Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Acute-on-chronic liver failure (ACLF) is a dynamic syndrome that develops on the basis of chronic liver disease. Its key characteristics include acute decompensation of chronic liver disease, severe systemic inflammatory response, and intrahepatic or extrahepatic organ failure, with an exceptionally high short-term (28-day) mortality rate. Currently, liver transplantation is the most effective treatment for ACLF. However, challenges such as liver shortages and organ allocation may lead to delays in transplantation, causing some critically ill ACLF patients to miss the optimal surgical window, thereby significantly worsening their prognosis. Conversely, some ACLF patients may achieve substantial recovery with medical management yet still undergo liver transplantation, leading to unnecessary utilization of scarce donor organs. To maximize patient survival benefits and optimize the use of valuable liver grafts, precise identification of the optimal timing for liver transplantation in ACLF is essential. This review explores the ideal timing for liver transplantation in ACLF patients by examining the definition of ACLF, commonly used scoring systems both nationally and internationally, and the latest research on transplantation indications.

OBJECTIVE To optimize the prescription pre-review system in our hospital and evaluate its application effects. METHODS Aiming at the problems of imperfect rule base and high false positive rate in the early operation of the system， optimization measures were taken， including improving the content of the rule base， adjusting the interception level and prompt mode， refining the working model of prescription review pharmacists， and strengthening clinical communication. A retrospective cohort study was conducted， with prescription data from June to December 2023 （before optimization） as the control group and June to December 2024 （after optimization） as the observation group. Through inter group comparative analysis， the actual effect of optimizing the prescription pre-approval system was evaluated. RESULTS The prescription qualified rate increased from （82.51± 4.04）% before optimization to （90.98±1.55）% after optimization； the false positive rate decreased from （20.87±1.64）% before optimization to （7.41±2.04）% after optimization. The monthly range of prescription qualified rate narrowed from 10.24% to 4.11%， and the coefficient of variation decreased from 4.92% to 1.73%. The monthly range of false positive rate slightly increased from 4.40% to 5.34%， the coefficient of variation rose from 8.32% to 26.18%. CONCLUSIONS Through multi-dimensional optimizations of the prescription pre-review system in our hospital， its prescription review efficiency has been significantly enhanced， the quality of prescriptions has steadily improved， and the accuracy of reviews has notably improved.

Objective To investigate the impact of minocycline(MC)on myocardial cell damage in rats with chronic heart failure(CHF)by regulating the hypoxia-inducible factor 1α(HIF-1α)/B-cell lymphoma-2/adenovirus E1B 19-kDa interacting protein(BNIP3).Methods All rats were randomly divided into Sham,CHF,positive drug(LP),low dose MC,high dose MC(HMC),and HMC+HIF-1α activator(DMOG)groups.Cardiac function was detected using echocardiography.HE staining,transmission electron microscopy,and TUNEL assay were used to evaluate myocardial pathology and apoptosis.Enzyme-linked immunosorbent assay was applied to quantify tumor necrosis factor α(TNF-α),interleukin-1β,superoxide dismutase(SOD),and malondialdehyde(MDA).Quantitative real-time PCR was used to detect the mRNA levels of Bcl-2 and Bcl-2-related X protein(Bax),while Western blotting was applied to detect the expres-sion of HIF-1α,BNIP3,Beclin-1,and microtubule-associated protein 1 light chain 3(LC3)proteins.Results Compared to rats in the sham group,rats from the CHF group exhibited increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),cell apoptosis rate,TNF-α,IL-1β,MDA,Bax,HIF-1α,BNIP3,Beclin-1,and LC3Ⅱ/Ⅰwith decreased left ventricular ejection fraction(LVEF),left ventricular shortening fraction(LVFS),SOD,and Bcl-2 levels(P<0.05).Compared with CHF group,rats from LP group,LMC group and HMC group exhibited decreased levels of LVEDD,LVESD,apoptosis rate,TNF-α,IL-1β,MDA,Bax,HIF-1α,BNIP3,Beclin-1,LC3Ⅱ/Ⅰ,and increased levels of LVEF,LVFS,SOD and Bcl-2(P<0.05).DMOG attenuated the protective effect of high-dose MC on myocardial cell damage in rats of the CHF group(P<0.05).Conclusion MC improves myocardial cell damage in rats of CHF group by inhibiting the HIF-1α/BNIP3 signaling pathway.

