BACKGROUND:In the process of intervening in the development of osteoarthritis,platelet-rich plasma plays an important role by intervening in autophagy,apoptotic cytokines and signal transduction pathways.OBJECTIVE:To summarize the structure of cytokines and signaling pathways involved in the diagnosis of osteoarthritis by platelet-rich plasma in recent years,as well as its correlation with chondrocyte apoptosis and autophagy,in order to provide effective targets for the future treatment of osteoarthritis.METHODS:Literature search was conducted in CNKI,WanFang Data,VIP,PubMed,Web of Science,and Medline databases using "platelet-rich plasma,chondrocyte,apoptosis,autophagy,osteoarthritis,cytokines,signaling pathway" as Chinese and English search terms.A systematic summary and induction were made for the 66 included articles.RESULTS AND CONCLUSION:Current research has shown that platelet-rich plasma can promote cartilage repair and assist bone tissue healing through various pathways,mainly divided into three aspects:(1) Platelet-rich plasma regulates the extension,closure,and maturation of microautophagosomes,promotes chondrocyte megaautophagy and molecular chaperone-mediated cell autophagy under specific conditions,enhances the expression of autophagy-related factors such as LC3Ⅱ/Ⅰ and Beclin1,inhibits the expression of P62/SQSTM1.Currently,there is no clear research directly exploring the specific effect of platelet-rich plasma on heat shock proteins,and further research is needed in this field in the future.(2) The various growth factors released by platelet-rich plasma inhibit the expression of pro-apoptotic factors Caspase,interleukin-1β,and tumor necrosis factor alpha,promote the expression of anti-apoptotic factor Bcl-2,and prevent chondrocyte apoptosis and degeneration.(3) By activating the PI3K/AKT/mTOR signaling pathway,NF-κB signal transduction pathway,death receptor pathway,mitochondrial stress pathway and other pathways,platelet-rich plasma inhibits the expression of Bax and Caspase,and prevents the release of cytochrome c,thereby inhibiting the death and necrotic apoptosis of chondrocytes.In general,platelet-rich plasma promotes cartilage repair,supports cartilage regeneration,and plays an anti-inflammatory role,and its biological effect in chondrocytes usually depends on the regulation of autophagy and apoptosis-related cytokines and signaling pathways.

BACKGROUND:In the process of intervening in the development of osteoarthritis,platelet-rich plasma plays an important role by intervening in autophagy,apoptotic cytokines and signal transduction pathways.OBJECTIVE:To summarize the structure of cytokines and signaling pathways involved in the diagnosis of osteoarthritis by platelet-rich plasma in recent years,as well as its correlation with chondrocyte apoptosis and autophagy,in order to provide effective targets for the future treatment of osteoarthritis.METHODS:Literature search was conducted in CNKI,WanFang Data,VIP,PubMed,Web of Science,and Medline databases using "platelet-rich plasma,chondrocyte,apoptosis,autophagy,osteoarthritis,cytokines,signaling pathway" as Chinese and English search terms.A systematic summary and induction were made for the 66 included articles.RESULTS AND CONCLUSION:Current research has shown that platelet-rich plasma can promote cartilage repair and assist bone tissue healing through various pathways,mainly divided into three aspects:(1) Platelet-rich plasma regulates the extension,closure,and maturation of microautophagosomes,promotes chondrocyte megaautophagy and molecular chaperone-mediated cell autophagy under specific conditions,enhances the expression of autophagy-related factors such as LC3Ⅱ/Ⅰ and Beclin1,inhibits the expression of P62/SQSTM1.Currently,there is no clear research directly exploring the specific effect of platelet-rich plasma on heat shock proteins,and further research is needed in this field in the future.(2) The various growth factors released by platelet-rich plasma inhibit the expression of pro-apoptotic factors Caspase,interleukin-1β,and tumor necrosis factor alpha,promote the expression of anti-apoptotic factor Bcl-2,and prevent chondrocyte apoptosis and degeneration.(3) By activating the PI3K/AKT/mTOR signaling pathway,NF-κB signal transduction pathway,death receptor pathway,mitochondrial stress pathway and other pathways,platelet-rich plasma inhibits the expression of Bax and Caspase,and prevents the release of cytochrome c,thereby inhibiting the death and necrotic apoptosis of chondrocytes.In general,platelet-rich plasma promotes cartilage repair,supports cartilage regeneration,and plays an anti-inflammatory role,and its biological effect in chondrocytes usually depends on the regulation of autophagy and apoptosis-related cytokines and signaling pathways.

