ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg^-1）， metformin group （135 mg·kg^-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg^-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.

Objective To analyze the high risk factors of obstetric brachial plexus palsy(OBPP),and to explore how to evaluate the relationship between fault medical behavior and OBPP in the process of medical damage forensic identification.Methods A retrospective analysis was carried out on 25 cases of medical damage liability disputes related to OBPP from 2017 to 2021 in Beijing Fayuan Judicial Science Evidence Appraisal Center.The shortcomings of hospitals in birth weight assessment,delivery mode selection,labor process observation and shoulder dystocia management,and the causal relation-ship between them and the damage consequences of the children were summarized.Results Fault medi-cal behavior was assessed as the primary cause in 2 cases,equal cause in 10 cases,secondary cause in 8 cases,minor cause in 1 case,no causal relationship in 1 case,and unclear causal force in 3 cases.Conclusion In the process of forensic identification of OBPP,whether medical behaviors fulfill diagno-sis and treatment obligations should be objectively analyzed from the aspects of prenatal evaluation,de-livery mode notification,standardized use of oxytocin,standard operation of shoulder dystocia,etc.Meanwhile,it is necessary to fully consider the objective risk of different risk factors and the diffi-culty of injury prevention,and comprehensively evaluate the causal force of fault medical behavior in the damage consequences.

Eighteen compounds were isolated from the methanol extract of the fruits of Litsea cubeba by silica gel, ODS, Sephadex LH-20 column chromatography, semi-preparative RP-HPLC, chiral HPLC and recrystallization. Their structures were elucidated by spectroscopic analyses and by comparison with reported spectroscopic data and physicochemical properties, and the absolute configurations of the enantiomers were established by experimental and calculated electronic circular dichroism spectra. These compounds were identified as (+)-(R)-4-hydroxypiperitenone (1a), (-)-(S)-4-hydroxypiperitenone (1b), (3S,4S,6R)-3,6-dihydroxy-1-menthene (2), (4S,5R)-4-hydroxy-5-isopropyl-2-methylcyclohex-2-en-1-one (3), (R)-6-hydroxy-3-(2-hydroxypropan-2-yl)-6-methylcyclohex-2-enone (4), (4S,6R)-4-hydroxy-6-isopropyl-3-methylcyclohex-2-enone (5), (1R,3S,4R)-3-hydroxy isopulegol (6), subamone (7), (6S)-3,7-dimethyl-7-hydroxy-2(Z)-octen-6-olide (8), (6S)-6,7-dihydroxy-3,7-dimethyloct-2(Z)-enoate (9), holostylactone (10), sesamin (11), dimethylmatairesinol (12), p-hydroxybenzoylcarbinol (13), syringaldehyde (14), p-hydroxybenzaldehyde (15), 4-hydroxy-3-methoxybenzaldehyde (16), 5,4ʹ-dihydroxy-7-methoxyflavone (17). Among them, compounds 1a and 1b were a pair of new monoterpenoid enantiomers, 8 and 9 were new natural products, 2-7, 10, 11 and 17 were isolated from Litsea genus for the first time. The in vitro anti-inflammatory effects of compounds 1-17 were evaluated using lipopolysaccharide-stimulated RAW264.7 cells, the results showed that compound 14 exhibited significant anti-inflammatory activity with NO inhibitory rate of 66.27% at a concentration of 40 μmol·L^-1.

Objective To investigate the mechanism of the interaction between miR-9-5p and tissue metalloproteinase inhibitor 2(TIMP2)on autophagy and apoptosis in multiple myeloma(MM)cells.Methods Real-time fluorescence quantitative PCR(qRT-PCR)was used to detect expression levels of miR-9-5p and TIMP2 in bone marrow samples of 9 patients with newly diagnosed MM and 9 patients with recurrent MM.The correlation of expression levels between the two were analyzed.U266 cells were divided into the miR-control group,the miR-9-5p group,the pcDNA3.1 group,the pcDNA3.1-TIMP2 group,the miR-9-5p+pcDNA3.1 group,and the miR-9-5p+pcDNA3.1-TIMP2 group.The effects of overexpressed miR-9-5p and TIMP2 on autophagy and apoptosis in U266 cells were detected by flow cytometry,immunofluorescence staining and Western blot experiments.The dual luciferase report experiment verified the interaction between miR-9-5p and TIMP2.Results Compared with newly diagnosed MM patients,the expression level of miR-9-5p was increased and the expression level of TIMP2 was decreased in patients with recurrent MM.The expression levels of miR-9-5p and TIMP2 were negatively correlated(P<0.05).Compared with the miR-control group,the miR-9-5p group showed a decrease in the expression level of MAP1LC3B-Ⅱ,an increase in expression levels of MAP1LC3B-Ⅰ and SQSTM1,and a decrease in cell apoptosis rate(P<0.05).Compared with the pcDNA3.1 group,the expression level of MAP1LC3B-Ⅱ was increased in the pcDNA3.1-TIMP2 group,while the expression levels of MAP1LC3B-Ⅰ and SQSTM1 were decreased,and the apoptosis rate of cells increased(P<0.05).Bioinformatics and dual luciferase reporter experiments confirmed that TIMP2 was the target gene of miR-9-5p.Conclusion miR-9-5p inhibits autophagy and apoptosis in MM cells by targeting TIMP2,thereby promoting the occurrence and development of MM.