This article summarizes Professor Huang Guicheng's clinical experience in the syndrome differentiation and treatment of lumbar spinal stenosis using the theory of"diseases of tendons,bones and collaterals".It is believed that lumbar spinal stenosis be-longs to the syndrome of deficiency in the root and excess in the superficiality,and is closely related to the three zang organs of the liv-er,spleen and kidney.Deficiency of the liver and kidney leading to a lack of the source of qi and blood,insufficiency of the spleen and stomach giving rise to phlegm and blood stasis,and the invasion of wind,cold and dampness pathogens cause the disease.The key to the pathogenesis lies in the obstruction of the collaterals.Taking the principles of"nourishing the collaterals and strengthening the healthy qi,dredging the collaterals and expelling the pathogens"as the therapeutic principles,Professor Huang is proficient in using insect drugs.The medicinal power can directly reach the collaterals,so that the collaterals can be unobstructed and the qi and blood can flow smoothly,achieving the therapeutic effect of expelling the pathogens,unblocking the collaterals and restoring the healthy qi.

Objective To investigate the biomechanical differences in plantar pressure,postural stability,and plantar Visual Analogue Scale(VAS)scores between normal feet and unilateral/bilat-eral pes cavus,reveal their unique neuromechanical compensation mechanisms,and construct a sta-bility early warning model based on the minimum center of pressure(COP)trajectory classification.Methods A total of 70 patients with pes cavus from December 2023 to October 2024 were selected as study subjects,including 33 patients in the unilateral pes cavus group and 37 patients in the bilat-eral pes cavus group.During the same period,32 normal feet were included as normal foot group.A flat-panel plantar pressure testing system was used to collect dynamic plantar pressure data and COP trajectories from three groups at a self-selected walking speed.There were no statistically significant differences in baseline data such as age,gender,and body mass index among the three groups(P＞0.05).One-way analysis of variance and the Wilcoxon rank-sum test were used to compare the differences in maximum pressure,contact area,VAS scores,and the 95％confidence ellipse area of the COP among the three groups in 10 plantar regions.Results Patients with pes cavus exhibited lower peak pressure in the MF region compared to normal feet,while higher peak pressure in the M2,M3,and MH regions.Patients with bilateral pes cavus showed lower peak pressure in the T1 region compared to normal feet,and patients with unilateral pes cavus had lower peak pressure in the LH region compared to the normal group(P＜0.05).The plantar contact area in patients with pes cavus was reduced in the T1,M2,M3,M4,MF,and MH regions compared to normal feet(P＜0.05).The 95％confidence ellipse area of the COP was larger in both the bilateral and uni-lateral pes cavus groups compared to the normal foot group(P＜0.001).Unilateral pes cavus pres-ented a specific lateral COP drift(amplitude of 3 to 4 cm),which is a biomechanical manifestation of compensatory eversion of the unaffected foot.Patients with bilateral pes cavus exhibited a"bimod-al oscillation"trajectory(amplitude of 6 to 8 cm),suggesting possible vestibular-spinal regulatory dysfunction and the poorest postural stability.In the pes cavus group,there was a significant in-crease in pressure in the M2,M3,and MH regions,with peak pressures exceeding 190 kPa in pa-tients with bilateral pes cavus,which was highly correlated with plantar pain and could serve as a pain early warning threshold.Conclusion Unilateral and bilateral pes cavus exhibit significantly different neuromechanical compensation patterns.The classification based on the"lateral drift"and"bimodal oscillation"characteristics of the COP trajectory can serve as a stability early warning indi-cator for assessing fall risk.Decompression interventions targeting the key pressure regions of M2,M3,and MH(such as customized orthotic insoles)are the core strategies for alleviating pain and optimizing dynamic gait stability.

Objective To investigate the impact of minocycline(MC)on myocardial cell damage in rats with chronic heart failure(CHF)by regulating the hypoxia-inducible factor 1α(HIF-1α)/B-cell lymphoma-2/adenovirus E1B 19-kDa interacting protein(BNIP3).Methods All rats were randomly divided into Sham,CHF,positive drug(LP),low dose MC,high dose MC(HMC),and HMC+HIF-1α activator(DMOG)groups.Cardiac function was detected using echocardiography.HE staining,transmission electron microscopy,and TUNEL assay were used to evaluate myocardial pathology and apoptosis.Enzyme-linked immunosorbent assay was applied to quantify tumor necrosis factor α(TNF-α),interleukin-1β,superoxide dismutase(SOD),and malondialdehyde(MDA).Quantitative real-time PCR was used to detect the mRNA levels of Bcl-2 and Bcl-2-related X protein(Bax),while Western blotting was applied to detect the expres-sion of HIF-1α,BNIP3,Beclin-1,and microtubule-associated protein 1 light chain 3(LC3)proteins.Results Compared to rats in the sham group,rats from the CHF group exhibited increased left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),cell apoptosis rate,TNF-α,IL-1β,MDA,Bax,HIF-1α,BNIP3,Beclin-1,and LC3Ⅱ/Ⅰwith decreased left ventricular ejection fraction(LVEF),left ventricular shortening fraction(LVFS),SOD,and Bcl-2 levels(P<0.05).Compared with CHF group,rats from LP group,LMC group and HMC group exhibited decreased levels of LVEDD,LVESD,apoptosis rate,TNF-α,IL-1β,MDA,Bax,HIF-1α,BNIP3,Beclin-1,LC3Ⅱ/Ⅰ,and increased levels of LVEF,LVFS,SOD and Bcl-2(P<0.05).DMOG attenuated the protective effect of high-dose MC on myocardial cell damage in rats of the CHF group(P<0.05).Conclusion MC improves myocardial cell damage in rats of CHF group by inhibiting the HIF-1α/BNIP3 signaling pathway.

