Background: Diabetic peripheral neuropathy (DPN) is a common chronic complication of diabetes mellitus that significantly impairs patients’ quality of life. Traditional Chinese medicine (TCM), as a major component of complementary and alternative medicine, has accumulated numerous effective formulas for the clinical management of DPN. However, systematic approaches for optimizing TCM formulas remain limited. Objective: To establish a pathway-oriented approach for TCM formula optimization and to evaluate the efficacy and mechanisms of the optimized formula in DPN. Methods: We developed 2 formula optimization algorithms that defined pathway-oriented herbal correlation (HC) and herbal contribution (HO) to screen and construct a new herbal formula, Qihongtongbi (QHTB), for treating Qi deficiency and blood stasis syndrome complicated with DPN. An animal experiment was subsequently conducted to evaluate the therapeutic effectiveness of QHTB. A total of 32 specific-pathogen-free male ob/ob mice (18–20 g) were randomly divided into 4 groups: model, Mudan Granules (MDG), QHTB low- and high-dose groups (n = 8). Ten male C57BL/6J mice (18–20 g) served as the control group. Metabolomics analysis was further employed to elucidate the biological mechanisms underlying the effects of QHTB. Results: Based on our previous study on TCM medication patterns for treating DPN, 22 candidate herbs were selected for formula optimization. The top 5 candidate herbs (total HC = 25.24 × 10 ) exhibited HC values comparable to those of MDG (total HC = 26.1 × 10 ). These herbs were Carthamus tinctorius L. (HC = 5.40 × 10 ), Astragalus mongholicus Bunge (HC = 5.23 × 10 ), Salvia miltiorrhiza Bunge (HC = 5.15 × 10 ), Commiphora myrrha (T. Nees) Engl. (HC = 5.02 × 10 ), and Glycyrrhiza glabra L. (HC = 4.44 × 10 ). HO analysis showed that the cumulative HO of these 5 herbs exceeded 50%. In vivo experiments demonstrated that, compared with the model group, QHTB significantly lowered blood glucose (P < 0.05), enhanced nerve conduction velocity (P < 0.01), improved nociceptive hypersensitivity (P < 0.01), and ameliorated sciatic nerve morphology, with efficacy comparable to MDG. Serum and fecal metabolomics further revealed that QHTB exerted multipathway regulatory effects, among which nicotinate and nicotinamide metabolism represented a key mechanism. Conclusion: In summary, this study provides a methodological reference for the systematic optimization of TCM formulas.

