A 19-year-old female with a 2-day history of involuntary fast jerk-like movements of the left upper and lower extremities presented at the emergency department. Patient had no other known comorbidities and family history was unremarkable. Anti-streptolysin O titer (ASO) and C-reactive protein (CRP) were all normal. Two-dimensional echocardiography (2D Echo) revealed thickened anterior mitral valve leaflet with prolapsed A2 scallop, mild mitral regurgitation, thickened right coronary cusp of aortic valve without restriction of motion, trivial aortic regurgitation, other findings were unremarkable. Patient was managed as a case of Sydenham’s chorea secondary to acute rheumatic fever, with valvular heart disease secondary. Patient was initially started on valproic acid 500mg tablet every 8 hours, benzathine penicillin 1.2M units intramuscular, and carvedilol 12.5mg/tablet twice a day. The patient was then shifted to haloperidol 5mg ¼ tablet twice a day, diphenhydramine 50mg intravenously coinciding with haloperidol doses due to visual side effects of valproic acid. This report highlights the importance of a high index of suspicion and complete history and physical examination in order to diagnose and manage movement disorders in a low-income setting.

OBJECTIVE: To explore the role of antibiotic-eluting absorbable calcium sulfate in treating periprosthetic infection after one-stage revision of knee arthroplasty. METHODS: A retrospective analysis was performed on 36 patients(36 knees)who underwent phaseⅠrevision for periprosthesis infection after total knee arthroplasty from January 2018 to March 2022. All patients were underwent knee cavity puncture before operation and had positive results of aseptic body fluid culture, 21 patients received revision combined with antibiotic loaded calcium sulfate at stageⅠ(calcium sulfate group) during operation, and 15 patients underwent renovation at stageⅠ(revision group). There were 9 males and 12 females in calcium sulfate group, aged from 54 to 76 years old with an average of(67.6±6.2) years old. There were 15 patients in revision group, including 4 males and 11 females, aged from 60 to 75 years old with average of (69.6±4.1) years old. The levels of serum C-reactive protein (CRP), interleukin-6 (IL-6) at 7, 14, 30 and 90 days after operation were compared between two groups, and the rate of end-infection control at follow-up were compared. The systemic antibiotic application time, hospital stay and postoperative complications were observed between two groups. RESULTS: Calcium sulfate group were followed up for 12 to 29 months with an average of(18.9±4.2) months, and the infection control rate was 90.5%;while revision group were followed up 18 to 29 months with average of (21.6±3.7) months, and the infection control rate was 86.7% (13/15). There were no significant differences in follow-up time and infection control rate between two groups(P>0.05). Postoperative levels of CRP and IL-6 at 7, 14 and 30 days in calcium sulfate group were (32.79±11.48), (15.50±6.52), (9.36±3.32) mg·L^-1 and (17.31±6.15) pg·ml^-1, respectively;which were lower than those in revision group (40.65±11.32), (30.15±10.57), (18.97±5.86) mg·L^-1 and (25.54±6.73) pg·ml^-1, had statistical differences(P<0.05). There were no significant differences in IL-6 levels at 7 and 14 days after operation and CRP levels at 90 days after operation between two groups (P>0.05). The hospitalization time and systemic antibiotic application time in calcium sulfate group were (18.4±2.2) and (63.5±21.4) d, respectively;which were better than those in revision group (20.5±2.4) and (82.7±16.9) d, and had statistical differences(P<0.05). No significant wound complications and hypercalcemia were observed in calcium sulfate group. CONCLUSION Antibiotic eluted absorbable calcium sulfate could be used to treat periprosthetic knee infection, significantly reducing CRP levels in the early postoperative period, shortening hospital stay and systemic antibiotic application time, but it does not significantly improve the control rate of revision infection at stageⅠ.
Humans ; Male ; Female ; Aged ; Prosthesis-Related Infections/surgery* ; Middle Aged ; Calcium Sulfate/administration & dosage* ; Arthroplasty, Replacement, Knee/adverse effects* ; Retrospective Studies ; Anti-Bacterial Agents/therapeutic use* ; Interleukin-6/blood* ; C-Reactive Protein/metabolism* ; Reoperation ; Knee Prosthesis/adverse effects*

