This paper summarizes professor LI Guolie's clinical experience in treating orthostatic hypotension （OH） based on the theory of "raising the clear and directing the turbid downward". It is considered that the core pathogenesis of OH lies in the body's transition from a supine to an upright position， during which dysfunction of the middle jiao （焦） transformation and transportation， along with impaired pivot function， hinders the ascending of clear yang and the descending of turbid yin. Treatment should follow the general principle of "ascending the clear and directing the turbid downward"， placing emphasis on distinguishing the primary and secondary aspects. For cases where the clear yang fails to ascend， the self-formulated Li's Shengqing Jiangzhuo Decoction （李氏升清降浊汤）is used to supplement qi， raise the clear， and strengthen the middle jiao. For cases where the turbid yin fails to descend， the self-formulated Wuxiang Qingzhuo Beverage（五香清浊饮）with modifications is applied to resolve phlegm， eliminate stasis， harmonize the middle， and descend the turbid.

This paper summarizes professor LI Guolie's clinical experience in treating orthostatic hypotension （OH） based on the theory of "raising the clear and directing the turbid downward". It is considered that the core pathogenesis of OH lies in the body's transition from a supine to an upright position， during which dysfunction of the middle jiao （焦） transformation and transportation， along with impaired pivot function， hinders the ascending of clear yang and the descending of turbid yin. Treatment should follow the general principle of "ascending the clear and directing the turbid downward"， placing emphasis on distinguishing the primary and secondary aspects. For cases where the clear yang fails to ascend， the self-formulated Li's Shengqing Jiangzhuo Decoction （李氏升清降浊汤）is used to supplement qi， raise the clear， and strengthen the middle jiao. For cases where the turbid yin fails to descend， the self-formulated Wuxiang Qingzhuo Beverage（五香清浊饮）with modifications is applied to resolve phlegm， eliminate stasis， harmonize the middle， and descend the turbid.

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*

With the emergence of deep learning techniques based on convolutional neural networks, artificial intelligence (AI) has driven transformative developments in the field of medical image analysis. Recently, large language models (LLMs) such as ChatGPT have also started to achieve distinction in this domain. Increasing research shows the undeniable role of AI in reshaping various aspects of medical image analysis, including processes such as image enhancement, segmentation, detection in image preprocessing, and postprocessing related to medical diagnosis and prognosis in clinical settings. However, despite the significant progress in AI research, studies investigating the recent advances in AI technology in the aforementioned aspects, the changes in research hotspot trajectories, and the performance of studies in addressing key clinical challenges in this field are limited. This article provides an overview of recent advances in AI for medical image analysis and discusses the methodological profiles, advantages, disadvantages, and future trends of AI technologies.
Artificial Intelligence ; Humans ; Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer ; Deep Learning ; Diagnostic Imaging/methods*

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Various therapeuti modailities have been engineered for lung cancer treatment, but their clinic application is severely impeded by the poor therapy efficiency and immunosuppressive microenvironment. Herein, we fabricated a library of small molecule redox-labile nanoparticles (NPs) (i.e., diPTX-2C NPs, diPTX-2S NPs, and diPTX-2Se NPs) by the self-assembly of dimer paclitaxel (PTX) prodrug, and then utilized these NPs with the traditional Chinese medicine (TCM) Qi-Yu-San-Long-Fang (Q) for effective chemoimmunotherapy on Lewis lung carcinoma (LLC)-bearing mice models. Under the high concentration of glutathione (GSH) and H₂O₂, diPTX-2Se NPs could specifically release PTX in cancer cells and exert a higher selectivity and toxicity than normal cells. In LLC tumor-bearing mice, oral administration of Q not only effectively downregulated programmed death ligand-1 (PD-L1) expression, but also remodeled the immunosuppressive tumor immune microenvironment via the increase of CD4⁺ T and CD8⁺ T cell proportion and the repolarization of M2 into M1 macrophages in tumor tissues, collectively achieving superior synergistic treatment outcomes in combination with intravenous PTX prodrug NPs. Besides, we found that the combination regimen also demonstrated excellent chemoimmunotherapeutic performances on low-dose small established tumor and high-dose large established tumor models. This study may shed light on the potent utilization of Chinese and Western-integrative strategy for efficient tumor chemoimmunotherapy.

