Coronavirus disease 2019 (COVID-19) is a multi-system disease that can lead to various severe complications. Acute limb ischemia (ALI) has been increasingly recognized as a COVID-19-associated complication that often predicts a poor prognosis. However, the pathophysiology and molecular mechanisms underlying COVID-19-associated ALI remain poorly understood. Hypercoagulability and thrombosis are considered important mechanisms, but we also emphasize the roles of vasospasm, hypoxia, and acidosis in the pathogenesis of the disease. The angiotensin-converting enzyme 2 (ACE2) pathway, inflammation, and platelet activation may be important molecular mechanisms underlying these pathological changes induced by COVID-19. Furthermore, we discuss the hypotheses of risk factors for COVID-19-associated ALI from genetic, age, and gender perspectives based on our analysis of molecular mechanisms. Additionally, we summarize therapeutic approaches such as use of the interleukin-6 (IL-6) blocker tocilizumab, calcium channel blockers, and angiotensin-converting enzyme inhibitors, providing insights for the future treatment of coronavirus-associated limb ischemic diseases.
Humans ; COVID-19/physiopathology* ; Ischemia/etiology* ; SARS-CoV-2 ; Extremities/blood supply* ; Risk Factors ; Interleukin-6/antagonists & inhibitors* ; Acute Disease ; Angiotensin-Converting Enzyme 2

ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

ObjectiveBased on the concept of quality by design（QbD）， the processing process of calcined Pyritum was optimized， and its X-ray diffraction（XRD） fingerprint was established. MethodsThe safety， effectiveness and quality controllability of calcined Pyritum were taken as the quality profile（QTPP）， the color， hardness， metallic luster， phase composition， the contents of heavy metals and hazardous elements were taken as the critical quality attributes（CQAs）， and the calcination temperature， calcination time， paving thickness and particle size were determined as the critical process parameters（CPPs）. Differential thermal analysis， X-ray diffraction（XRD） and inductively coupled plasma mass spectrometry（ICP-MS） were used to analyze the correlation between the calcination temperature and CQAs of calcined Pyritum. Then， based on the criteria importance through intercriteria correlation（CRITIC）-entropy weight method， the optimal processing process of calcined Pyritum was optimized by orthogonal test. Powder XRD was used to analyze the phase of calcined Pyritum samples processed according to the best process， and the mean and median maps of calcined Pyritum were established by the superposition of geometric topological figures， and similarity evaluation and cluster analysis were carried out. ResultsThe results of single factor experiments showed that the physical phase of Pyritum changed from FeS₂ to Fe₇S₈ during the process of temperature increase， the color gradually deepened from dark yellow， and the contents of heavy metals and harmful elements decreased. The optimized processing process of calcined Pyritum was as follows：calcination temperature at 750 ℃， calcination time of 2.5 h， paving thickness of 3 cm， particle size of 0.8-1.2 cm， vinegar quenching 1 time［Pyritum-vinegar（10∶3）］. After calcination， the internal structure of Pyritum was honeycomb-shaped， which was conducive to the dissolution of active ingredients. XRD fingerprints of 13 batches of calcined Pyritum characterized by 10 common peaks were established. The similarities of the relative peak intensities of the XRD fingerprints of the analyzed samples were>0.96， and it could effectively distinguish the raw products and unqualified products. ConclusionTemperature is the main factor affecting the quality of calcined Pyritum. After processing， the dissolution of the effective components in Pyritum increases， and the contents of heavy metals and harmful substances decrease， reflecting the function of processing to increase efficiency and reduce toxicity. The optimized processing process is stable and feasible， and the established XRD fingerprint can be used as one of the quality control standards of calcined Pyritum.

