Identification of tumor heterogeneity associated with KRAS/TP53 co-mutation status in lung adenocarcinoma based on single-cell RNA sequencing.

Lung cancer stands as the predominant cause of cancer-related mortality globally. Lung adenocarcinoma (LUAD), being the most prevalent subtype, garners extensive attention due to its notable heterogeneity, which significantly influences tumor development and treatment approaches. This research leverages single-cell RNA sequencing (scRNA-seq) datasets to delve into the impact of KRAS/TP53 co-mutation status on LUAD. Moreover, utilizing the TCGA-LUAD dataset, we formulated a novel predictive risk model, comprising seven prognostic genes, through LASSO regression, and subjected it to both internal and external validation sets. The study underscores the profound impact of KRAS/TP53 co-mutational status on the tumor microenvironment (TME) of LUAD. Crucially, KRAS/TP53 co-mutation markedly influences the extent of B cell infiltration and various immune-related pathways within the TME. The newly developed predictive risk model exhibited robust performance across both internal and external validation sets, establishing itself as a viable independent prognostic factor. Additionally, in vitro experiments indicate that MELTF and PLEK2 can modulate the invasion and proliferation of human non-small cell lung cancer cells. In conclusion, we elucidated that KRAS/TP53 co-mutations may modulate TME and patient prognosis by orchestrating B cells and affiliated pathways. Furthermore, we spotlight that MELTF and PLEK2 not only function as prognostic indicators for LUAD, but also lay the foundation for the exploration of innovative therapeutic approaches.

Myofascial acupuncture versus routine acupuncture for mechanical neck pain: a protocol for a multicentre randomised controlled trial.

INTRODUCTION: Mechanical neck pain (MNP) is defined as pain in the area of the neck and/or neck-shoulder provoked by body mechanics and which adversely affects physical, psychological and social function. The treatments for MNP are limited. Previous studies and clinical experience have indicated that myofascial acupuncture might be a better treatment option for MNP, but the efficacy is controversial. Therefore, our aim is to compare the efficacy of myofascial acupuncture and routine acupuncture for MNP. METHODS AND ANALYSIS: The study is a multicentre, prospective randomised clinical trial. Patients will be recruited from four tertiary hospitals in China. A total of 438 participants with MNP will be randomly assigned into two groups, namely the 'Sancai-Tianbu' myofascial acupuncture group and the routine acupuncture group, at a ratio of 1:1. Each group will receive the acupuncture treatment twice a week for 21 days, totalling six sessions. The primary outcome will be the Visual Analogue Scale score. The secondary outcomes will be the Neck Disability Index, the cervical range of motion and the MOS 36-Item Short Form Health Survey. The assessments will be performed at baseline (immediately after allocation), pretreatment (5 min before every treatment), post-treatment (within 10 min after every treatment), postcourse (within 1 day after the course), and at 1, 3 and 6 months after the course. All patients will be included in the intent-to-treat analysis. Repeated-measure analysis of covariance will be used to determine the effects of the intervention on the outcome measures. ETHICS AND DISSEMINATION: Ethics approval was obtained from China Aerospace Science & Industry Corporation 731 Hospital, with permission number 2022-0204-01. Written informed consent will be obtained from the enrolled patients. Trial results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ChiCTR2200061453.

[Application of teaching method for the interpretation of acupoint names in the course of Science of Meridians and Acupoints].

The paper summarizes the valuable experience of the famous teachers of all generations in the teaching & research room of meridians and acupoints of Beijing University of CM. The shortcomings are presented when the acupoints are explained in accordance with the flowing route of meridians in classroom teaching of Science of Meridians and Acupoints. Hence, it is proposed that the acupoint names should be interpreted specially for the acupoints distributed on the same meridians or adjacent ones. It is suggested to emphasize the correlation of each acupoint with its adjacent ones from the perspective of the cultural connotation of acupoint names, and then, the differences and similarities in their clinical indications can be analyzed. Eventually, a new approach to the classroom teaching of Science of Meridians and Acupoints may be provided to guide the excavation of traditional cultural connotation and establish the cultural self-confidence and professional identity.

