Objective : To investigate the protective effect of dimethyl fumarate(DMF) on maternal intrahepatic cholestasis(ICP) during pregnancy induced by di(2-ethylhexyl) phthalate(DEHP) exposure and its mechanism. Methods : Thirty-two 8-week-old female institute of cancer research(ICR) mice were randomly divided into 4 groups: Ctrl group, DEHP group, DMF group and DEHP+DMF group. DEHP and DEHP+DMF groups were treated with DEHP(200 mg/kg) by gavage every morning at 9:00 a.m. DMF and DEHP+DMF groups were treated with DMF(150 mg/kg) from day 13 to day 16 of gestation by gavage. After completion of gavage on day 16 of pregnancy, maternal blood, maternal liver, placenta, and amniotic fluid were collected from pregnant mice after a six-hour abrosia. The body weight of the mother rats and the body weight of the fetus rats were sorted and analyzed; the levels of total bile acid(TBA), alkaline phosphatase(ALP), aspartate aminotransferase/alanine aminotransferase(AST/ALT) in serum and TBA in liver, amniotic fluid and placenta were detected by biochemical analyzer; HE staining was used to observe the pathological changes of liver tissue; Quantitative reverse transcription PCR(RT-qPCR) was used to detect the expression levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-6, IL-1, IL-18 and NOD-like receptor thermal protein domain associated protein 3(NLRP3) in the liver; Western blot was used to detect the expression of the nuclear factor KappaB(NF-κB) and NLRP3. Results : Compared with the control group, the body weight of the DEHP-treated dams and pups decreased(P<0.05); the levels of TBA, ALP, AST/ALT in the serum of dams and the levels of TBA in the liver, amniotic fluid, and placenta of dams increased(P<0.05); the histopathological results showed that liver tissue was damaged, bile ducts were deformed, and there was inflammatory cell infiltration around them; the levels of inflammation-related factors TNF-α, IL-6, IL-1, IL-18 and NLRP3 transcription in maternal liver increased(P<0.05); the expression of NF-κB and NLRP3 protein in maternal liver significantly increased( P<0. 05). Compared with the DEHP group,the body weight of both dams and fetuses significantly increased in DEHP + DMF group( P<0. 05); the levels of TBA,ALP,AST/ALT in the serum of dams and amniotic fluid of fetuses decreased( P<0. 05); the degree of liver lesions was improved; the transcription levels of inflammation-related factors TNF-α,IL-6,IL-1,IL-18 and NLRP3 in maternal liver decreased( P<0. 05); the expression of NF-κB and NLRP3 protein in maternal liver significantly decreased( P<0. 05). Conclusion DMF can effectively protect the DEHP exposure to lead to female ICP,and its mechanism may be through inhibiting the NF-κB/NLRP3 pathway and reducing liver inflammation.

AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.

Acute-on-chronic liver failure （ACLF） is an acute and critical illness with a high short-term mortality rate， and current therapies mainly focus on elimination of causes， organ support， and prevention of complications. Although liver transplantation is the most effective treatment modality， its clinical application is limited， and traditional Chinese medicine has shown significant advantages and characteristics in the treatment of ACLF. In traditional Chinese medicine， ACLF is classified into the same category as diseases such as “jaundice”， and unlike traditional jaundice which is mostly characterized by excess and heat syndromes， the syndrome of ACLF has gradually transformed from Yang jaundice to Yin jaundice due to the changing disease spectrum of ACLF. With reference to the pathogenesis of ACLF in Western medicine and traditional Chinese medicine theories， this article discusses the essential pathogenesis of ACLF in traditional Chinese medicine， explores the evolution of ACLF syndromes， and reviews the research advances in the clinical efficacy and mechanisms of traditional Chinese medicine based on the three-factor differentiation-based treatment of damp-heat， blood stasis-heat， and spleen deficiency， as well as the safety of spleen-strengthening and Yang-warming drugs in the clinical treatment of ACLF， in order to provide ideas， methods， and evidence for the application of traditional Chinese medicine in ACLF.