Objective:To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis.Methods:The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ 2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result:Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III–IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ 2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ 2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ 2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ 2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ 2=6.293, P=0.043). The proportions of TNM Stage III–IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ 2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ 2=13.994, P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ 2=10.457, P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ 2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ 2=5.086, P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ 2=19.791, P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ 2=4.601, P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ 2=11.996, P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ 2=7.643, P=0.006), had a higher proportion of TNM Stage III–IV disease (60.2% [100/166] vs. 24.2% [8/33], χ 2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ 2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively ( P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS ( P=0.026). Conclusions:Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.

Objective:To investigate the impact of relative locations of multiple foci and microsatellite status of sporadic, synchronous, multiple, primary, colorectal carcinomas on clinicopathological features and prognosis.Methods:The clinicopathologic and prognostic data of 278 patients with sporadic, synchronous, multiple, primary, colorectal carcinomas who had been admitted to the Department of Colorectal Surgery at Zhejiang Cancer Hospital from January 2008 to July 2022 were retrospectively collected. The patients were categorized into three groups based on the relative locations of their multiple cancer foci: (1) a right-sided group that comprised patients with multiple cancer foci in the cecum, ascending colon, hepatic flexure of the colon, and transverse colon; (2) a left-sided group that comprised patients with multiple cancer foci in the splenic flexure of the colon, descending colon, sigmoid colon, and rectum; and (3) a left- and right-sided group that comprised patients with multiple cancer foci in the right half of the colon and left half of the colon/rectum. Additionally, the patients were further divided into two groups based on microsatellite status: a high microsatellite instability (MSI-H) and a low MSI/stable MSI (MSI/L&MSS) group. We compared differences in clinical characteristics and prognostic indicators between these groups. The χ 2 test was utilized to compare selected clinical characteristics, whereas Kaplan-Meier survival analyses and log-rank tests were performed to compare their effects on prognosis. Result:Among 278 patients with SSCRC, 256 (92.1%) presented with two cancer foci and 22 (7.9%) with more than two foci. Additionally, 255 patients (91.7%) had adenocarcinomas, whereas the remaining 23 (8.3%) had mucinous adenocarcinomas. Lymph node metastases were identified in 136 patients (48.9%); the cancer foci had infiltrated beyond the muscular layer in 238 (85.6%); and 147 patients (52.9%) were diagnosed with TNM Stage III–IV disease. There were 155 patients (55.8%) in the left-sided group, 55 (19.8%) in the right-sided group, and 68 (24.5%) in the left- and right-sided group. Immunohistochemical examination of all four mismatch repair proteins were performed in 199 cases, revealing that 166 of these patients had MSI/L&MSS