OBJECTIVES: To explore the underlying pharmacological mechanisms and its potential effects of Chinese medicine herbal formula Sini Powder (SNP) on hepatocellular carcinoma (HCC). METHODS: The active components of SNP and their in vivo distribution were identified using ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Construction of component-target-disease networks, protein-protein interaction network, Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, and molecular docking were employed to analyze the active components and anti-HCC mechanisms of SNP. Cell viability assay and wound healing assay were utilized to confirm the effect of SNP-containing serum (2.5%, 5.0%, 10%, 20%, and 40%), isoprenaline or propranolol (both 10, 100, and 1,000 µ mol/L) on proliferation and migration of HepG 2 or Huh7 cells. Meanwhile, the effect of isoprenaline or propranolol on the β 2 adrenergic receptor (ADRB2) mRNA expression on HepG2 cells were measured by real-time quantitative reverse transcription (RT-qPCR). Mice with subcutaneous tumors were either subjected to chronic restraint stress (CRS) followed by SNP administration (364 mg/mL) or directly treated with SNP (364 mg/mL). These two parallel experiments were performed to validate the effects of SNP on stress responses. Stress-related proteins and hormones were quantified using RT-qPCR, enzyme-linked immunosorbent assay, and immunohistochemistry. Metagenomic sequencing was performed to confirm the influence of SNP on the gut microbiota in the tumor-bearing CRS mice. RESULTS: The distribution of the 12 active components of SNP was confirmed in various tissues and feces. Network pharmacology analysis confirmed the anti-HCC effects of the 5 active components. The potential anti-HCC mechanisms of SNP may involve the epidermal growth factor receptor (EGFR), proto-oncogene tyrosine-protein kinase Src (SRC) and signal transducer and activator of transcription 3 (STAT3) pathways. SNP-containing serum inhibited the proliferation of HepG2 and Huh7 cells at concentrations of 2.5% and 5.0%, respectively, after 24 h of treatment. Furthermore, SNP suppressed tumor progression in tumor-bearing mice exposed to CRS. SNP treatment also downregulated the expressions of stress-related proteins and pro-inflammatory cytokines, primarily by modulating the gut microbiota. Specifically, the abundance of Alistipes and Prevotella, which belong to the phylum Bacteroidetes, increased in the SNP-treated group, whereas Lachnospira, in the phylum Firmicutes, decreased. CONCLUSION SNP can combat HCC by alleviating stress responses through the regulation of gut microbiota.
Animals ; Gastrointestinal Microbiome/drug effects* ; Liver Neoplasms/microbiology* ; Carcinoma, Hepatocellular/microbiology* ; Humans ; Drugs, Chinese Herbal/therapeutic use* ; Powders ; Cell Proliferation/drug effects* ; Mice ; Molecular Docking Simulation ; Cell Line, Tumor ; Hep G2 Cells ; Receptors, Adrenergic, beta-2/genetics* ; Stress, Physiological/drug effects* ; Cell Movement/drug effects* ; Male ; Protein Interaction Maps/drug effects* ; Cell Survival/drug effects* ; Proto-Oncogene Mas

Traditional Chinese medicine (TCM) exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets. However, the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians, which has been a major challenge in the global acceptance and application of TCM. Therefore, a standardized TCM prescription system needs to be explored to promote its clinical application. In this study, we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation. We tested its efficacy against intracerebral hemorrhage (ICH). First, the top 100 ICH targets in the GeneCards database were screened according to their relevance scores. Then, SymMap and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases were applied to find out the target-related ingredients and ingredient-containing herbs, respectively. The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets. The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions. The absorbed components in the serum were detected. In a mouse model of ICH, the new prescription exerted multifaceted effects, including improved neurological function, as well as attenuated neuronal damage, cell apoptosis, vascular leakage, and neuroinflammation. These effects matched well with the core pathological changes in ICH. The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise, multipronged, unbiased, and standardized TCM prescriptions for complex diseases. This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.

