ObjectiveTo clarify the associations between plasma fibrinogen （Fbg） and volumetric bone mineral density （vBMD） as well as osteoporosis measured by quantitative computed tomography （QCT）， and to explore the role of plasma Fbg in early screening and diagnosis of osteoporosis. MethodsPatients with hypertension who were hospitalized in the Department of Endocrinology of Sun Yat-sen Memorial Hospital of Sun Yat-sen University from January 2018 to June 2022 and underwent QCT examinations were included for cross-sectional analysis. The study analyzed the correlation between plasma Fbg and osteoporosis in patients. The diagnostic efficacy of plasma Fbg for osteoporosis was evaluated by the area under the receiver operating characteristic （ROC） curve （AUC）. ResultsTotally 441 subjects were included in the analysis， with an average age of 46.0±14.5 years and a prevalence of osteoporosis of 6.4% （28/441）. As the level of plasma fibrinogen increased， the incidence of osteoporosis significantly increased （P<0.000 1）while the average bone mineral density of L1 and L2 were significantly decreased （P<0.05）. Compared with the first quartile of plasma Fbg（1.99g/L -2.37g/L）， the risk of osteoporosis in the fourth quartile of plasma Fbg （3.67g/L-4.46g/L） increased by 8.85 times after adjusting for related confounding factors. ConclusionThis study found a negative correlation between plasma fibrinogen levels and bone density in patients with hypertension. Plasma fibrinogen levels may serve as a potential screening indicator for osteoporosis， aiding in early diagnosis and therapeutic monitoring. This discovery offers a new perspective for the study of bone metabolic diseases and warrants further investigation.

Prostate cancer is the second most common malignancy and the sixth leading cause of cancer-related death in men worldwide. Radical prostatectomy (RP) is the standard treatment for localized prostate cancer, but the procedure often results in postoperative erectile dysfunction (ED). The poor efficacy of phosphodiesterase 5 inhibitors after surgery highlights the need to develop new therapies to enhance cavernous nerve regeneration and improve the erectile function of these patients. In the present study, we aimed to examine the potential of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in preserving erectile function in cavernous nerve injury (CNI) mice. We found that HB-EGF expression was reduced significantly on the 1 st day after CNI in penile tissue. Ex vivo and in vitro studies showed that HB-EGF promotes major pelvic ganglion neurite sprouting and neuro-2a (N2a) cell migration. In vivo studies showed that exogenous HB-EGF treatment significantly restored the erectile function of CNI mice to 86.9% of sham levels. Immunofluorescence staining showed that mural and neuronal cells were preserved by inducing cell proliferation and reducing apoptosis and reactive oxygen species production. Western blot analysis showed that HB-EGF upregulated protein kinase B and extracellular signal-regulated kinase activation and neurotrophic factor expression. Overall, HB-EGF is a major promising therapeutic agent for treating ED in postoperative RP.
Animals ; Male ; Heparin-binding EGF-like Growth Factor/therapeutic use* ; Erectile Dysfunction/etiology* ; Mice ; Penis/drug effects* ; Nerve Regeneration/drug effects* ; Penile Erection/drug effects* ; Peripheral Nerve Injuries/drug therapy* ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Cell Movement/drug effects* ; Prostatectomy/adverse effects* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism*

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Objective: To investigate the mechanism of electroacupuncture (EA) for treating depression and to explore the role of brevican in the medial prefrontal cortex (mPFC) in modulating stress susceptibility and the antidepressant effects of EA in rats. Methods: Twenty-four Sprague–Dawley (SD) rats were equally divided into three groups: green fluorescent protein (GFP) + control, GFP + chronic unpredicted mild stress (CUMS), and short-hairpin RNA targeting on brevican (shBcan) + CUMS. Another 24 SD rats were equally divided into CUMS + GFP, CUMS + GFP + EA, and CUMS + shBcan + EA groups. Behavioral tests were conducted to assess depression-like behavior. Western blot analysis was used to evaluate the expression of brevican, aggrecan, GLuA1, and PSD95 in mPFC subregions. Results: Behavioral parameter evaluation show that rats in the shBcan + CUMS group exhibited a significantly reduced sucrose preference (P = .0002) and increased immobility time (P = .0011) compared to those in rats in the GFP + CUMS group. Western blotting showed that brevican expression was significantly downregulated in the PrL of the shBcan + CUMS group compared with that in the GFP + CUMS group (P = .0192). Furthermore, compared to the CUMS + GFP + EA group, the CUMS + shBcan + EA group exhibited a significantly decreased sucrose preference (P = .0334), increased immobility time (P = .0465), and increased latency to food (P = .0261). In the CUMS + shBcan + EA group, the EA-induced brevican and PSD95 overexpression was reversed, compared with that in the CUMS + GFP + EA group (P = .0454 and P = .0198, respectively). Conclusion EA exerts its antidepressant effects through the modulation of brevican expression in rats. Our findings highlight the important role for brevican in stress susceptibility, which could be a potential target for treating depression.