Use of Capillary Electrophoresis Migration Position for the Presumptive Identification of Hemoglobin Variants Prevalent in China.

Capillary electrophoresis (CE) is increasingly being used to screen for hemoglobinopathies. We here report the migration position of hemoglobin (Hb) variants prevalent in China determined by CE. The CE migration position showed excellent precision and minor inter-individual variation. We conclude that the CE migration position can be used as a reliable indicator for identifying Hb variants and can also help to establish a well-characterized library of Hb variants for their refined presumptive identification.

[Translational research of the advancement of multidisciplinary intersection in acupuncture-moxibustion technology innovation].

At present, acupuncture and moxibustion widely spread around the world, and its development is closely rela-ted to multidisciplinary integration. Interdisciplinary approaches are of great concern to the innovation and promotion of acupuncture-moxibustion therapy. Acupuncture and moxibustion, combined with optics, electrics, magnetics, infrared ray, microwave and other technologies, create the advanced and practical instrument for diagnosis and treatment of acupuncture and moxibustion and have made important contribution to clinical and teaching work. In the paper, focusing on the unique advantages of the science of acupuncture and moxibustion, the application of interdisciplinary approaches was explored to the promotion of acupuncture-moxibustion technology in its innovation and development, while the existing problems and countermeasures are further considered in the translational process of acupuncture-moxibustion technology to clinical application.

Hb Guangxi [ß65(E9)Lys→Glu (AAG>GAG); HBB: c.196A>G]: A Novel ß-Globin Variant.

We report a novel variant found in a female from Guilin municipality in the Guangxi Zhuang Autonomous Region of the People's Republic of China. This variant can be readily detected by both cation exchange high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Sanger sequencing revealed a novel mutation on the ß-globin gene [ß65(E9)Lys→Glu (AAG>GAG); HBB: c.196A>G]. We named this novel hemoglobin (Hb) variant Hb Guangxi for the place of origin of the proband.

Compound Heterozygosity for an Unstable Novel Hemoglobin Variant, Hb Dongguan [α52(E1)Ser→Cys (TCT>TGT); HBA1: c.158C>G], and the - -SEA (Southeast Asian) α-Thalassemia Deletion.

Here we report a 67-year-old Chinese male carrying an unstable novel hemoglobin (Hb) variant in compound heterozygosity with the - -SEA (Southeast Asian) α-thalassemia (α-thal) deletion. Hemoglobin analysis by capillary electrophoresis (CE) revealed a rapid degradation feature of the variant. Sanger sequencing of the Hb gene revealed a novel homozygous mutation in exon 2 of the α1-globin gene [α52(E1)Ser→Cys (TCT>TGT); HBA1: c.158C>G]. We named this novel variant Hb Dongguan for the place of origin of the proband. Additionally, gap-polymerase chain reaction (gap-PCR) indicated the presence of the heterozygous - -SEA α-thal deletion.

A Novel ß-Globin Gene Mutation: Hb Shenzhen [ß90(F6)Glu→Ala, HBB: c.272A>C].

We report a novel ß-globin chain variant, Hb Shenzhen [ß90(F6)Glu→Ala, HBB: c.272A>C], in a 52-year-old Chinese individual. The hemoglobin (Hb) variant takes the position of the Hb D zone using capillary electrophoresis. Sanger sequencing revealed a novel base mutation on the ß-globin gene, HBB: c.272A>C, that resulted in a transition of glutamic acid to alanine at exon 2 of the ß-globin gene. We named this novel variant Hb Shenzhen for the geographic origin of this proband.

Hb Hubei [α114(GH2)Pro→His, HBA1: c.344C>A]: A Novel Hemoglobin Variant of the α1-Globin Chain.

We report here a novel α1-globin chain variant, Hb Hubei [α114(GH2)Pro→His, HBA1: c.344C>A], in a Chinese individual. The proband, a 28-year-old Chinese female, was discovered following routine Hb A1c analysis using cation exchange high performance liquid chromatography (HPLC). Sanger sequencing revealed a novel missense mutation, HBA1: c.344C>A (CCC>CAC), in exon 2 of the α1-globin gene. The mutation caused a transition of proline to histidine at position α114(GH2) on the α1-globin chain. This new variant was named Hb Hubei after the geographic origin of the proband.

