Compilation instruction for Expert Consensus on Clinical Application of Binghuang Fule Ointment elaborates on the formulation methods and evidence-based basis of the consensus. To address the problems of insufficient evidence on efficacy， vague indications， and a lack of uniform standard for Binghuang Fule Ointment in clinical application， 34 experts from 29 medical institutions across China participated in the compilation under the lead of the Institute of Basic Research in Clinical Medicine and Xiyuan Hospital， China Academy of Chinese Medical Sciences， as well as China-Japan Friendship Hospital. The compilation strictly adhered to the WHO Handbook for Guideline Development （GB/T 1.1—2020）， and the Guidance of Instructions for Compiling Expert Consensus on Clinical Practice of Chinese Patent Medicine. Through multidisciplinary collaboration， the compilation was completed using the Grading of Recommendations Assessment， Development and Evaluations （GRADE） evidence grading system. The detailed workflow included various key links. In clinical question construction， 15 items were screened by the nominal group method. In evidence retrieval， Chinese and English databases， along with gray literature， were covered to obtain 116 clinical and 33 pharmaceutical studies. In safety assessment， drug monitoring data and clinical research results were integrated， clarifying local adverse skin reactions and contraindications. Ultimately， 8 recommendations were formed by the GRADE grid method， while 16 consensus suggestions were reached via the majority vote rule. The results showed that the Binghuang Fule Ointment was applicable to eczema， psoriasis， neurodermatitis， tinea pedis， and other diseases. The Consensus also elucidated the syndrome differentiation points， usage and dosage for different diseases （such as adjustment of course and application frequency）， as well as the indications of combination medication. Additionally， safety assessment suggested that the Ointment should be used with caution in individuals with skin ulceration or hypersensitivity. To ensure methodological rigor， the compilation process went through three rounds of internal and external expert reviews， while a comprehensive analysis was conducted by literature analysis， the Delphi method， and other methods. This compilation instruction provided methodological support for the clinical transformation of the Consensus through key links， including project initiation， international registration， informed consent， conflict-of-interest statements， evidence evaluation， and popularization. The Consensus will be continuously improved through a dynamic revision mechanism in the future.

Compilation instruction for Expert Consensus on Clinical Application of Binghuang Fule Ointment elaborates on the formulation methods and evidence-based basis of the consensus. To address the problems of insufficient evidence on efficacy， vague indications， and a lack of uniform standard for Binghuang Fule Ointment in clinical application， 34 experts from 29 medical institutions across China participated in the compilation under the lead of the Institute of Basic Research in Clinical Medicine and Xiyuan Hospital， China Academy of Chinese Medical Sciences， as well as China-Japan Friendship Hospital. The compilation strictly adhered to the WHO Handbook for Guideline Development （GB/T 1.1—2020）， and the Guidance of Instructions for Compiling Expert Consensus on Clinical Practice of Chinese Patent Medicine. Through multidisciplinary collaboration， the compilation was completed using the Grading of Recommendations Assessment， Development and Evaluations （GRADE） evidence grading system. The detailed workflow included various key links. In clinical question construction， 15 items were screened by the nominal group method. In evidence retrieval， Chinese and English databases， along with gray literature， were covered to obtain 116 clinical and 33 pharmaceutical studies. In safety assessment， drug monitoring data and clinical research results were integrated， clarifying local adverse skin reactions and contraindications. Ultimately， 8 recommendations were formed by the GRADE grid method， while 16 consensus suggestions were reached via the majority vote rule. The results showed that the Binghuang Fule Ointment was applicable to eczema， psoriasis， neurodermatitis， tinea pedis， and other diseases. The Consensus also elucidated the syndrome differentiation points， usage and dosage for different diseases （such as adjustment of course and application frequency）， as well as the indications of combination medication. Additionally， safety assessment suggested that the Ointment should be used with caution in individuals with skin ulceration or hypersensitivity. To ensure methodological rigor， the compilation process went through three rounds of internal and external expert reviews， while a comprehensive analysis was conducted by literature analysis， the Delphi method， and other methods. This compilation instruction provided methodological support for the clinical transformation of the Consensus through key links， including project initiation， international registration， informed consent， conflict-of-interest statements， evidence evaluation， and popularization. The Consensus will be continuously improved through a dynamic revision mechanism in the future.

