This paper summarizes Professor SUN Yuanzheng's academic thought and clinical experience in treating diabetic retinopathy (DR) with yuan-primary and luo-connecting meridian-regulating acupuncture. Professor SUN considers that the fundamental cause of DR lies in visceral dysfunction, with stagnation in the ocular collateral vessels and impairment of the mysterious orifices being the core pathogenesis. He proposes the treatment model of "regulating viscera, unblocking ocular collaterals, and opening mysterious orifices" based on yuan-primary and luo-connecting meridian-regulating acupuncture. Yuan-primary and luo-connecting points are used to balance qi, blood, yin, and yang of the viscera. Baihui (GV20) is stimulated with transcranial repetitive acupuncture to activate the yang qi of the governor vessel and invigorate qi in the twelve meridians, improving systemic microcirculation. Combining this with stimulation of ocular areas, Fengchi (GB20), and periocular points, the stasis in the ocular collaterals are cleared and the mysterious orifices are unblocked, addressing both the root and manifestations of DR.
Humans ; Diabetic Retinopathy/physiopathology* ; Acupuncture Therapy/history* ; Meridians ; Acupuncture Points ; Qi

Objective:To investigate the effects of electroheating on pathologic pain, endoplasmic reticulum stress and EGFR/JAK/STAT signaling pathway in rats with knee osteoarthritis.Methods:Totally 40 SPF SD male rats were divided into normal group (10 rats) and modeling group (40 rats) with random number table method. The model of knee osteoarthritis was prepared by injecting sodium iodoacetate into the joint cavity. The successfully modeled rats were divided into model group, sodium hyaluronate group, and electroheating needle group, with 10 rats in each group. After successful modeling, sodium hyaluronate group was injected with 0.1 ml sodium hyaluronate into joint cavity. The electrothermal acupuncture group was treated with electrothermal acupuncture, and the normal group and the model group were given the same volume of normal saline at the same time, once a day, for two weeks. The mechanical pain threshold (PWT) and thermal pain threshold (PWL) in rats were detected. The pathological morphology of cartilage was detected by HE staining. Immunohistochemical staining was used to detect the expressions of glucose regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) in cartilage tissue. Western blot was used to detect the expressions of EGFR, JAK, and STAT proteins, while RT-PCR was used to detect the mRNA levels of GRP78, CHOP, EGFR, JAK, and STAT in cartilage tissue.Results:The normal group had normal cartilage tissue structure, orderly distribution of synovial cells, neat arrangement of chondrocytes, and no inflammatory cell infiltration. The model group had synovial hyperplasia and hypertrophy, irregular arrangement of synovial cells and a large number of hyperplasia, disordered arrangement of chondrocytes and increased number of inflammatory cell infiltration. Compared with the model group, the PWT and PWL in cartilage tissues of sodium hyaluronate group and electrothermal acupuncture group increased ( P<0.05), the expressions of GRP78 and CHOP in cartilage tissues decreased ( P<0.05), the protein expressions of EGFR, JAK1 and STAT1 in cartilage tissue decreased, and the mRNA expressions of GRP78, CHOP, EGFR, JAK1 and STAT1 in cartilage tissue decreased ( P<0.05). Conclusion:Electroheating needle can improve pathological pain in knee osteoarthritis model rats, and its mechanism may be related to inhibiting endoplasmic reticulum stress and regulating the EGFR/JAK/STAT signaling pathway.

Pyran- and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans, respectively, exhibiting diverse physiological and medical bioactivities. However, the biosynthetic mechanisms for their core structures remain poorly understood. Here we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in plants. These included three distinct P. praeruptorum prenyltransferases (PpPT1-3) responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors, and two novel CYP450 cyclases (PpDC and PpOC) crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran scaffolds. Biochemical analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring refactoring. The possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific mutagenesis. We identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic process. This study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