Objective To investigate the trends in the global burden due to cystic echinococcosis from 1990 to 2021, and to predict the global burden of cystic echinococcosis from 2022 to 2035, so as to provide insights into formulation of the cystic echinococcosis control strategy. Methods The global age-standardized prevalence, mortality, disability-adjusted life years (DALYs) rates and their 95% uncertainty intervals (UI) of cystic echinococcosis from 1990 to 2021 were captured from the Global Burden of Disease Study 2021 (GBD 2021) database, and the trends in the global burden of cystic echinococcosis from 1990 to 2021 were analyzed using the Joinpoint regression model. The associations between the global burden of cystic echinococcosis and socio-demographic index (SDI) were examined using a smoothing spline model and frontier analysis, and the global burden of cystic echinococcosis was projected from 2022 to 2035 using the Bayesian age-period-cohort (BAPC) model. Results The global agestandardized prevalence, mortality and DALYs rates of cystic echinococcosis were 7.69/10⁵ [95% UI: (6.27/10⁵, 9.51/10⁵)], 0.02/10⁵ [95% UI: (0.01/10⁵, 0.02/10⁵)], and 1.32/10⁵ [95% UI: (0.99/10⁵, 1.69/10⁵)] in 2021. The global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a rise by 0.14% per year from 1990 to 2021, and the global age-standardized mortality and DALYs rates of cystic echinococcosis appeared a tendency towards a decline by 4.68% and 4.01% per year from 1990 to 2021, respectively. Joinpoint regression analysis showed that global age-standardized prevalence of cystic echinococcosis appeared a tendency towards a decline from 1990 to 2000 [annual percent change (APC) = −0.66%, 95% confidence interval (CI): (−0.70%, −0.61%)] and from 2005 to 2015 [APC = −0.88%, 95% CI: (−0.93%, −0.82%)], and towards a rise from 2000 to 2005 [APC = 3.68%, 95% CI: (3.49%, 3.87%)] and from 2015 to 2021 [APC=0.30%, 95%CI: (0.19%, 0.40%)].Theagestandardized prevalence (r = −0.17, P < 0.05), mortality (r = −0.67, P < 0.05) and DALYs rates of cystic echinococcosis (r = −0.60, P < 0.05) all correlated negatively with SDI across 21 geographical regions from 1990 to 2021, and the age-standardized mortality (r = −0.61, P < 0.05) and DALYs rates (r = −0.44, P < 0.05) both correlated negatively with SDI across 204 countries and territories in 2021. Frontier analysis revealed that the age-standardized DALYs rate of cystic echinococcosis was still not in line with the frontier in some high-SDI countries or territories. In addition, the global age-standardized prevalence was projected with the BAPC model to appear a tendency towards a rise among both men [estimated annual percent change (EAPC) = 0.18%, 95% CI: (0.13%, 0.23%)] and women [EAPC = 0.29%, 95% CI: (0.24%, 0.34%)] from 2022 to 2035, and the global age-standardized mortality [men: EAPC = −4.71%, 95% CI: (−4.71%, −4.37%); women: EAPC = −4.74%, 95% CI: (−4.74%, −4.74%)] and DALYs rates [men: EAPC = −3.35%, 95% CI: (−3.36%, −3.34%); women: EAPC = −3.17%, 95% CI: (−3.18%, −3.16%)] were projected to appear a tendency towards a decline among both men and women. Conclusions The global burden of cystic echinococcosis appeared an overall tendency towards a decline from 1990 to 2021; however, the global prevalence of cystic echinococcosis is projected to appear a tendency towards a rise from 2022 to 2035. Intensified cystic echinococcosis control programmes are recommended.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

ObjectiveTo explore the protective effect and mechanism of Zingiberis Rhizoma Recens alcohol extract on lipopolysaccharide （LPS）-induced acute lung injury in mice. MethodBalb/c mice were randomly divided into normal group， model group， dexamethasone group， and low- and high-dose Zingiberis Rhizoma Recens groups. Mice in the normal group were instilled with normal saline through the nose， and the other groups were instilled with normal saline containing LPS （50 μg）. After 30 minutes of modeling， the dexamethasone group was gavaged with 5 mg·kg^-1 of dexamethasone acetate solution， the low- and high-dose Zingiberis Rhizoma Recens groups were gavaged with different doses of （7， 14 g·kg^-1） of Zingiberis Rhizoma Recens alcohol extract， and the normal group and the model group were gavaged with the same volume of water. After 24 hours of modeling， the total number of white blood cells in bronchoalceolar lavage fluid （BALF） was detected by cell counter， and the levels of the inflammatory factors including tumor necrosis factor （TNF）-α， interleukin （IL）-1β， IL-6， and superoxide dismutase （SOD）， and myeloperoxidase （MPO） was detected by enzyme-linked immunosorbent assay （ELISA）. Haematoxylin-eosin （HE） staining method was used to observe the pathological changes of lung tissue in each group， and the Western blot was used to detect the protein expression of nuclear transcription factor （NF）-κB p65， phosphorylation （p）-NF-κB p65， and Toll-like receptor 4 （TLR4） in lung tissue. ResultCompared with the normal group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the model group was increased （P<0.01）， and the level of SOD was decreased （P<0.05）. Pathological damage of lung tissue was obvious， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was increased （P<0.01）. Compared with the model group， the white blood cell count in BALF and the levels of TNF-α， IL-1β， IL-6， and MPO in the treatment group was decreased （P<0.05，P<0.01）， and the level of SOD was increased （P<0.05，P<0.01）. Pathological damage of lung tissue was alleviated， and the protein expression of NF-κB p65， p-NF-κB p65， and TLR4 in lung tissue was decreased （P<0.01）. ConclusionZingiberis Rhizoma Recens alcohol extract may play a protective role in LPS-induced acute lung injury in mice by inhibiting the TLR4/NF-κB signaling pathway.

