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.

This paper summarized the experience of fire needling combined with black cloth ointment in the treatment of keloid. In terms of the pathogenesis of keloid， it is believed that "phlegm causes stasis， and then stasis accumulates into tumors" is the key； the internal obstruction of phlegm and stasis caused by insufficient endowment and invasion of external pathogens is the root of the disease， while the endogenous generation of phlegm and dampness is the branch. It is therefore proposed to explore the etiology and pathogenesis of keloid from the perspective of "phlegm-stasis-tumor"， and the treatment principle is mainly to eliminate phlegm， dispel stasis and dissolve tumors， supplemented with heat-clearing and toxin-resolving. Treatment methods include oral administration of Chinese herbal medicinals and external treatment. Self-made formula for keloid is taken orally， with the main functions of dissolving phlegm， dispelling stasis and clearing heat， to finally dissolve the tumors. For external treatment， fire needling is used to pierce the skin and to open the striae and interstices， and force out the toxin pathogens such as phlegm-heat and stasis-heat with fire power， thereby clearing heat， dissolving phlegm， dispelling stasis and resolving toxins. Black cloth ointment can be used to the affected area to unblock meridians and collaterals， clear heat-toxin and dissolve phlegm-stasis， thereby softening hardness and dissipating masses.

A 65-year-old male patient was admitted for recurrent lymph node enlargement for 5 years and elevated creatinine for 6 months. This patient was diagnosed with angioimmunoblastic T-cell lymphoma 5 years ago and underwent multiple lines of anti-tumor therapy, including cytotoxic chemotherapy; epigenetic modifying drugs such as chidamide and azacitidine; the immunomodulator lenalidomide; and targeted therapy such as rituximab, a CD20-targeting antibody, and brentuximab vedotin, which targets CD30. Although the tumor was considered stable, multiple virus activation (including BK virus, JC virus, and cytomegalovirus) accompanied by the corresponding organ damage (polyomavirus nephropathy, cytomegalovirus retinitis, and progressive multifocal leukoencephalopathy) occurred during anti-tumor treatment. Anti-tumor therapy was suspended and ganciclovir was used. The serum viral load decreased and organ functions were stabilized. The purpose of this report was to raise clinicians′ awareness of opportunistic virus reactivation during anti-tumor treatment.

Objective:To investigate the clinicopathological features and the prognosis of IgA nephropathy (IgAN) in children with massive proteinuria.Methods:It was a retrospective cohort study. Clinical data of IgAN children with massive proteinuria admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2008 to December 2021 were retrospectively analyzed. Patients were divided into effective group and ineffective group according to whether urine protein turned negative after 6 months of initial treatment. The follow-up endpoint event was defined as a reduction in proteinuria of less than 50% or end-stage renal disease (ESRD) achievement. MedCalc software was used to perform Kaplan-Meier survival analysis, and Log-rank test was used to compare the difference of renal survival between the two groups.Results:A total of 127 patients were diagnosed as primary IgAN by renal biopsy, of whom 57 patients with IgAN showed massive proteinuria. These 57 IgAN patients with macroproteinuria accounted for 44.9% of the total IgAN patients and were enrolled in the study. Among the 57 cases, 33 cases (57.9%) were Lee's grade Ⅲ, 11 cases (19.3%) were below Lee's grade Ⅲ, and 13 cases (22.8%) were above Lee's grade Ⅲ. The follow-up time was 4.0 (3.0,5.8) years. In the initial treatment, among 57 patients, 46 (80.7%) were effective (effective group) and 11 (19.3%) were ineffective (ineffective group). Compared with the effective group, the ineffective group had a higher proportion of concurrent AKI at the onset of disease and longer recovery time of renal function, with significant difference (7/11 vs. 13/46, χ2=4.878, P=0.027). Compared with the effective group, the proportion of Lee grade Ⅲ or above was higher in the ineffective group, and the difference was statistically significant (5/11 vs. 8/46, χ2=3.971, P=0.046). There were significant differences in endocapillary hypercellularity (E1), segmental glomerulosclerosis or adhesion (S1) and cellular/fibrocellular crescents (C2) of Oxford classification between IgAN children with Lee grade Ⅲ or below and those over Lee grade Ⅲ (11/13 vs. 20/44, χ2=6.204, P=0.013; 12/13 vs. 17/44, χ2=11.566, P=0.001; 9/13 vs. 7/44, χ2=14.131, P=0.001). Among 57 patients, endpoint events occurred in 2 patients who both were urinary protein unmitigated, and none of the children progressed to ESRD. There was no significant difference in cumulative renal survival between the two groups by Kaplan-Meier survival analysis and Log-rank test ( χ2=0.537, P=0.460) after addition of calcineurin inhibitors (CNIs) to the initial treatment ineffective group. Conclusions:Macroproteinuria is the prominent manifestation of IgAN in children. The pathological type is mainly Lee grade Ⅲ. Children with macroproteinuria have a good prognosis in the short and medium term after active treatment. For IgAN with macroproteinuria that does not respond well to initial treatment, AKI is more common at onset, and renal function recovery time is longer. The application of CNIs may have a certain effect on improving the renal outcome of IgAN with massive proteinuria.