OBJECTIVE: To explore clinical characteristics, lesion sites and correlation differences of different types of diabetic foot gangrene, and to provide evidence-based basis for clinical classification of diabetic foot gangrene. METHODS: A retrospective analysis was conducted on 266 patients with newly diagnosed diabetic foot gangrene who were admitted from January 2018 to December 2018, including 183 males and 83 females, aged from 35 to 92 years old with an average of (69.55±10.84) years old, and they were divided into wet gangrene group and dry gangrene group according to the different natures of gangrene. There were 139 patients in wet gangrene group, including 98 males and 41 females, aged from 35 to 90 years old with an average of (68.95±10.93) years old. There were 127 patients in dry gangrene group, including 85 males and 42 females, aged from 38 to 92 years old with an average of (70.21±10.75) years old. Body mass index (BMI), waist-to-hip ratio (WHR), body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, and Wagner grade between two groups were recorded to evaluate symptoms and signs. The white blood cell count (WBC), neutrophil percentage (NEUT%), and C-reactive protein (C-reactive protein), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), and interleukin-6 (IL-6) in peripheral blood between two groups were detected and compared to evaluate the infection status;the severity of diabetic peripheral neuropathy (DPN) was evaluated by using Toronto Clinical Scoring System (TCSS);the degree of pain in patients with diabetic foot gangrene was evaluated by numerical rating scale (NRS); ankle-brachial index (ABI) and popliteal artery blood flow velocity were used to evaluate the degree of arterial lesions. Spearman correlation analysis was used to analyze the correlations between gangrene TCSS, ABI and age, BMI, WHR, body temperature, calf skin temperature difference, WBC, NEUT%, CRP, ESR, PCT, IL-6, NRS, and Wagner classification indicators. RESULTS: The body temperature, skin temperature difference between the affected and healthy sides of the lower extremities, Wagner grade, WBC, NEUT%, CRP, ESR, PCT, IL-6, TCSS score, ABI, and popliteal artery blood flow velocity in wet gangrene group were higher than those in dry gangrene group (P<0.01), and BMI, WHR, and NRS score in dry gangrene group were higher than those in wet gangrene group;the differences were all statistically significant (P<0.01). The results of Spearman correlation analysis showed TCSS score of gangrene patients was correlated with body temperature (r=0.214), calf skin temperature difference (r=0.364), WBC (r=0.240), NEUT% (r=0.291), CRP (r=0.347), ESR (r=0.167), PCT (r=0.241), IL-6 (r=0.316), and popliteal fossa arterial blood flow velocity (r=0.261) and Wagner grade (r=0.273) were positively correlated, and the differences were statistically significant (P<0.01). ABI was negatively correlated with age (r=-0.183), BMI (r=-0.252), WHR (r=-0.288), and NRS score (r=-0.354), and the differences were statistically significant (P<0.01). CONCLUSION Diabetic foot gangrene is an extremely difficult and critical disease. Wet gangrene has a significant synergic effect with infection and neuropathy, while dry gangrene is closely related to vascular occlusion. The main contradiction of gangrene could be revealed through blood vessels, nerves and infection, providing evidence-based basis for the selection of debridement timing, anti-infection strategies and revascularization, with the aim of reducing the risk of amputation.
Humans ; Male ; Female ; Aged ; Middle Aged ; Diabetic Foot/diagnosis* ; Aged, 80 and over ; Adult ; Retrospective Studies ; Gangrene/physiopathology* ; C-Reactive Protein