Objective:To summarize the clinical characteristics of elderly patients with stage Ⅰ diffuse large B-cell lymphoma (DLBCL) and analyze the factors associated with prognosis.Methods:A case series study was conducted by retrospectively collecting clinical data from patients aged over 60 years with newly diagnosed stage Ⅰ DLBCL across 20 medical centers in Jiangsu Province, China, between June 2010 and April 2023. The involved site, classification and treatment plan were summarized. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Statistical analyses were performed using the Kaplan-Meier method, and Cox regression model.Results:The study included 255 patients with a median age of 69 years, of whom 130 (51.0%) were male, 66 (25.9%) were aged ≥75 years and 26 (10.1%) had a high Charlson Comorbidity Index (CCI) score of ≥2. Extranodal involvement was observed in 163 (63.9%) patients, with the stomach (37.4%, 61/163), intestine (19.0%, 31/163), testes (11.0%, 18/163), and breast (7.4%, 12/163) being the most frequently affected sites. The non-germinal center B-cell (non-GCB) subtype was prevalent in 63.7% of patients (142/223), with no significant difference between the nodal and extranodal groups ( P=0.681). Furthermore, 73.9% (184/249) and 11.7% (29/249) of patients received the R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and R-miniCHOP regimen, respectively. The overall 3-year PFS rate was 81.5%, and the 3-year OS rate was 85.6%. Patients aged ≥75 years ( HR=2.910, 95% CI 1.565-5.408, P=0.001) and/or with a CCI score ≥2 ( HR=2.324, 95% CI 1.141-4.732, P=0.020) had a significantly poorer PFS. Incorporating age ≥75 years and CCI score ≥2 into the stage-modified international prognostic index (sm-IPI) can better stratify the prognosis of elderly patients with stage Ⅰ DLBCL. The 3-year PFS rate was 48.7% in the high-risk group versus 85.7% in the low-risk group ( P<0.001). Conclusions:Our findings show that the elderly patients with stage Ⅰ DLBCL were predominantly characterized by extranodal involvement (particularly in the stomach and intestinal tract) and non-GCB subtype. Age ≥75 years and CCI ≥2 were identified as independent prognostic factors. The newly established sm-IPI-75-CCI incorporating these factors demonstrated superior prognostic discrimination compared to conventional risk assessment systems.

Objective:To identify and observe the pathogenic genes and clinical phenotypes of a family with a special platelet phenotype, Hermansky-Pudlak syndrome type 6 (HSP6).Methods:A retrospective clinical study. In November 2019, one proband and three family members from six HSP families who visited Henan Eye Hospital were included in the study. The child's medical history and family history were inquired in detail. The proband and all family members underwent best corrected visual acuity (BCVA), fundus color photography, frequency-domain optical coherence tomography, and general physical examination. The proband underwent platelet transmission electron microscopy (PTEM) and colonoscopy. Peripheral venous blood was collected from the proband, her parents and younger brother, and genomic DNA was extracted. Whole exome sequencing (WES) was used to screen pathogenic genes and their loci. Bioinformatics analysis determines the pathogenicity of gene variation sites. Fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blot were used to verify the related variations.Results:The proband (Ⅱ-1) was a 7-year-old female. The BCVA in both eyes was 0.1, who exhibited mild horizontal nystagmus and iris depigmentation. Fundus examination revealed obvious depigmentation and an underdeveloped fovea centralis. At the age of 7, the patient underwent colonoscopy due to acute gastrointestinal bleeding. A polyp approximately 5 mm in size was found on the floor of the sigmoid colon, with erosion and mucosal leukoplakia on its surface. PTEM showed that the number of platelet dense granules was normal, but the nuclei were small or exhibited low compactness. The skin on both lower legs showed pigmentation. The clinical phenotypes of the proband’s parents (Ⅰ-1, Ⅰ-2) and younger brother (Ⅱ-2) showed no obvious abnormalities. WES revealed that the proband carried compound heterozygous variants in exon 1 of the HPS6 gene: c.60_64dup (p.L22fs) (M1) and c.1147_1148del (p.L383fs) (M2). The mother carried the M1 variant, while the father and younger brother carried the M2 variant. Bioinformatics analysis predicted that both variants were pathogenic. RT-qPCR results showed that, compared with the relative expression level of HPS6 wt mRNA, the relative expression levels of HPS6 L22fs and HPS6 L383fs mRNA were significantly decreased ( t = 3.549, 4.560; P<0.05). Western blot analysis demonstrated that the HPS6 L383fs protein was truncated, whereas the HPS6 L22fs protein was not detected. Conclusions:This family is a special HPS6 with a normal number of dense platelet granules. The compound heterozygous variations of M1 and M2 in the HPS6 gene are pathogenic genes in this family.