OBJECTIVE: To investigate the associations between eight serum per- and polyfluoroalkyl substances (PFASs) and regional fat depots, we analyzed the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 cycles. METHODS: Multiple linear regression models were developed to explore the associations between serum PFAS concentrations and six fat compositions along with a fat distribution score created by summing the concentrations of the six fat compositions. The associations between structurally grouped PFASs and fat distribution were assessed, and a prediction model was developed to estimate the ability of PFAS exposure to predict obesity risk. RESULTS: Among females aged 39-59 years, trunk fat mass was positively associated with perfluorooctane sulfonate (PFOS). Higher concentrations of PFOS, perfluorohexane sulfonate (PFHxS), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), and n-perfluorooctanoate (n-PFOA) were linked to greater visceral adipose tissue in this group. In men, exposure to total perfluoroalkane sulfonates (PFSAs) and long-chain PFSAs was associated with reductions in abdominal fat, while higher abdominal fat in women aged 39-59 years was associated with short-chain PFSAs. The prediction model demonstrated high accuracy, with an area under the curve (AUC) of 0.9925 for predicting obesity risk. CONCLUSION PFAS exposure is associated with regional fat distribution, with varying effects based on age, sex, and PFAS structure. The findings highlight the potential role of PFAS exposure in influencing fat depots and obesity risk, with significant implications for public health. The prediction model provides a highly accurate tool for assessing obesity risk related to PFAS exposure.
Humans ; Fluorocarbons/blood* ; Female ; Adult ; Middle Aged ; Male ; Environmental Pollutants/blood* ; Abdominal Fat ; Nutrition Surveys ; Alkanesulfonic Acids/blood* ; Obesity ; Environmental Exposure

Objective To investigate the relationship between single nucleotide polymorphisms(SNPs)in the eNOS gene and genetic susceptibility to systemic lupus erythematosus(SLE)in Hainan.Methods Blood samples were collected from SLE patients(SLE group,n=214)and healthy controls(control group,n=214)from January 2020 to December 2022 at the First Affiliated Hospital of Hainan Medical College and Hainan Provincial People's Hospital.The bases of eNOS gene rs3918188,rs1799983 and rs1007311 loci in each group were detected by SNaPshot sequencing technology.Logistic regression was used to analyze the correlation between genotypes,alleles and gene models(dominant model,recessive model,and overdominant model)of the above 3 target loci of the eNOS gene and genetic susceptibility to SLE.Haplotype analysis was conducted using HaploView 4.2 software to investigate the relationship between haploid and genetic susceptibility to SLE at each site.Results The results of logistic regression analysis revealed that the CC genotype and the C allele at rs3918188 locus were risk factors for genetic susceptibility to SLE(CC vs.AA:OR=2.449,P<0.05;C vs.A:OR=2.133,P<0.001).In recessive model at rs3918188 locus,CC genotype carriers had an increased risk of SLE development compared with AA+AC genotype carriers(OR=2.774,P<0.001).In contrast,in overdominant model at this locus,AC genotype carriers had a decreased risk of SLE occurrence compared with AA+CC genotype carriers(OR=0.385,P<0.001).In addition,polymorphisms of rs1799983 and rs1007311 were not associated with susceptibility to SLE in genotype,allele type and the 3 genetic models(P>0.05).Haplotype analysis revealed a strong linkage disequilibrium between the rs1007311 and rs1799983 loci of the eNOS gene,but no significant correlation was found between haplotype and genetic susceptibility to SLE(P>0.05).Conclusion The CC genotype and C allele at rs3918188 locus of eNOS gene may be risk factors for SLE in Hainan,while the risk of SLE occurrence is reduced in carriers of AC genotype under the overdominant model.