Objective To investigate the mechanism by which miR-148a affects M2 macrophage polarization and inhibits liver cancer cell proliferation through Wnt3a/β-catenin. Methods The mRNA expression levels of miR-148a, CD206 and interleukin-10 (IL-10) in tumor tissues and adjacent non-tumor liver tissues of 84 patients with liver cancer were detected by real-time quantitative PCR. THP-1 cells were separated into blank group (conventional culture), M2 group (200 nmol/L phorbol ester, 20 ng/mL IL-4, 20 ng/mL IL-13), M2 combined with negative control (miR-NC) group (transfected with miR-NC on the basis of M2 group), M2 combined with miR-148a mimics (transfected with miR-148a mimics on the basis of M2 group) group, M2 combined with miR-148a mimics combined with Wnt3a (treated with 100 μg/L Wnt3a on top of M2 combined with miR-148a mimics group) group. The proliferation of HuH7 cells was detected by CCK-8 and EdU methods. Apoptosis and M2 macrophage marker CD206 was detected by flow cytometry. The level of IL-10 in cell supernatant was detected by chemiluminescence method; The mRNA levels of miR-148a, CD206 and IL-10 were detected by real-time quantitative PCR. The protein levels of Wnt3a and β-catenin were detected by Western blot. Results The expressions of CD206, IL-10 mRNA, Wnt3a and β-catenin in tumor tissue were higher than those in non-tumor liver tissues, and the miR-148a level was decreased. The mRNA expression of M2 macrophage markers CD206 and IL-10 were significantly increased. Compared with the blank group, the OD450 value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were increased in M2 group, while the apoptotic rate and miR-148a level were decreased. Compared with M2 group and M2 combined with miR-NC group, the OD₄₅₀ value, EdU positive rate, the mRNA expressions of CD206 and IL-10, the level of IL-10 in the supernatant, and the expressions of Wnt3a and β-catenin were decreased in M2 combined with miR-148a mimics group, while the apoptotic rate and miR-148a level were increased. Wnt3a reversed the inhibitory effect of miR-148a overexpression on the proliferation of liver cancer cells. Conclusion Overexpression of miR-148a inhibits M2 polarization of macrophages and prevents the proliferation of liver cancer cells, which may be related to the inhibition of the Wnt3a/β-catenin pathway.
Humans ; MicroRNAs/metabolism* ; Wnt3A Protein/metabolism* ; Liver Neoplasms/metabolism* ; Cell Proliferation/genetics* ; beta Catenin/genetics* ; Macrophages/metabolism* ; Interleukin-10/metabolism* ; Apoptosis/genetics* ; Cell Line, Tumor ; Female ; Male ; Mannose Receptor ; Lectins, C-Type/metabolism* ; Mannose-Binding Lectins/metabolism* ; Middle Aged ; Receptors, Cell Surface/metabolism*

Objective To explore the influences of long-chain noncoding RNA DHRS4-AS1 (lncRNA DHRS4-AS1) on the proliferation, invasion, migration, and apoptosis of thyroid cancer (TC) cells by regulating the microRNA-221-3p (miR-221-3p)/suppressor of cytokine signaling 3 (SOCS3) signaling axis. Methods Quantitative real-time PCR (qRT-PCR) was applied to detect the expression of lncRNA DHRS4-AS1, miR-221-3p, and SOCS3 mRNA in TC cell lines, and the optimal cell line was selected for subsequent experiments. FTC-133 cells were divided into five groups: control group, pcDNA-NC group, DHRS4-AS1 group, DHRS4-AS1 combined with agomir NC group, and DHRS4-AS1 combined with miR-221-3p-agomir group. Transfection efficiency was assessed using qRT-PCR. Dual luciferase reporter assays were applied to verify the targeting interaction between lncRNA DHRS4-AS1, SOCS3, and miR-221-3p. Western blot analysis was used to detect the expression of SOCS3 in FTC-133 cells. EdU method was used to measure cell proliferation. Flow cytometry was applied to measure the apoptosis of FTC-133 cells. Scratch experiment was applied to measure the migration of FTC-133 cells. Transwell chamber was applied to detect the invasion of FTC-133 cells. Nude mouse transplantation tumor experiment was used to observe the effect of lncRNA DHRS4-AS1 on the growth of TC transplantation tumors. Results Dual luciferase reporter assays showed a targeting relationship between lncRNA DHRS4-AS1, miR-221-3p, and SOCS3. LncRNA DHRS4-AS1 and SOCS3 were downregulated and miR-221-3p was upregulated in FTC-133 cells. Overexpression of lncRNA DHRS4-AS1 inhibited proliferation, migration, and invasion of FTC-133 cells, while inducing apoptosis. Conversely, miR-221-3p overexpression reversed these inhibitory effects, and suppressed the apoptosis. Nude mouse transplantation experiment observed that overexpression of lncRNA DHRS4-AS1 resulted in a decrease in tumor tissue quality and volume, and a decrease in miR-221-3p expression and an increase in SOCS3 expression. Conclusion LncRNA DHRS4-AS1 is downregulated in FTC-133 cells. Overexpression of lncRNA DHRS4-AS1 can inhibit the proliferation, invasion, and migration of TC cells and induce apoptosis by regulating the miR-221-3p/SOCS3 signaling axis.
MicroRNAs/metabolism* ; Suppressor of Cytokine Signaling 3 Protein/metabolism* ; Humans ; RNA, Long Noncoding/metabolism* ; Apoptosis/genetics* ; Cell Proliferation/genetics* ; Cell Movement/genetics* ; Thyroid Neoplasms/physiopathology* ; Animals ; Signal Transduction/genetics* ; Cell Line, Tumor ; Mice, Nude ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic ; Mice ; Mice, Inbred BALB C

