OBJECTIVE To optimize the extraction process of organic acids from Angelica sinensis using deep eutectic solvents （DESs）， and conduct characterization， antioxidant activity evaluation， and extraction mechanism analysis. METHODS The conductor-like screening model for realistic solvation with segment activity coefficients （COSMO-SAC） was employed to screen the types of DESs. With total organic acid content as the response value， single-factor experiments and Box-Behnken response-surface methodology were used to optimize the extraction conditions. Using A. sinensis decoction pieces and/or A. sinensis methanol extract as references， scanning electron microscope and Fourier transform infrared spectrometer （FTIR） were applied to characterize the products. Additionally， the 1，1-diphenyl-2-picrylhydrazyl （DPPH） and 2，2′-azino-bis（3-ethylbenzothiazoline-6- sulfonic acid） （ABTS） free radical scavenging capacities were determined. Density functional theory （DFT） was used to analyze the extraction mechanism of ferulic acid and chlorogenic acid by the DESs. RESULTS & CONCLUSIONS The optimal DESs was choline chloride-propanediol. The optimal extraction conditions for organic acids from A. sinensis were as follows： choline chloride- propanediol molar ratio of 1∶1， DESs water content of 70%， solid-liquid ratio of 1∶10， heating temperature of 57 ℃， and heating and stirring time of 8 min. In three validation experiments， the total organic acid content was 2.92 mg/g， yielding a relative error of 0.34% compared to the predicted value （2.91 mg/g）. Compared with A. sinensis decoction pieces and methanol extracts， the agglomerated structure of the DESs extract powder almost disappeared， showing the presence of lamellar structures similar to those of the intestinal wall. Compared with the methanol extract， the DES extract exhibited higher FTIR characteristic peak intensity and peak area integration， as well as stronger scavenging capacities against DPPH and ABTS free radicals. The extraction of organic acids from A. sinensis by DESs is the result of the combined effects of polarity matching， hydrogen bonding， and structural adaptation.

Objective:To analyze and compare the pathological data characteristics of patients with simple papillary thyroid carcinoma (PTC) and PTC combined with Hashimoto’s thyroiditis (HT), so as to provide clinical treatment ideas.Methods:A retrospective analysis was performed on the medical records of 326 PTC patients who met the requirements and underwent surgical treatment in the Department of Thyroid and Breast Surgery, Nanjing Hospital of Traditional Chinese Medicine from Jan. 2020 to May. 2022. There were 81 males and 245 females. They were divided into PTC group and HT-PTC group, according to whether they were combined with HT. Clinical data were collected and organized. The collection indicators included patient gender, age, body mass index (BMI), five preoperative thyroid function items including free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), BRAF gene mutation, single or bilateral lesions, single or multiple lesions, largest postoperative pathological tumor lesions diameter, cervical lymph node metastasis (LNM) status, etc. At the same time, all patients were divided into CLNM group and no CLNM group according to CLNM status. The two groups were compared in terms of gender, age ≥55 years old, whether combined with HT, number of lesions, unilateral and bilateral, extraglandular invasion, microcarcinoma, and BRAF gene. Statistical software was used to analyze the results. t test, χ2 test, and logistic regression analysis were adopted. P<0.05 indicates that the difference is statistically significant. Results:The proportion of female patients in both groups was higher, and the proportion of female patients in the HT-PTC group (90/100, 90%) was higher than that in the PTC group (155/226, 69.59%). HT-PTC patients were younger than patients in the PTC group (43.03±12.72 vs. 43.70±12.63) years old, and their TSH (2.71±1.69 vs. 2.02±1.46) uIU/mL was higher. The differences were statistically significant (all P<0.05). There were no statistically significant differences in BMI, FT3, FT4, T3, or T4 (all P>0.05). The HT-PTC group had a lower proportion of BRAF gene mutations [87/100 (87%) vs. 212/226 (93.8%) ], a smaller maximum tumor diameter (1.06±0.73 vs. 1.32±0.97 cm), and a lower proportion of CLNM [37 /100 (37%) vs. 118/226 (52.2%) ]. The number of LNMs with metastasis is less (3.33±2.21 vs. 4.76±4.00), and it was more likely to be multifocal [44/100 (44%) vs. 73/226 (32.74%) ]. All differences were statistically significant (all P<0.05), and the differences in bilateral gland lobes involvement and extra-glandular invasion were not statistically significant. When accompanied by CLNM, gender (male vs. female) [55/100 (35.45%/64.52%) vs. 26/145 (15.2%/84.85%) ], age ≥ 55 years (yes vs. no) [21/134 (13.55) %/86.45%) vs. 50/121 (29.24%/70.76%) ], HT (yes vs. no) [37/118 (23.87%/76.13%) vs. 63/108 (36.84%/63.16%), number of lesions (single focus vs. multiple focus) [90/65 (41.94%/50.06%) vs. 119/52 (69.59%/30.41%) ], microcarcinoma (yes vs. no) [83/72 (53.55%/45.45%) vs. 139/32 (81.29%/18.71%) ] and extraglandular invasion (with vs. without) [38/117 (24.52%/75.48%) vs. 27/144 (17.42%/84.21%) ] had statistics significance (both P<0.05). There was no statistical significance in bilateral lesion involvement or BRAF gene mutation (all P>0.05). Multivariate logistic regression analysis showed that age, microcarcinoma, HT, gender, and number of lesions were independent risk factors for CLNM, and male gender and multifocal cancer were risk factors for CLNM. Age ≥55 years, microcarcinoma, and combined HT were negatively associated with CLNM. Conclusions:HT may promote the occurrence of PTC, but can inhibit its development. In the short term, patients with HT can have a better prognosis than those with simple PTC.