Hb Sichuan [α67(E16)Thr→Ile, HBA2: c.203C>T]: A Novel Hemoglobin Variant That Can Be Detected by Glycated Hemoglobin Electrophoresis.

We report a novel α2-globin chain hemoglobin (Hb) variant in a 23-year-old female of Chinese Han nationality. The Hb variant can be detected by glycated Hb electrophoresis (CapillaryS2, Hb A1c program). However, Hb fractions analyzed by capillary electrophoresis (CE) (CapillaryS2, Hb program) and high performance liquid chromatography (HPLC), (VARIANT II™ ß-Thalassemia Short Program) showed no suspicious Hb variant. Sanger sequencing revealed a novel mutation [α67(E16)Thr→Ile, HBA2: c.203C>T]. We named this novel variant Hb Sichuan after the geographic origin of the proband.

TGF-ß Mediates Renal Fibrosis via the Smad3-Erbb4-IR Long Noncoding RNA Axis.

Transforming growth factor ß (TGF-ß)/Smad3 signaling plays a role in tissue fibrosis. We report here that Erbb4-IR is a novel long non-coding RNA (lncRNA) responsible for TGF-ß/Smad3-mediated renal fibrosis and is a specific therapeutic target for chronic kidney disease. Erbb4-IR was induced by TGF-ß1 via a Smad3-dependent mechanism and was highly upregulated in the fibrotic kidney of mouse unilateral ureteral obstructive nephropathy (UUO). Silencing Erbb4-IR blocked TGF-ß1-induced collagen I and alpha-smooth muscle actin (α-SMA) expressions in vitro and effectively attenuated renal fibrosis in the UUO kidney by blocking TGF-ß/Smad3 signaling. Mechanistic studies revealed that Smad7, a downstream negative regulator of TGF-ß/Smad signaling, is a target gene of Erbb4-IR because a binding site of Erbb4-IR was found on the 3' UTR of Smad7 gene. Mutation of this binding site prevented the suppressive effect of Erbb4-IR on the Smad7 reporter activity; in contrast, overexpression of Erbb4-IR largely inhibited Smad7 but increased collagen I and α-SMA transcriptions. Thus, kidney-specific silencing of Erbb4-IR upregulated renal Smad7 and thus blocked TGF-ß/Smad3-mediated renal fibrosis in vivo and in vitro. In conclusion, the present study identified that Erbb4-IR is a novel lncRNA responsible for TGF-ß/Smad3-mediated renal fibrosis by downregulating Smad7. Targeting Erbb4-IR may represent a precise therapeutic strategy for progressive renal fibrosis.

NIR Light Propulsive Janus-like Nanohybrids for Enhanced Photothermal Tumor Therapy.

Au-BP7@SP nanohybrids with active motion under NIR laser irradiation can effectively enhance the temperature of tumor potentially by converting the kinetic energy to thermal energy, enhancing the killing efficiency of the tumor cells compared with Au@SP. The study provides an insight of nanohybrids' effect on photothermal treatment and opens a new avenue to cancer treatment by using self-propulsion Janus nanohybrids.

Bio-inspired metal ions regulate the structure evolution of self-assembled peptide-based nanoparticles.

We report an assembly and transformation process of a supramolecular module, BP-KLVFF-RGD (BKR) in solution and on specific living cell surfaces for imaging and treatment. The BKR self-assembled into nanoparticles, which further transformed into nanofibers in situ induced by coordination with Ca(2+) ions.

Reorganization of self-assembled supramolecular materials controlled by hydrogen bonding and hydrophilic-lipophilic balance.

