ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease （DKD） via the nuclear factor erythroid 2-related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H quinone oxidoreductase 1 （NQO1） signaling pathway. MethodsSpecific pathogen-free （SPF） male C57BL/6 mice were assigned into a control group （n=10） and a modeling group （n=50）. The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group， a semaglutide （40 μg·kg^-1） group， and high-， medium-， and low-dose （18.2， 9.1， 4.55 g·kg^-1， respectively） Yishen Tongluo prescription groups， with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured， and the kidney index （KI） was calculated. Serum levels of creatinine （SCr）， blood urea nitrogen （BUN）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin， periodic acid-Schiff， periodic acid-silver methenamine， and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin （β2-MG）， neutrophil gelatinase-associated lipocalin （NGAL）， kidney injury molecule-1 （KIM-1）， liver fatty acid-binding protein （L-FABP）， nitric oxide synthase （NOS）， glutathione （GSH）， total antioxidant capacity （T-AOC）， and 8-hydroxy-2'-deoxyguanosine （8-OHdG）. Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 （Keap1） and malondialdehyde （MDA）. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group， the DKD model group showed rises in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with glomerular hypertrophy， renal tubular dilation， thickened basement membrane， mesangial expansion， and collagen deposition. Additionally， the model group showed elevated levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， lowered levels of GSH and T-AOC， up-regulated expression of MDA and Keap1， and down-regulated expression of Nrf2， HO-1， NQO1， and glutamate-cysteine ligase catalytic subunit （GCLC） （P<0.05）. Compared with the model group， the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose， 24-h urine protein， KI， SCr， BUN， and ALT levels， along with alleviated pathological injuries in the renal tissue. In addition， the three groups showed lowered levels of β2-MG， NGAL， KIM-1， L-FABP， NOS， and 8-OHdG， elevated levels of GSH and T-AOC， down-regulated expression of MDA and Keap1， and up-regulated expression of Nrf2， HO-1， NQO1， and GCLC （P<0.05）. ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway， mitigating oxidative stress， and reducing renal tubular injuries.

Objective: To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway. Methods: Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue. Results: Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated. Conclusion Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.

OBJECTIVE: To observe the impact of indirect moxibustion with Taiyi moxa stick on pain severity and the quality of life in the patients with back myofascitis, and evaluate its clinical effect and safety. METHODS: Seventy-two patients with back myofascitis were randomly divided into an observation group (36 cases, 1 cases dropped out) and a control group (36 cases, 3 cases dropped out). Three to six ashi points were selected using acupoint diagnosis methods. In the observation group, the indirect moxibustion with Taiyi moxa stick was operated at the ashi points, once every other day, three times a week. In the control group, the topical treatment with diclofenac sodium gel was given at ashi points, three times daily. The treatment was delivered consecutively for 2 weeks in the two groups. The scores of visual analogue scale (VAS) and the short-form McGill pain questionnaire (SF-MPQ) were recorded before treatment, after 1 and 2 weeks of treatment, and after 4 weeks of treatment completion (follow-up visit) in the two groups separately. The difference value between VAS score after 2 weeks of treatment and that before treatment was taken as the primary outcome. The SF-36 score was observed before treatment, after 2 weeks of treatment and during the follow-up visit, and the safety was evaluated in the two groups. RESULTS: The difference value of VAS scores was (-4.57±1.50) points and (-2.40±1.31) points in the observation group and the control group, respectively, the reduction of the score in the observation treatment was larger than that of the control group (P<0.001). After 1 and 2 weeks of treatment and during the follow-up visit, VAS and SF-MPQ scores were reduced when compared with those before treatment (P<0.05) in the two groups, and VAS and SF-MPQ scores in the observation group were lower than those in the control group (P<0.05). In the follow-up visit, VAS and SF-MPQ scores in the observation group were dropped in comparison with those after 1 week of treatment (P<0.05), and these scores in the control group were elevated compared with those after 2 weeks of treatment (P < 0.05). After 2 weeks of treatment and during the follow-up visit, the score of each dimension and total score of SF-36 scale were increased in comparison with those before treatment in the observation group (P<0.05); and the scores of the dimensions except that of mental health of SF-36 scale were elevated in the control group (P<0.05). During the follow-up visit, in the control group, the scores of physical functioning, bodily pain, general health and role emotional were elevated when compared with those before treatment (P<0.05). After 2 weeks of treatment and during the follow-up visit, the score of every dimension and total score of SF-36 scale in the observation group were higher than those in the control group (P<0.05). During the follow-up visit, the score of bodily pain was increased when compared with that after 2 weeks of treatment in the observation group (P<0.05), while the scores of bodily pain and vitality were dropped in the control group (P<0.05). No adverse event happened in the two groups. CONCLUSION The indirect moxibustion with Taiyi moxa stick effectively reduces pain severity and improves the quality of life in the patients with back myofascitis. This therapy presents the superior and persistent effect compared with topical application of diclofenac sodium gel.
Humans ; Female ; Male ; Moxibustion ; Middle Aged ; Adult ; Treatment Outcome ; Acupuncture Points ; Young Adult ; Aged ; Quality of Life ; Myofascial Pain Syndromes/therapy*

