen year. The formula recorded in Sanyin Jiyi Bingzheng Fanglun for treating the epidemic diseases characterized by excessive earth， prevalent dampness and wetness， and invasion of pathogenic factors into the kidney water in Jia Chen year is Fuzi Shanzhuyutang. Therefore， elucidating the compatibility principle of Fuzi Shanzhuyutang is of great significance for clinical prescription and medication modification in Jia Chen year. According to the Tangye Jingfa Tu theory on the deficiency or excess of syndrome of five Zang-organs and the reinforcing and reducing effects of Chinese medicinal materials of five flavors， this article dissects Fuzi Shanzhuyutang regarding the etiology and pathogenesis of the main indications， as well as the five-element properties and efficacy characteristics of Chinese medicinal materials constituting this formula. It explains the compatibility principles of Fuzi Shanzhuyutang and puts forward suggestions for modifying the formula to address different indications， providing a reference for guiding clinical syndrome differentiation and treatment.

Tangye Jingfa Tu is an important content in the ancient book Fuxingjue from Dunhuang， implying the fundamental principles of formula compatibility in traditional Chinese medicine （TCM）. Our research group has delved into nearly 200 formulas （both classical and contemporary formulas） recorded in the Fangjixue under the theoretical framework of the deficiency or excess syndrome of five Zang-organs together with the reinforcing and reducing effects of Chinese medicinal materials of five flavors. We have initially elucidated the essential principles of the correspondence between formulas and syndromes， revealing the deep-level logic of medicinal material selection and compatibility， thus enriching the understanding about the core characteristics and essence of the diseases and syndromes targeted by formulas. The lunar year of 2024 is Jia Chen year. The formula recorded in Sanyin Jiyi Bingzheng Fanglun for treating the epidemic diseases characterized by excessive earth， prevalent dampness and wetness， and invasion of pathogenic factors into the kidney water in Jia Chen year is Fuzi Shanzhuyutang. Therefore， elucidating the compatibility principle of Fuzi Shanzhuyutang is of great significance for clinical prescription and medication modification in Jia Chen year. According to the Tangye Jingfa Tu theory on the deficiency or excess of syndrome of five Zang-organs and the reinforcing and reducing effects of Chinese medicinal materials of five flavors， this article dissects Fuzi Shanzhuyutang regarding the etiology and pathogenesis of the main indications， as well as the five-element properties and efficacy characteristics of Chinese medicinal materials constituting this formula. It explains the compatibility principles of Fuzi Shanzhuyutang and puts forward suggestions for modifying the formula to address different indications， providing a reference for guiding clinical syndrome differentiation and treatment.

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

Objective:To investigate the effects of the Epley and Semont procedures with varying lateral angles of the head on posterior semicircular canal benign paroxysmal positional vertigo （PC-BPPV）. Methods:A total of 115 patients with unilateral PC-BPPV were randomly divided into five groups: Epley group, Semont group, Semont+10° group, Semont+20° group, and Semont+30° group, with 23 patients in each group. Corresponding reduction treatments were performed. Results:The total effective rates for the Epley group, Semont group, Semont+10° group, Semont+20° group, and Semont+30° group were 95.7% （22/23）, 4.3% （1/23）, 30.4% （7/23）, 52.2% （12/23）, and 87.0% （20/23） respectively. The inefficiencies were 4.3% （1/23）, 95.7% （22/23）, 69.6% （16/23）, 47.8% （11/23）, and 13.0% （3/23）. Statistically significant differences were observed in the total effective rates among the five groups （χ²=54.11, P<0.01）. The total effective rates in the Semont group, Semont+10° group, and Semont+20° group were significantly different from that of the Epley group （P<0.01）, while no statistically significant difference was found between the Semont+30° group and the Epley group （P= 0.608>0.012 5）. Conclusion:Among the four Semont methods with different lateral lying angles, the total effective rate of reduction treatment increased with the elevation of the lateral lying angle on the affected side. The efficacy of the Semont+30° group in treating PC-BPPV was not significantly different from the Epley group's reduction effect, which was markedly superior to that of the other four Semont methods at different angles. Therefore, the Semont+30° reduction technique is recommended for the treatment of PC-BPPV.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Benign Paroxysmal Positional Vertigo/therapy* ; Head ; Posture ; Semicircular Canals/physiopathology* ; Treatment Outcome

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

Ovarian tumor (OT) is the most lethal form of gynecologic malignancy, with minimal improvements in patient outcomes over the past several decades. Metastasis is the leading cause of ovarian cancer-related deaths, yet the underlying mechanisms remain poorly understood. Psychological stress is known to activate the glucocorticoid receptor (NR3C1), a factor associated with poor prognosis in OT patients. However, the precise mechanisms linking NR3C1 signaling and metastasis have yet to be fully elucidated. In this study, we demonstrate that chronic restraint stress accelerates epithelial-mesenchymal transition (EMT) and metastasis in OT through an NR3C1-dependent mechanism involving nuclear protein 1 (NUPR1). Mechanistically, NR3C1 directly regulates the transcription of NUPR1, which in turn increases the expression of snail family transcriptional repressor 2 (SNAI2), a key driver of EMT. Clinically, elevated NR3C1 positively correlates with NUPR1 expression in OT patients, and both are positively associated with poorer prognosis. Overall, our study identified the NR3C1/NUPR1 axis as a critical regulatory pathway in psychological stress-induced OT metastasis, suggesting a potential therapeutic target for intervention in OT metastasis.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*