Thousands of variant gene sequences of SARS-CoV-2 have been emerged since the COVID-19 epidemic broke out in Dec.2019.Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.1),Delta(B.1.617.2)and Omicron(B.1.1.529)were the most representative variants.With the continuous emergence of new variants,the predomi-nant strain in the global pandemic as of Jan.2025 is the Omicron BA.2.86-derived mutant,JN.1.The effectiveness of drugs against Omicron variants remains a key research focus in the treatment of SARS-CoV-2 infections.The infectiousness and pathogenicity of the variants altered remarkably due to mutations in the genome on S protein of the mutant strains,and these emerging variants are more likely to evade immunity and were more infectious than the previous prevalent variants.During the process of combating with the constantly emerging novel variants,drugs showed various effects on treatment of diseases caused by different variants.New drugs and treatment coun-termeasures are constantly updated with the prevalence of various variants.The current status of research on pres-ent drugs for treatment of SARS-CoV-2 and the therapeutic effects on emerging variants are reviewed in the article so as to provide reference for prevention and treatment of the upcoming evolved variants.

Thousands of variant gene sequences of SARS-CoV-2 have been emerged since the COVID-19 epidemic broke out in Dec.2019.Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.1),Delta(B.1.617.2)and Omicron(B.1.1.529)were the most representative variants.With the continuous emergence of new variants,the predomi-nant strain in the global pandemic as of Jan.2025 is the Omicron BA.2.86-derived mutant,JN.1.The effectiveness of drugs against Omicron variants remains a key research focus in the treatment of SARS-CoV-2 infections.The infectiousness and pathogenicity of the variants altered remarkably due to mutations in the genome on S protein of the mutant strains,and these emerging variants are more likely to evade immunity and were more infectious than the previous prevalent variants.During the process of combating with the constantly emerging novel variants,drugs showed various effects on treatment of diseases caused by different variants.New drugs and treatment coun-termeasures are constantly updated with the prevalence of various variants.The current status of research on pres-ent drugs for treatment of SARS-CoV-2 and the therapeutic effects on emerging variants are reviewed in the article so as to provide reference for prevention and treatment of the upcoming evolved variants.

Objective To construct a prediction model for in-hospital mortality in the elderly(≥65 years)patients undergoing unsynchronous cardioversion in ICU and to evaluate its effectiveness.Methods A retrospective study was conducted on 276 elderly eligible patients in the ICU of the Ninth and the First Medical Centers of Chinese PLA General Hospital between June 2022 and August 2024.According to their clinical outcomes,they were divided into a non-in-hospital dead group(111 cases)and an in-hospital dead group(165 cases).Clinical data were collected,and pre-dictive factors for in-hospital mortality were screened.And then a nomogram prediction model was developed based on the obtained predictive factors,which was evaluated with ROC curve and deci-sion curve analyses.Results When compared to the non-in-hospital dead group,the in-hospital dead group had significantly higher heart rate,ratio of hemodialysis,and levels of alanine amin-otransferase,aspartate aminotransferase,lactate dehydrogenase,alkaline phosphatase,serum cre-atinine,blood glucose,lactate,low base excess,sequential organ failure assessment(SOFA)score,model for end-stage liver disease score,and larger proportions of ventricular fibrillation/flutter and structural heart disease induced by pulseless ventricular tachycardia,and had significantly lower Glasgow Coma Scale(GCS)(P＜0.05).Multivariate logistic regression analysis identified body temperature＞37℃(OR=0.426,95％CI:0.198-0.915,P=0.029),chronic obstructive pulmonary disease(OR=2.333,95％CI:1.217-4.473,P=0.011),GCS score(OR=0.622,95％CI:0.410-0.944,P=0.026),hemoglobin(OR=0.817,95％CI:0.715-0.934,P=0.003),lactate(OR=1.365,95％CI:1.174-1.587,P=0.000),heart rate＞100 bpm(OR=2.757,95％CI:1.397-5.441,P=0.003),and SOFA score(OR=1.112,95％CI:1.032-1.198,P=0.005)as pre-dictors of in-hospital mortality.ROC curve analysis showed an AUC value of above indicators combined together in the prediction was 0.797,with a sensitivity of 76.97％and a specificity of 65.77％.Calibration curve analysis demonstrated good consistency between predicted and observed outcomes.Decision curve analysis indicated favorable clinical utility of the model.Conclusion This study identifies independent risk factors for in-hospital mortality among elderly patients in the ICU who underwent asynchronous cardioversion.Based on these factors,a nomo-gram model is established,demonstrating good discrimination,calibration,and model fit,with high clinical applicability.