Interpreting genes of interest is essential for identifying molecular mechanisms, but acquiring such information typically involves tedious manual retrieval. To streamline this process, the fanyi package offers tools to retrieve gene information from sources like National Center for Biotechnology Information (NCBI), significantly enhancing accessibility. Additionally, understanding the latest research advancements and sharing achievements are crucial for junior researchers. However, language barriers often restrict knowledge absorption and career development. To address these challenges, we developed the fanyi package, which leverages artificial intelligence (AI)-driven online translation services to accurately translate among multiple languages. This dual functionality allows researchers to quickly capture and comprehend information, promotes a multilingual environment, and fosters innovation in academic community. Meanwhile, the translation functions are versatile and applicable beyond biomedicine research to other domains as well. The fanyi package is freely available at https://github.com/YuLab-SMU/fanyi.

Objective:To summarize the clinical features and postoperative efficacy of patients with oval window atresia accompanied by facial nerve aberration.Methods:The clinical data of patients with congenital middle ear malformation with facial nerve aberration admitted to our hospital from January 2015 to March 2023 were retrospectively analyzed. There were 97 cases (133 ears) in total. Among them, 39 patients (44 ears) had complete follow-up data, including 27 male patients and 12 females, aged 7-48 years old, with an average age of 17.8 years old. Of these, 14 cases (16 ears) were patients combined with facial nerve aberration, and 25 cases (28 ears) were without facial nerve aberration. The results of imaging examination, pure-tone audiometry, selection of surgical strategy, intraoperative findings and postoperative hearing improvement were summarized and analyzed. The malformations of malleus, incus, stapes, oval window and facial nerve were recorded. Prism 9 software was used to statistically analyze the mean bone conductance and air-bone gap of patients before and after surgery.Results:All the 14 patients (16 ears) with middle ear malformation accompanied by facial nerve aberration and oval window atresia showed poor hearing and no facial palsy since childhood. High resolution CT (HRCT) examination of temporal bone, pure tone audiometry and Gelle test were performed before surgery. The malformations of malleus, incus, stapes, oval window and facial nerve were recorded. Preoperative high-resolution CT (HRCT) examination of temporal bone found 12 ears with 4 or more deformities, accounting for 75.00%, in the group of patients with facial nerve malformation. The preoperative average bone conductive threshold was (15.3±10.4) dB and the average air-bone gap was (46.3±10.6) dB in pure-tone audiometry (0.5, 1, 2, 4kHz). According to the different degrees of facial nerve and ossicle malformation, we performed three different hearing reconstruction strategies for the 14 patients (16 ears) with facial nerve aberration and oval window atresia, including 7 ears of incus bypass artificial stape implantation, 7 ears of Malleostapedotomy (MS) and 2 ears of Malleus-cochlear-prothesis (MCP). After 3 months to 18 months of follow-up, all patients showed no facial paralysis. The postoperative mean bone conductive threshold was (15.7±7.9) dB and air-bone gap was (19.8±8.5) dB. There were significant differences in mean air-bone gap before and after operation ( t=7.766, P<0.05), and there was no significant difference between the mean bone conductive threshold before and after surgery ( t=0.225, P=0.824). There was no significant difference of mean reduction of air-bone gap between patients with and without facial nerve aberration ( t=1.412, P=0.165). There was no significant difference between the three hearing reconstruction strategies. There was no significant displacement of the Piston examined by U-HRCT. Conclusion:For patients of middle ear malformation whose facial nerve cover the oval window partially, incus bypass artificial stape implantation or Malleostapedotomy (MS) can be selected according to the specific condition of auditory ossis malformation, and for patients whose facial nerve completely covers the oval window area, Malleus-cochlear-prothesis (MCP) can be selected. Three types of stapes surgery are safe and reliable for patients with oval window atresia accompanied by facial nerve aberration. There was no significant difference in efficacy between them. Preoperative HRCT assessment of middle ear malformation is effective. There is no significant difference of surgical effect with or without facial nerve aberration. The U-HRCT can be used to evaluate the middle ear malformation before surgery and the Piston implantation status after surgery. Due to the risks of surgery, those who do not want to undergo surgery can choose artificial hearing AIDS, such as hearing aid, vibrating soundbridge, bone bridge or bone-anchored hearing aid.