Objective To explore the effect of sorafenib on HeLa cell proliferation by inducing cell apoptosis and autophagy and its impact on drug resistance.Methods The drug-resistant cell strains were constructed through in-termittent induction method,with concentrations of 0,2.5,5.0,7.5,10.0,15.0,20.0 μmol/L.HeLa cells were incubated with increasing concentrations of sorafenib with each concentration for 1 week.The drug-resistant cell strains with stable passages were collected.MTT assay was used to detect the effect of sorafenib on cell prolifer-ation.Cell cycle distribution was analyzed by flow cytometry.The change in the expression of drug-resistant and ap-optotic genes in the parents and drug-resistant cell strains under different drug concentrations was examined by semi-quantitative PCR.The changes of apoptotic related marker proteins LC3-Ⅰ and LC3-Ⅱ were detected by Westernblot.Results Stable drug-resistant strains were successfully obtained;Drug-treated cells were more blocked in the G1 phase.In drug-resistant cells,the expression of apoptosis suppressor gene Bcl-2 was significantly decreased and the apoptotic gene Bax as well as the drug-resistant genes were all significantly increased(P＜0.05).The LC3-Ⅱ/LC3-Ⅰ ratio of drug-resistant cells was significantly higher than that of parent cells(P＜0.05).Conclusions Sorafenib may block the cell cycle,suppress malignant cell proliferation and promote autophage.On one hand,autophagy participates in the development of cell drug resistance and promotes cell survival.On the other hand,drug-induced autophagy may activate some of apoptotic signaling pathway in drug-resistant cells and promote the reversal of cell drug resistance.

Objective:To observe the effect of Ginsenoside Re on the proliferation and protein secretion of primary cardiac fibroblasts (CFs) cultured in high glucose by vitro, and the regulation of Wnt/β-catenin signaling pathway.Methods:The myocardial fibroblast proliferation model induced by high glucose in vitro was used. Cell proliferation was detected by MTT method, cell cycle was measured by flow cytometry, concentration of type Ⅰ,Ⅲ collagens and TGF-β 1 protein were tested by ELISA assay. Protein expression of β-catenin, GSK-3β and p-GSK-3β were determined by Western blot. Results:Compared with the model group, the cell proliferation in Ginsenoside Re high, medium, low group were significantly decreased ( P<0.01), the percentage of cells in G 0 + G 1 phase was increased ( P<0.01), and the percentage of cells in S + G 2 + M phase was decreased ( P<0.01), the content of TGF-β 1 was significantly decreased( P<0.01). The content of type Ⅲ collagen [(6.566±1.620)ng/ml,(7.170±0.470)ng/ml vs. (11.241±2.234)ng/ml] in Ginsenoside Re high, medium group were significantly decreased ( P<0.01). The expression of β-catenin (0.281±0.016, 0.301±0.021 vs. 0.409±0.037) was significantly decreased and the expression of p-GSK-3β (0.369±0.049 vs. 0.268±0.048) in Ginsenoside Re high, medium group were significantly increased ( P<0.01). Conclusion:Ginsenoside Re plays an important role in inhibiting CFs proliferation and reducting the synthesis of collagen and TGF-β 1 by regulating abnormal expression of Wnt/β-catenin signaling pathway. It has the potential to delay the myocardial fibrosis of diabetes mellitus.