OBJECTIVE: To investigate the role of multiple serological methods in the identification of complex antibodies. METHODS: The blood group antigens were detected by saline and microcolumn agglutination methods. The saline method was used to screen and identify IgM-type antibodies in the patient's serum, while the polybrene, anti-globulin, microcolumn agglutination, enzymic and absorption-elution methods were used to screen and identify IgG-type antibodies. RESULTS: The patient was B/CCDee/Jk(a-b+)/Fy(a-b+) blood type. The serum reacted with panel cells, and the reaction presented anti-E pattern in the saline medium. It was fully positive in the microcolumn agglutination card, except 2 negative ones after using papain to treat the panel cells. Referring to the pattern table, it was concluded that there existed anti-c, anti-E, and anti-Jk^a antibodies, and one antibody corresponding to an antigen that was easily destroyed by papain. The red blood cells with specific phenotype were selected for absorption-elution to identify IgG-type anti-c, anti-E, anti-Jk^a and anti-Fy^a antibodies. CONCLUSION It is confirmed that IgM-type anti-E, and IgG-type anti-c, anti-E, anti-Jk^a and anti-Fy^a antibodies exist in the patient's serum by multiple serological methods.
Humans ; Papain ; Blood Group Antigens ; Erythrocytes ; Immunoglobulin G ; Immunoglobulin M

OBJECTIVE: To investigate the efficacy of integrated Chinese and Western medicine extending the progression-free survival (PFS) and overall survival (OS) of limited-stage small cell lung cancer (LS-SCLC) patients after the first-line chemoradiotherapy. METHODS: The data of 67 LS-SCLC patients who received combined treatment of CM and Western medicine (WM) between January 2013 and May 2020 at the outpatient clinic of Guang'anmen Hospital were retrospectively analyzed. Thirty-six LS-SCLC patients who received only WM treatment was used as the WM control group. The medical data of the two groups were statistically analyzed. Survival analysis was performed using the product-limit method (Kaplan-Meier analysis). The median OS and PFS were calculated, and survival curves were compared by the Log rank test. The cumulative survival rates at 1, 2, and 5 years were estimated by the life table analysis. Stratified survival analysis was performed between patients with different CM administration time. RESULTS: The median PFS in the CM and WM combination treatment group and the WM group were 19 months (95% CI: 12.357-25.643) vs. 9 months (95% CI: 5.957-12.043), HR=0.43 (95% CI: 0.27-0.69, P<0.001), respectively. The median OS in the CM and WM combination group and the WM group were 34 months (95% CI could not be calculated) vs. 18.63 months (95% CI: 16.425-20.835), HR=0.40 (95% CI: 0.24-0.66, P<0.001), respectively. Similar results were obtained in the further stratified analysis of whether the duration of CM administration exceeded 18 and 24 months (P<0.001). CONCLUSION The combination treatment of CM and WM with continuing oral administration of CM treatment after the first-line chemoradiotherapy for LS-SCLC patients produced better prognosis, lower risks of progression, and longer survival than the WM treatment alone. (Registration No. ChiCTR2200056616).
Humans ; Small Cell Lung Carcinoma/drug therapy* ; Lung Neoplasms/drug therapy* ; Retrospective Studies ; Prognosis ; Combined Modality Therapy

In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50％of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.