AIM: To analyze changes in the ocular surface parameters of keratoconus after long-term wearing of rigid gas permeable contact lens(RGPCL).METHODS:Prospective case study. A total of 113 keratoconus patients(213 eyes)fitted with RGPCL in the optometry center of Gansu Provincial Hospital from January 2018 to January 2022 were included. They were divided into three groups according to the severity of keratoconus, including 42 cases(80 eyes)in mild keratoconus group, 54 cases(102 eyes)in moderate keratoconus group and 17 cases(31 eyes)in severe keratoconus group. Furthermore, the non-invasive tear break-up time(NIBUT), non-invasive tear meniscus height(NITMH), red eye index, lipid layer thickness, fluorescent corneal staining, meibomian gland secretory function, Schirmer I test and ocular surface disease index(OSDI)scores were observed by Keratograph analyzer before and after wearing RGPCL for 1 wk, 1, 3, 6, 12 mo, respectively.RESULTS: There were no statistical significance in the age, NIBUT, NITMH, lipid layer thickness, meibomian gland secretory function and Schirmer I test among the three groups(P>0.05), while there were statistical significance in the sphere, cylinder, spherical equivalent, best corrected visual acuity(BCVA), non-contact intraocular pressure(IOPNCT), anterior, posterior corneal surface Kmax, corneal surface thickness at the thinnest point, eye redness index, fluorescent corneal staining, and OSDI(P<0.05). In the mild keratoconus group, NIBUT had statistical differences at 3, 6 and 12 mo after wearing RGPCL(P<0.05), NITMH had statistical differences in 6 and 12 mo(P<0.05), the eye redness index, fluorescent corneal staining and OSDI scores had statistical differences in 1 wk and 1 mo(P<0.05), and lipid layer thickness and meibomian gland secretory function had statistical differences in 12 mo(P<0.05). In the moderate keratoconus group, there were statistical differences in NIBUT at 6 and 12 mo after wearing lenses(P<0.05); there were statistical differences in the NITMH, lipid layer thickness and meibomian secretory function at 12 mo after wearing lens(P<0.05); there were statistical differences in the eye redness index at 1 wk, 1 and 3 mo after wearing RGPCL(P<0.05); there were statistical differences in the fluorescent corneal staining at 1 wk after wearing RGPCL(P<0.05); there were statistical differences in the OSDI at 1 wk and 1 mo after wearing RGPCL(P<0.05). In the severe keratoconus group, there were statistical differences in the NIBUT, NITMH and eye redness index at 1 wk, 1, 3, 6 and 12 mo after wearing RGPCL(P<0.05); there were statistical differences in the lipid layer thickness at 6,12 mo after wearing RGPCL(P<0.05); there were statistical differences in the fluorescent corneal staining and OSDI scores at 1 wk, 6 and 12 mo after wearing RGPCL(P<0.05); there were statistical differences in the meibomian secretory function at 6 and 12 mo after wearing RGPCL(P<0.05); and there were statistical differences in the Schirmer I test at 12 mo after wearing RGPCL(P<0.05).CONCLUSION: Long-term wearing of RGPCL can affect the ocular surface microcirculation in keratoconus patients, thus making differences in patients subjective. However, it has no significant impact on the visual quality of patients. Therefore, long-term wearing of RGPCL is safely to control the progression of keratoconus.