Objective:To compare the clinical effective of clavicular hook plate with extra suture hole and traditional hook plate in the treatment of acute acromioclavicular dislocation.Methods:This study retrospectively analyzed the clinical data of traumatic acromioclavicular dislocation patients who were treated by operation from March 2017 to September 2020. The patients were included in traditional hook plate (THP) group and triangle stabilization technique hook plate (TSTHP) group according fracture fixations. TSTHP group adopted clavicular hook plate with extra suture hole. There were 27 patients in THP group with 18 male patients and 9 female patients; average age with 37.56±8.94 years old; 16 patients injured left side and 11 patients injured right side; crush injuries of 10 patients, traffic injuries of 9 patients and sports injuries of 8 patients; Rockwood classification of type III (9 patients), type IV (10 patients) and type V (8 patients). There were 20 patients in TSTHP group with 15 male patients and 5 female patients; average age with 38.95±9.91 years old; 13 patients injured left side and 7 patients injured right side; crush injuries of 9 patients, traffic injuries of 8 patients and sports injuries of 3 patients; Rockwood classification of type III (5 patients), type IV (9 patients) and type V (6 patients). The operation time, intraoperative bleeding, postoperative coracoclavicular space, visual analogue scale (VAS) and shoulder joint Constant-Murley score were compared between the two groups.Results:The operation time and blood loss of THP group and TSTHP group were 51.07±11.27 min, 87.41±15.34 ml and 55.65±8.59 min, 90.50±14.32 ml, respectively. The difference was not statistically significant ( t=1.52, 0.70, all P>0.05). Patients in both groups were followed up for 12 to 14 months after operations, with an average of 12.28 months. Six months after surgery, the coracoclavicular spaces of THP group and TSTHP group were 12.16±0.90 mm and 11.26±0.70 mm, respectively. The difference was statistically significant ( t=3.70, P<0.001). Postoperative VAS scores (2 days, 3 months, 6 months and 12 months) of TSTHP group [1.8±0.77, 0.00(0.00, 1.00), 0.00 (0.00, 0.00), 0.00(0.00, 0.00)] were significantly better than THP group [4.22±1.25, 2.00 (1.00, 3.00), 1.00 (0.00, 1.00), 0.00 (0.00, 1.00)]. The difference was statistically significant ( t=7.65, P<0.001; Z=4.85, P<0.001; Z=3.44, P=0.001; Z=2.96, P=0.003). Postoperative Constant-Murley scores (3 months, 6 months and 12 months) of TSTHP group (87.00±5.18, 91.25±2.75, 92.30±2.74) were significantly better than THP group (76.96±5.21, 83.22±3.86, 85.22±3.49). The difference was statistically significant ( t=6.54, 7.93, 7.51; P<0.001). The postoperative complication rates of THP group were higher than TSTHP group [70.4% (19/27) vs. 5.0% (1/20)]. Conclusion:In the treatment of acute acromioclavicular dislocation, the clavicular hook plate with extra suture hole can obtain satisfactory clinical effect compared with the THP, and clavicular hook plate with extra suture hole is more conducive to early recovery of shoulder function and reduce postoperative complications.

A 65-Year-old male patient with squamous cell lung cancer received chemotherapy with paclitaxel (210 mg by an IV infusion on day 1) and carboplatin (0.5 g by an IV infusion on day 1; 21 days was a cycle) and targeted therapy with apatinib (0.25 g orally once daily). About 1 hour after the first oral administration of apatinib, the patient developed dyspnea, chest tightness, followed by limb numbness and fatigue. About 1 hour after the second administration, the above symptoms recurred, accompanied by lower limb pain, speak disability, and arrhythmia. The symptoms were considered to be related to apatinib. The drug was stopped and the treatments including noninvasive ventilator assisted breathing, antiallergic, antispasmodic, and antiasthmatic were given. Five days later, the above symptoms disappeared.

A 65-Year-old male patient with squamous cell lung cancer received chemotherapy with paclitaxel (210 mg by an IV infusion on day 1) and carboplatin (0.5 g by an IV infusion on day 1; 21 days was a cycle) and targeted therapy with apatinib (0.25 g orally once daily). About 1 hour after the first oral administration of apatinib, the patient developed dyspnea, chest tightness, followed by limb numbness and fatigue. About 1 hour after the second administration, the above symptoms recurred, accompanied by lower limb pain, speak disability, and arrhythmia. The symptoms were considered to be related to apatinib. The drug was stopped and the treatments including noninvasive ventilator assisted breathing, antiallergic, antispasmodic, and antiasthmatic were given. Five days later, the above symptoms disappeared.

Abstract Myopia is a common refractive error in the process of development. With the high incidence and low age of myopia in children and adolescents, it has become a worldwide public health problem, seriously endangering physical and mental health. The prevention and control of myopia has a long way to go. Low concentration atropine, as an M type choline receptor inhibitor, has been proved by medical research to effectively delay the progress of myopia. This paper reviews the relevant studies at home and abroad in recent years. The optimal concentration of low concentration atropine, the best clinical regimen and possible potential side effects were discussed. From the point of view of school public health, this paper discusses the significance of low concentration atropine for the prevention and control of myopia among school age students, in order to provide a reliable basis and new ideas for the follow up clinical application of atropine and myopia prevention and control strategies for school students.