Objective To establish a model of radiation-induced myocardial fibrosis in mice, and study the effect of TGF-β/SMAD pathway on radiation-induced myocardial fibrosis in mice and the protective effect of pirfenidone capsules (PFD) on radiation-induced myocardial fibrosis. Methods Male C57BL/6J mice were randomly divided into control group, irradiation group, and drug intervention groups (low-dose PFD + irradiation group and high-dose PFD + irradiation group). After radiation exposure, the control group and the irradiation group were given sodium carboxymethyl cellulose by gavage, while the low-dose PFD + irradiation group and the high-dose PFD + irradiation group were given PFD at 150 and 300 mg/kg daily by gavage for 12 consecutive weeks, respectively. The body weights of mice were measured and recorded weekly. The pathological changes of heart tissues in mice were observed by H&E and Masson’s trichrome staining. The expression levels of TGF-β, SMAD2, and SMAD3 mRNAs in mouse heart tissues were detected by RT-PCR. The expression levels of TGF-β, SMAD2, and SMAD3 proteins in mouse heart tissues were detected by Western blot. The expression levels of CK and CK-MB in mouse heart tissues were detected by blood biochemical tests. Results H&E and Masson’s trichrome staining showed severe myocardial fibrosis in the irradiation group compared with the control group. Compared with the irradiation group, the two groups with drug intervention showed reduced heart disease and myocardial fibrosis. RT-PCR and Western blot showed that the expression levels of TGF-β, SMAD2, and SMAD3 were up-regulated in the irradiation group compared with the other three groups (P < 0.05). The expression levels of TGF-β, SMAD2, and SMAD3 were down-regulated in the two groups treated with PFD compared with the irradiation group (P < 0.05). The expression levels of CK and CK-MB in mouse heart tissues were down-regulated in the two groups treated with PFD compared to irradiation group (P < 0.05). Conclusion Radiation has long-term effects on normal heart tissue, causing myocardial damage and promoting myocardial fibrosis. The up-regulation of TGF-β/SMAD pathway is related to the formation of radiation-induced myocardial fibrosis. PFD can mitigate the progression of myocardial fibrosis and protect heart tissue by down-regulating TGF-β/SMAD pathway.

Diabetic cataract, a prevalent ocular complication of diabetes mellitus, arises from a complex interplay of pathological mechanisms, with oxidative stress and glycation stress playing central roles. Autophagy, a critical cellular self-protection mechanism, sustains intracellular homeostasis by selectively degrading damaged organelles and misfolded proteins, thereby counteracting the detrimental effects of oxidative and glycation stress under hyperglycemic conditions. Emerging evidence indicates a synergistic interaction between glycation stress and oxidative stress, which may exacerbate autophagic dysfunction and accelerate the onset and progression of diabetic cataract. However, the precise molecular mechanisms underlying this relationship remain incompletely understood. This review systematically examines the regulatory role of autophagy inthe pathogenesis of diabetic cataract, with a particular focus on how autophagic impairment influences disease progression under the combined effects of glycation and oxidative stress. By elucidating these mechanisms, the paper aims to provide novel insights into molecular diagnostic approaches and targeted therapeutic strategies for diabetic cataract.

ObjectiveTo investigate a suspected outbreak of healthcare-associated infection with carbapenem-resistant Klebsiella pneumoniae (CRKP) in a geriatric emergency ward, and to provide references for the prevention and control of multidrug-resistant bacteria in a hospital in Shanghai. MethodsOn-site epidemiological investigation, combined with environmental hygiene monitoring and pulsed field gel electrophoresis (PFGE) molecular typing method, were adopted to investigate a suspected outbreak of CRKP infection in the geriatric emergency ward of a hospital from October to November 2022, aiming at finding out factors caused the outbreak before taking corresponding control measures. ResultsA total of 3 cases of healthcare-associated CRKP infection were identified, of which 2 cases were homologous to a previous case of community-associated CRKP infection. What’s more, the 2 cases lived in the same ward with the latter and with adjacent beds, but the third case was non-homologous to the community-associated infection case. A total of 46 samples were collected from the environmental surfaces and the hands of healthcare workers, of which 7 samples tested positive for CRKP and were identical to the strains from the 2 healthcare-associated infection cases and the 1 community-associated infection case, originating from the bedrails, bedside tables, surface of non-invasive ventilator, bed curtains and panels of monitoring equipment, with a detection rate of 15.22%. But none of the 11 samples from the hands of healthcare workers tested positive for CRKP. The outbreak was effectively controlled after taking specific prevention and control measures such as strengthening personnel management, intensifying environmental cleaning and disinfection and strictly enforcing hand hygiene among healthcare workers. Subsequently, no similar new cases were reported during the 14-day follow-up period. ConclusionIncomplete environmental cleaning and disinfection, as well as inadequate enforcement of hand hygiene among heatheare workers may have contributed to the suspected outbreak of CRKP in the geriatric emergency ward. Early warning and timely investigation of suspected outbreaks of multidrug-resistant bacteria are crucial for preventing and controlling such outbreaks in hospitals.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.
Humans ; Drugs, Chinese Herbal/pharmacology* ; COVID-19 Drug Treatment ; SARS-CoV-2/drug effects* ; COVID-19/therapy* ; Medicine, Chinese Traditional/methods* ; Antiviral Agents/pharmacology* ; Animals

Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

OBJECTIVE: Acupuncture therapies are known for their effectiveness in treating a variety of gastric diseases, although the mechanisms underlying these effects are not fully understood. This study tested the effectiveness of electroacupuncture (EA) at acupoints Zhongwan (RN12) and Weishu (BL21) for managing gastric motility disorder (GMD) and investigated the underlying mechanisms involved. METHODS: A GMD model was used to evaluate the impact of EA on various aspects of gastric function including the amplitude of gastric motility, electrogastrogram, food intake, and the rate of gastric emptying. Immunofluorescence techniques were used to explore the activation of spinal neurons by EA, specifically examining the presence of cholera toxin B subunit (CTB)-positive neurons and fibers emanating from acupoints RN12 and BL21. The stimulation of γ-aminobutyric acid (GABA)-ergic neurons in the spinal dorsal horn, the inhibition of sympathetic preganglionic neurons in the spinal lateral horn, and their collective effects on the activity of sympathetic nerves were examined. RESULTS: EA at RN12 and BL21 significantly improved gastric motility compromised by GMD. Notably, EA activated spinal neurons, with CTB-positive neurons and fibers from RN12 and BL21 being detectable in both the dorsal root ganglia and the spinal dorsal horn. Further analysis revealed that EA at these acupoints not only stimulated GABAergic neurons in the spinal dorsal horn but also suppressed sympathetic preganglionic neurons in the spinal lateral horn, effectively reducing excessive activity of sympathetic nerves triggered by GMD. CONCLUSION EA treatment at RN12 and BL21 effectively enhances gastric motility in a GMD model. The therapeutic efficacy of this approach is attributed to the activation of spinal neurons and the modulation of the spinal GABAergic-sympathetic pathway, providing a neurobiological foundation for the role of acupuncture in treating gastric disorders. Please cite this article as: Zhang MT, Liang YF, Dai Q, Gao HR, Wang H, Chen L, Huang S, Wang XY, Shen GM. A spinal neural circuit for electroacupuncture that regulates gastric functional disorders. J Integr Med. 2025; 23(1): 56-65.
Electroacupuncture ; Animals ; Male ; Acupuncture Points ; Stomach Diseases/physiopathology* ; Rats, Sprague-Dawley ; Gastrointestinal Motility ; Rats ; Gastric Emptying ; Neurons ; Spinal Cord ; Stomach/physiopathology*

Objective To explore the clinical efficacy of dual plasma molecular adsorption(DPMAS)sequential plasma exchange(PE)artificial liver mode in the treatment of liver failure(LF).Methods Eighty-five patients with LF receiving the artificial liver treatment in the Affiliated Hospital of Zunyi Medical Univer-sity from January 2020 to December 2023 were selected as the study subjects and divided into the study group(n=52)and the control group(n=33)according to the different treatment modes.The study group conduc-ted DPMAS sequential PE treatment and the control group underwent the PE treatment.The liver function[total bilirubin(TBIL),alanine aminotransferase(ALT),aspartate aminotransferase(AST),serum albumin(ALB),globulin(GLO),prealbumin(PAB)],Hb,coagulation function[platelet(PLT),plasminogen activity(PTA),international normalized ratio(INR),fibrinogen(FIB)]before treatment and at 24 h after treatment were compared between the two groups.Results Compared with before treatment,the levels of TBIL,ALT,AST,GLO and Hb after the first and second treatment in the two groups were decreased,ALB level in the control group and PAB level after the second time treatment was increased(P＜0.05).Compared with after the first treatment,the levels of TBIL,ALT and GLO after the second treatment in the two groups and the levels of AST and Hb in the study group were decreased,ALB level in the study group and PAB level in the two groups were increased(P＜0.05).Compared with before treatment,the levels of PLT and FIB after the first treatment in the two groups and INR level in the control group were decreased,PTA level in the control group was increased(P＜0.05).Compared with before treatment,the levels of PLT,INR and FIB after the second treatment in the two groups were decreased,PTA level was increased(P＜0.05).Compared with be-fore treatment,the levels of PLT,INR and FIB after the second treatment in the two groups were decreased,and PTA level was increased(P＜0.05).Compared with after the first treatment,PTA level after the second treatment in the study group was increased and INR level was decreased.Conclusion PE and DPMAS sequen-tial PE all could improve the liver function in the patients with LF,moreover the two times treatment has more significant effect.

Advancements in artificial intelligence(AI)and emerging technologies are rapidly expanding the exploration of chemical space,facilitating innovative drug discovery.However,the transformation of novel compounds into safe and effective drugs remains a lengthy,high-risk,and costly process.Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development.Despite this need,no comprehensive tool currently supports systematic evaluation and efficient screening.Here,we present druglikeFilter,a deep learning-based framework designed to assess drug-likeness across four critical dimensions:1)physicochemical rule evaluated by systematic determination,2)toxicity alert investigated from multiple perspectives,3)binding affinity measured by dual-path analysis,and 4)compound synthesizability assessed by retro-route prediction.By enabling automated,multidimensional filtering of compound libraries,druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates,which can be freely accessed at https://idrblab.org/drugfilter/.

Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.