Objective:To investigate the clinical effect of free flap transfer with anastomosis of anterior interosseous artery and accompanying veins as the recipient vessels in reconstruction of forearm defects.Methods:A retrospective study was conducted on 5 patients who received free flaps transfers with anastomoses of anterior interosseous artery and accompanying veins in reconstruction of forearm defects with exposed bone and tendon in the Department of Orthopaedics of the First Affiliated Hospital of Anhui Medical University between July 2022 and November 2023. All patients were males, aged 31 to 54 years old with an average age of 41.8 years old. Two patients had defects of dorsal ulnar forearm, 2 of distal forearm and 1 of radial palmar forearm. The defected areas after debridement sized 11.0 cm×4.5 cm-20.0 cm×6.0 cm. Free anterolateral thigh perforator flaps (ALTPF), sized 13.0 cm×6.0 cm-22.0 cm×7.0 cm, were used in 4 patients to reconstruct the forearm defects. A free superficial circumflex iliac artery perforator flap was used in 1 patient with the flap sized at 12.0 cm×5.5 cm. All donor sites were directly sutured. Scheduled postoperative follow up was carried out to evaluate the blood supply to the flaps, texture, appearance, fracture healing and the function of the affected limb, as well as the flap sensation according to the criteria for sensory function of British Medical Research Council (BMRC).Results:All 5 patients had received 4 to 16 (mean 8.8) months of follow-up. All flaps survived completely without necrosis or infection. All flaps were good in colour and texture. The blood supply to hands was good, without a symptoms of coldness and fear of cold of hand. At the final follow-up review, sensation of flaps was assessed according to the criteria for sensory function of BMRC and the sensation of the flaps had recovered to S 2~S 3+. The appearance of flaps was good. Conclusion:Free flap with the anterior interosseous artery and accompanying veins as the recipient vessels in the treatment of forearm defects can achieve satisfactory clinical effect, however, further clinical studies are required.

OBJECTIVE: To explore clinical efficacy of unilateral and bilateral nail-rod system fixation in single-level intervertebral fusion fixation of lumbar disc herniation (LDH) and instability with unilateral dual-channel spinal endoscopy. METHODS: The clinical data of 63 patients with LDH complicated with instability treated by unilateral double-channel spinal endoscopy from March 2021 to June 2022 were retrospectively analyzed. According to intraoperative fixation methods, the patients were divided into two groups, included unilateral nail rod system fixation group(unilateral group) and bilateral nail rod system fixation group(bilateral group). There were 31 patients in unilateral group, including 15 males and 16 females; aged from 40 to 67 years old with an average of (54.65±7.32) years old; 3 patients with L_3,4, 15 patients with L_4,5, 13 patients with L₅S₁. There were 32 patients in bilateral group, including 18 males and 14 females, aged from 43 to 68 years old with an average of (56.19±6.63) years old;4 patients with L_3,4, 17 patients with L_4,5, 11 patients with L₅S₁. The time of operation, length of incision, operation time, length of hospital stay, cost of treatment, occurrence of complications and adverse events were recorded and compared between two groups. Visual analogue scale (VAS) of lumbar and leg pain, Japanese Orthopaedic Association (JOA) and Oswestry disability index (ODI) were compared before operation, 3 and 12 months after operation. MacNab standard was used to evaluate clinical effect. RESULTS: Both of two groups were successfully completed operation and followed up. In unilateral fixation group, follow-up time, operation time, incision length, postoperative ambulation time, hospital stay and treatment cost were (11.81±1.08) months, (122.48±13.86) min, (3.15±0.45) cm, (3.06±0.73) d, (6.87±1.09) d, and (3.49±0.09) ten thousand yuan;while (11.47±1.16) months, (134.94±10.94) min, (6.45±0.83) cm, (3.19±0.86) d, (7.03±1.03) d, (3.77±0.12) ten thousand yuan in bilateral fixation group, respectively;there were significant differences in operation time, incision length and treatment cost between two groups (P<0.05), no significant difference in follow-up time, postoperative ambulation time and hospital stay (P>0.05). There were no significant difference in VAS of low back pain, JOA score, ODI and MacNab grade between two groups before and after operation (P>0.05). No significant complications and adverse events were observed between two groups after operation. CONCLUSION Both of unilateral and bilateral nail rod system for the treatment of LDH with instability could achieve the expected results. Unilateral fixation has more advantageous than bilateral fixation in terms of operation time, incision length and treatment cost. For patients with osteoporosis before operation or insufficient fixation strength of unilateral pedicle nails during surgery, bilateral fixation is feasible to enhance reliability of fixation.
Humans ; Male ; Female ; Middle Aged ; Spinal Fusion/methods* ; Endoscopy/methods* ; Aged ; Adult ; Intervertebral Disc Displacement/surgery* ; Lumbar Vertebrae/surgery* ; Retrospective Studies