Objective To evaluate the clinical efficacy of a novel sleep-aid decoction in treating elderly insomnia patients with different traditional Chinese medicine (TCM) constitutional types, and its effects on neurotransmitter and inflammatory factor levels. Methods A total of 200 patients with four different TCM constitutions-peaceful, Qi-deficient, Yin-deficient, and Yang-deficient-were recruited. Peripheral blood neurotransmitter and inflammatory factor levels were measured for variations among insomnia patients across different constitutions. These patients were treated using the novel sleep-aid decoction, the effects of which were evaluated based on changes in neurotransmitters and inflammatory factors. Results Compared to the peaceful constitution group, insomnia patients with Qi-deficient, Yin-deficient, and Yang-deficient constitutions exhibited significantly elevated baseline levels of neurotransmitters (5-HT, GABA) and inflammatory factors (IL-6, TNF-α, IL-1β, CRP). Following the treatment, the Qi-deficient and Yin-deficient groups showed a marked increase in 5-HT levels, restored balance of Glu, GABA, and melatonin, and significant reductions in IL-6 and TNF-α levels. The overall effective rate was 83.5%, with optimal efficacy observed in the Qi-deficient (97.72%) and Yin-deficient (95.34%) groups. Conclusion The novel sleep-aid decoction is effective in treating insomnia in elderly patients, with the best results observed in the Qi-deficient and Yin-deficient constitution groups.
Humans ; Sleep Initiation and Maintenance Disorders/blood* ; Aged ; Male ; Female ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Middle Aged ; Tumor Necrosis Factor-alpha/blood* ; Sleep Aids, Pharmaceutical/therapeutic use* ; Anti-Inflammatory Agents/therapeutic use* ; Interleukin-6/blood* ; Interleukin-1beta/blood* ; Neurotransmitter Agents/blood* ; Aged, 80 and over ; C-Reactive Protein/metabolism*