The prefrontal cortex (PFC) plays a pivotal role in orchestrating higher-order emotional and cognitive processes, a function that depends on the precise modulation of synaptic activity. Although pharmacological studies have demonstrated that dopamine signaling through dopamine D1 receptor (DRD1) in the PFC is essential for these functions, the cell-type-specific and molecular mechanisms underlying the neuromodulatory effects remain elusive. Using cell-type-specific knockout mice and patch-clamp recordings, we investigated the regulatory role of DRD1 on neurons and astrocytes in synaptic transmission and plasticity. Furthermore, we explored the mechanisms by which DRD1 on astrocytes regulate synaptic transmission and plasticity at the cellular level, as well as emotional and cognitive functions at the behavioral level, through two-photon imaging, microdialysis, high-performance liquid chromatography, transcriptome sequencing, and behavioral testing. We found that conditional knockout of the Drd1 in astrocytes (CKO^AST) increased glutamatergic synaptic transmission and long-term potentiation (LTP) in the medial prefrontal cortex (mPFC), whereas Drd1 deletion in pyramidal neurons did not affect synaptic transmission. The elevated level of d-serine in the mPFC of CKO^AST mice increased glutamatergic transmission and LTP through NMDA receptors. In addition, CKO^AST mice exhibited abnormal emotional and cognitive function. Notably, these behavioral changes in CKO^AST mice could be reversed through the administration of d-serine degrease to the mPFC. These results highlight the critical role of the astrocytic DRD1 in modulating mPFC synaptic transmission and plasticity, as well as higher brain functions through d-serine, and may shed light on the treatment of mental disorders.

Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.

Objective To construct a prediction model for in-hospital mortality in the elderly(≥65 years)patients undergoing unsynchronous cardioversion in ICU and to evaluate its effectiveness.Methods A retrospective study was conducted on 276 elderly eligible patients in the ICU of the Ninth and the First Medical Centers of Chinese PLA General Hospital between June 2022 and August 2024.According to their clinical outcomes,they were divided into a non-in-hospital dead group(111 cases)and an in-hospital dead group(165 cases).Clinical data were collected,and pre-dictive factors for in-hospital mortality were screened.And then a nomogram prediction model was developed based on the obtained predictive factors,which was evaluated with ROC curve and deci-sion curve analyses.Results When compared to the non-in-hospital dead group,the in-hospital dead group had significantly higher heart rate,ratio of hemodialysis,and levels of alanine amin-otransferase,aspartate aminotransferase,lactate dehydrogenase,alkaline phosphatase,serum cre-atinine,blood glucose,lactate,low base excess,sequential organ failure assessment(SOFA)score,model for end-stage liver disease score,and larger proportions of ventricular fibrillation/flutter and structural heart disease induced by pulseless ventricular tachycardia,and had significantly lower Glasgow Coma Scale(GCS)(P＜0.05).Multivariate logistic regression analysis identified body temperature＞37℃(OR=0.426,95％CI:0.198-0.915,P=0.029),chronic obstructive pulmonary disease(OR=2.333,95％CI:1.217-4.473,P=0.011),GCS score(OR=0.622,95％CI:0.410-0.944,P=0.026),hemoglobin(OR=0.817,95％CI:0.715-0.934,P=0.003),lactate(OR=1.365,95％CI:1.174-1.587,P=0.000),heart rate＞100 bpm(OR=2.757,95％CI:1.397-5.441,P=0.003),and SOFA score(OR=1.112,95％CI:1.032-1.198,P=0.005)as pre-dictors of in-hospital mortality.ROC curve analysis showed an AUC value of above indicators combined together in the prediction was 0.797,with a sensitivity of 76.97％and a specificity of 65.77％.Calibration curve analysis demonstrated good consistency between predicted and observed outcomes.Decision curve analysis indicated favorable clinical utility of the model.Conclusion This study identifies independent risk factors for in-hospital mortality among elderly patients in the ICU who underwent asynchronous cardioversion.Based on these factors,a nomo-gram model is established,demonstrating good discrimination,calibration,and model fit,with high clinical applicability.