Objective To investigate the effects of icariin on high glucose-induced autophagy and apoptosis of podocytes,and the regulating effects on mammalian target of rapamycin(mTOR)/serine-threonine kinase(Akt)/cyclic adenosine monophosphate response element binding protein(CREB)pathway.Methods The mouse podocytes MPC5 were taken and divided into five groups:normal control group(5.5 mmol·L-1 glucose),high glucose group(30 mmol·L-1 glucose),icariin group(30 mmol·L-1glucose+5 μmol·L-1icariin),GDC-0349 group(30 mmol·L-1glucose+50 μmol·L-1 GDC-0349),icariin+GDC-0349 group(30 mmol·L-1 glucose+5 μmol·L-1 icariin+50 μmol·L-1 GDC-0349).Cultured for 48 hours,the tetramethylazozolium salt method was used to detect the viability of MPC5 cells;acridine orange staining was used to observe the autophagy of MPC5 cells;apoptosis of MPC5 cells was detected by flow cytometry;Western blotting was used to detect the expression of autophagy[microtubule associated protein one light chain 3(LC3)II,LC3Ⅰ,autophagy-related protein(Beclin-1)],apoptosis[Bcl-2 related X protein(Bax),B cell lymphoma-2(Bcl-2)]and mTOR/Akt/CREB pathway-related proteins of MPC5 cells.Results Compared with the normal control group,the cell viability,expression levels of Bcl-2,phosphorylated mTOR(p-mTOR)/mTOR,phosphorylated Akt(p-Akt)/Akt,phosphorylated CREB(p-CREB)/CREB protein of MPC5 cells in the high glucose group were significantly decreased(P＜0.05),the autophagy ability was enhanced,the autophagosome showed orange fluorescence,and the apoptosis rate,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bax protein expression levels were significantly increased(P＜0.05).Compared with the high glucose group,the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt,p-CREB/CREB protein expression levels of MPC5 cells in icariin group were significantly increased,the autophagy ability was further enhanced,the number of autophagosomes was increased,the autophagosomes showed brick red fluorescence(P＜0.05),the apoptosis rate and Bax protein expression level were significantly decreased(P＜0.05),and the cell viability,LC3Ⅱ/LC3Ⅰ,Beclin-1,Bcl-2,p-mTOR/mTOR,p-Akt/Akt and p-CREB/CREB proteins expression levels of MPC5 cells in GDC-0349 group were significantly decreased,the autophagy ability was weakened,the number of autophagosomes was reduced,the autophagosomes showed orange fluorescence(P＜0.05),and the apoptosis rate and Bax protein expression level were significantly increased(P＜0.05);icariin+GDC-0349 could reverse the effect of icariin on high glucose induced MPC5 cells(P＜0.05).Conclusion Icariin promotes elevated glucose-induced podocyte autophagy and inhibits apoptosis by activating the mTOR/Akt/CREB pathway.

The pre-research of medical device standards is of great significance for the enactment and amendment of standards.This study discusses four aspects and explores how to promote more scientific and reasonable pre-research.Based on the pre-research practice of medical device standards project,this study puts forward relevant work ideas and suggestions.

Objective:To investigate the safety and feasibility of endoscopic thyroidectomy by gasless trans subclavian approach (ETGTA) in treatment of papillary thyroid carcinoma (PTC) .Methods:The clinical data of 148 patients with PTC radical operation admitted to the Department of Thyroid and Breast Surgery, Nanjing Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine from Jul. 2020 to May. 2022 were retrospectively analyzed. They were divided into subclavian approach group (53 cases) and modified miccoli group (95 cases) according to different surgical approaches. The operation time, intraoperative bleeding volume, postoperative drainage flow, postoperative drainage days, postoperative hospital stay, postoperative complications and cosmetic satisfaction were recorded in the 2 groups. Statistical software was used to analyze the results, including t test, Mann-Whitney U test, χ2 test, etc. P<0.05 was considered statistically significant. Results:There were no significant differences in age, sex ratio, maximum diameter, stage, tumor lesion or surgical method between the 2 groups ( P>0.05). The postoperative drainage days increased in the subclavian group than in the modified miccoli group (4.57±2.45 vs. 2.98±1.07) ( P<0.01), but there was no statistical difference in operation time, intraoperative blood loss, postoperative drainage, or postoperative hospital stay between the two groups ( P>0.05). The incidence of swallowing discomfort at 1 month [5.6% (3/53) vs. 18.9% (18/95), P=0.04] and 3 months [0% (0/53) vs. 7.4% (7/95) , P=0.04], anterior cervical area tightness or stiffness at 1 month [0% (0/53) vs. 11.6% (11/95), P=0.01] and 3 months [0% (0/53) vs. 8.4% (8/95), P=0.03] were less than that of the modified miccoli group, and the difference was statistically significant (4.1±0.7 vs. 2.4±0.8) ( P<0.01), and the cosmetic satisfaction of the subclavian approach was higher than that of the modified miccoli group ( P<0.01). There was no significant difference in postoperative temporary recurrent laryngeal nerve injury, postoperative 3d neck pain, postoperative hand-foot numbness or postoperative hematoma between the two groups (all P>0.05) . Conclusion:The radical resection of papillary thyroid carcinoma without inflatable subclavicular approach is safe and feasible, with few postoperative complications and better cosmetic effect, which is worth popularizing.