This article summarizes Professor Huang Guicheng's clinical experience in the syndrome differentiation and treatment of lumbar spinal stenosis using the theory of"diseases of tendons,bones and collaterals".It is believed that lumbar spinal stenosis be-longs to the syndrome of deficiency in the root and excess in the superficiality,and is closely related to the three zang organs of the liv-er,spleen and kidney.Deficiency of the liver and kidney leading to a lack of the source of qi and blood,insufficiency of the spleen and stomach giving rise to phlegm and blood stasis,and the invasion of wind,cold and dampness pathogens cause the disease.The key to the pathogenesis lies in the obstruction of the collaterals.Taking the principles of"nourishing the collaterals and strengthening the healthy qi,dredging the collaterals and expelling the pathogens"as the therapeutic principles,Professor Huang is proficient in using insect drugs.The medicinal power can directly reach the collaterals,so that the collaterals can be unobstructed and the qi and blood can flow smoothly,achieving the therapeutic effect of expelling the pathogens,unblocking the collaterals and restoring the healthy qi.

Acute-on-chronic liver failure (ACLF) is a dynamic syndrome that develops on the basis of chronic liver disease. Its key characteristics include acute decompensation of chronic liver disease, severe systemic inflammatory response, and intrahepatic or extrahepatic organ failure, with an exceptionally high short-term (28-day) mortality rate. Currently, liver transplantation is the most effective treatment for ACLF. However, challenges such as liver shortages and organ allocation may lead to delays in transplantation, causing some critically ill ACLF patients to miss the optimal surgical window, thereby significantly worsening their prognosis. Conversely, some ACLF patients may achieve substantial recovery with medical management yet still undergo liver transplantation, leading to unnecessary utilization of scarce donor organs. To maximize patient survival benefits and optimize the use of valuable liver grafts, precise identification of the optimal timing for liver transplantation in ACLF is essential. This review explores the ideal timing for liver transplantation in ACLF patients by examining the definition of ACLF, commonly used scoring systems both nationally and internationally, and the latest research on transplantation indications.

Objective:To study the effects of different single cell phenotypes on the prognosis of patients with intrahepatic cholangiocarcinoma by using spatial analysis, providing clues for obtaining potential immunotherapeutic targets.Methods:This study was a retrospective cohort study. A total of 41 intrahepatic cholangiocarcinoma (ICC) patients who underwent surgery in Beijing Youan Hospital Affiliated to Capital Medical University from February 2013 to June 2019 were enrolled. According to the 5-year survival situation, the patients were divided into survival group ( n=10) and death group ( n=31). A metal label-based tissue imaging mass panel containing 36 related markers was designed and constructed for staining different components in tumor samples. Through the analysis of the type and quantity of different metacluster and spatial location information and combined with the clinical outcomes of patients with information, certain metaclusters were found related to the prognosis of patients. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), paired t-test was used for comparison between groups. Measurement data with skewed distribution were expressed as median, and rank sum test was used for comparison between groups. The chi-square test was used to compare the counting data between groups. Results:36 biomarkers of 41 ICC patients were located and quantified to generate 1 476 single-cell resolution histological images. The expression information of various markers was analyzed by t-distributed Stochastic Neighbor Embedding (tSNE), and subgroups annotations (1-29) were added. It revealed that the density of metacluster 7(CD8 + T cells) was lower in survival group. The density of metacluster 16(Bcl-2 + CK7 + cancer cells) within tumors, as well as the density of metacluster 3(Vista + GB + CD11b + neutrophils) within stroma were higher in death group. Conclusion:The density of metacluster 7(Activated CD8 + T cells), metacluster 16(Bcl-2 + CK7 + tumor cells) and a novel neutrophil metacluster 3(Vista + GB + CD11b + neutrophils) correlated with ICC patients prognosis.