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.

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

Objective·To investigate the performance and psychological mechanisms of inhibitory control in patients with alcohol use disorder(AUD)under different emotional contexts,and to examine the influence of emotion regulation difficulties on inhibitory control.Methods·A total of 28 male AUD inpatients(AUD group)and 28 age-and education-matched healthy controls(HC group)were recruited.The emotional Go/Nogo task(angry/neutral facial expressions)was used to evaluate the subjects'behavioral inhibition,and the hierarchical drift-diffusion model(HDDM)was used to quantify the cognitive parameters(drift rate,decision threshold,and non-decision time).The Difficulties in Emotion Regulation Scale(DERS)and Alcohol Use Disorder Identification Test(AUDIT)were used for clinical evaluation.The moderated mediation effects were tested by bootstrap method.Results·The AUD group scored higher than the HC group on the DERS total score and all sub-dimensions(goal-directed behavior,impulse control,strategy access,and emotional clarity),and the difference was statistically significant(all P<0.05).At the behavioral level,compared with the HC group,the AUD group had elevated commission error rates[F(1,54)=8.62,P=0.005]and omission error rates[F(1,54)=4.28,P=0.043],and the reaction time of angry face stimuli was generally prolonged[F(1,54)=12.26,P=0.001].Cognitive modeling showed that the drift rate of the AUD group was significantly lower than that of the HC group[F(1,54)=15.56,P<0.001],indicating impaired information processing efficiency.The moderated mediation model showed that,under the condition of angry face stimuli,the drift rate partially mediated the relationship between group and commission error rate,and the total indirect effect value was 9.564(95%CI 3.874?16.387).Further analysis showed that the conditional indirect effect increased to 10.133(95%CI 3.963?17.927)at high levels of emotion regulation difficulty(one standard deviation above the mean),and to 9.011(95%CI 3.778?14.921)at low levels(one standard deviation below the mean).Conclusion·The deficits in information processing efficiency of AUD patients partly explains the impairment of inhibitory control,and this effect is associated with individual emotion regulation capacity.It is suggested that abnormal processing of social threat information may be an important factor affecting the impairment of inhibitory control in AUD patients,especially in individuals with weak emotion regulation ability.

Objective:This study sought to examine the clinicopathological features of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) and to discuss its differential diagnosis.Methods:A total of 36 MEITL cases, collected between June 2015 and January 2024 from the Fourth Affiliated Hospital of Soochow University and the First Affiliated Hospital, College of Medicine, Zhejiang University, were analyzed. Patients underwent immunohistochemistry, in situ hybridization for Epstein-Barr virus-encoded small RNA (EBER), and T-cell receptor (TCR) gene rearrangement testing. Clinical data, laboratory results, and follow-up information were collected for correlation analysis.Results:The cohort included 36 patients (20 males and 16 females) aged 17-76 years (median: 57 years). Tumors outside the intestine were observed in 22 cases (61%). A total of 32 patients (89%) underwent surgical intervention and/or chemotherapy, and one patient received auto-HSCT. The median follow-up duration was 11.5 months (range: 8-73 months), with a median overall survival of 6 months (range: 1-67 months) ; 34 patients died during the follow-up period. Morphologically, nine cases (25%) exhibited significant pleomorphism. Immunohistochemical analysis revealed that high expression levels of both P53 and c-Myc were correlated with atypical morphology ( P=0.003 and P=0.016, respectively). Notably, patients with high P53 expression had significantly shorter survival times than those with low P53 expression ( χ2=4.922, P=0.027), whereas survival did not differ significantly based on c-Myc expression levels ( χ2=0.034, P=0.854). Furthermore, a PD-L1 CPS score ≥10 was observed in 22 cases (68.8%). Scattered EBER positivity in background cells was identified in four cases. All tested cases (17/17, 100.0%) showed clonal TCR gene rearrangements. Conclusions:MEITL is a rare but highly aggressive lymphoma with distinct clinical and pathological features. A subset of cases may exhibit atypical morphological patterns, complicating the diagnostic process. Improving awareness of this neoplasm is helpful for early and precise diagnosis as well as the estabolishment of novel therapy regimen.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To evaluate the role of hippocampal activating transcription factor 5 (ATF5) in cognitive impairment induced by neuropathic pain and the relationship with mitochondrial unfolded protein response(mtUPR) in mice.Methods:This study was conducted in 2 parts. Experiment Ⅰ Twenty-four SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 2 groups ( n=12 each) using a random number table method: sham operation group (S1 group) and neuropathic pain group (NP group). Neuropathic pain was induced by chronic constriction injury to the sciatic nerve. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model and at 7, 14, 21 and 28 days after developing the model. Mouse cognitive function was assessed using the novel object recognition test from 30-31 days after developing the model. After the end of the novel object recognition test, mice were sacrificed and the hippocampal CA1 region was harvested for determination of the expression of ATF5 (by Western blot) and the expression of ATF5 in neurons, microglia and astrocytes (by immunofluorescence double staining). Experiment Ⅱ Thirty-six SPF healthy male C57BL/6 mice, aged 6-8 weeks, weighing 20-25 g, were divided into 3 groups ( n=12 each) using a random number table method: sham operation group (S2 group), neuropathic pain + ATF5 up-regulation group (NA group), and neuropathic pain + empty virus group (NE group). On day 14 after developing the model, a virus that specifically up-regulated ATF5 expression in neurons and empty virus were injected into the hippocampal CA1 region. The MWT and TWL were measured at days 28 and 35 after developing the model. The novel object recognition test was performed on day 36 after developing the model to evaluate the cognitive function. After the end of the behavioral test, mice were sacrificed and the hippocampal CA1 region was harvested for detection of the expression of ATF5 and mtUPR marker proteins (Lon protease [LONP1] and heat shock protein 60 [HSP60]) by Western blot. Results:Experiment Ⅰ Compared with S1 group, no statistically significant change was found in the MWT and TWL before developing the model ( P>0.05), the MWT and TWL were significantly decreased on days 7, 14, 21 and 28 after developing the model, the discrimination index (DI) was decreased at day 31 after developing the model, the expression of ATF5 was down-regulated, the expression of ATF5 in neurons was down-regulated ( P<0.05), and no statistically significant change was found in the expression of ATF5 in mircrolia and astrocytes in NP group ( P>0.05). Experiment Ⅱ Compared with S2 group, the MWT and TWL were significantly decreased on days 28 and 35 after developing the model in NE group and NA group, DI was decreased, and the expression of ATF5, LONP1 and HSP60 was down-regulated in NE group ( P<0.05), and no significant change was found in NA group ( P>0.05). Compared with NE group, no significant change was found in the MWT and TWL in NA group ( P>0.05), DI was significantly increased, and the expression of ATF5, LONP1 and HSP60 was up-regulated in NA group ( P<0.05). Conclusions:Down-regulated ATF5 in the hippocampus is involved in the process of cognitive impairment caused by neuropathic pain, and the mechanism may be related to the inhibition of mtUPR.