Objective:To search, evaluate and integrate the best evidence of the best evidence for emergency service surge capacity.Methods:According to the "6S" model of evidence resources, the related evidence on emergency service surge capacity in Guidelines International Network, National Guideline Clearinghouse, Canadian Medical Association CPG Infobase, Scottish Intercollegiate Guidelines Network, European Society for Emergency Medicine, the American College of Emergency Physicians, Emergency Nurses Association, Cochrane Library, PubMed, Embase, CINAHL, Web of Science, BMJ Best Practice, UpToDate,CKNI, Wanfang, and VIP database were searched by computer. The retrieval time limit was from the establishment of the database to Dec 31, 2023. Literature quality assessment and data extraction were performed by 2 researchers.Results:A total of 11 articles were included in this study, including 1 guideline, 7 expert consensuses and 3 systematic reviews, which summarized 43 pieces of evidence involving 7 categories, namely core elements, organizational management, space management, personnel allocation, material allocation, education and training, and support services.Conclusions:The best evidence summarized in this study can provide a reference for emergency service to improve surge capacity. In clinical application, emergency departments should focus on organizational, space, personnel and materials management, combined with the type of emergency events, to maximize their routine, emergency and crisis response capabilities, so as to respond to medical surges effectively.

Objective To investigate the effect and mechanism of Nuanxinkang on plaque formation in obstructive sleep apnea-hypopnea syndrome(OSAHS)comorbid with atherosclerosis(AS)mice by inhibiting endothelial-to-mesenchymal transition(EndMT).Methods Male ApoE-/-mice were randomly divided into six groups:control group,model group,atorvastatin group(2.6 mg·kg-1)and Nuanxinkang low-,medium-and high-dose groups(crude drug 3.5,7.0,14.0 g·kg-1),with eight mice in each group.The mice were exposed to chronic intermittent hypoxia(CIH)environment during sleep for a long time,and fed with high-fat diet to replicate OSAHS comorbid with AS mouse model.Oil red O staining was used to observe the formation of plaque on aortic intima in mice.Masson trichrome staining was used to evaluate the collagen content of atherosclerotic plaques in the aortic root of mice.The expressions of endothelial cell marker CD31 and EndMT marker Vimentin in aortic plaque were detected by immunofluorescence.Blood lipid levels were determined by ELISA;the mRNA expression levels of EndMT markers α-SMA and Cdh2 in aortic tissue were detected by qPCR.Results Compared with the control group,the area of aortic atherosclerotic plaque in the model group was significantly increased(P＜0.01),and the area of collagen deposition in the aortic root plaque was significantly increased(P＜0.01).The number of CD31 positive cells in the plaque were significantly decreased(P＜0.01),and the number of Vimentin positive cells were significantly increased(P＜0.01).Serum TG,T-CHO and LDL-C levels were significantly increased(P＜0.01),and HDL-C level was significantly decreased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue were significantly increased(P＜0.01).Compared with the model group,the area of aortic atherosclerotic plaque in Nuanxinkang groups were significantly reduced(P＜0.05,P＜0.01),and the collagen deposition area of aortic root atherosclerotic plaque were significantly reduced(P＜0.05,P＜0.01).The number of CD31 positive expression cells in the plaque of Nuanxinkang high-dose group were significantly increased(P＜0.05),and the number of Vimentin positive expression cells in the plaque of Nuanxinkang medium-and high-dose groups were significantly decreased(P＜0.05,P＜0.01).The serum TG level of mice in the high-dose group of Nuanxinkang was significantly decreased(P＜0.01).The serum T-CHO and LDL-C levels of mice in each Nuanxinkang administration group were significantly decreased(P＜0.05,P＜0.01).The serum HDL-C levels of mice in the medium-and high-dose groups of Nuanxinkang were significantly increased(P＜0.01).The mRNA expression levels of α-SMA and Cdh2 in aortic tissue of mice in each treatment group were significantly decreased(P＜0.01).Conclusion Nuanxinkang can effectively reduce the plaque formation in OSAHS comorbid with atherosclerosis mice,which may be related to its inhibition of EndMT and reduction of collagen fiber formation.