Objective To use direct dilution method to pretreat human urine, and to determine 19 elements in human urine using inductively coupled plasma mass spectrometry, and to evaluate the uncertainty of the entire experimental process. Methods The relevant mathematical models were established according to JJF 10591-2012 ^“Evaluation and Expression of Measurement Uncertainty^” and CNAS-GL006 ^“Guidance for Evaluation of Uncertainty in Chemical Analysis^”. Taking molybdenum as an example, the uncertainty sources in the determination of 19 elements in human urine by inductively coupled plasma method were analyzed and evaluated, including sample pretreatment, sample repeated measurement, standard solution preparation and standard curve fitting. Results The extended uncertainty of molybdenum in human urine is 2.12μg/L, and the measurement result of molybdenum is (44.8±2.12)μg/L. The measurement result of 19 elements in human urine ranges from less than the detection limit to 601μg/L, and the extended uncertainty range is 0.38~33.6μg/L.Conclusion It was found from the calculation that the uncertainty of the determination result was mainly affected by the uncertainty of the sample repeated measurement and the standard curve fitting. By adjusting the range of standard curve and increasing the number of parallel sample measurement, the uncertainty was reduced and the quality of detection was improved.

OBJECTIVE: To observe the effect of acupuncture at "pelvic floor six needles" for mild to moderate female stress urinary incontinence (SUI). METHODS: A total of 60 patients with mild to moderate female SUI were randomly divided into an observation group and a control group, 30 cases each group. The control group received Kegel exercise. The observation group received acupuncture at "pelvic floor six needles" on the basis of the treatment as the control group, bilateral Zhongliao (BL33), Zhibian (BL54), Huiyang (BL35), Shuidao (ST28), Dahe (KI12) and Guanyuan (CV4) were selected, once every other day, 3 times a week, 4 weeks as a course of treatment, a total of 2 courses were required. Before treatment and after 4, 8 weeks of treatment, urine leakage in 1 hour, International Consultation on Incontinence questionnaire short form (ICI-Q-SF) score, and incontinence quality of life questionnaire (I-QOL) score were observed in the two groups, and the clinical efficacy was evaluated. RESULTS: After 8 weeks of treatment, urine leakage in 1 hour and ICI-Q-SF scores in both groups were decreased compared with those before treatment (P<0.05), and urine leakage in 1 hour and ICI-Q-SF score in the observation group were lower than those in the control group (P<0.05). After 4, 8 weeks of treatment, I-QOL scores were increased compared with those before treatment in both groups (P<0.05), and the I-QOL scores in the observation group were higher than those in the control group (P<0.01, P<0.001). The total effective rate of the observation group was 93.3% (28/30), which was higher than 73.3% (22/30) in the control group (P<0.05). CONCLUSION Acupuncture at "pelvic floor six needles" could improve the clinical symptoms and quality of life in patients with mild to moderate female SUI to a certain degree.
Humans ; Female ; Acupuncture Therapy/instrumentation* ; Urinary Incontinence, Stress/physiopathology* ; Middle Aged ; Adult ; Exercise Therapy ; Acupuncture Points ; Pelvic Floor/physiopathology* ; Aged ; Treatment Outcome ; Quality of Life

