Low albumin combined with low-molecular-weight heparin as risk factors for liver injury using azvudine: Evidence from an analysis of COVID-19 patients in a national prospective pharmacovigilance database.

OBJECTIVE: Azvudine is an effective treatment for patients infected with common COVID-19. However, physicians have reported a series of adverse reactions, including multiple cases of liver injury, caused by azvudine in clinical practice. This study assessed the incidence, clinical features, and associated risk factors of liver injury induced by azvudine in real-world settings, offering guidance for safe clinical use. MATERIALS AND METHODS: This study utilized the Chinese Hospital Pharmacovigilance System (CHPS) to retrospectively analyze the treatment of COVID-19 patients with azvudine at Changsha Central Hospital from December 19, 2022, to June 6, 2023. A case-control study was conducted to analyze the occurrence of azvudine-induced liver injury in COVID-19 patients who triggered a CHPS alert compared to normal COVID-19 patients. RESULTS: Among the total of 2,141 COVID-19 patients, 31 (1.45%) developed azvudine-induced liver injury, which is classified as an occasional adverse reaction. Liver injury was observed in 93.55% of patients between days 4 and 12 of the azvudine treatment, with elevated transaminases as the primary clinical manifestation. Univariate and binary logistic regression analyses indicated that low albumin levels and co-administration of low-molecular-weight heparin were statistically significant risk factors (p < 0.05). CONCLUSION: This study represents the first investigation of azvudine-induced liver injury and high-risk patients using the CHPS. The findings provide valuable insights to promote the safety of anti-COVID-19 drugs, serving as an important reference for future drug safety measures.

[Association of EGFR gene G719S and T790M mutations with cervical cancer].

OBJECTIVE: To establish a rapid and accurate "on/off" switch technique consisted of 3'-phosphorothioate-modified allele-specific primers and exo+ polymerase to screen the G719S and T790M mutations of epidermal growth factor receptor (EGFR) gene. The switch was used to identify cervical cancer patients who are sensitive to tyrosine kinase inhibitor (TKI). METHODS: Allele-specific primers targeting recombinant wild-type and mutation-type templates were designed with 3' terminal phosphorothioate modification. Two-directional primer extension was carried out using Pfu polymerase. The G719S and T790M mutations were detected by the technique among cervical cancer tissues. The results were verified by Sanger sequencing. RESULTS: No mutation was detected among the 80 cervical cancer cases, and the results were consistent with that of Sanger sequencing. No significant difference was found between the frequencies of the G719S and T790M mutations between the patient and the control groups (P> 0.05). CONCLUSION: A sensitive "on/off" switch technique for detecting the two EGFR mutations was established. The G719S and T790M mutations are not associated with cervical cancer.

Mechanism of NF-κB signaling pathway and autophagy in the regulation of osteoblast differentiation.

OBJECTIVE: The objective of the present work was to investigate a possible mechanism of NF-κB signaling pathway and autophagy in the regulation of osteoblast differentiation, and provide experimental basis for the study of tooth eruption disorder. METHODS: Mouse osteoblast-like (MC3T3-E1) cells were inoculated with a cell density of 70%. According to the grouping experimental design, Western blot and monodansylcadaverine (MDC) detection were conducted after dosing for 24 h. The cells were divided into the following five groups: blank control group; 6.25 µg/mL SN50 group; 12.5 µg/mL SN50 group; 25 µg/mL SN50 group and 50 µg/mL SN50 group. RESULTS: Western blot analysis revealed that the expression of LC3 protein was present in the blank control group; 6.25 µg/mL SN50 group; 12.5 µg/mL SN50 group and 50 µg/mL SN50 group, with no significant differences among these groups. However, the expression of LC3 protein was significantly lower in the 25 µg/mL SN50 group. MDC detection showed that, in the blank control group; 6.25 µg/mL SN50 group; 12.5 µg/mL SN50 group and 50 µg/mL SN50 group, there was obvious green fluorescence in the cytoplasm of the osteoblasts. However, in the 25 µg/mL SN50 group, it was found that there were significantly fewer green fluorescent particles. CONCLUSION: The osteoblast itself had a strong function of autophagy. The appropriate concentration of SN50 in blocking the NF-κB pathway of the osteoblast was associated with the obvious inhibition of autophagy. However, the relationship between NF-κB signaling pathway and autophagy in the process of tooth eruption requires further study.

Effects of periodontal therapy on serum lipid profile and proinflammatory cytokines in patients with hyperlipidemia: a randomized controlled trial.

OBJECTIVE: The aim of this study was to evaluate whether periodontal treatment in patients with periodontitis and hyperlipidemia may have any influence on plasma lipids and pro-inflammatory cytokine levels. MATERIAL AND METHODS: We randomly assigned 109 patients with hyperlipidemia and chronic periodontitis into group 1 (n = 55) and group 2 (n = 54). Patients in group 1 underwent a standard cycle of supragingival mechanical scaling and polishing. Patients in group 2 underwent the adjunctive full-mouth intensive removal of subgingival dental plaque biofilms with the use of scaling and root planning. Periodontal parameters, total cholesterol (TC), triglyceride (TRG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-alpha (TNF-α), interleukin(IL)-1ß(IL-1ß), and IL-6 were evaluated before treatment and 2 and 6 months after treatment. RESULTS: Two and 6 months after treatment, TRG levels were significantly lower in group 2 than in group 1 (P < 0.05), and the levels of HDL-C were significantly higher (P < 0.05). Two and 6 months after therapy, the levels of TNF-α were significantly lower in group 2 than in group 1 (P < 0.05), as were the levels of IL-1ß (P < 0.001) and IL-6 (P < 0.001). CONCLUSIONS: Intensive periodontal treatment of participants with hyperlipidemia and chronic periodontitis improved serum lipid levels and decreased circulating pro-inflammatory cytokine levels. CLINICAL RELEVANCE: This study showed that intensive treatment of periodontitis results in an improvement in serum lipid levels and a decrease in serum proinflammatory cytokine levels in patients with periodontitis and hyperlipidemia. These findings may contribute to present knowledge that periodontal therapy may be beneficial for individuals with hyperlipidemia.