A 31-year-old man sought medical evaluation for a 2-year history of edema and proteinuria, with prior pathology suggesting atypical membranous nephropathy (MN). Despite treatment with a combination of steroids, calcineurin inhibitors, and four courses of rituximab (1 g, intravenous injection), the patient′s nephrotic syndrome showed no relief (24 h urine protein peaked at 31.18 g/d), indicating refractory nephrotic syndrome. Later in the disease course, a sudden surge of creatinine level (322.5 μmol/L) prompted a renal biopsy, which revealed concurrent acute interstitial nephritis. Further treatment involving steroids, cyclophosphamide, and a fifth rituximab infusion (1 g, intravenous injection) resulted in improvement in renal function (serum creatinine: 322.5?147 μmol/L), but the MN failed to achieve partial relief. Subsequent treatment with the novel humanized CD20 monoclonal antibody obinutuzumab (1 g, intravenous injection) was initiated. In the latest follow-up, anti-phospholipase-A2-receptor antibody (PLA2R) antibody were negative, B cells were eliminated, serum albumin was 36 g/L, urine protein-to-creatinine ratio was 4 810 mg/g, and serum creatinine was 162 μmol/L. This case underscores the potential efficacy of obinutuzumab in refractory MN. For advanced MN cases, prompt identification of the cause of acute kidney injury is crucial, emphasizing the need for targeted interventions to potentially stall renal function decline.