Acute suppurative thyroiditis(AST) is a rare thyroid disease, mostly caused by infections such as Staphylococcus aureus, and it is difficult to distinguish from subacute thyroiditis(SAT) at the beginning of the disease. Here we report the clinical data of a young male patient who was initially misdiagnosed as SAT, but was clinically diagnosed as AST with DNSIs accompanied by LS. The clinical features and treatment, combined with related literature, aim to enhance clinicians' understanding of this disease.

[Objective]To understand"theory of sweat pore(Xuanfu)"and its relationship with dysuria,as well as explore Professor SUN Jie's clinical experience in using"theory of sweat pore"to treat dysuria.[Methods]Through the research method of grounded theory,this paper analyzed and constructed a theoretical model that used"theory of sweat pore"to differentiate and treat the dysuria.The clinical documents of 135 cases of"dysuria"came from Professor SUN Jie's clinical diagnosis and treatment database.Besides,according to the qualitative research method by grounded theory,it concluded the core and built the theoretical framework by the three-level coding analysis.[Results]This study concluded that Professor SUN Jie summarized his experience to conclude the core category of"paying attention to the deficiency and excess of sweat pore,regulating and promoting Qi and body fluid".Two categories of"treatment based on syndrome differentiation with theory of sweat pore"and"treatment based on the principle"of dredging and assisting sweat pore were extracted.Based on this,Professor SUN Jie's experience in distinguishing and treating dysuria was derived,which focused on syndrome differentiation and treatment with sweat pore and on distinguishing the deficiency and stagnation of sweat pore and the nature of evil stagnation,and establishing treatment principle of dredging and assisting sweat pore,dispelling evil and supplementing deficiency as the treatment method.When using herbs,he used the prescriptions represented by Cassia Twig and Poria Cocos as the core,and combined alleviating water to dredge and assist sweat pore,warming and dredging to assist sweat pore,particularly good at using herbs of activating Yang.[Conclusion]Based on the research and summary of"theory of sweat pore",this paper summarized Professor SUN Jie's experience in using"theory of sweat pore"to treat dysuria,and constructed a theoretical model for Professor SUN Jie's use of"theory of sweat pore"in the treatment of dysuria.

Objective:To investigate the necessity of internal fixation of the fibular fracture in the treatment of degree Ⅱ ankle supination-external rotation injury by the Dias-Tachdjian classification in children.Methods:A retrospective study was conducted to analyze the data of 69 children with ankle fracture (degree Ⅱ ankle supination-external rotation injury by the Dias-Tachdjian classification) who had been treated at Department of Orthopedic Trauma, The People's Hospital of Weifang and Department of Pediatric Orthopedics, Tianjin Hospital from January 2015 to October 2021. There were 41 males and 28 females with an age of (10.1±1.4) years, and 37 left and 32 right sides affected. The patients were divided into 2 groups according to whether internal fixation of the fibular fracture was performed. Group A consisted of 21 cases with fibular internal fixation and group B of 48 cases without fibular internal fixation. The preoperative data, operation time and operation expenses were recorded and compared between the 2 groups. At the last follow-up, the anteroposterior and lateral radiographs of bilateral full length lower limbs and ankle joints were taken; the lateral distal tibial angle (LDTA) and the anterior distal tibial angle (ADTA) on the affected side, and the disparity between bilateral ankle tibiotalar angles were measured; ankle function was assessed according to the ankle-hindfoot score of American Association of Foot and Ankle Surgery (AOFAS); the occurrence of premature physeal closure (PPC) was recorded.Results:There was no significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for (19.5±4.1) months. At the last follow-up, the LDTA on the affected side was 89.6° (87.9°, 90.5°) in group A and 88.6°±1.9° in group B; the ADTA on the affected side was 80.9° (79.0°, 81.4°) in group A and 80.0° (78.6°, 81.2°) in group B; the disparity between bilateral ankle tibiotalar angles was 1.1°±0.5° in group A and 1.2°±0.5° in group B; the AOFAS ankle-hindfoot score was (89.5±5.2) points in group A and 89.0 (87.0, 92.0) points in group B. There was no statistically significant difference between the 2 groups in the above items ( P>0.05). The incidence of PPC was, respectively, 14.3% (3/21) and 14.6% (7/48) in groups A and B, showing no statistically significant difference ( P>0.05). Conclusions:In the treatment of degree Ⅱ ankle supination-external rotation injury in children, internal fixation of the fibular fracture has no significant effect on the imaging angles or the function of the ankle joint. After anatomic reduction of the distal tibia, the fibular fracture can be treated without internal fixation to reduce operational trauma, shorten operation time and reduce operation expenses.