Objective:To investigate the effect of ultra-early enteral nutrition (UEEN) support on the prognosis of young and middle-aged postoperative patients with cerebral hemorrhage.Methods:The clinical data of young and middle-aged patients (aged 18-59 years) admitted to Tianjin Fifth Central Hospital from January 2020 to June 2023 after surgery for intracerebral hemorrhage were retrospectively analyzed, and the general data, nutritional indexes, gastrointestinal complications, neurological function recovery and long-term prognosis of the patients were recorded. According to the time of initiation of enteral nutrition (EN) support, patients were divided into UEEN group (EN implementation within 12 hour after surgery) and early enteral nutrition (EEN) group (EN implementation within 24 to 48 hour after surgery). The differences of the above indexes between the two groups were analyzed and compared.Results:A total of 64 young and middle-aged postoperative patients with cerebral hemorrhage were enrolled, including 32 cases in the UEEN group and 32 cases in the EEN group. There were no significant differences in gender, age, proportion of hypertension and diabetes, Glasgow coma score (GCS) on admission and surgical methods between the two groups. In terms of nutritional indexes, serum total protein, albumin and hemoglobin levels of patients in both groups on day 7 after admission were lower than those on day 1, and higher than those on day 3, and the above indexes levels in UEEN group were significantly higher than those in EEN group on day 7 [total protein (g/L): 63.05±5.79 vs. 59.02±6.63, albumin (g/L): 40.40±5.26 vs. 37.66±4.63, hemoglobin (g/L): 133.33±12.58 vs. 123.80±22.12, all P < 0.05]. In terms of gastrointestinal complications, the incidence of stress ulcer in the UEEN group within 14 days after admission was significantly lower than that in the EEN group [12.5% (4/32) vs. 31.3% (10/32), P < 0.05], but there was no statistically significant difference in feeding intolerance symptoms between the two groups. In terms of neurological recovery and long-term prognosis, GCS scores and Barthel index scores of 14 days after admission were higher than those of 1 day after admission, but there was no statistical significance between the two groups. Six months after surgery, Glasgow outcome scale (GOS) and Barthel index score of the UEEN group were significantly higher than those of the EEN group (GOS score: 3.81±1.06 vs. 3.18±1.07, Barthel index score: 60.78±7.24 vs. 54.52±5.13, both P < 0.05). Conclusion:UEEN support can improve the nutritional level of young and middle-aged postoperative patients with cerebral hemorrhage, reduce the occurrence of postoperative gastrointestinal complications, promote the recovery of neurological function, and improve the long-term prognosis.