SkinPro Ointment is an emulsion-based preparation derived from a traditional Tibetan medical empirical formula and developed using modern pharmaceutical technology. It is an exclusive patented product of Tibet Hairong Tangguo Pharmaceutical Co. Ltd. and has been listed as a National Protected Traditional Chinese Medicine Variety， the Pharmacopoeia of the People's Republic of China， and classified as a Category B product in the National Basic Medical Insurance Catalog. The ointment possesses the functions of clearing heat and drying dampness， activating blood circulation and dispelling wind， relieving itching and reducing inflammation. Clinically， it is used for skin pruritus caused by dampness-heat accumulation or blood-heat with wind-dryness， as well as pruritic skin diseases such as neurodermatitis， eczema， tinea pedis， and psoriasis. To clarify the standards for its clinical application and promote rational drug use， a consensus working group comprising 34 national experts in dermatology， evidence-based medicine， and pharmacy was established. Through expert interviews， the nominal group technique， and questionnaire surveys， 15 clinical issues were identified. The Grading of Recommendations Assessment， Development and Evaluation （GRADE） evidence grading system was employed to assess the quality of evidence， leading to the formulation of the Expert Consensus on the Clinical Application of SkinPro Ointment. This consensus specifies that the intended users are physicians and pharmacists in medical institutions at all levels. It standardizes the clinical application of the ointment， including syndrome characteristics， dosage and course of treatment， combination therapy， precautions， and contraindications. Recommendations and consensus suggestions were formed addressing the 15 clinical issues， covering the following key areas： ①Indications and TCM syndromes： In TCM， the ointment mainly treats conditions such as "damp sores" （Shichuang）， "white scaling" （Baibi）， "collar sores" （Shelingchuang）， and "damp foot Qi" （Jiaoshiqi）， corresponding to eczema， psoriasis， neurodermatitis， and tinea pedis in Western medicine. The relevant TCM syndromes are identified as dampness-heat accumulation or blood-heat with wind-dryness. ②Usage and dosage： For external use， apply to the affected area 3 times daily. The dosage should follow the fingertip unit （FTU） principle. A treatment course of 1-2 weeks is recommended for mild to moderate cases； for serious cases， the course should be followed as prescribed by a physician. ③Combined therapy： The ointment can be used as monotherapy for mild cases. For moderate to severe cases， combination therapy is recommended， with reference to relevant clinical guidelines. ④Safety： Common adverse reactions include skin rashes， pruritus， and erythema. The ointment is contraindicated in patients with broken skin or obvious exudation at the affected area， as well as in patients with known hypersensitivity to any of its components. Contact with sensitive areas such as the eyes and oral mucosa should be avoided. Modern research shows that the ointment also has potential efficacy in other dermatological conditions， such as adult atopic dermatitis， tinea cruris， exfoliative keratolysis， acne vulgaris， and Malassezia folliculitis. This consensus provides a scientific basis for promoting the rational clinical use of SkinPro Ointment， improving its therapeutic efficacy， and reducing medication risks. Future updates will be dynamically revised according to emerging clinical issues and new evidence.

The polymerase 1 and transcript release factor (PTRF)-cytoplasmic phospholipase A2 (cPLA2) phospholipid remodeling pathway facilitates tumor proliferation in glioma. Nevertheless, blockade of this pathway leads to the excessive activation of oncogenic receptors on the plasma membrane and subsequent drug resistance. Here, CD26/dipeptidyl peptidase 4 (DPP4) was identified through screening of CRISPR/Cas9 libraries. Suppressing PTRF-cPLA2 signaling resulted in the activation of the epidermal growth factor receptor (EGFR) pathway through phosphatidylcholine and lysophosphatidylcholine remodeling, which ultimately increased DPP4 transcription. In turn, DPP4 interacted with EGFR and prevented its ubiquitination. Linagliptin, a DPP4 inhibitor, facilitated the degradation of EGFR by blocking its interaction with DPP4. When combined with the cPLA2 inhibitor AACOCF3, it exhibited synergistic effects and led to a decrease in energy metabolism in glioblastoma cells. Subsequent in vivo investigations provided further evidence of a synergistic impact of linagliptin by augmenting the sensitivity of AACOCF3 and strengthening the efficacy of temozolomide. DPP4 serves as a novel target and establishes a constructive feedback loop with EGFR. Linagliptin is a potent inhibitor that promotes EGFR degradation by blocking the DPP4-EGFR interaction. This study presents innovative approaches for treating glioma by combining linagliptin with AACOCF3 and temozolomide.