Objective:To evaluate the efficacy and safety of non-submucosal injection in endoscopic submucosal excavation (ESE) for small submucosal tumors originating in the muscularis propria of the stomach.Methods:A total of 138 patients diagnosed as having small gastric muscularis propria tumors (≤2 cm) at Digestive Endoscopy Center of Zhejiang Provincial Hospital of Chinese Medical from November 2018 to October 2020 were randomly divided into the observation group with non-submucosal injection of ESE and the control group with submucosal injection of ESE for a randomized controlled trial. The exposure time, tumor removal time, operation cost, hospitalization period, numbers of metal clips and complications of the two groups were analyzed and compared.Results:A total of 138 patients were enrolled, including 76 patients in the observation group and 62 patients in the control group. All lesions were successfully and completely removed. Compared with the control group, the observation group had shorter median tumor exposure time [2.00 min VS 3.30 min, Z=-2.426, P =0.045], shorter median tumor removal time [16.8 min VS 34.4 min, Z=-4.324, P<0.001], less median surgical cost [2 903 yuan VS 3 178 yuan, Z=-5.112, P<0.001], and fewer metal clips used (4.0±0.6 VS 5.1±1.3, t=1.452, P=0.003). The incidence of postoperative abdominal distension of the observation group was lower [9.2% (7/76) VS 22.6% (14/62), χ2=2.512, P=0.049], the incidence of postoperative abdominal pain of this group was lower too [11.8% (9/76) VS 32.3% (20/62), χ2=4.242, P=0.014], but there was no significant difference in the period of hospitalization, incidence of postoperative fever or perforation ( P>0.05). Conclusion:Non-submucosal injection of ESE is safe and effective for submucosal tumors smaller than 2.0 cm originating from the muscularis propria of the stomach , which might be more advantageous than traditional ESE.

Objective: To compare the effect of bone-anchored versus tooth-borne rapid palatal expansion (RPE) combined with maxillary protraction in the treatment of skeletal class Ⅲ patients with maxillary hypoplasia. Methods: Twenty-six skeletal class Ⅲ patients with maxillary hypoplasia in the late mixed or early permanent dentition were selected. All the patients underwent RPE combined with maxillary protraction in the Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University from August 2020 to June 2022. The patients were divided into 2 groups. Thirteen patients were enrolled in the bone-anchored RPE group [4 males and 9 females, aged (10.2±1.7) years] and the others were in the tooth-borne RPE group [5 males and 8 females, aged (10.1±1.0) years]. Ten sagittal linear indices [Y-Is distance (the distance from the incisor edge of the maxillary incisor to the vertical reference axis), Y-Ms distance (the distance from the mesial contact point of the maxillary first molar to the vertical reference axis), the relative distance between the maxillary and mandibular molars, overjet, etc.], 6 vertical linear indices [PP-Ms distance (the distance changes from Ms to the palatal plane), etc.] and 8 angle indices [SN-MP angle (the upper external angle of the intersection of the sella-nasion plane and the mandibular plane), U1-SN angle (the lower internal angle of the intersection of the long axis of the maxillary central incisor and the sella-nasion plane), etc.] were measured on the cephalometric radiographs before and after the treatment. Six coronal indicators (the inclination of the left and right first maxillary molar, etc.) were measured on cone-beam CT images before and after the treatment. The proportion of skeletal and dental factors in the changes of overjet were calculated. The differences of the index changes between groups were compared. Results: After the treatment, the anterior crossbite were corrected in both groups, and classⅠor classⅡ molar relationship were attained. In bone-anchored group, the changes of Y-Is distance, Y-Ms distance and maxillary and mandibular molar relative distance were (3.23±0.70), (1.25±0.34) and (2.54±0.59) mm, respectively, significantly less than those in the tooth-borned group in which the corresponding changes were (4.96±0.97) mm (t=-5.92, P<0.001), (3.12±0.83) mm (t=-7.53, P<0.001) and (4.92±1.35) mm (t=-5.85, P<0.05), respectively. The change of overjet in the bone-anchored group was (4.45±1.25) mm, significantly less than that in the tooth-borned group (6.14±1.29) mm (t=-3.38, P<0.05). Skeletal and dental factors accounted for 80% and 20% of the overjet changes in the bone-anchored group, respectively. While in the tooth-borned group, skeletal and dental factors accounted for 62% and 38% of the overjet changes, respectively. The PP-Ms distance change in the bone-anchored group [(-1.62±0.25) mm] was significantly less than that in the tooth-borned group [(2.13±0.86) mm] (t=-15.15, P<0.001). The changes of SN-MP and U1-SN in the bone-anchored group were -0.95°±0.55° and 1.28°±1.30°, respectively, significantly less than those corresponding indices in the tooth-borned group (1.92°±0.95°, t=-9.43, P<0.001; 7.78°±1.94°, t=-10.04, P<0.001). In the bone-anchored group, the inclination changes of maxillary bilateral first molars in the left and right sides were 1.50°±0.17° and 1.54°±0.19°, significantly less than the corresponding indices in the tooth-borned group (2.26°±0.37°, t=6.47, P<0.001; 2.25°±0.35°, t=6.81, P<0.001). Conclusions: The bone-anchored RPE with maxillary protraction could reduce the adverse tooth compensation effect, including the protrusion of maxillary anterior incisors, the increase of overjet and mandibular plane angle, and the mesial movement, extrusion and buccal inclination of maxillary molars.