OBJECTIVE: To observe the effects of Xingnao Kaiqiao acupuncture technique (for regaining consciousness and opening orifice) on methylation of N6-methyladenosine (m6A), and key methyltransferases and demethylases, so as to clarify the mechanism of acupuncture on cerebral ischemia-reperfusion injury (CIRI). METHODS: Of 68 male Sprague-Dawley rats of SPF grade, 15 rats were randomly selected as a sham-operation group, and the remaining rats were subjected to the model of middle cerebral artery occlusion using the suture ligation. CIRI was induced by ischemia for 2 h followed by reperfusion. Rats that failed to modeling or died were excluded. The rest 45 rats were randomly divided into three groups, i.e. model group, acupuncture group, and non-point acupuncture group, with 15 rats in each group. The rats in the acupuncture group were treated with acupuncture at bilateral "Neiguan" (PC6) and "Shuigou" (GV26). In the non-point acupuncture group, acupuncture was delivered at three non-points, located 3 mm below the bilateral midaxillary line and 3 mm lateral to the tip of the coccyx. One intervention was operated in these two acupuncture groups and the needles were retained for 30 min. Before modeling start and 2 h after ischemia, a laser speckle flowmeter was used to monitor the cerebral blood perfusion. In 2 h of ischemia and 24 h of reperfusion, the neurological behavioral score was evaluated. The volume of rat cerebral infarction was determined by triphenyltetrazolium chloride (TTC) staining, and the level of m6A methylation in ischemic cortical area was detected by Dot blot, and the protein and mRNA expression of the demethylase i.e. fat mass and obesity-associated protein (FTO), AlkB homolog 5 (ALKBH5) and key methyltransferases, i.e. methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and Wilms' tumor 1-associated protein (WTAP) in ischemic cortical area were detected by Western blot and real-time PCR. RESULTS: Cerebral blood perfusion decreased by>70% after 2 h ischemia. Compared with the sham-operation group, the neurobehavioral score and the percentage of cerebral infarction volume increased in the model group (P<0.01); the level of m6A methylation in the ischemic cortical area increased (P<0.01), the protein and mRNA expression of FTO decreased (P<0.01), and that of ALKBH5, METTL3, and METTL14 increased (P<0.01, P<0.05) in the model group. When compared with the model group and the non-point acupuncture group, the acupuncture group showed a decrease in the neurobehavioral score and the percentage of cerebral infarction volume (P<0.01), the level of m6A methylation in the ischemic cortical area was reduced (P<0.01, P<0.05), and the protein and mRNA expression of FTO was elevated (P<0.01). CONCLUSION Xingnao Kaiqiao acupuncture technique presents its protective effect on the brain in the rats with CIRI, which is related to up-regulating the expression of FTO and modulating m6A methylation.
Animals ; Rats, Sprague-Dawley ; Male ; Acupuncture Therapy ; Reperfusion Injury/genetics* ; Rats ; Brain Ischemia/genetics* ; Humans ; Adenosine/metabolism* ; Methylation ; Acupuncture Points ; Cerebral Cortex/metabolism*

Globally, over 300 million surgeries are performed each year, and more than 50% of surgeries involve patients aged 65 and older. Aging poses significant challenges to perioperative brain health, as the deterioration of brain structure and function increases susceptibility to postoperative neurological complications. Protecting perioperative brain health remains a worldwide clinical challenge. With senescence, the brain undergoes a progressive decline in homeostasis across various molecular, cellular, and regional functions. Anesthetics and surgical stimuli may accelerate the disruption of brain homeostasis and exacerbate age-related neurodegeneration. This review provides a framework for understanding how anesthesia and surgery can affect brain health in the aging population and contribute to postoperative neurological complications, with a particular focus on perioperative neurocognitive disorder.

OBJECTIVE: To investigate the effectiveness of delayed replantation of degloving skin preserved at 4℃ in treatment of limb degloving injuries. METHODS: Between October 2020 and October 2023, 12 patients with limb degloving injuries were admitted. All patients had severe associated injuries or poor wound conditions that prevented primary replantation. There were 7 males and 5 females; age ranged from 29 to 46 years, with an average of 39.2 years. The causes of injury included machine entanglement in 6 cases, traffic accidents in 5 cases, and sharp instrument cuts in 1 case. Time from injury to hospital admission was 0.5-3.0 hours, with an average of 1.3 hours. Injury sites included upper limbs in 7 cases and lower limbs in 5 cases. The range of degloving skin was from 5 cm×4 cm to 15 cm×8 cm, and all degloving skins were intact. The degloving skin was preserved at 4℃. After the patient's vital signs became stable and the wound conditions improved, it was trimmed into medium-thickness skin grafts for replantation. The degloving skin was preserved for 3 to 7 days. At 4 weeks after replantation, the viability of the degloving skin grafts was assessed, including color, elasticity, and sensation of pain. The Vancouver Scar Scale (VSS) was used to assess the scars of the skin grafts during follow-up. RESULTS: At 4 weeks after replantation, 8 cases of skin grafts completely survived and the color was similar with normal skin, with a survival rate of 66.67%. The elasticity of skin grafts (R0 value) ranged from 0.09 to 0.85, with an average of 0.55; moderate pain was reported in 4 cases, mild pain in 3 cases, and no pain in 5 cases. All patients were followed up 12 months. Over time, the VSS scores of all 12 patients gradually decreased, with a range of 4-11 at 12 months (mean, 6.8). CONCLUSION For limb degloving injuries that cannot be replanted immediately and do not have the conditions for deep low-temperature freezing preservation, the method of preserving the degloving skin at 4℃ for delayed replantation can be chosen.
Humans ; Male ; Adult ; Replantation/methods* ; Female ; Degloving Injuries/surgery* ; Middle Aged ; Skin Transplantation/methods* ; Treatment Outcome ; Extremities/injuries* ; Time Factors ; Skin/injuries* ; Tissue Preservation/methods*

