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.

ObjectiveTo investigate the anti-inflammatory, antioxidant, and goblet cell-stimulating effects of a suspension of Ophiopogon japonicus (L. f.) Ker Gawl. (O. japonicus, Mai Dong) extract combined with hyaluronic acid (HA) in the mouse model with dry eye disease (DED).MethodsA DED mouse model was induced using benzalkonium chloride (BAK), followed by treatment with O. japonicus extract-containing eye drops at varying concentrations. Experimental groups included a normal control, a DED model control, a positive control, and an O. japonicus extract-treated group. Corneal fluorescein staining and tear break-up time (TBUT) were used to assess tear film stability and ocular surface integrity. Enzyme-linked immunosorbent assay (ELISA) measured inflammatory factor levels in corneal and conjunctival tissues, whereas Western blot (WB) analyzed key antioxidant and inflammatory markers, including nuclear factor erythroid 2-related factor (2Nrf2) and heme oxygenase 1 (HO-1). Periodic acid-schiff (PAS) staining and immunofluorescence were used to evaluate goblet cell density and mucin secretion.ResultsO. japonicus extract significantly improved corneal damage, reduced fluorescein staining scores, prolonged TBUT, and increased tear secretion. It downregulated inflammatory markers, including interleukin-8 (IL-8), interleukin-1β (IL-1β), and interferon-γ (IFN-γ) while upregulating Nrf2, HO-1, and the interleukin-13 (IL-13)/IFN-γ ratio, alleviating oxidative stress and inflammation. PAS staining showed increased conjunctival goblet cell density and restored mucin secretion, enhancing tear film stability.ConclusionO. japonicus extract demonstrated significant anti-inflammatory, antioxidant, and goblet cell-stimulating effects in a DED model, with good biocompatibility and promising therapeutic potential. Future research should optimize extraction processes and validate their efficacy and safety in clinical settings.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Studies have suggested that the nucleus accumbens (NAc) is implicated in the pathophysiology of major depression; however, the regulatory strategy that targets the NAc to achieve an exclusive and outstanding anti-depression benefit has not been elucidated. Here, we identified a specific reduction of cyclic adenosine monophosphate (cAMP) in the subset of dopamine D1 receptor medium spiny neurons (D1-MSNs) in the NAc that promoted stress susceptibility, while the stimulation of cAMP production in NAc D1-MSNs efficiently rescued depression-like behaviors. Ketamine treatment enhanced cAMP both in D1-MSNs and dopamine D2 receptor medium spiny neurons (D2-MSNs) of depressed mice, however, the rapid antidepressant effect of ketamine solely depended on elevating cAMP in NAc D1-MSNs. We discovered that a higher dose of crocin markedly increased cAMP in the NAc and consistently relieved depression 24 h after oral administration, but not a lower dose. The fast onset property of crocin was verified through multicenter studies. Moreover, crocin specifically targeted at D1-MSN cAMP signaling in the NAc to relieve depression and had no effect on D2-MSN. These findings characterize a new strategy to achieve an exclusive and outstanding anti-depression benefit by elevating cAMP in D1-MSNs in the NAc, and provide a potential rapid antidepressant drug candidate, crocin.