ObjectiveTo explore the effect and mechanism of the classic famous prescription Anmeidan （AMD） developed in the Qing Dynasty in regulating the hepatic neurotransmitters and circadian rhythm in the rat model of insomnia via the orexin-1 receptor （OX1R）/phosphatidylinositol-specific phospholipase Cβ-1 （PLCβ-1）/protein kinase Cα （PKCα）/extracellular signal-regulated kinase 1/2 （ERK1/2） signaling pathway. MethodSixty SPF-grade SD rats were randomized into blank， model， suvorexant （30 mg·kg^-1·d^-1）， and low-， medium-， and high-dose （4.55， 9.09， 18.09 g·kg^-1·d^-1， respectively） AMD groups， with 10 rats in each group. The rats in other groups except the blank group were modeled by intraperitoneal injection of p-chlorophenylalanine （PCPA） and administrated with corresponding drugs by gavage， and the blank group received an equal volume of normal saline. The general condition， body mass， and 24 h autonomic activity of each group were observed. The pathological changes of the liver tissue were observed by hematoxylin-eosin（HE）staining and Masson staining. The expression of gamma-aminobutyric acid （GABA）， 5-hydroxytryptamine （5-HT）， epinephrine （EPI）， norepinephrine （NE）， and acetylcholine （ACh） in the liver tissue was detected by enzyme-linked immunosorbent assay. The glutamate （Glu） expression in the liver tissue was detected by the biochemical method. The mRNA levels of biological clock genes Per1， Per2， Cry1， Cry2， Bmal1， and Bmal2 in the liver were determined by Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）. The protein and mRNA levels of factors in the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway in the liver were determined by Western blot and Real-time PCR， respectively. ResultCompared with the blank group， the modeling decreased the body mass （P<0.05， P<0.01） and caused mania and disturbed resting rhythms （P<0.01）， hepatic muscle fiber fracture， and edema with inflammatory cell infiltration. In addition， the modeling decreased the GABA， 5-HT， EPI， NE， and ACh content， increased Glu content （P<0.01）， down-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.01）， up-regulated the mRNA levels of Bmal1 and Bmal2 （P<0.01）， and promoted the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both protein and mRNA levels （P<0.01）. Compared with the model group， suvorexant and AMD increased the body mass （P<0.05， P<0.01）， alleviated the mania， and increased the resting time and frequency （P<0.05， P<0.01）. Moreover， the medications elevated the levels of GABA， 5-HT， EPI， NE， and ACh， lowered the Glu level， up-regulated the mRNA levels of Per1， Per2， Cry1， and Cry2 （P<0.05， P<0.01）， down-regulated the mRNA levels of Bmal1 and Bmal2， and inhibited the expression of OX1R， PLCβ-1， PKCα， and ERK1/2 at both mRNA and protein levels （P<0.05， P<0.01）. ConclusionAMD can regulate hepatic neurotransmitters and improve circadian rhythm in insomniac rats by inhibiting the OX1R/PLCβ-1/PKCα/ERK1/2 signaling pathway， and high-dose AMD demonstrated the strongest effect.

Objective To evaluate the effects and the possible mechanisms based on the synaptic plasticity regulated by the orexin signalling pathway of the classic Qing Dynasty prescription AnMeidan(AMD),whose"Raw and cooked jujube kernel"used and without the prescription on learning and memory in a rat model of insomnia.Methods The insomnia model was constructed by intraperitoneal injection of p-chlorophenylalanine(PCPA)into rats,and AMD was administered by gavage and a decoction of the formula was disassembled.Observing 24 h autonomous activity using the EthoVision XT animal motion trajectory tracking system,Morris water maze was used to evaluate the learning and memory ability;hematoxylin-eosin(HE)and Nissl staining were used to observe the neuronal changes in rat hippocampal CA1 area;Golgi staining and immunohistochemistry(IHC)were used to observe the neuronal dendritic changes in rat hippocampal CA1 area,and the changes in synaptic plasticity proteins,synaptophysin(SYN),microtubule-associated protein 2(MAP-2),glial fibrillary acidic protein43(GFAP-43);Western blotting and Reverse transcription-qPCR(RT-qPCR)were used to detect hippocampal orexin A(OXA)/phosphatidylinositol-specific phosphodiesterase Cβ1(PLCβ-1)/protein kinase Cα(PKCα)/extracellular signalling-regulated kinase(ERK1/2)signalling pathway protein and gene expression.Results Compared with the blank group,the model group showed prolonged upper platform latency,decreased number of crossing stations,decreased distance travelled by periplatform range I activity,the frequency and duration of mania increase,while the frequency and duration of stillness decrease(P<0.01),damaged muscle fibres in the CA1 region of the hippocampus,uneven staining of the nuclei,decreased and disorganized Nyctal microsomes,reduced dendritic spine length and number(P<0.05),and faded staining and decreased expression of SYN,MAP-2,and GFAP-43(P<0.01),hippocampal OXA protein and gene expression increased(P<0.01),and PLCβ-1,PKCα,ERK1/2 protein and gene expression decreased(P<0.01).Compared with the model group,Suvorexant and AMD,AMD desiccated,and cooked jujube seed increased the static frequency、number of times they traversed the station,the distance travelled in the first quadrant and the range of periportal activities,and the time of periportal range I activities(P<0.05,P<0.01);hippocampal muscle fibres were more neatly arranged,the number of Nissin bodies increased,and dendritic spine lengths and numbers were increased(P<0.05),and the SYN,MAP-2,and GFAP-43 expression was elevated(P<0.05,P<0.01),OXA expression was decreased(P<0.01,P<0.05),and PLCβ-1,PKCα,ERK1/2 expression was elevated(P<0.01,P<0.05).Compared with the AMD group,both AMD de-raw and ripe date palm kernel groups could increase the number of times and distances they traversed the stations(P<0.05,P<0.01),decrease the length and number of dendritic spines(P<0.05),decrease the expression of SYN,MAP-2,GFAP-43,and OXA proteins in hippocampal CA1 region(P<0.01),and elevate the PLCβ-1,PKCα,and ERK1/2 expression(P<0.05).Conclusion AMD can regulate the synaptic plasticity of hippocampus in insomniac rats through regulating the OXA/PLCβ-1/PKCα/ERK1/2 signalling pathway to improve the learning memory,the effect of"raw and cooked jujube kernel"used together was better than that of"raw and cooked jujube kernel"used separately.