Supramolecular assembly to form a large variety of nanostructures has received increasing attention for diverse applications, in particular biomedical applications involving drug delivery, bioimaging, therapy and regenerative medicine. Meanwhile, the modulation of morphology and structure of nanoassemblies is a still big challenge. Herein, we report a series of supramolecular structures (BP-KLVFFG-PEG, BKP) and elucidate that their morphological transformation process is modulated by H-bonding, π-π interactions and hydrophilic/lipophilic balance (HLB). Our studies reveal that the hydrophobic and π-π interactions initially drive the self-assembly of BKP into nanoparticles in J-type aggregates in water, and the H-bonding interactions further induce an in situ spontaneous morphology transformation into nanofibers. The conversion rate is related to the length of the hydrophilic chains. The nanofibers are maintained by ß-sheet H-bonds with parallel structure. Our results provide insight into the relationship between molecular structures and morphological transformations of self-assembled nanomaterials, which will guide the design of complex self-assembled materials in biological conditions.

Protective effect of epigallocatechin gallate, a major constituent of green tea, against renal ischemia-reperfusion injury in rats.

BACKGROUND: Renal ischemia-reperfusion (I/R) injury plays an important role in the acute kidney injury. The pathogenetic mechanisms potential I/R injury is involved in apoptosis and inflammation. Epigallocatechin gallate (EGCG), a major constituent of green tea, has been shown to have anti-inflammatory and anti-apoptotic activities. This study aimed to explore the underlying effects and mechanisms of EGCG on renal I/R injury in a rat model. MATERIALS AND METHODS: We induced renal I/R injury in SD rats by clamping the left renal artery for 45 min followed by 24-h reperfusion, along with a contralateral nephrectomy. We randomly allocated 30 rats to three groups (n = 10): sham group, IRI group, and EGCG group. We preconditioned rats intraperitoneally with EGCG (50 mg/kg) or vehicle (50 mg/kg) 45 min before inducing renal ischemia. We collected serum and kidneys at 24 h after reperfusion. Renal function and histologic damage were assessed. We also determined markers of inflammation and apoptosis in kidneys or serum. RESULTS: EGCG pretreatment can significantly reduce renal dysfunction, histologic change and the expression of tumor necrosis factor-α, IL-1ß, IL-6, Bax and cleavage caspase 3 induced by I/R injury and increase the expression of Bax and caspase 3. Moreover, EGCG pretreatment can further induce the activation of p38 mitogen-activated protein kinase in kidney, with no influence on the expression of p38. CONCLUSIONS: EGCG treatment can decrease renal ischemia-reperfusion injury by suppressing inflammation and cell apoptosis. Thus, EGCG may represent a potential strategy to reduce renal I/R injury.

Progress of animal research on electro-acupuncture treatment for depression(△).

This paper summarized the Chinese literatures in the previous 5 years about the pre-clinical animal researches on the application of electro-acupuncture (EA) treatment for depression, searched in China National Knowledge Infrastructure (CNKI). The efficiency of EA treatment for depression and the mechanism of it were discussed, to shed light on new ideas and new fronts for the further research on depression in clinical or pre-clinical fields.

[Effect of lifting-thrusting reinforcing-reducing manipulations of acupuncture on serum ferritin content and total iron binding capacity in blood-deficiency syndrome rabbits].

OBJECTIVE: To observe the influence of lift-thrust reinforcing-reducing manipulations of acupuncture on serum ferritin (SF) content and total iron binding capacity (TIBC) in blood-deficiency syndrome rabbits so as to study its underlying mechanisms. METHODS: Sixty Japanese white rabbits were randomized into blank control,model, acupuncture needle-retaining, reinforcing-manipulation (reinforcing) and reducing-manipulation (reducing) groups (n = 12 in each group). Blood-deficiency syndrome model was duplicated by bleeding (about 10 mL/time, once every other day, for 5 times) and food restriction (half of the normal quantity). Bilateral "Zusanli" (ST 36) were punctured by using filiform needles. The needles were not lifted and thrust for rabbits of the needle-retaining group, but lifted and thrust for 15 min for rabbits of the reinforcing and reducing groups. The treatment was given once every other day, 10 times altogether. Serum SF and TIBC levels were assayed by radioimmunoassay. RESULTS: Following modeling, compared to the blank control group, serum SF content was decreased significantly (P < 0.05), while TIBC level was increased considerably in the model group (P < 0.05). On day 17 after acupuncture treatment, serum SF contents of both reinforcing and reducing groups were up-regulated significantly in comparison with pre-treatment after modeling in the same one group (P < 0.05), while TIBC levels in these two groups were down-regulated evidently compared with pre-treatment (P < 0.05). In comparison with the model group, serum SF content in the reducing group was up-regulated apparently and TIBC levels in both reinforcing and reducing groups were down-regulated remarkably (P < 0.05). On day 32 after the treatment, serum SF contents were increased markedly and TIBC levels decreased remarkably in the needle-retaining, reinforcing and reducing groups in comparison with pre-treatment after modeling (P < 0.05). No significant differences were found between the reinforcing and reducing groups in both serum SF and TIBC levels (P > 0.05). CONCLUSION: Both reinforcing and reducing manipulation of acupuncture of "Zusanli" (ST 36) can up-regulate serum SF content and down-regulate TIBC level in blood-deficiency syndrome rabbits, which may contribute to their effects in improving blood-deficiency syndrome and has no significant difference.