ObjectiveTo explore the underlying mechanism by which the Chinese medicine compound Yitangkang granule（YTK） treats diabetic kidney disease （DKD） by observing its effects on podocyte autophagy through the regulation of phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/forkhead transcription factor O1 （FoxO1） signaling pathway mediated by silent information regulator 1 （SIRT1） via advanced glycation end products （AGE）/receptor for AGE （RAGE） axis. MethodNinety-six 8-week-old healthy male SPF-grade Wistar rats were selected and randomly divided into blank control group （B）， model control group， high-dose YTK （40 g·kg^-1）， medium-dose YTK （20 g·kg^-1）， low-dose YTK （10 g·kg^-1）， and Western medicine control （20 mg·kg^-1 losartan） groups. The DKD rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin. After successful modeling， the rats in each group received the corresponding treatments for eight weeks. The levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and catalase （CAT） were measured according to the instructions of the respective assay kits. Hematoxylin and eosin （HE） staining was used to observe pathological changes in kidney tissues. Immunohistochemistry was employed to detect the average optical density values of α-smooth muscle actin （α-SMA）， fibronectin （FN）， desmin， and nephrin. Western blot analysis was used to measure the expression levels of PI3K， phosphorylated PI3K （p-PI3K）， Akt， phosphorylated Akt （p-Akt）， RAGE， SIRT1， Caspase-3， and FoxO1 proteins in kidney tissues of DKD rats. ResultCompared with the blank control group， the model group showed significantly lower levels of SOD， GSH-Px， and CAT， and significantly higher levels of MDA （P<0.01）. The rats exhibited severe kidney damage. The positive expression of podocyte marker proteins α-SMA， FN， and desmin increased significantly， while nephrin and podocin significantly decreased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 proteins were significantly elevated， while SIRT1 and FoxO1 protein levels were significantly reduced （P<0.01）. Compared with the model control group， rats in the YTK treatment groups showed significantly higher levels of SOD， GSH-Px， and CAT， and significantly lower levels of MDA in serum （P<0.01）. The degree of kidney damage was reduced to varying extents. The average optical density values of podocyte marker proteins α-SMA， FN， and desmin were significantly decreased， while nephrin and podocin significantly increased （P<0.01）. The expression levels of PI3K， p-PI3K， Akt， p-Akt， RAGE， and Caspase-3 in kidney tissues were significantly reduced， while SIRT1 and FoxO1 expression levels significantly increased （P<0.01）. The Chinese medicine groups demonstrated a clear dose-response trend. ConclusionYTK may alleviate kidney pathological damage， reduce proteinuria， and protect kidney function in DKD rats， thereby delaying the progression of DKD by improving podocyte autophagy through the AGE-RAGE axis-mediated SIRT1 regulation of the PI3K/Akt/FoxO1 signaling pathway. Additionally， a dose-response relationship was observed in the Chinese medicine groups.

Objective:To evaluate the efficacy of oral midazolam solution for preoperative sedation in the pediatric outpatients undergoing root canal treatment under general anesthesia.Methods:One hundred and forty-seven pediatric patients of either sex, aged 2-7 yr, weighing 10-30 kg, of American Society of Anesthesiologists Physical Status classificationⅠ or Ⅱ, were divided into 3 groups ( n=49 each) using a random number table method: oral midazolam solution group (OM group), midazolam injection group (M group), and dexmedetomidine group (D group). In OM group, patients received oral midazolam solution at a dose of 0.5 mg/kg along with a placebo (an equivalent amount of normal saline based on body weight) administered via nasal drops. In M group, patients were given oral midazolam injection at a dose of 0.5 mg/kg along with a placebo via nasal drops. In D group, patients were administered a placebo orally along with dexmedetomidine at a dose of 2 μg/kg via nasal drops. The Induction Compliance Checklist (ICC) scores upon entering the operating room, sedation success rates (ICC score ≤ 3), drug acceptance scores, mask acceptance scores, and separation anxiety scores were recorded. The emergence time, time of stay in postanesthesia care unit (PACU), and occurrence of adverse events such as bradycardia, hypotension, hypoxemia, and laryngospasm during surgery and in PACU were recorded. Results:A total of 143 pediatric patients were finally included in the study, with 48 cases in OM group, 48 cases in M group and 47 cases in D group. Compared with M and D groups, the ICC scores upon entry to the operating room were significantly decreased, the sedation success rates were increased, drug acceptance scores were increased, separation anxiety scores were decreased, and mask acceptance scores were decreased in OM group ( P<0.05). Compared with D group, the ICC scores upon entry to the operating room were significantly decreased, the sedation success rates were increased, and mask acceptance scores were decreased in M group ( P<0.05). There were no statistically significant differences in the emergence time, time of stay in PACU, and incidence of adverse events during surgery and in PACU among the three groups ( P>0.05). Conclusions:Oral midazolam solution provides good effect with less adverse reactions when used for preoperative sedation in the pediatric outpatients undergoing root canal treatment under general anesthesia.