Objective To investigate the neuroprotective effect of TGP on PS rats and determine the impact on the Ste20-like proline/alanine-rich kinase/Na+-K+-Cl cotransport(SPAK/NKCC1)signaling pathway.Methods After PS model was successfully established in 60 male SD rats(7 weeks old),they were randomly divided into model group,low-and high-dose TGP groups,high-dose TGP+negative control group,and high-dose TGP+WNK3 overexpression group,with 12 rats in each group.Another 12 healthy rats served as the control group.After modeling,50 or 200 mg/kg TGP was given to the rats of corresponding groups intragastrically,the overexpression plasmids of WNK3 were given to the rats from the high-dose TGP+WNK3 overexpression group through tail vein injection,and same volume of normal saline was given to the control group.All of these agents were administrated once per day for 7 consecutive days.ELISA was applied to de-tect serum levels of IL-6,IL-1β,MDA and SOD.HE staining was applied to detect the pathological morphology of the substantia nigra region in brain tissue.TUNEL staining was used to observe neuronal apoptosis.Immunohistochemistry was conducted to measure the expression of α-synucle-in(α-syn),and Western blotting for the expression of Bax,Bcl-2 and SPAK/NKCC1 signaling pathway related proteins(WNK3,p-SPAK,SPAK,p-NKCC1 and NKCC1).Results Compared with the model group,the pathological damage of neurons in substantia nigra was reduced in low-and high dose TGP groups,reduced contents of IL-6,IL-1β and MDA,lower neuronal apoptotic rate,and declined expression of Bax,α-syn,WNK3,p-SPAK/SPAK,and p-NKCC1/NKCC1,but raised SOD content and Bcl-2 expression level(88.39±8.96 U/mg,119.57±12.01 U/mg vs 60.28±6.14 U/mg,P＜0.05;0.57±0.06,0.82±0.09 vs 0.38±0.04,P＜0.05).The intervention with WNK3 overexpression resulted in more severe pathological damage to neurons in the sub-stantia nigra,increased contents of IL-6,IL-1β and MDA,higher neuronal apoptotic rate,enhanced expression of Bax,α-syn,WNK3,p-SPAK/SPAK,and p-NKCC1/NKCC1,and reduced SOD con-tent and Bcl-2 expression level when compared with the high-dose TGP+negative control group(P＜0.05).Conclusion TGP exerts neuroprotective effects on PS rats,and its mechanism is re-lated to the inhibition of the SPAK/NKCC1 signaling pathway.

Objective:To investigate the incidence of postoperative infection and its risk factors in patients with oral squamous cell carcinoma (OSCC), so that to provide a clinical basis for the prevention and management of postoperative infection in these patients.Methods:Ninety-seven patients pathologically diagnosed with OSCC who underwent surgical treatment in the Department of Oral and Craniomaxillofacial Oncology, Shanghai Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine between December 2020 and March 2022 were included. This study was a clinical retrospective cohort study. The clinical characteristics and preoperative laboratory indicators of the included patients were collected. Based on the presence or absence of infection, the patients were divided into infection group and non-infection group. Chi-square test and independent samples t test were used for statistical methods. Binary logistic regression analysis was used to identify influencing factors for postoperative infection, and interaction terms were introduced to assess effect modification between variables. Results:Among the 97 patients, 46(47.42%) developed postoperative infections, of which 44(95.65%) were pulmonary infections. The proportion of hypertension in the infection group was 43.48%(20/46), which was higher than 23.53%(12/51) in the non-infection group, and the difference was statistically significant ( χ2=4.35, P=0.037). The preoperative glycosylated hemoglobin level in the infection group was 6.26%±0.85%, which was higher than that in the non-infection group (5.77%±0.57%), and the difference was statistically significant ( t=-2.81, P=0.007). Binary logistic regression analysis showed that male (odds ratio ( OR)=0.598, 95% confidence interval ( CI) 0.519 to 0.689, P<0.001), absence of diabetes ( OR=0.416, 95% CI 0.340 to 0.509, P<0.001), and absence of hypertension ( OR=0.647, 95% CI 0.569 to 0.735, P<0.001) were protective factors against postoperative infection. Age>60 years ( OR=1.159, 95% CI 1.031 to 1.304, P=0.014) and alcohol consumption ( OR=1.262, 95% CI 1.024 to 1.555, P=0.029) were risk factors for postoperative infection. Effect modification analysis found that males without diabetes ( OR=0.027, 95% CI 0.001 to 0.687, P=0.029) and the absence of both diabetes and hypertension ( OR=0.378, 95% CI 0.163 to 0.880, P=0.024) were also protective factors against postoperative infection. Conclusions:Risk factors for postoperative infection in OSCC include elder age, alcohol consumption, hypertension, and poor preoperative glycemic control. Therefore, clinical practice should enhance preoperative assessment, promote lifestyle modifications, optimize perioperative blood pressure management, implement glycemic control, and provide perioperative alcohol cessation interventions to reduce the risk of postoperative infection.

This paper expounds Professor Li Guolie's academic thought and clinical experience in treating the halitosis of spleen and stomach damp-heat type based on the theory of"lightness removing excess".It is proposed that"lightness"has five meanings:light and clear medicinal properties,light dosage,concise compatibility,light decoction method and light treatment method;"excess"covers the syndromes of external and internal injuries,obstruction of qi mechanism and mixed deficiency and excess.The location of the halitosis of spleen and stomach damp-heat type is centered on the spleen and stomach in the middle energizer,involving the lungs,liver,and kidneys,with syndromes of mixed deficiency and excess;the core pathogenesis is the stagnation of qi mechanism in the mid-dle energizer and the diffusion of damp-heat turbid evil in the triple energizers.The theory of"lightness removing excess"is used to guide the treatment of spleen and stomach diseases of damp-heat type,and the treatment principle of"triple energizers being divided and eliminated,and lightness being able to penetrate and reach the evil"is proposed.The upper energizer is promoted to activate the pivot of qi transformation,the middle energizer is adjusted to restore the mechanism of ascending and descending,and the lower energi-zer is penetrated to guide the turbid evil out.The self-made"Wuxiang Qingzhuo Yin"is used to gargle to quickly remove the turbid e-vil and symptoms,forming an internal and external coordinated diagnosis and treatment method of"light dosage to regulate the pivot,ingenious method to clear the obstruction",which provides new ideas and theoretical basis for the clinical diagnosis and treatment of spleen and stomach diseases of damp-heat type.