and 33 MSI-H disease. In the left-sided, left- and right-sided, and right-sided groups, the proportion of women was 16.8% (26/155), 26.5% (18/68), and 49.1% (27/55), respectively; these differences are statistically significant (χ 2=22.335, P<0.001). The proportions of patients with more than three cancer foci were 5.2% (8/155), 16.2% (11/68), and 5.5% (3/55), respectively; these differences are statistically significant (χ 2=8.438, P=0.015). The proportions of mucinous adenocarcinomas were 4.5% (7/155), 8.8% (6/68), and 18.2% (10/55), respectively; these differences are statistically significant (χ 2=10.026, P=0.007). The proportions of patients with lymph node metastases were 55.5% (86/155), 48.5% (33/68), and 30.9% (17/55); these differences are statistically significant (χ 2=9.817, P=0.007). The proportions of patients with Stage T3 & T4 disease in each group according to location were 81.3% (126/155), 88.2% (60/68), and 94.5% (52/55), respectively; these differences are statistically significant (χ 2=6.293, P=0.043). The proportions of TNM Stage III–IV tumors were 59.4% (92/155), 54.4% (37/68), and 32.7% (18/55), respectively; these differences are statistically significant (χ 2=11.637, P=0.003). Age, size of cancer foci, presence of distant metastasis, adenoma, nerve invasion, and vascular invasion did not differ significantly between the three groups (all P>0.05). Compared with those with MSI-H, patients with MSI/L&MSS disease were more likely to be aged >65 years and male (50.6% [84/166] vs. 15.2% [5/33], χ 2=13.994, P<0.001; 80.7% [134/166] vs. 54.5% [18/33], χ 2=10.457, P=0.001), more likely to be in the left-sided group (63.3% [105/166] vs. 24.2% [8/33], χ 2=18.232, P<0.001), had a higher proportion of cancer foci of diameter <4 cm (54.8% [91/166] vs. 33.3% [11/33], χ 2=5.086, P=0.024), and a lower proportion of mucinous adenocarcinomas (4.2% [7/166] vs. 27.3% [9/33], χ 2=19.791, P<0.001), more likely to develop distant metastases (22.3% [37/166] vs. 6.1% [2/33], χ 2=4.601, P=0.032), more likely to have lymph node metastases (57.2% [95/166) vs. 24.2% [8/33], χ 2=11.996, P<0.001) and nerve invasion (28.9% [48/166] vs. 6.1% [2/33], χ 2=7.643, P=0.006), had a higher proportion of TNM Stage III–IV disease (60.2% [100/166] vs. 24.2% [8/33], χ 2=14.374, P<0.001), and a smaller proportion of family history of tumors (28.9% [48/166] vs. 60.6% [20/33], χ 2=12.228, P<0.001). All the above-listed differences are statistically significant (all P<0.05). The differences in number of cancer foci, depth of infiltration, presence or absence of adenomas, and vascular invasion were not statistically significant (all P>0.05). In the 33 patients with MSI-H status and mismatch repair protein loss, the highest frequency of deletion was found in PMS-2 (66.7%, 22/33), followed by MLH-1 (57.6%, 19/33), whereas the proportions of MSH-2 (33.3%, 11/33) and MSH-6 (24.2%, 8/33) deletions were relatively low. There were statistically significant differences in the 3-year overall survival rates among the groups according to relative locations of cancer foci. The 3-year overall survival rates were 96.8%, 79.6%, and 88.5% in the right-sided, left- and right-sided, and left-sided groups, respectively ( P=0.021). As to microsatellite status, the 3-year overall survival rate of patients with MSI-H disease was 93.8%, which is significantly better than the 78.4% for those with MSI/L & MSS ( P=0.026). Conclusions:Among sporadic, synchronous, multiple, primary, colorectal carcinomas, those with right-sided disease had the deepest local infiltration, whereas those with left-sided disease had the greatest number of lymph node metastases, most advanced clinical TNM stage, lowest percentage of MSI-H disease, and the poorest prognosis.