Stiff person syndrome (SPS) is a rare neuro-immune disorder characterized by exaggerated startle responses and muscle spasms in response to minor stimuli. SPS is often misdiagnosed as panic disorder or agoraphobia. This paper reported a case of a patient with SPS presenting symptoms similar to panic attack. The patient had been misdiagnosed as dystonia, anxiety disorder and panic attack. The patient was finally correctly diagnosed through multiple disciplinary team discussions. This study integrates a comprehensive understanding of symptomatology and patient-reported experiences with targeted neurological evaluations and supplementary diagnostic tools to improve the accuracy of etiological diagnoses. This study aims to enhance the ability of psychiatrists to recognize somatic diseases presenting with psychiatric symptoms and to improve clinical diagnostic and treatment levels.

Objective:The study aimed to validate the Neuroception of Psychological Safety Scale (NPSS) in terms of reliability and validity among individuals with mental disorders in China.Methods:The Study followed Brislin′s translation principles to adapt the scale into Chinese. From February to June 2023, a total of 638 hospitalized patients with mental disorders (477 with schizophrenia and 161 with mood disorders) were selected through gender-stratified simple random sampling from the Shanghai Pudong New Area Mental Health Center and the Shanghai Baoshan Mental Health Center. The Chinese version of the NPSS and the Security Questionnaire (SQ) were administered. The reliability of the scale was measured using split-half reliability and test-retest reliability. Validity was assessed through content validity, structural validity, convergent validity, and discriminative validity analyses. In addition, SQ was used as a criterion tool to test the validity of the criterion through Pearson correlation analysis.Results:The Chinese version of the NPSS contained 29 items, with total scores ranging from 29 to 145. Higher total scores indicated greater psychological safety. Item analysis showed a decider value of 10.58 to 20.80 (>3), and the correlation between items and total scores ranged from 0.579 to 0.749 (all P<0.05). The item-level content validity index (I-CVI) for the items ranged from 0.86 to 1.00, while the average scale-level content validity index (S-CVI/Ave) was 0.99. Exploratory factor analysis extracted three common factors: social participation, empathy, and bodily sensations, which is consistent with the structure of the original scale, explaining a cumulative variance contribution rate of 62.551%. Confirmatory analysis revealed a satisfactory model fit, with average variance extracted (AVE) values for the three dimensions ranging from 0.523 to 0.645, and composite reliability(CR) ranging from 0.905 to 0.938. The standard loading coefficients for the items ranged from 0.608 to 0.859, and inter-factor correlation coefficients were all smaller than the square roots of their respective AVE values. Pearson correlation analysis indicated significant positive relationships between the Chinese NPSS and SQ ( r=0.822-0.846, P<0.01). Reliability analysis showed Cronbach′s alpha coefficients of 0.903-0.959 for the total scale and subscales. After a 3-week interval, test-retest reliability (70 patients) ranged from 0.874 to 0.983, and split-half reliability was 0.869-0.969. All model fit indices met established criteria. Conclusions:The Chinese version of the NPSS demonstrates good reliability and validity, making it suitable for both research and clinical applications in assessing psychological security among individuals with schizophrenia and mood disorders.