Objective To explore the primary etiology of pregnancy complicated with pulmonary hypertension,analyze the pregnancy outcome and related influencing factors of patients,and provide new evidence-based medical data for guiding the pregnancy management of these patients.Methods A total of 57 pregnant women with pulmonary hypertension who terminated their pregnancy in the General Hospital of Northern Theater Command were selected and divided into the mild group(26 cases),the moderate group(20 cases)and the severe group(11 cases)according to the severity of pulmonary hypertension,and 138 pregnant women with normal pulmonary artery pressure during the same period were selected as the control group.The clinical data of pregnant women in all groups were collected and compared,and the primary etiology of pulmonary hypertension,the pregnancy outcome of patients with different severity of pulmonary hypertension and its related influencing factors were analyzed.Results Congenital heart disease(CHD)was the main primary etiology of pregnant women with pulmonary hypertension,accounting for 63.2%.There was significant difference in the proportion of patients with complex CHD in different groups(P<0.05).The proportion of patients with grade Ⅲ to Ⅳ heart function in the severe group was significantly higher than those in the control group,the mild group and the moderate group,with statistically significant differences(P<0.05).The proportion of patients with abnormal electrocardiogram in the severe group was higher than those in the mild group and the control group,and the differences were statistically significant(P<0.05).The delivery rate of full-term live infants in the control group and the mild group were much higher than those in the moderate group and the severe group,and the differences were statistically significant(P<0.05).The stillbirth rate in the severe group was higher than those in the other groups,and the differences were statistically significant(P<0.05).The neonatal asphyxia rate in the control group and the mild group were lower than those in the moderate group and the severe group,and the differences were statistically significant(P<0.05).The birth weight of newborns in the control group and the mild group were higher than those in the moderate group and the severe group,and the differences were statistically significant(P<0.05).Conclusion The most common primary etiology of pregnancy complicated with pulmonary hypertension is CHD.Pregnant women with mild or moderate pulmonary hypertension have lower risk of adverse pregnancy outcomes than pregnant women with severe pulmonary hypertension.Doppler two-dimensional ultrasound evaluation and monitoring of pulmonary artery pressure of pregnant women can be used to intervene in time to improve pregnancy and fetal outcome.

Purpose: The prognosis of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) is extremely poor, and systemic therapy is currently the mainstream treatment. This study aimed to assess the efficacy and safety of lenvatinib combined with anti–programmed cell death-1 antibodies and transcatheter arterial chemoembolization (triple therapy) in patients with HCC and PVTT. Materials and Methods: This retrospective multicenter study included patients with HCC and PVTT who received triple therapy, were aged between 18 and 75 years, classified as Child-Pugh class A or B, and had at least one measurable lesion. The overall survival (OS), progression-free survival (PFS), objective response rates, and disease control rates were analyzed to assess efficacy. Treatment-related adverse events were analyzed to assess safety profiles. Results: During a median follow-up of 11.23 months (range, 3.07 to 34.37 months), the median OS was greater than 24 months, and median PFS was 12.53 months. The 2-year OS rate was 54.9%. The objective response rate and disease control rate were 69.8% (74/106) and 84.0% (89/106), respectively; 20.8% (22/106) of the patients experienced grade 3/4 treatment-related adverse events and no treatment-related deaths occurred. The conversion rate to liver resection was 31.1% (33/106), with manageable postoperative complications. The median OS was not reached in the surgery group, but was 19.08 months in the non-surgery group. The median PFS in the surgery and non-surgery groups were 20.50 and 9.00 months, respectively. Conclusion Triple therapy showed promising survival benefits and high response rates in patients with HCC and PVTT, with manageable adverse effects.