Objective:To explore changes in the serum TBNK lymphocyte subset levels in patients with lung cancer undergoing chemother-apy and analyze their correlation with prognosis.Methods:Ninety-two patients undergoing standard regimen lung cancer chemotherapy who attended Beijing Jingmei Group General Hospital from January 2020 to June 2023 were selected.The level of TBNK lymphocyte subpop-ulations was detected before the first chemotherapy and after one and three cycles of chemotherapy.Their prognosis was evaluated 3 months after the end of chemotherapy and assigned into the remission group(63 cases)and the non-remission group(29 cases).The correl-ation between the levels of TBNK lymphocyte subsets and prognosis was analyzed.Results:The CD3+,CD3+CD4+,and CD3-CD19+levels in the stage Ⅲ group were lower than those in the stage Ⅳ group after one and three cycles of chemotherapy,while the CD3+CD8+and CD3-CD16+CD56+levels were higher than those in the stage Ⅳ group(P<0.05).The CD3+,CD3+CD4+,and CD3-CD19+levels in the remission group were lower than those in the non-remission group after one and three cycles of chemotherapy,while the CD3+CD8+and CD3-CD16+CD56+levels were higher than those in the non-remission group(P<0.05).The staging and prognosis of lung cancer patients un-dergoing chemotherapy positively correlated with CD3+,CD3+CD4+,and CD3-CD19+,and negatively correlated with CD3+CD8+and CD3-CD16+CD56+(P<0.05).The area under the curve(AUC)of the TBNK lymphocyte subsets combined to predict the prognosis of lung can-cer patients after three cycles of chemotherapy was the highest,reaching 0.907(P<0.05).The TBNK lymphocyte subsets have a good risk warning effect on the prognosis of patients with lung cancer undergoing chemotherapy.Conclusions:Changes in peripheral blood TBNK lymphocyte subsets in patients with lung cancer undergoing chemotherapy were associated with immune function status and prognosis.Monitoring the levels of the relevant indicators can predict the prognosis of patients with lung cancer undergoing chemotherapy.

Objective:This study investigates the influence of the apolipoprotein E ε4(APOE ε4)genotype on the relationship between glucose-lipid metabolism disorders and diabetes-related cognitive impairment(DCI).Methods:A case-control study was conducted involving 891 patients with type 2 diabetes mellitus(T2DM)with a mean age of(62.1±13.8)years, all of whom underwent elective surgery at the First Hospital of Shanxi Medical University between January 2017 and December 2022.Among these participants, 229 were diagnosed with DCI(case group), while 662 were cognitively normal(control group).Routine clinical information was collected, and peripheral venous blood samples were analyzed for glycated hemoglobin(HbA1c)and blood lipid levels.The single nucleotide polymorphisms rs429358 and rs7412 were analyzed to determine the presence of the APOE ε4 genotype.Stepwise Logistic regression was employed to identify independent risk factors for DCI, and subgroup analyses were performed to evaluate the effect of the APOE ε4 genotype on the relationship between HbA1c and blood lipid levels in relation to DCI risk. Results:Among all patients, female gender( OR=1.915, 95% CI: 1.393-2.631, P<0.001), longer duration of T2DM( OR=1.169, 95% CI: 1.087-1.257, P<0.001), elevated triglycerides( OR=1.161, 95% CI: 1.041-1.294, P=0.007), and being an APOE ε4 carrier( OR=1.638, 95% CI: 1.115-2.405, P=0.012)were identified as independent risk factors for developing DCI.High levels of low-density lipoprotein(LDL)were found to be independently associated with an increased risk of DCI specifically in APOE ε4 carriers( OR=1.408, 95% CI: 1.060-1.870, P=0.018), but not in non-APOE ε4 carriers( P>0.05).In contrast, elevated HbA1c was independently associated with a higher risk of DCI in non-APOE ε4 carriers( OR=1.220, 95% CI: 1.040-1.430, P=0.014), but not in APOE ε4 carriers( P>0.05).Additionally, elevated triglycerides were independently linked to an increased risk of DCI across the entire sample and within each APOE ε4 genotype subgroup. Conclusions:The APOE genotype plays a significant role in modulating the relationship between dyslipidemia and the risk of developing DCI.This highlights the critical importance of lipid metabolism disorders and APOE risk genes in both the development and progression of DCI.These findings offer valuable insights for future clinical and mechanistic studies focused on DCI.