OBJECTIVE: To investigate the effectiveness of Flow-through bridge anterolateral thigh flap transplantation in the treatment of complex calf soft tissue defects. METHODS: The clinical data of the patients with complicated calf soft tissue defects, who were treated with Flow-through bridge anterolateral thigh flap (study group, 23 cases) or bridge anterolateral thigh flap (control group, 23 cases) between January 2008 and January 2022, were retrospectively analyzed. All complex calf soft tissue defects in the two groups were caused by trauma or osteomyelitis, and there was only one major blood vessel in the calf or no blood vessel anastomosed with the grafted skin flap. There was no significant difference between the two groups in general data such as gender, age, etiology, size of leg soft tissue defect, and time from injury to operation ( P>0.05). The lower extremity functional scale (LEFS) was used to evaluate the sufferred lower extremity function of the both groups after operation, and the peripheral blood circulation score of the healthy side was evaluated according to the Chinese Medical Association Hand Surgery Society's functional evaluation standard for replantation of amputated limbs. Weber's quantitative method was used to detect static 2-point discrimination (S2PD) to evaluate peripheral sensation of the healthy side, and the popliteal artery flow velocity, toenail capillary filling time, foot temperature, toe blood oxygen saturation of the healthy side, and the incidence of complications were compared between the two groups. RESULTS: No vascular or nerve injury occurred during operation. All flaps survived, and 1 case of partial flap necrosis occurred in both groups, which healed after free skin grafting. All patients were followed up 6 months to 8 years, with a median time of 26 months. The function of the sufferred limb of the two groups recovered satisfactorily, the blood supply of the flap was good, the texture was soft, and the appearance was fair. The incision in the donor site healed well with a linear scar, and the color of the skin graft area was similar. Only a rectangular scar could be seen in the skin donor area where have a satisfactory appearance. The blood supply of the distal limb of the healthy limb was good, and there was no obvious abnormality in color and skin temperature, and the blood supply of the limb was normal during activity. The popliteal artery flow velocity in the study group was significantly faster than that in the control group at 1 month after the pedicle was cut, and the foot temperature, toe blood oxygen saturation, S2PD, toenail capillary filling time, and peripheral blood circulation score were significantly better than those in the control group ( P<0.05). There were 8 cases of cold feet and 2 cases of numbness on the healthy side in the control group, while only 3 cases of cold feet occurred in the study group. The incidence of complications in the study group (13.04%) was significantly lower than that in the control group (43.47%) ( χ ²=3.860, P=0.049). There was no significant difference in LEFS score between the two groups at 6 months after operation ( P>0.05). CONCLUSION Flow-through bridge anterolateral thigh flap can reduce postoperative complications of healthy feet and reduce the impact of surgery on blood supply and sensation of healthy feet. It is an effective method for repairing complex calf soft tissue defects.
Humans ; Thigh/surgery* ; Plastic Surgery Procedures ; Leg/surgery* ; Cicatrix/surgery* ; Retrospective Studies ; Soft Tissue Injuries/surgery* ; Treatment Outcome ; Lower Extremity/surgery* ; Skin Transplantation/methods* ; Perforator Flap

To explore pathogens in several tick species in endemic areas of Shandong province,unfed ticks and parasitic ones were collected in seven areas of Shandong province during 2021-2022 and morphologically identified.Five common tick-borne pathogens were detected by PCR with universal primers on the tick samples and phylogenetic analysis based on the sequences from positive pathogens were also performed as well.The results showed that the collected tick samples included 2 genera and 4 species,respectively comprising 145 of Haemaphysalis longicornis,2of Hae.concinna,2of Hae.campanulate,and 5 of Rhipicephalus sanguineus.A total of 34 collected ticks were found with spotted fever group Rickettsia infection,with a total positive rate of 22.08%,29 samples carried Anaplasma,with a total infection rate of 18.83%,the total infection rate of Theileria and Borrelia burgdorferi were revealed as 5.84% and 0.65%,respectively,and no positive samples were detected for Borrelia recurrentis.In conclusion,Hae.longicornis was shown as the dominant tick species in the sampling areas in Shandong province,and various pathogens were found harbored in different tick species.Local surveillance and awareness of tick-borne diseases should be strengthened for the purpose of efficient prevention and control measures.

Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".
China ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs/adverse effects* ; Reference Standards

Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.
China ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal/adverse effects* ; Humans ; Medicine, Chinese Traditional ; Nonprescription Drugs/adverse effects* ; Pharmacovigilance