Objective To explore the clinical application of salpingectomy with preserving salpingum mesothelium under single-port laparoscopy and its influence on ovarian reserve function and assisted pregnancy outcome.Methods From January 2019 to January 2022,80 cases of salpingectomy in Shuangyashan Double Mine Hospital were selected and randomly divided into control group(n=40)and observation group(n=40).The control group was treated with multi-hole laparoscopic salpingectomy with salpingum mesothelium preserved,while the observation group treated with single-hole laparoscopic salpingectomy with salpingum mesothelium preserved.The operation conditions(operation time,intraoperative blood loss,exhaust time,etc.),anti-Mullerian hormone(AMH)before and one month after operation,ovarian function(basal sinus follicle count),postoperative complications,assisted pregnancy outcome and cosmetic effect were analyzed.Results The exhaust time and postoperative hospitalization time in the observation group were shorter than those in the control group,and the operation time was longer than that in the control group(P＜0.05).One month after operation,AMH in both groups decreased,and the number of sinus follicles in observation group A was lower than that in control group.The complication rate was lower than that of the control group(P＜0.05).After a one-year follow-up,there was no significant difference in ovulation rate and pregnancy rate between the two groups(P＞0.05).Follow-up for 3 months showed that the cosmetic effect of the observation group was better than that of the control group(95.00％vs 72.50％)(P＜0.05).Conclusion Single-port laparoscopic salpingectomy with salpingum mesothelium preservation is safe,cosmetic and minimally invasive,and has little adverse effect on ovarian reserve function,which is helpful for successful pregnancy assistance and worthy of clinical application and promotion.

Objective: To verify the feasibility and accuracy of the transanal multipoint full-layer puncture biopsy (TMFP) technique in determining the residual status of cancer foci after neoadjuvant therapy (nCRT) in rectal cancer. Methods: Between April 2020 and November 2022, a total of 78 patients from the Beijing Chaoyang Hospital of Capital Medical University, the Beijing Friendship Hospital of Capital Medical University, the Qilu Hospital of Shandong University, the Zhongnan Hospital of Wuhan University with advanced rectal cancer received TMFP after nCRT participated in this prospective multicenter trial. There were 53 males and 25 females, aged (M(IQR)) 61 (13) years (range: 35 to 77 years). The tumor distance from the anal verge was 5 (3) cm (range: 2 to 10 cm). The waiting time between nCRT and TMFP was 73 (26) days (range: 33 to 330 days). 13-point transanal puncture was performed with a 16 G tissue biopsy needle with the residual lesion as the center. The specimens were submitted for independent examination and the complications of the puncture were recorded. The consistency of TMFP and radical operation specimen was compared. The consistency of TMPF with clinical remission rates for the diagnosis of complete pathological remission was compared by sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Statistical analysis between groups was performed using the χ² analysis, and a paired χ² test was used to compare diagnostic validity. Results: Before TMFP, clinical complete response (cCR) was evaluated in 27 cases. Thirty-six cases received in vivo puncture, the number of punctures in each patient was 13 (8) (range: 4 to 20), 24 cases of tumor residue were found in the puncture specimens. The sensitivity to judgment (100% vs. 60%, χ²=17.500, P<0.01) and accuracy (88.5% vs. 74.4%, χ²=5.125, P=0.024) of TMFP for the pathologic complete response (pCR) were significantly higher than those of cCR. Implement TMFP based on cCR judgment, the accuracy increased from 74.4% to 92.6% (χ²=4.026, P=0.045). The accuracy of the in vivo puncture was 94.4%, which was 83.3% of the in vitro puncture (χ²=1.382, P=0.240). Overall, the accuracy of TMFP improved gradually with an increasing number of cases (χ²=7.112, P=0.029). Conclusion: TMFP is safe and feasible, which improves the sensitivity and accuracy of rectal cancer pCR determination after nCRT, provides a pathological basis for cCR determination, and contributes to the safe development of the watch and wait policy.