Objective:To observe the clinical efficacy of manual therapy based on the Discovery of Posture Secret (DPS) in treating adolescent idiopathic scoliosis (AIS).Methods:Thirty-six AIS patients were randomly divided into an observation group of 17 and a control group of 16. In addition to 10 minutes of side-shift training each week, the control group was given 20 minutes of sling exercise training (SET), while the observation group underwent weekly 20-minute manual therapy sessions based on DPS on the days without SET. Before and after the 4 weeks of treatment spine curvature (Cobb angle), clavicular angle (CA), angle of trunk rotation (ATR) and vertebral rotation (VR) were measured, and the Scoliosis Research Society′s patient questionnaire 22 (SRS-22) was administered.Results:After the treatment the average Cobb angle, CA, ATR and SRS-22 score of the observation group had improved significantly compared with before the treatment. The average Cobb angle, ATR and SRS-22 score of the control group were also significantly higher, but the improvements were not as great as in the observation group. There was no significant difference in VR improvement between the two groups.Conclusion:Manual therapy based on the DPS can effectively ameliorate the scoliosis and shoulder imbalance of AIS patients.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Venous thromboembolism (VTE) is a complication in children with acute lymphoblastic leukemia (ALL). The Chinese Children's Cancer Group-ALL-2015 protocol was carried out in China, and epidemiology, clinical characteristics, and risk factors associated with VTE were analyzed. We collected data on VTE in a multi-institutional clinical study of 7640 patients with ALL diagnosed in 20 hospitals from January 2015 to December 2019. First, VTE occurred in 159 (2.08%) patients, including 90 (56.6%) during induction therapy and 108 (67.92%) in the upper extremities. T-ALL had a 1.74-fold increased risk of VTE (95% CI 1.08-2.8, P = 0.022). Septicemia, as an adverse event of ALL treatment, can significantly promote the occurrence of VTE (P < 0.001). Catheter-related thrombosis (CRT) accounted for 75.47% (n = 120); and, symptomatic VTE, 58.49% (n = 93), which was more common in patients aged 12-18 years (P = 0.023), non-CRT patients (P < 0.001), or patients with cerebral thrombosis (P < 0.001). Of the patients with VTE treated with anticoagulation therapy (n = 147), 4.08% (n = 6) had bleeding. The VTE recurrence rate was 5.03% (n = 8). Patients with VTE treated by non-ultrasound-guided venous cannulation (P = 0.02), with residual thrombus (P = 0.006), or with short anticoagulation period (P = 0.026) had high recurrence rates. Thus, preventing repeated venous puncture and appropriately prolonged anticoagulation time can reduce the risk of VTE recurrence.
Humans ; Child ; Venous Thromboembolism/etiology* ; East Asian People ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/epidemiology* ; Risk Factors ; Thrombosis/chemically induced* ; China/epidemiology* ; Anticoagulants/adverse effects* ; Recurrence

One hundred Alzheimer′s disease (AD) patients with behavioral and psychological symptoms of dementia (BPSD) treated with donepezil+risperidone group ( n=50, group 1) or hydrochloride memantine+risperidone group ( n=50, group 2) in geriatric departments of Hangzhou Seventh People′s Hospital were enrolled in the study. Montreal cognitive assessment scale (MoCA), positive and negative syndrome scale (PANSS), treatment emergent symptom scale (TESS) were applied for evaluation; and blood routine examination, blood biochemistry, eletrocardiogram were performed in two groups before and after treatment. After treatment, MoCA score in group 2 (16.10±3.90) was significantly higher than that in group 1 (18.14±3.71)( t=-3.99, P<0.01), and PANSS score in group 2 (86.66±6.62) was significantly lower than that in group 1 (109.50±11.51; t=12.67, P<0.01). The incidence rates of dry mouth (16%,8/50), extrapyramidal side effects (10%,5/50) and the total score of TESS (3.92±2.02) in group 2 were markedly lower than those of group 1 [44%(22/50), 36%(18/50), (12.49±1.45);χ 2=9.33,9.54, t=17.90,all P<0.01]. Meanwhile, group 2 had significantly lower influences on the levels of blood lipids and fasting blood glucose (all P<0.01). The risperidone dose used in group 2 was significantly lower than that in group 1 [(2.06±0.50) vs. (3.85±0.89)mg, t=14.40, P=0.04].The results suggest that hydrochloridememantine combined with risperidone is more effective with less side effects compared to donepezil combined with risperidone for AD patients with BPSD.