[Valacyclovir as an adjunct to full-mouth scaling and root planing of advanced chronic periodontitis:a randomized clinical trail].

PURPOSE: The aim of this study was to evaluate the clinical benefit of valacyclovir when performing full-mouth periodontal debridement in patients with advanced chronic periodontitis. METHODS: Fifty-nine patients with advanced chronic periodontitis were randomly assigned into control-treatment group(n=29) and intensive-treatment group(n=30). All patients were given instructions of basic oral hygiene and a standard cycle of supragingival mechanical scaling and polishing. Patients in the intensive-treatment group received oral valacyclovir for 1 week, while patients in the control-treatment group received placebo. Thereafter, patients in both groups underwent full-mouth intensive removal of subgingival dental plaque biofilms with the use of scaling and root planing within 48 hours. Periodontal parameters were evaluated before treatment and 2 or 6 months after treatment. The data was statistically analyzed using SPSS17.0 software package. RESULTS: No significant difference in clinical parameters was noted before treatment. 2 and 6 months after treatment, the mean percentage reduction of sites with BOP and PD≥4 mm were significantly higher in the intensive-treatment group than in the control-treatment group (P<0.05). Similarly, patients in the intensive-treatment group had higher mean PD reduction than those in the control-treatment group 2 months (P<0.05) and 6 months after therapy (P<0.05). However, the mean values of CAL reduction were slightly and not significantly higher in the intensive-treatment group than in the control-treatment group after therapy. CONCLUSIONS: It may be concluded that valacyclovir significantly improves clinical results of full-mouth non-surgical periodontal debridement in advanced chronic periodontitis.

[Fingertip replantation with anastomosis of palm vein and retaining the nail].

OBJECTIVE: To study the replantation methods and clinical results of amputated fingertip. METHODS: From October 2007 to June 2011, 18 fingers of 13 cases were replanted with anastomosis of palm vein and retaining the nail, including 9 males and 4 females,with an average age of 26 years old ranging from 17 to 45 years old. The time from injury to therapy was from 30 min to 5 h, time of broken finger ischemia was from 1.5 to 7 h. All broken fingers were preservation under normal temperature. RESULTS: All fingers were survived, no vascular crisis happened. All cases were followed up from 3 to 24 months with an average of 14 months. The length and shape of replanted fingers were similar to that of the healthy side. The new nails were smooth, the function was perfect,the sense of pain and touched sensation had been recovered. Their two-piont discriminations ranged from 3 to 6 mm with an average of 5 mm. According to the assessment standard of Chinese Medical Association of Hand Surgery, the results were excellent in 14 cases, good in 3 cases, poor in 1 case. CONCLUSION: Fingertip replantation with anastomosis of palm vein and retaining the nail is regained satisfactory appearance and function of the digits with a high survival rate.

Could MTA be a novel medicine on the recurrence therapy for GCTB?

Giant cell tumor of bone (GCTB) is a benign locally aggressive bone tumor with a shown clinical behavior of local recurrences and rare distant metastases. Surgical treatment of GCTB is associated with high morbidity, and local recurrence. Due to the high rate of pulmonary metastases recurrent GCTB may be considered as a severe disease. If the tumor reaches close to the articulating surface a subchondral bone graft can be performed without risking a higher recurrence rate. Mineral trioxide aggregate (MTA) has been widely used to repair various kinds of tooth perforations. MTA is a powder aggregate containing mineral oxides with a good biological action and may facilitate the regeneration of the periodontal ligament and formation of bone. MTA used was able to induce bone regeneration and had its action optimized. Study has showed that, in the presence of MTA, cells grow faster and produce more mineralized matrix gene expression in osteoblasts. We hypothesize that MTA may has anti-recurrence properties. For the clinical point of view, we can apply MTA in the GCTB to induce bone production, then to inhibit the recurrent of the cases. MTA may be the therapy of choice for primary as well as recurrent giant cell tumors of bone.

Inhibition of Behcet's disease by calcitonin.

Behcet's disease (BD) is a chronic, multisystem inflammatory disorder characterized by relapsing oral aphthous and genital ulcers, ocular inflammation, erythemanodosum and folliculitis-like lesions of the skin, arthritis, and central nervous system involvement. Its pathogenesis has not been fully elucidated but the etiology is accepted to be multifactorial, therefore the treatment of Behcet's disease continues to be a major therapeutic challenge. The identification of novel therapeutic agents for the treatment of these disorders is important. Calcitonin (CT), a peptide hormone secreted in response to hypercalcemia, has the dual effect of inhibiting osteoclast recruitment as well as their resorptive activity. A number of reviews have concluded that salmon calcitonin is safe and effective in the treatment of osteoporosis. Calcitonin abrogated the stimulating effect of RANKL or prednisolone; similar results were obtained with OPG. Additionally, the analgesic activity of salmon calcitonin has been shown in several controlled prospective double-blind studies to improve pain. Exogenous calcitonin is thought to cross the blood-brain barrier and to accumulate slowly in the brain, inducing analgesia once sufficient receptors are occupied. Since CT could antagonize resorptive and analgesic activity by competitively binding to CTR and has been considered as a specific antagonist, we postulate that the CT could function as a novel agent to inhibit BD. In our opinion, if the hypothesis proved to be practical, CT could be widely used in clinical settings to treat BD.