Objective To evaluate the effects and the possible mechanisms based on the synaptic plasticity regulated by the orexin signalling pathway of the classic Qing Dynasty prescription AnMeidan(AMD),whose"Raw and cooked jujube kernel"used and without the prescription on learning and memory in a rat model of insomnia.Methods The insomnia model was constructed by intraperitoneal injection of p-chlorophenylalanine(PCPA)into rats,and AMD was administered by gavage and a decoction of the formula was disassembled.Observing 24 h autonomous activity using the EthoVision XT animal motion trajectory tracking system,Morris water maze was used to evaluate the learning and memory ability;hematoxylin-eosin(HE)and Nissl staining were used to observe the neuronal changes in rat hippocampal CA1 area;Golgi staining and immunohistochemistry(IHC)were used to observe the neuronal dendritic changes in rat hippocampal CA1 area,and the changes in synaptic plasticity proteins,synaptophysin(SYN),microtubule-associated protein 2(MAP-2),glial fibrillary acidic protein43(GFAP-43);Western blotting and Reverse transcription-qPCR(RT-qPCR)were used to detect hippocampal orexin A(OXA)/phosphatidylinositol-specific phosphodiesterase Cβ1(PLCβ-1)/protein kinase Cα(PKCα)/extracellular signalling-regulated kinase(ERK1/2)signalling pathway protein and gene expression.Results Compared with the blank group,the model group showed prolonged upper platform latency,decreased number of crossing stations,decreased distance travelled by periplatform range I activity,the frequency and duration of mania increase,while the frequency and duration of stillness decrease(P<0.01),damaged muscle fibres in the CA1 region of the hippocampus,uneven staining of the nuclei,decreased and disorganized Nyctal microsomes,reduced dendritic spine length and number(P<0.05),and faded staining and decreased expression of SYN,MAP-2,and GFAP-43(P<0.01),hippocampal OXA protein and gene expression increased(P<0.01),and PLCβ-1,PKCα,ERK1/2 protein and gene expression decreased(P<0.01).Compared with the model group,Suvorexant and AMD,AMD desiccated,and cooked jujube seed increased the static frequency、number of times they traversed the station,the distance travelled in the first quadrant and the range of periportal activities,and the time of periportal range I activities(P<0.05,P<0.01);hippocampal muscle fibres were more neatly arranged,the number of Nissin bodies increased,and dendritic spine lengths and numbers were increased(P<0.05),and the SYN,MAP-2,and GFAP-43 expression was elevated(P<0.05,P<0.01),OXA expression was decreased(P<0.01,P<0.05),and PLCβ-1,PKCα,ERK1/2 expression was elevated(P<0.01,P<0.05).Compared with the AMD group,both AMD de-raw and ripe date palm kernel groups could increase the number of times and distances they traversed the stations(P<0.05,P<0.01),decrease the length and number of dendritic spines(P<0.05),decrease the expression of SYN,MAP-2,GFAP-43,and OXA proteins in hippocampal CA1 region(P<0.01),and elevate the PLCβ-1,PKCα,and ERK1/2 expression(P<0.05).Conclusion AMD can regulate the synaptic plasticity of hippocampus in insomniac rats through regulating the OXA/PLCβ-1/PKCα/ERK1/2 signalling pathway to improve the learning memory,the effect of"raw and cooked jujube kernel"used together was better than that of"raw and cooked jujube kernel"used separately.