Objective : To explore the regulatory effects of ResolvinD1 (RVD1) on autophagy and apoptosis of cardiomyocytes in aging rats , and the effects of RVD1 on mitochondria⁃associated endoplasmic reticulum membranes (MAMs) of myocardial tissue . Methods : Thirty 18⁃month⁃old SD rats were randomly divided into model group , low⁃dose RVD1 group and high⁃dose RVD1 group , with 10 rats in each group , and another 10 6 ⁃month⁃old SD rats were selected as control group . The low⁃dose RVD1 group and high⁃dose RVD1 group were injected with 50 ng/ml and 100 ng/ml RVD1 through the tail vein , respectively , control group and model group were injected with the same amount of phosphate buffered saline (PBS) for 21 days . The β ⁃galactosidase activity of rat myocardial tissue was determined by p ⁃nitrophenol method , the histopathological changes of rat myocardial tissue were detected by hematoxylin⁃eosin (HE) staining , and the collagen deposition in rat myocardial tissue was observed by Masson staining , apoptosis of rat myocardial cells was detected by dUTP in situ end labeling mediated by terminal deoxynucleotide transferase(TUNEL) , the expression of autophagy marker microtubule⁃associated protein 3 (LC3) was detecotide transferase(TUNEL) , the expression of autophagy marker microtubule⁃associated protein 3 (LC3) was detected by immunohistochemical S ⁃P method , the ratio of LC3 ⁃ Ⅱ/LC3 ⁃ Ⅰ and the expression of Beclin⁃1 , p62 in rat myocardial tissue were determined by Western blot , the structure of MAMs in rat myocardial tissue was observed by transmission electron microscopy , the expression levels of glucose⁃regulatory protein 75 (GRP75) , volt⁃dependent anion channel 1 (VDAC1) and mitochondrial fusion protein 2 (Mfn2) in rat myocardial tissue were determined by Western blot . Results : Compared with model group , β ⁃galactosidase activity of myocardial tissue decreased in low⁃dose RVD1 group and high⁃dose RVD1 group (P < 0. 05) , myocardial fiber breakage and myocardial cell damag were significantly alleviated , collagen fiber deposition was significantly reduced , and the proportion of TUNEL positive cells in myocardial tissue decreased (P < 0. 05) , the positive rate of LC3 protein increased (P < 0. 05) , the ratio of LC3 ⁃ Ⅱ/LC3 ⁃ Ⅰ increased , the relative expression level of Beclin⁃1 protein was up⁃regulated and the relative expression level of p62 protein was down⁃regulated ( P < 0. 05) , the structure of MAMs was tighter , and the percentage of MAMs in mitochondrial circumference also increased (P < 0. 05) , the relative protein expressions of GRP75 , VDAC1 and Mfn2 were up⁃regulated (P < 0. 05) . Compared with low⁃dose RVD1 group , β ⁃galactosidase activity in high⁃dose RVD1 group further decreased ( P < 0. 05) , no obvious damage was observed in myocardial tissue , collagen fiber deposition was further decreased , the proportion of TUNEL positive cells in myocardial tissue decreased (P < 0. 05 ) , and the positive rate of LC3 protein increased ( P < 0. 05 ) , LC3 ⁃ Ⅱ/LC3 ⁃ Ⅰ ratio increased , Beclin⁃1 relative expression level was up⁃regulated and p62 relative expression level was down⁃regulated (P < 0. 05) , the structure of MAMs was more compact , and their percentage in mitochondrial circumference further increased (P < 0. 05 ) , the relative expressions of GRP75 , VDAC1 and Mfn2 were further up⁃regulated ( P <0. 05) . Conclusion RVD1 can activate autophagy , alleviate myocardial apoptosis and collagen fiber deposition, and promote mitochondria⁃associated endoplasmic reticulum membranes in aging rats .

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
Humans ; Benzydamine ; Esophageal Neoplasms/drug therapy* ; Esophageal Squamous Cell Carcinoma/drug therapy* ; Molecular Docking Simulation ; Phosphorylation ; Cell Proliferation ; Cell Line, Tumor ; Apoptosis ; Cyclin-Dependent Kinase 2

Based on the theory of ascending and descending of center qi， it is believed that yang deficiency and water dampness， as well as abnormal circulation of center qi， are the core pathogenesis of psoriasis. The common pathogenic evolution of psoriasis includes wood constraint and blood stagnation， lung metal fluid exhaustion. In the later stage of psoriasis， a mixture of deficiency and excess patterns， as well as cold and heat in complexity， are often observed. Treatment focuses on warming yang and resolving dampness to restore proper qi ascending and descending， and the therapeutic formulas such as Ganjiang Lingzhu Decoction （甘姜苓术汤）， Zexie Decoction （泽泻汤）， Zhenwu Decoction （真武汤）， and Linggui Zhugan Decoction （苓桂术甘汤） are suggested based on the nature and location of the disease. To unblock the qi movement through discharging the liver and rectifying the lung， Xiaochaihu Decoction （小柴胡汤） and Danzhi Xiaoyao Powder （丹栀逍遥散） are commonly used as the foundation with modifications. To balance yin and yang through clearing the heart and nourishing the kidneys， a self-designed Changzhong Decoction （畅中汤） is utilized. Following the theory of ascending and descending of center qi， it is suggested to combine cold and warm medicinals and mediate the center earth， so as to promote the circulation of the center qi， restore the clear and the turbid， and keep four-dimensional smooth flow of qi， providing a reference for traditional Chinese medicine treatment for psoriasis.