Objective:To investigate the effects and mechanisms of Nicorandil, an ATP-sensitive potassium channel (KATP) opener, on pyroptosis and inflammatory responses in microglia(BV2) induced by oxygen-glucose deprivation/reoxygenation (OGD/R).Methods:BV2 cells were divided into control group, OGD/R group, and OGD/R+ Nicorandil group.And the cells were subjected to oxygen-glucose deprivation for 3 hours and then reoxygenated for 24 hours to establish an OGD/R cell model. OGD/R+ Nicorandil group cells were incubated with 5 μg/mL Nicorandil culture medium for 24 hours after oxygen-glucose deprivation for 3 hours.The cell proliferation activity was detected by CCK8 assay.Calcein/propidium iodide (calcein/PI) assay kit was used to detect the membrane porosity rupture rate of cell in each group.Western blot analysis was performed to detect the protein expression levels of nuclear factor-κB (NF-κB), phosphorylated NF-κB (p-NF-κB), inhibitor of nuclear factor-κB α(IκB-α), phosphorylated IκB-α (p-IκB-α), absent in melanoma 2 (AIM2), cleaved-caspase-1, gasdermin D-N (GSDMD-N), interleukin-18 (IL-18), and interleukin-1β (IL-1β). Immunofluorescence was used to detect the protein expression levels of AIM2 and GSDMD-N in each group. Statistical analysis was performed by SPSS 26.0 software. One-way ANOVA was used for multiple group comparisons, and LSD test was used for pairwise comparisons.Results:(1) There were statistically significant differences in the membrane porosity rupture rates among the three groups ( F=615.882, P<0.05). The membrane porosity rupture rate in the Nicorandil group was lower than that in the OGD/R group ((41.50±3.04)%, (59.44±3.66)%, P<0.05). (2) Western blot results showed that the protein expression levels of p-NF-κB, NF-κB, p-IκB-α, and IκB-α were significantly different among the three groups ( F=10.000, 62.652, 67.121, 101.023, all P<0.05). The levels of p-NF-κB, NF-κB and p-IκB-α in the OGD/R+ Nicorandil group ((0.60±0.13), (0.87±0.06), (0.55±0.06), respectively) were lower than those in the OGD/R group ((1.02±0.09), (1.03±0.09), (0.86±0.04), respectively) (all P<0.05). The level of IκB-α in the OGD/R+ Nicorandil group ((0.63±0.05), (0.46±0.06)) was higher than that in the OGD/R group( P<0.05). (3) The protein expression levels of AIM2, cleaved-caspase-1, GSDMD-N, IL-18, and IL-1β were significantly different among the three groups ( F=65.926, 12.428, 66.447, 44.831, 52.960, all P<0.05). The levels of AIM2, cleaved-caspase-1, GSDMD-N, IL-18 and IL-1β in the OGD/R+ Nicorandil group ((0.78±0.04), (0.71±0.09), (0.54±0.04), (0.72±0.07), (0.50±0.08), respectively) were lower than those in the OGD/R group ((0.94±0.09), (0.89±0.09), (0.85±0.04), (0.90±0.07), (0.99±0.03), respectively) (all P<0.05). (4) Immunofluorescence results showed statistically significant differences in the fluorescence intensity of pyroptosis marker proteins AIM2 and GSDMD-N among the three groups ( F=36.353, 46.817, both P<0.05). The fluorescence intensities of AIM2 ((124.36±7.91), (140.19±5.63)) and GSDMD-N ((134.16±5.18), (147.45±5.63))in the OGD/R+ Nicorandil group were lower than those in the OGD/R group (both P<0.05). Conclusion:Nicorandil can mitigate BV2 cell damage following oxygen-glucose deprivation, inhibiting the release of pro-inflammatory factors. The mechanism may be related to the downregulation of the expression of NF-κB related proteins and inhibition of AIM2 inflammasome-mediated pyroptosis after OGD/R.

Objective:To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice.Methods:Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate′s parents used the JCard to measure jaundice at the neonate′s cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson′s correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis.Results:Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) μmol/L, with a range of 23.7-717.0 μmol/L. The JCard level was (221.4±77.0) μmol/L and the TcB level was (252.5±76.0) μmol/L. Both the JCard and TcB values showed good correlation ( r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2?μmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0?μmol/L. The TcB value of 205.2?μmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 μmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 μmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 μmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 μmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 μmol/L (both P<0.05). Conclusions:JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 μmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 μmol/L).

Objectives: . Considerable research has been focused on independent predictors of difficult laryngeal exposure (DLE) during suspension laryngoscopy. However, previous studies have yielded inconsistent results and conclusions. Consequently, we performed a meta-analysis of the existing literature with the aim of identifying significant parameters for a standardized preoperative DLE prediction system. Methods: . We systematically retrieved articles from the PubMed, Embase, Web of Science, China National Knowledge Infrastructure, and Wanfang databases up to October 2022. Data from eligible studies were extracted and analyzed using the R programming language. The effect measures included odds ratios (ORs) with 95% confidence intervals (CIs) for dichotomous variables and mean differences (MDs) with 95% CIs for continuous variables. Results: . The search yielded 1,574 studies, of which 18 (involving a total of 2,263 patients) were included. Pooled analysis demonstrated that patients with DLE during microsurgery tended to be male (OR, 1.73; 95% CI, 1.16–2.57); were older (MD, 5.47 years, 95% CI, 2.44–8.51 years); had a higher body mass index (BMI; MD, 1.19 kg/m2; 95% CI, 0.33–2.05 kg/m2); had a greater neck circumference (MD, 2.50 cm; 95% CI, 1.56–3.44 cm); exhibited limited mouth opening (MD, −0.52 cm; 95% CI, −0.88 to −0.15 cm); had limited neck flexibility (MD, −10.05 cm; 95% CI, −14.10 to −6.00 cm); displayed various other anatomical characteristics; and had a high modified Mallampati index (MMI) or test score (OR, 3.37; 95% CI, 2.07–5.48). Conclusion . We conducted a comprehensive and systematic analysis of the factors relevant to DLE. Ultimately, we identified sex, age, BMI, neck circumference, MMI, inter-incisor gap, hyomental distance, thyromental distance, sternomental distance, and flexion-extension angle as factors highly correlated with DLE.