[Effect of losartan on renal expression of monocyte chemoattractant protein-1 and transforming growth factor-ß(1) in rats after unilateral ureteral obstruction].

OBJECTIVE: To investigate the effect of losartan on the expression of monocyte chemoattractant protein-1 (MCP1) and transforming growth factor-ß(1) (TGF-ß(1)) in the kidney of rats with unilateral urethral obstruction (UUO) and evaluate protective effect of losartan against reanal interstitial fibrosis. METHODS: Rat models of UUO were treated with losartan at the routine dose, high dose, and very high dose (50, 200, and 500 mg/kg daily, respectively), and saline was given to UUO model rats and rats with sham operation. At 7, 14, and 21 days, the tail cuff blood pressure (TCP), 24-h urine protein (Upro), serum Scr, BUN, K(+), percentage of renal damage and renal interstitial fibrosis (%INT) were measured in the rats. MCP1 protein in the renal tissues was detected using immunohistochemistry, and MCP1 and TGF-ß(1) mRNA expressions were assayed using RT-PCR. RESULTS: As the UUO prolonged, Upro, TCP, tubular damage, %INT, and MCP1 and TGF-ß(1) mRNA expressions all increased significantly (P<0.05). High and very high doses of losartan, compared with the routine dose, obviously reversed these changes. CONCLUSION: High-dose losartan can effectively control blood pressure, reduce renal damage and fibrosis, and inhibit MCP1 and TGF-ß(1) expression in rats with UUO, and at a very high dose, losartan can more effectively reduce 24-h Upro than the high-dose group. High and very high doses of losartan offer better protective effect on the kidney in rats with UUO.

[Association of osteopontin gene polymorphism with lupus nephritis in Chinese Han population].

OBJECTIVE: To investigate the possible association of a single nucleotide polymorphism (SNP) at position 9250 in exon 7 of osteopontin gene (OPN gene 9250) with lupus nephritis (LN) in southern Chinese patients. METHODS: Altogether 109 patients with LN (12 males and 97 females) diagnosed according to the American College of Rheumatology criteria (revised in 1982) for systemic lupus erythematosus (SLE) and 180 healthy ethnically matched controls (34 males and 146 females), all Han people living in South China, were enrolled in this study with informed consent. Blood samples from all subjects were collected in EDTA tube for genomic DNA extraction according to the standard isolation procedures. OPN gene 9250 polymorphism was typed by PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS: All the genotype frequencies of OPN gene 9250 were in Hardy-Weinberg equilibrium. Compared with the controls, LN patients showed significantly lower frequency of TT genotype of OPN gene 9250 (70% vs 51%, P<0.05) and significantly higher frequency of TC genotype (29.4% vs 45%, P<0.05). There were significant differences in OPN gene 9250 allele and phenotype frequencies between LN patients and the controls (P<0.05). Compared with the female controls, the frequency of TT genotype of OPN gene 9250 was significantly lower in female LN patients (68.5% vs 54%, P<0.05), and there was a significant difference in OPN gene 9250 allele frequency between them (P<0.05). CONCLUSION: OPN gene 9250 polymorphism appears to be associated with the susceptibility to LN in southern Chinese Han population.