Objective:To investigate the effects of electroacupuncture on duodenal inflammation and intestinal mucosal barrier function in functional dyspepsia(FD)rats based on the Toll-like receptors 4(TLR4)/myeloid differentiation factor 88(Myd88)pathway.Methods:Sixty male Sprague-Dawley rats were randomly divided into a blank group(n=10)and a modeling group(n=50).The FD model was induced in the modeling group using a multi-factor comprehensive intervention.Forty successful model rats were randomly allocated into a model(FD)group,an electroacupuncture(EA)group,a TLR4 inhibitor(TAK242)group,and an EA+TAK242 group,with 10 rats in each group.In the EA group,following acupuncture at Zusanli(ST36)and Taichong(LR3),a filiform needle was perpendicularly inserted 3 mm into the lateral side of Zusanli(ST36)bilaterally,positioned between the Stomach Meridian and the Gallbladder Meridian at the lateral edge of the tibia,serving as an auxiliary electrode.An EA instrument was then connected to Zusanli(ST36)and the auxiliary electrode on the same side for intervention.The TAK242 group received tail vein injections of TLR4 inhibitor TAK242[0.5 mg/(kg·bw)],while the EA+TAK242 group received both TAK242 injections and EA intervention.Intragastric residual rate and small intestinal propulsion rate were observed in each group.Immunohistochemistry was used to detect tryptase expression in the duodenum;enzyme-linked immunosorbent assay was used to measure serum concentrations of 5-hydroxytryptamine(5-HT)and 5-hydroxyindole acetic acid(5-HIAA);Western blotting was used to analyze TLR4,MyD88,zonula occludens-1(ZO-1),and junctional adhesion molecule A(JAM-A)protein expression in the duodenal tissue.Results:In the FD group,the intragastric residual rate increased,small intestinal propulsion rate decreased,ZO-1 and JAM-A protein expression decreased,duodenal tryptase mean optical density increased,serum 5-HT and 5-HIAA levels increased significantly,and TLR4 and MyD88 protein expression increased significantly compared to the blank group(P<0.01).Compared to the FD group,the EA,TAK242,and EA+TAK242 groups showed a decreased gastric residual rate,increased small intestinal propulsion rate,increased ZO-1 and JAM-A protein expression,decreased optical density of duodenal tryptase,and significantly reduced serum 5-HT and 5-HIAA,as well as decreased TLR4 and MyD88 protein levels(P<0.01).Compared to the EA group,the TAK242 group had a higher intragastric residual rate and lower small intestinal propulsion rate(P<0.05),decreased TLR4 protein expression(P<0.05),no significant change in MyD88 protein expression(P>0.05),increased optical density of duodenal tryptase(P<0.05),increased serum 5-HT and 5-HIAA levels(P<0.05),and decreased ZO-1 and JAM-A protein expression(P<0.05).In the EA+TAK242 group,the intragastric residual rate was significantly lower,small intestinal propulsion rate was significantly higher,TLR4 and MyD88 protein expression was significantly lower,optical density of duodenal tryptase was significantly lower,and ZO-1 and JAM-A protein expression levels were significantly higher compared to the EA and TAK242 groups(P<0.01).Conclusion:EA promotes gastrointestinal motility,restores intestinal mucosal barrier function,and reduces inflammatory responses in FD rats,potentially through the down-regulation of the TLR4/Myd88 pathway.

Objective:To analyze the clinical and electrophysiological characteristics of patients with sensory neuronopathies (SNN), and to evaluate the significance of electrophysiological markers in the diagnosis and assessment of disease progression.Methods:A retrospective analysis was performed to evaluate the clinical manifestations, electrophysiological characteristics, and spinal cord magnetic resonance imaging (MRI) features of 8 cases diagnosed with SNN at the Third Central Hospital of Tianjin between 2015 and 2023. The neurophysiological examination mainly included limb nerve conduction study (NCS), same core needle electrode electromyography, somatosensory evoked potential (SEP), skin sympathetic reflex (SSR), and contact heat evoked potential (CHEP).Results:Among the 8 cases with SNN, 7 cases exhibited asymmetrical onset and a non-length-dependent pattern. All the 8 cases presented with severe deep sensory ataxia, accompanied by superficial sensory abnormalities and tendon areflexia. Paraneoplastic SNN were the most prevalent etiological subtype (4 cases), all of whom presented peripheral neuropathy as the initial symptom. Among these 4 cases, malignancies were identified in 3 cases and 3 cases presented with anti-Hu antibodies. Among the remaining 4 patients, 2 cases were autoimmune and the other 2 cases were idiopathic. NCS results of the 8 cases revealed decrease or absence of sensory nerve action potential (SNAP) amplitudes, with normal sensory conduction velocities. Six cases showed abnormal SEP, including 2 cases of central damage and 4 cases of peripheral damage, 5 cases had abnormal SSR, and 2 cases exhibited abnormal CHEP. Motor nerve conduction studies were normal in all 8 cases. Six patients underwent spinal MRI, and 4 exhibited abnormal signals in dorsal columns.Conclusions:The hallmark clinical manifestation of SNN is sensory ataxia, characterized by substantial impairment of superficial sensation, typically manifesting in a non-length-dependent distribution. Beyond the widespread and significant reduction in SNAP amplitudes, SNN may also exhibit additional electrophysiological impairments, such as those observed in SEP, SSR and CHEP.SEP combined with spinal cord MRI can improve the detection rate for damages in the central sensory conduction pathway.