Group painting art therapy is a kind of therapy using painting art as the medium,which helps the individuals to improve their mental health and achieve recovery through group participation.In this kind of therapy,the participants express their emotions,thoughts and experiences through painting,share them with others,and obtain support and feedback,thereby this process promotes self-awareness,emotional expression and social interaction.The empirical research results indicate that when the group painting art therapy is ap-plied to the patients with schizophrenia during the rehabilitation phase,it has multifaceted effects,including al-leviating psychotic symptoms,improving medication adherence,relieving emotional distress,enhancing sleep quality,increasing self-awareness,improving cognitive function,and increasing social functioning and overall quality of life.In terms of intervention methods,the researchers have assessed the application efficacy of sole group painting art therapy in the rehabilitation of schizophrenia patients and have also explored its combined application with other treatments.For the future,more long-term follow-up studies can be conducted,and in-terdisciplinary cooperation can be strengthened,while focusing on community resource construction.

Objective: The impact of prophylactic salpingectomy on the prevention of epithelial ovarian cancer (EOC) remains unclear, particularly in Asian populations where data is lacking. In this systematic review and meta-analysis study, we sought to assess whether prophylactic salpingectomy could reduce the incidence of ovarian cancer in the general population of multiple ethnicities. Methods: A systematic review and meta-analysis were conducted using PubMed/MEDLINE, EMBASE, the Cochrane Library, and Web of Science to assess the effectiveness of salpingectomy, bilateral salpingectomy (BS), and unilateral salpingectomy (US) in reducing the risk of EOC and evaluating postoperative outcomes. Results: The final analyses included 6 eligible trials (5,747,056 patients), including 1 cohort study and 5 case-control studies. The analyses of these studies demonstrated that women who underwent salpingectomy had a significantly reduced risk of EOC compared to those who did not receive salpingectomy (odds ratio [OR]=0.63; 95% confidence interval [CI]=0.45–0.89; p=0.007). Five studies (5,746,469 patients) indicated a significant reduction in EOC risk among patients who underwent BS (OR=0.48; 95% CI=0.33–0.69; p<0.001).On the other hand, in the analysis of 4 studies (5,745,887 patients) that examined US, the association with EOC risk was not significant despite the protective trend (OR=0.82; 95% CI=0.64–1.06; p=0.12). Conclusion Our results indicate BS is an effective strategy for reducing the risk of sporadic EOC, but the results did not lead to the same conclusion for patients who underwent US. When a candidate or patient is undergoing a hysterectomy or has other benign diseases, prophylactic BS may be a safe surgical procedure that carries future benefits in terms of EOC risk.

Objective: The impact of prophylactic salpingectomy on the prevention of epithelial ovarian cancer (EOC) remains unclear, particularly in Asian populations where data is lacking. In this systematic review and meta-analysis study, we sought to assess whether prophylactic salpingectomy could reduce the incidence of ovarian cancer in the general population of multiple ethnicities. Methods: A systematic review and meta-analysis were conducted using PubMed/MEDLINE, EMBASE, the Cochrane Library, and Web of Science to assess the effectiveness of salpingectomy, bilateral salpingectomy (BS), and unilateral salpingectomy (US) in reducing the risk of EOC and evaluating postoperative outcomes. Results: The final analyses included 6 eligible trials (5,747,056 patients), including 1 cohort study and 5 case-control studies. The analyses of these studies demonstrated that women who underwent salpingectomy had a significantly reduced risk of EOC compared to those who did not receive salpingectomy (odds ratio [OR]=0.63; 95% confidence interval [CI]=0.45–0.89; p=0.007). Five studies (5,746,469 patients) indicated a significant reduction in EOC risk among patients who underwent BS (OR=0.48; 95% CI=0.33–0.69; p<0.001).On the other hand, in the analysis of 4 studies (5,745,887 patients) that examined US, the association with EOC risk was not significant despite the protective trend (OR=0.82; 95% CI=0.64–1.06; p=0.12). Conclusion Our results indicate BS is an effective strategy for reducing the risk of sporadic EOC, but the results did not lead to the same conclusion for patients who underwent US. When a candidate or patient is undergoing a hysterectomy or has other benign diseases, prophylactic BS may be a safe surgical procedure that carries future benefits in terms of EOC risk.