Alzheimer's disease (AD), characterized by β-amyloid (Aβ) aggregation and neuroinflammation, remains a formidable clinical challenge. Herein, we present an innovative nose-to-brain delivery platform utilizing lactoferrin (Lf)-functionalized lipid nanoparticles (LNPs) co-encapsulating α-mangostin (α-M) and β-site APP cleaving enzyme 1 (BACE1) siRNA (siB). This dual-modal therapeutic system synergistically combines the neuroprotective and microglia-reprogramming capabilities of α-M with the transcriptional silencing of BACE1 via siB, thereby simultaneously inhibiting Aβ production and enhancing its clearance. Fabricated via a microfluidic approach, the LNPs exhibited uniform particle size distribution, great encapsulation efficiency, and robust colloidal stability. Upon intranasal administration, Lf-functionalization enabled superior brain-targeting efficacy through receptor-mediated transcytosis. In vitro studies demonstrated that α-M reversed Aβ-induced low-density lipoprotein receptor downregulation, promoting microglial phagocytosis and autophagic degradation of Aβ, while siB effectively suppressed BACE1 expression, abrogating Aβ synthesis. In vivo investigations in APP/PS1 transgenic mice revealed remarkable cognitive recovery, substantial Aβ plaque reduction, and alleviation of neuroinflammation and oxidative stress. This intricately designed LNP system, exploiting a non-invasive and efficient nose-to-brain delivery route, provides a biocompatible, synergistic, and transformative therapeutic strategy for the multifaceted management of AD.

Purpose To examine the clinicopathologic,immunohistochemical,and molecular genetic characteristics and differential diagnosis of low-grade oncocytic tumor(LOT)of kidney with CK7 positive and CD117 negative,so as to enhance the understanding of this tumor among pathologists.Methods A total of five cases of renal LOT from the First Affiliated Hospi-tal of Soochow University between December 2016 and February 2023 were included in this analysis.The clinicopathological fea-tures,immunophenotype,genetic characteristics,and prognosis were evaluated using HE staing,immunohistochemical staining,and Sanger sequencing.Additionally,relevant literature was re-viewed to supplement the findings.Results Among the cohort of five patients,four were female and one was male,aged 57-70 years with a median age of 65 years and an average age of 64.8 years.Clinical presentation revealed that only the first case exhibited frequent urination accompanied by intermittent lumba-go,while the remaining cases were asymptomatic and incidental-ly discovered.Imaging studies demonstrated space-occupying le-sions with clear boundaries and even internal echoes on B-ultra-sonography,and patchy low-density shadows in the center with obvious edge enhancement on CT.Grossly,the tumor was nodu-lar,with a maximum diameter ranging from 2.1 to 7.6 cm,and an average diameter of 4.04 cm,with a solid section.Micro-scopically,the boundary of LOT was consistently well-defined,with a thick capsule.The arrangement of tumor cells was ob-served to be both dense and sparse,accompanied by fresh bleed-ing foci and proteinoid secretions.Focal lymphocyte aggrega-tion,hepatic plate like and hepatic sinusoid like structures,thick-walled blood vessels,false nodules of tumor cells,and old hemorrhage were also noted.The tumor cells exhibited uniformi-ty in shape,appearing round or polygonal,with eosinophilic and fine granular cytoplasm.The nuclei were of similar size and shape,appearing round or oval with a clear nuclear membrane.The histological features of the tumor included 2-grade small nu-cleoli,perinuclear halos,binuclear cells,and nuclear shrink-age,but no mitotic figures were detected.The immunophenotyp-ic analysis revealed strongly diffuse expression of CK7 in the tumor cells,while CD117 was negative.The Ki67 proliferation index was low.Sanger sequencing identified mutations in mTORC1 pathway genes in four cases,including three mutations in MTOR and one mutation in RHEB.The patients underwent either local or radical nephrectomy,and were followed up for a period ranging from 2 to 52 months,during which all patients re-mained free of recurrence.Conclusion The low-grade,eosino-philic,and rare renal tumor known as LOT exhibits inert behav-ior.At present,the follow-up results show that complete resec-tion of local operation is sufficient,and the prognosis is good.It is important to distinguish this lesion from other eosinophilic re-nal tumors.