PURPOSE: To screen laboratory markers with predictive value in early spinal surgical site infections (SSI) that are diagnosed within 30 days postoperatively. METHODS: Patients who underwent surgical treatment for internal spinal fixation between March 2022 and March 2023 in our hospital were retrospectively studied. The inclusion criteria were aged >18 years, undergoing internal fixation surgery, complete medical records with >30 days of postoperative follow-up, diagnosis was made within 30 days postoperatively, and an informed consent form was obtained. The exclusion criteria were abnormal white blood cell count or neutrophil percentage in the preoperative blood routine and combined diseases that may affect the C-reactive protein (CRP) or procalcitonin (PCT) values, including lower respiratory tract infection, renal insufficiency, and liver disease. We collected patients' personal information, surgical information, and blood laboratory data, including CRP, PCT, lymphocyte-neutrophil ratio, platelet-neutrophil ratio, and routine blood tests on preoperative and postoperative days 3, 5, and 7, from these patients. These data were statistically analyzed to determine which laboratory markers were statistically significant. The diagnostic value and optimal diagnostic threshold of these laboratory markers were further determined by receiver operating characteristic curve analysis. RESULTS: A total of 106 patients were enrolled in this study, of whom 8 patients were diagnosed with early SSI. A total of 4 laboratory markers were screened, namely, CRP on postoperative day 7 (optimal diagnostic threshold of ≥64.1 mg/L, sensitivity of 100%, specificity of 76.5%, area under the curve (AUC) of 0.908), PCT on postoperative day 7 (optimal diagnostic threshold of ≥0.2 ng/mL, sensitivity of 87.5%, specificity of 94.1%, AUC of 0.967), lymphocyte count on postoperative day 5 (optimal diagnostic threshold of ≤0.67 × 10⁹/L, sensitivity of 50%, specificity of 95.9%, AUC of 0.760), and lymphocyte count on postoperative day 7 (optimal diagnostic threshold of ≤1.32 × 10⁹/L, sensitivity of 87.5%, specificity of 55.1%, AUC of 0.721). CONCLUSION We concluded that CRP and PCT levels on postoperative day 7 and lymphocyte counts on postoperative days 5 and 7 are useful markers in screening for early spinal SSI.
Humans ; Retrospective Studies ; Male ; Female ; Biomarkers/blood* ; Middle Aged ; C-Reactive Protein/analysis* ; Surgical Wound Infection/blood* ; Procalcitonin/blood* ; Adult ; Aged ; Postoperative Period ; ROC Curve ; Predictive Value of Tests ; Spine/surgery*

Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

Ribosomally synthesized and post-translationally modified peptides (RiPPs) constitute a vast and diverse family of bioactive peptides. These peptides, synthesized by ribosomes and subsequently modified by various tailoring enzymes, possess a wide chemical space. Among these modifications, radical S-adenosylmethionine (rSAM) enzymes employ unique radical chemistry to introduce a variety of novel peptide structures, which are crucial for their activity. This review examines the major types of modifications in RiPPs catalyzed by rSAM enzymes, incorporating recent advancements in protein structure analysis techniques and computational methods. Additionally, it elucidates the diverse catalytic mechanisms and substrate selectivity of these enzymes through an analysis of the latest crystal structures.
Protein Processing, Post-Translational ; S-Adenosylmethionine/chemistry* ; Ribosomes/metabolism* ; Peptides/metabolism* ; Biological Products/metabolism* ; Humans

Cancer represents a significant disease that profoundly impacts human health and longevity. Projections indicate a 47% increase in the global cancer burden by 2040 compared to 2020, accompanied by a further rise in the associated economic burden. Consequently, there is an urgent need to discover and develop new alternative drugs to mitigate the global impact of cancer. Natural products (NPs) play a crucial role in the identification and development of anticancer therapeutics. This study identified ustusolate E (UE) and its analog 11α-hydroxy-ustusolate E (HUE) from strain Aspergilluscalidoustus TJ403-EL05, and examined their antitumor activities and mechanisms of action. The findings demonstrate that both compounds significantly inhibited the proliferation and colony formation of AGS (human gastric cancer cells) and 786-O (human renal clear cell carcinoma cells), induced irreversible DNA damage, blocked the cell cycle at the G₂/M phase, and further induced apoptosis in tumor cells. To the best of the authors' knowledge, this is the first report on the anticancer effects of UE and HUE and their underlying mechanisms. The present study suggests that HUE and UE could serve as lead compounds for the development of novel anticancer drugs.
Humans ; Apoptosis/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Cell Line, Tumor ; Phosphatidylinositol 3-Kinases/genetics* ; Signal Transduction/drug effects* ; Tumor Suppressor Protein p53/genetics* ; Cell Proliferation/drug effects* ; Antineoplastic Agents/pharmacology* ; Sesquiterpenes/pharmacology* ; Aspergillus/chemistry*