The use of checkpoint-blockade antibodies is still restricted in several malignancies due to the modest efficacy, despite considerable success in anti-tumor immunotherapy. The poor response of cancer cells to immune destruction is an essential contributor to the failure of checkpoint therapy. We hypothesized that combining checkpoint therapy with natural-product chemosensitizer could enhance immune response. Herein, a targeted diterpenoid derivative was integrated with the checkpoint blockade (anti-CTLA-4) to improve immunotherapy using thermosensitive liposomes as carriers. In vivo, the liposomes enabled the co-delivery of the two drug payloads into the tumor. Consequently, the regulatory T cell proliferation was restrained, the cytotoxic T cell infiltration was enhanced, and the profound immunotherapeutic effect was achieved. In addition, the immunotherapeutic effect of another clinically used checkpoint antibody, anti-PD-1, also benefited from the diterpenoid derivative. Of note, our mechanism study revealed that the targeted diterpenoid derivative increased the sensitivity of cancer cells to immune attack via THBS1 downregulation and the resultant destruction of THBS1-CD47 interaction. Collectively, co-delivering THBS1 inhibitor and checkpoint blockade is promising to boost cancer immunotherapy. We first time discovered that THBS1 suppression could strengthen checkpoint therapy.

Objective:To observe the effect of abdominal electroacupuncture(EA)on intestinal function in patients with constipation after stroke. Methods:A total of 100 patients with post-stroke constipation were divided into an observation group and a control group by the random number table method,with 50 cases in each group.The control group was treated with oral lactulose,10 mL each time,3 times a day,for 2 consecutive weeks.The observation group was treated with additional abdominal EA at Tianshu(ST25),Fushe(SP13),and Daheng(SP15)on the basis of oral lactulose,30 min for needle retention each time,once a day,for 2 consecutive weeks.The total effective rate after treatment,constipation symptom score,the score of patient assessment of constipation quality of life scale(PAC-QOL),serum motilin(MTL)level,and the score of mini-mental state examination(MMSE)were compared between the two groups. Results:After 2 weeks of treatment,the total effective rate was 93.5%in the observation group and 76.1%in the control group,and the difference between the two groups was statistically significant(P<0.05).The constipation symptom score,PAC-QOL score,MMSE score,and MTL level changed significantly after treatment in both groups(P<0.05).After treatment,the constipation symptom score and PAC-QOL score in the observation group were lower than those in the control group,while the MMSE score and MLT level were higher than those in the control group,and the differences between the two groups were statistically significant(P<0.05). Conclusion:On the basis of oral lactulose,EA at abdominal points can significantly improve the intestinal and cognitive function of stroke patients simultaneously.

Color is an important indicator for evaluating the ornamental traits of horticultural plants, and plant pigments is a key factor affecting the color phenotype of plants. Plant pigments and their metabolites play important roles in color formation of ornamental organs, regulation of plant growth and development, and response to adversity stress. It has therefore became a hot topic in the field of plant research. Virus-induced gene silencing (VIGS) is a vital genomics tool that specifically reduces host endogenous gene expression utilizing plant homology-dependent defense mechanisms. In addition, VIGS enables characterization of gene function by rapidly inducing the gene-silencing phenotypes in plants. It provides an efficient and feasible alternative for verifying gene function in plant species lacking genetic transformation systems. This paper reviews the current status of the application of VIGS technology in the biosynthesis, degradation and regulatory mechanisms of plant pigments. Moreover, this review discusses the potential and future prospects of VIGS technology in exploring the regulatory mechanisms of plant pigments, with the aim to further our understandings of the metabolic processes and regulatory mechanisms of different plant pigments as well as improving plant color traits.
Plant Viruses/genetics* ; Plants/genetics* ; Gene Silencing ; Plant Development ; Gene Expression Regulation, Plant ; Genetic Vectors