The purpose of this study was to prepare high affinity monoclonal antibodies(mAbs)a-gainst bovine viral diarrhea virus(BVDV)and establish a double antibody sandwich ELISA detec-tion method.BVDV was purified by differential ultracentrifugation and used to immunize BALB/c mice.Hybridoma cells were prepared by fusing spleen cells from the immunized mice with SP2/0 cells.Positive cells were screened by indirect ELISA.A double-antibody sandwich ELISA method for detecting BVDV was developed using monoclonal antibody 4D11 as the capture antibody and HRP-labeled monoclonal antibody 3F3 as the detection antibody.The results of the ELISA and the determination of the variable region gene sequence of monoclonal antibodies indicated that the two monoclonal antibodies recognize different antigenic epitopes.Specificity tests showed that two monoclonal antibodies specifically recognize BVDV and did not cross-react with other bovine viru-ses associated with diarrhea.Indirect immunofluorescence assay and Western blot assay demonstra-ted that both mAbs exhibited strong reactivity with BVDV.The double antibody sandwich ELISA detection method established in this study had good specificity.The sensitivity test revealed that the method could detect a minimum virus amount of 3.1 × 104 TCID50.The reproducibility test showed that the inter-batch coefficient of variation(Cv)was between 2.47％and 7.44％,and the intra-batch Cv was between 1.71％and 9.89％,indicating good reproducibility.The establishment of this method provides an effective technical tool for the rapid diagnosis and prevention and con-trol of BVDV.

The purpose of this study was to prepare high affinity monoclonal antibodies(mAbs)a-gainst bovine viral diarrhea virus(BVDV)and establish a double antibody sandwich ELISA detec-tion method.BVDV was purified by differential ultracentrifugation and used to immunize BALB/c mice.Hybridoma cells were prepared by fusing spleen cells from the immunized mice with SP2/0 cells.Positive cells were screened by indirect ELISA.A double-antibody sandwich ELISA method for detecting BVDV was developed using monoclonal antibody 4D11 as the capture antibody and HRP-labeled monoclonal antibody 3F3 as the detection antibody.The results of the ELISA and the determination of the variable region gene sequence of monoclonal antibodies indicated that the two monoclonal antibodies recognize different antigenic epitopes.Specificity tests showed that two monoclonal antibodies specifically recognize BVDV and did not cross-react with other bovine viru-ses associated with diarrhea.Indirect immunofluorescence assay and Western blot assay demonstra-ted that both mAbs exhibited strong reactivity with BVDV.The double antibody sandwich ELISA detection method established in this study had good specificity.The sensitivity test revealed that the method could detect a minimum virus amount of 3.1 × 104 TCID50.The reproducibility test showed that the inter-batch coefficient of variation(Cv)was between 2.47％and 7.44％,and the intra-batch Cv was between 1.71％and 9.89％,indicating good reproducibility.The establishment of this method provides an effective technical tool for the rapid diagnosis and prevention and con-trol of BVDV.