Objective:To investigate the association between serum IgG concentration and renal prognosis in patients with IgA nephropathy (IgAN).Methods:It was a multi-center retrospective cohort study, patients with biopsy proven primary IgAN who were recorded in the Chinese IgA Nephropathy Information Registration System between April 1996 and September 2018 were included. Exclusion criteria were: (1) age <18 years; (2) <8 glomeruli in biopsy specimens; (3) estimated glomerular filtration rate (eGFR) <15 ml·min -1·(1.73 m 2) -1 at biopsy; (4) missing baseline serum IgG values; (5) incomplete follow-up data; (6) follow-up duration <12 months. Enrolled patients were divided into 3 groups according to the baseline tertiles of serum IgG: ≤9.50 g/L (G1 group), 9.51-11.99 g/L (G2 group), and ≥12.00 g/L (G3 group). Clinical, and pathological parameters were compared across groups. The endpoint events were defined as doubled serum creatinine level from baseline, or end-stage renal disease (ESRD). Results:A total of 1 976 IgAN patients were included in this study, 631 were in G1 group, 664 in G2 group, and 681 in G3 group. The comparison of baseline clinical data showed that there were statistically significant differences among the three groups in terms of gender, age, microscopic hematuria, edema, body mass index, systolic blood pressure, diastolic blood pressure, hemoglobin, serum creatinine, eGFR, 24-hour urine protein quantity, blood uric acid, blood albumin, serum IgA, serum IgM, the proportion of using immunosuppressants, and the proportion of using glucocorticoids (all P<0.05). In terms of pathology, the higher the serum IgG concentration, the relatively less severe the overall renal pathological damage. The results of univariate Cox regression analysis showed that gender, systolic blood pressure, diastolic blood pressure, hemoglobin, serum creatinine, eGFR, 24-hour urine protein quantity, total protein, serum albumin, globulin, serum IgG, Oxford renal pathological classification, glomerular sclerosis ratio, and glomerular IgM deposition were all associated with the occurrence of renal endpoint events (all P<0.05). Based on clinical practice and previous studies, after adjusting for gender, age, systolic blood pressure, diastolic blood pressure, eGFR, 24-hour urine protein quantity, body mass index, Oxford renal pathological classification, glomerular sclerosis ratio, and the use of renin-angiotensin-aldosterone system inhibitors, glucocorticoids, and immunosuppressants, multivariate Cox regression analysis showed that as a continuous variable, the baseline serum IgG level ( HR=0.91, 95% CI 0.87-0.96) was independently associated with the risk of renal endpoint events in IgAN patients; as a categorical variable, with serum IgG ≤ 9.50 g/L as the reference, serum IgG 9.51-11.99 g/L and serum IgG ≥ 12.00 g/L were independent factors for the occurrence of renal endpoint events in IgAN patients ( HR=0.69, 95% CI 0.49-0.96, P=0.027; HR=0.50, 95% CI 0.34-0.74, P<0.001). During a median follow-up of 33(21, 53) months started from the date of renal biopsy and continued until December 31, 2019, the median follow-up duration was 33 (21, 53) months, and a total of 232 patients (11.74%) reached the composite endpoint. Kaplan-Meier survival analysis showed that the higher the serum IgG concentration in patients with IgAN, the higher their cumulative renal survival rate (Log-rank test, χ2=47.176, P<0.001). Conclusion:The higher level of serum IgG at diagnosis is associated with better clinicopathologic features and renal outcomes, and may portend better renal survival in IgAN patients.