Objective:To investigate the impact of small extracellular vesicles(sEVs) derived from perirenal adipose cells on the biological behavior of renal tubular epithelial cells under diabetic conditions and the underlying molecular mechanisms.Methods:Primary perirenal adipose cells were extracted from db/m and db/db mice for in vitro culture. The culture supernatant was collected and sEVs(NDM-sEVs PRAT-Adipo, DM-sEVs PRAT-Adipo) were extracted by ultracentrifugation. The sEVs were incubated with human renal tubular epithelial cell line(HK-2) to observe changes in their proliferation, apoptosis, autophagy, and epithelial-mesenchymal transition(EMT) levels. The protein composition of sEVs was analyzed using mass spectrometry to explore the molecular mechanisms. Results:CCK8 results showed that the proliferation level of HK-2 cells after DM-sEVs PRAT-Adipo intervention did not change significantly compared with the two control groups(Ctrl group and NDM-sEVs PRAT-Adipo intervention group). Western Blot(WB) results indicated that there were no significant changes in apoptosis levels(Bcl-2, Cleaved-caspase 3, Caspase 3) and autophagy levels(p62, LC3BⅠ, LC3BⅡ) in the DM-sEVs PRAT-Adipo intervention group compared with the two control groups. WB and immunofluorescence results demonstrated that DM-sEVs PRAT-Adipo intervention upregulated the expression levels of mesenchymal cell marker proteins(Vimentin, α-SMA, Snail2) and downregulated the expression level of epithelial cell marker protein ZO-1 in HK-2 cells compared with the two control groups. Mass spectrometry analysis of sEVs revealed that the differential proteins between DM-sEVs PRAT-Adipo and NDM-sEVs PRAT-Adipo were enriched in EMT-related pathways. Among them, the enrichment of thrombospondin(THBS1) in DM-sEVs PRAT-Adipo might be involved in the regulation of EMT in HK-2 cells. Conclusion:Under diabetic conditions, sEVs secreted by PRAT-derived adipocytes promote the upregulation of EMT in renal tubular epithelial cells, a process that may be mediated by the enrichment of THBS1 in sEVs.

Objective To investigate the current status of off-label drug use(OLDU)management in tertiary hospitals of Guizhou province and to provide baseline evidence for developing a unified administration regulation for OLDU in Guizhou province.Methods In line with the relevant policies and regulations,a questionnaire including basic information about the person filling out the form,basic information about the hospitals,and information about OLDU was developed.The questionnaire was sent to 84 tertiary hospitals in Guizhou province through the Wenjuanxing.Results A total of 84 questionnaires were distributed and recovered,with a response rate of 100.00%.Of the 84 hospitals,77 had OLDU,of which 68(88.31%)had established a management system for OLDU.Among the 77 hospitals with OLDU,65(84.42%),42(54.55%),58(75.32%),36(46.75%),15(19.48%),and 21(27.27%)hospitals respectively,required approval from the Committee on Drug Administration and Pharmacotherapy before OLDU,restricted the qualifications of doctors prescribing OLDU,required informed consent from patients or their families before OLDU,recorded the matters and reasons in the medical records of patients treated with OLDU,followed up patients in their files and evaluated the reasonableness of the OLDU,and carried out special reviews for OLDU.Only 30(38.96%)hospitals have set up a catalogue of OLDUs,and 58(75.32%)hospitals have urgent needs to set up a unified provincial catalogue of OLDUs.Conclusion The pharmacy administration level of OLDU in tertiary hospitals of Guizhou province is relatively low,so there is an urgent need to establish a unified OLDU management system and medication catalog.

During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.