Objective:To investigate the effects of electroacupuncture on duodenal inflammation and intestinal mucosal barrier function in functional dyspepsia(FD)rats based on the Toll-like receptors 4(TLR4)/myeloid differentiation factor 88(Myd88)pathway.Methods:Sixty male Sprague-Dawley rats were randomly divided into a blank group(n=10)and a modeling group(n=50).The FD model was induced in the modeling group using a multi-factor comprehensive intervention.Forty successful model rats were randomly allocated into a model(FD)group,an electroacupuncture(EA)group,a TLR4 inhibitor(TAK242)group,and an EA+TAK242 group,with 10 rats in each group.In the EA group,following acupuncture at Zusanli(ST36)and Taichong(LR3),a filiform needle was perpendicularly inserted 3 mm into the lateral side of Zusanli(ST36)bilaterally,positioned between the Stomach Meridian and the Gallbladder Meridian at the lateral edge of the tibia,serving as an auxiliary electrode.An EA instrument was then connected to Zusanli(ST36)and the auxiliary electrode on the same side for intervention.The TAK242 group received tail vein injections of TLR4 inhibitor TAK242[0.5 mg/(kg·bw)],while the EA+TAK242 group received both TAK242 injections and EA intervention.Intragastric residual rate and small intestinal propulsion rate were observed in each group.Immunohistochemistry was used to detect tryptase expression in the duodenum;enzyme-linked immunosorbent assay was used to measure serum concentrations of 5-hydroxytryptamine(5-HT)and 5-hydroxyindole acetic acid(5-HIAA);Western blotting was used to analyze TLR4,MyD88,zonula occludens-1(ZO-1),and junctional adhesion molecule A(JAM-A)protein expression in the duodenal tissue.Results:In the FD group,the intragastric residual rate increased,small intestinal propulsion rate decreased,ZO-1 and JAM-A protein expression decreased,duodenal tryptase mean optical density increased,serum 5-HT and 5-HIAA levels increased significantly,and TLR4 and MyD88 protein expression increased significantly compared to the blank group(P<0.01).Compared to the FD group,the EA,TAK242,and EA+TAK242 groups showed a decreased gastric residual rate,increased small intestinal propulsion rate,increased ZO-1 and JAM-A protein expression,decreased optical density of duodenal tryptase,and significantly reduced serum 5-HT and 5-HIAA,as well as decreased TLR4 and MyD88 protein levels(P<0.01).Compared to the EA group,the TAK242 group had a higher intragastric residual rate and lower small intestinal propulsion rate(P<0.05),decreased TLR4 protein expression(P<0.05),no significant change in MyD88 protein expression(P>0.05),increased optical density of duodenal tryptase(P<0.05),increased serum 5-HT and 5-HIAA levels(P<0.05),and decreased ZO-1 and JAM-A protein expression(P<0.05).In the EA+TAK242 group,the intragastric residual rate was significantly lower,small intestinal propulsion rate was significantly higher,TLR4 and MyD88 protein expression was significantly lower,optical density of duodenal tryptase was significantly lower,and ZO-1 and JAM-A protein expression levels were significantly higher compared to the EA and TAK242 groups(P<0.01).Conclusion:EA promotes gastrointestinal motility,restores intestinal mucosal barrier function,and reduces inflammatory responses in FD rats,potentially through the down-regulation of the TLR4/Myd88 pathway.

Objective:To analyze the clinical and electrophysiological characteristics of patients with sensory neuronopathies (SNN), and to evaluate the significance of electrophysiological markers in the diagnosis and assessment of disease progression.Methods:A retrospective analysis was performed to evaluate the clinical manifestations, electrophysiological characteristics, and spinal cord magnetic resonance imaging (MRI) features of 8 cases diagnosed with SNN at the Third Central Hospital of Tianjin between 2015 and 2023. The neurophysiological examination mainly included limb nerve conduction study (NCS), same core needle electrode electromyography, somatosensory evoked potential (SEP), skin sympathetic reflex (SSR), and contact heat evoked potential (CHEP).Results:Among the 8 cases with SNN, 7 cases exhibited asymmetrical onset and a non-length-dependent pattern. All the 8 cases presented with severe deep sensory ataxia, accompanied by superficial sensory abnormalities and tendon areflexia. Paraneoplastic SNN were the most prevalent etiological subtype (4 cases), all of whom presented peripheral neuropathy as the initial symptom. Among these 4 cases, malignancies were identified in 3 cases and 3 cases presented with anti-Hu antibodies. Among the remaining 4 patients, 2 cases were autoimmune and the other 2 cases were idiopathic. NCS results of the 8 cases revealed decrease or absence of sensory nerve action potential (SNAP) amplitudes, with normal sensory conduction velocities. Six cases showed abnormal SEP, including 2 cases of central damage and 4 cases of peripheral damage, 5 cases had abnormal SSR, and 2 cases exhibited abnormal CHEP. Motor nerve conduction studies were normal in all 8 cases. Six patients underwent spinal MRI, and 4 exhibited abnormal signals in dorsal columns.Conclusions:The hallmark clinical manifestation of SNN is sensory ataxia, characterized by substantial impairment of superficial sensation, typically manifesting in a non-length-dependent distribution. Beyond the widespread and significant reduction in SNAP amplitudes, SNN may also exhibit additional electrophysiological impairments, such as those observed in SEP, SSR and CHEP.SEP combined with spinal cord MRI can improve the detection rate for damages in the central sensory conduction pathway.