Recombinant human interferon α2b(rhIFNα2b)is widely used as an antiviral therapy agent for the treatment of hepatitis B and hepatitis C.The current identification test for rhIFNα2b is complex.In this study,an anti-rhIFNα2b nanobody was discovered and used for the development of a rapid lateral flow strip for the identification of rhIFNα2b.RhIFNα2b was used to immunize an alpaca,which established a phage nanobody library.After five steps of enrichment,the nanobody I22,which specifically bound rhIFNα2b,was isolated and inserted into the prokaryotic expression vector pET28a.After subsequent purification,the physicochemical properties of the nanobody were determined.A semiquantitative detection and rapid identification assay of rhIFNα2b was developed using this novel nanobody.To develop a rapid test,the nanobody I22 was coupled with a colloidal gold to produce lateral-flow test strips.The developed rhIFNα2b detection assay had a limit of detection of 1 μg/mL.The isolation of I22 and successful construction of a lateral-flow immunochromatographic test strip demonstrated the feasibility of performing ligand-binding assays on a lateral-flow test strip using recombinant protein products.The principle of this novel assay is generally applicable for the rapid testing of other com-mercial products,with a great potential for routine use in detecting counterfeit recombinant protein products.

Objective: To evaluate the quality status of recombinant human interferon α2a injections and find out some quality problems. Methods:The statutory testing methods combining with the exploratory studies were used to examine the samples, and the quality status of recombinant human interferon α2a injections was evaluated by statistical analysis of the results. Results: All 28 bat-ches of the injections were qualified using the statutory testing methods. The exploratory studies showed that if the specific activity was determined, the qualified rate was only 87. 0%. All 7 batches of drug substances were qualified using the statutory testing methods. The exploratory studies showed that if the related protein was determined, the qualified rate was 57. 1%. Conclusion:At present the quality of recombinant human interferonα2a injections is generally good. The current standards are feasible;however, improvement is still needed. Specific activity determination should be supplemented the standards for drug products and related protein determination should be supplemented the standards of drug substances.

Objective:To examine the osmolality of domestic recombinant human interferon α2b injection to provide evidence for the improvement of the national quality standard. Methods:Totally 66 batches of recombinant human interferonα2b injection produced by 9 manufacturers were withdrawn, and the osmolality was determined according to the appendix of Chinese Pharmacopoeia Ⅲ(2010 edition). The results were analyzed with statistical methods. Results:The pass rate of osmolality was 98. 5%. The osmolality of more than 90% of the batches was between 85% and 115% of the intermediate value set by the manufacturers. Conclusion:Comprehensive understanding of the quality control of osmolality of domestic recombinant human interferon α2b injection is obtained, which provides data support for the improvement of quality standard of osmolality.

Objective To explore surgical options and clinical outcome of preperitoneal hernia repair (TAPP) and totally ext raperitoneal hernia repair (TEP) in inguinal hernia repair.Methods The clinical data of 302 patients underwent laparoscopic herniorrhaphy were retrospectively analyzed.Results None of patient s was changed to open operation.The TAPP and TEP outcome measures:the unilateral hernia surgery time from (31.2 ± 8.3) min and (55.3 ± 15.2) min,bilateral hernia surgery time was (46.2 ± 11.2)min and (80.2 ± 23.2) min; blood loss was (6.4 ± 2.0) ml and (7.2 ± 1.6) ml,bed activity for the first was (16.0 ± 1.8) h and (16.0 ± 1.5) h,hospital stay was (3.0 ±0.6) d and (3.1 ±0.8) d.Conclusions Laparoscope herniorrhaphy is safe due to lower recurrence and complications.It also has the advantages of slight pain and rapid recovery.

To investigate the clinical characteristics and angio-architecture features of patients with dural arteriovenous fistulas (DAVF).The clinical data of 48 patients with DAVF were analyzed retrospectively.All patients were diagnosed by digital subtract angiography and 43 cases were also examined by MRI.Patients were divided into the bleeding group and non-bleeding group,whose clinical features and angio-architecture were compared.Of 48 cases,13 patients demonstrated intracranial bleeding,and men were more common in bleeding group (M/F:10/3) than in non-bleeding group (M/F:15/20) (P =0.036).The Cognard scores of bleeding group and nou-bleeding group were 3.77 ±0.28 and 2.49 ±0.21,respectively (P =0.002) ; however,there was no significant difference in age and the number of feeding artery between two groups.The results indicate that male patients with high Cognard scores tend to intracranial bleeding.