Haematitum and Limonitum are two iron-containing mineral medicines included in the 2020 edition of the Chinese Pharmacopoeia. They have similar main components and major differences in their property, flavor, channel tropism, and clinical uses. In this study, we investigated the surface properties, mineral composition, mineral dissociation, elemental composition, and iron state of Haematitum and Limonitum to explore their mineralogical differences. Scanning electron microscopy(SEM), specific surface and porosity analyzer, X-ray diffractometer(XRD), X-ray photoelectron spectrometer(XPS), and advanced mineral identification and characterization system(AMICS) were used to analyze the mineralogy of Haematitum and Limonitum. The results showed that Haematitum had an angular surface with granular attachments and a specific surface area of 17.04 m~2·g~(-1). In comparison, Limonitum had a smooth and flat surface with a bundled acicular crystal structure and a specific surface area of 46.29 m~2·g~(-1). Haematitum consists of 31 detectable minerals containing 18 elements, with the major element, iron(44.5% Fe~(2+) and 55.5% Fe~(3+)) distributed in 17 minerals, including hematite, iron oxide, knebelite, siderite, and magnesioferrite. Limonitum consists of 32 detectable minerals containing 17 elements, with the major element, iron(14.5% Fe~(2+) and 85.5% Fe~(3+)) distributed in 19 minerals, including limonite, iron oxide, chlorite, and knebelite. In summary, the elemental composition of Haematitum and Limonitum does not differ greatly, but there are large differences in the mineral composition and iron state. The large specific surface area and strong adsorption capacity of Limonitum may be one of the mechanisms of its anti-diarrheal action. The Fe_2O_3 and illite contained in Haematitum and Limonitum may be the key substances for their hemostasis effects. The mineralogical differences are expected to provide a reference for explaining the scientific connotation of mineral medicine and laying a material foundation for studying its mechanism of action.
Iron/analysis* ; Minerals/chemistry* ; Drugs, Chinese Herbal/chemistry* ; X-Ray Diffraction ; Microscopy, Electron, Scanning ; Photoelectron Spectroscopy

Objective Radial artery occlusion(RAO)is one of the common complications following coronary intervention via the traditional radial artery approach.This study aims to evaluate the clinical effectiveness of retrograde recanalization of occluded radial arteries through the distal transradial approach(dTRA)approach.Methods A total of 35 patients with RAO admitted to the cardiovascular department of the Anhui Chest hospital between December 2022 and April 2024,who were scheduled to undergo coronary intervention and had attempted recanalization of RAO via dTRA approach were selected.The primary result was the success rate of recanalizing RAO via dTRA.The secondary results included factors influencing the failure of recanalization via dTRA,postoperative puncture complications,and the patency rate at the 3-month follow-up.Results This study divided the patients into a successful group(29 cases,82.9％)and a failed group(6 cases,17.1％)based on whether the distal radial artery was successfully opened and occluded.The proportion of smoking(100.00％vs.17.24％,P=0.040),history of diabetes(100.00％vs.10.34％,P=0.025),and chronic total occlusion of coronary artery(83.33％vs.17.24％,P=0.030)in the failure group were higher than those in the success group,and the difference was statistically significant.The application rate of balloon tracking assisted technology in the failed group(16.67％vs.58.62％,P=0.045),and the diameter of the radial artery at 3 days after surgery[(1.63±0.13)mm vs.(2.13±0.32)mm,P=0.021]and the peak radial artery blood flow velocity at 3 days postoperatively[(0.10±0.78)m/s vs.(0.50±0.13)m/s,P＜0.001]were all lower in the successful group,and the differences were statistically significant.Logistic regression analysis 3 days after surgery showed that chronic complete occlusion of the coronary artery was an independent risk factor for surgical opening failure(OR 0.042,95％CI 0.004-0.438,P=0.008).After 3 months of follow-up,the patency rate of the successful group was 55.2％.Conclusions Retrograde recanalization of RAO via dTRA is safe and feasible,but its long-term patency rate is not high.