Delayed diabetic wound healing has placed an enormous burden on society. The key factors limiting wound healing include unresolved inflammation and impaired angiogenesis. Platelet-rich plasma (PRP) gel, a popular biomaterial in the field of regeneration, has limited applications due to its non-injectable properties and rapid release and degradation of growth factors. Here, we prepared an injectable hydrogel (DPLG) based on PRP and laponite by a simple one-step mixing method. Taking advantages of the non-covalent interactions, DPLG could overcome the limitations of PRP gels, which is injectable to fill irregular injures and could serve as a local drug reservoir to achieve the sustained release of growth factors in PRP and deferoxamine (an angiogenesis promoter). DPLG has an excellent ability in accelerating wound healing by promoting macrophage polarization and angiogenesis in a full-thickness skin defect model in type I diabetic rats and normal rats. Taken together, this study may provide the ingenious and simple bioactive wound dressing with a superior ability to promote wound healing.

Objective:To evaluate the pancreatic subclinical dysfunction after intensity-modulated radiation therapy (IMRT) for gastric cancer by analyzing biochemical indexes and pancreatic volume changes, and to reduce the dose of pancreas by dosimetric prediction and dose limitation.Methods:30 patients with gastric cancer who received 45 Gy postoperative adjuvant radiotherapy were retrospectively selected. The pancreas was delineated and its dose and anatomical relationship with planning target volume (PTV) were evaluated. Fasting blood glucose, serum lipase and amylase, and pancreatic volume changes before and after radiotherapy were analyzed. The correlation between the changes of biochemical indexes and volume and pancreatic dose was evaluated by Pearson analysis. The threshold of the dosimetric prediction was obtained by receiver operating characteristic (ROC) curve. Finally, the feasibility of dosimetric limitation in IMRT was assessed.Results:The pancreatic volume of 30 patients was 37.6 cm 3, and 89.0% of them were involved in PTV. D mean of the pancreas was 45.92 Gy, and 46.45 Gy, 46.46 Gy and 45.80 Gy for the pancreatic head, body and tail, respectively. The fasting blood glucose level did not significantly change. The serum lipase levels were significantly decreased by 66% and 77%(both P<0.001), and the serum amylase levels were significantly declined by 24% and 38%(both P<0.001) at 6 and 12 months after radiotherapy. Pancreatic volumes of 22 patients was decreased by 47% within 18 months after radiotherapy. ROC curve analysis showed that pancreatic V 45Gy had the optimal predictive value for the decrease by 1/3 of serum lipase and amylase levels at 6 months and serum amylase level at 12 months after radiotherapy, and the cut-off value was V 45Gy<85%. Pancreatic D mean yielded the optimal predictive value for the decrease by 2/3 of serum lipase level at 12 months after radiotherapy, and the cut-off value was D mean<45.01 Gy. After" whole pancreas" and" outside PTV pancreas" dose limit, V 45Gy of the pancreas was decreased by 11% and 7%, D mean of the pancreas was declined by 2% and 2%, and D mean of the pancreatic tail was decreased by 3%, respectively. Conclusions:Serum lipase and amylase levels significantly decline at 6 and 12 months after adjuvant radiotherapy for gastric cancer, and pancreatic volume is decreased significantly within 18 months after radiotherapy. Pancreatic V 45Gy<85% and D mean<45.01 Gy are the dose prediction values for the decrease of serum lipase and amylase levels. The dose can be reduced to certain extent by dosimetric restriction.