Diabetic peripheral neuropathy (DPN) is the common chronic complication of diabetes, which can lead to foot ulcers, gangrene, and amputation in severe cases, seriously affecting their quality of life. DPN belongs to the category of "arthralgia", "hemorrhoids" and other categories of TCM, and the main pathogenesis is the deficiency of qi and blood, yin and yang, and the obstruction of the meridians by phlegm and stasis. Clinically, DPN is more common with qi deficiency and blood stasis syndrome. Based on the theory of "qi meridian constant communication" in the Huang Di Nei Jing, this article proposed that for patients with DPN with qi deficiency and blood stasis syndrome, the treatment should be based on the principle of "invigorating qi and activating blood circulation, dissolving stasis and arthralgia", so that the patients' qi meridian can be accessible, delay the disease progression, and provide reference for the TCM treatment of DPN.

Background::Differentiated thyroid cancer (DTC) is commonly diagnosed in women of child-bearing age, but whether pregnancy influences the prognosis of DTC remains controversial. This study aimed to summarize existing evidence regarding the association of pregnancy with recurrence risk in patients previously treated for DTC.Methods::We searched PubMed, Embase, Web of Science, Cochrane, and Scopus based on the prespecified protocol registered at PROSPERO (CRD42022367896). After study selection, two researchers independently extracted data from the included studies. For quantitative data synthesis, we used random-effects meta-analysis models to pool the proportion of recurrence (for pregnant women only) and odds ratio (OR; comparing the risk of recurrence between the pregnancy group and the nonpregnancy group), respectively. Then we conducted subgroup analyses to explore whether risk of recurrence differed by response to therapy status or duration of follow-up time. We also assessed quality of the included studies.Results::A total of ten studies were included. The sample size ranged from 8 to 235, with participants’ age at pregnancy or delivery ranging from 28 to 35 years. The follow-up time varied from 0.1 to 36.0 years. The pooled proportion of recurrence in all pregnant patients was 0.13 (95% confidence intervals [CI]: 0.06-0.25; I2: 0.58). Among six included studies reporting response to therapy status before pregnancy, we observed a trend for increasingly higher risk of recurrence from excellent, indeterminate, and biochemically incomplete to structurally incomplete response to therapy ( Ptrend <0.05). The pooled risk of recurrence in the pregnancy group showed no evidence of a significant difference from that in the nonpregnancy group (OR: 0.75; 95% CI: 0.45-1.23; I2: 0). The difference in follow-up time (below/above five years) was not associated with either the proportion of recurrence in all pregnant patients ( P >0.05) or the OR of recurrence in studies with a comparison group ( P >0.05). Two included studies that focused on patients with distant metastasis also did not show a significant difference in disease recurrence between pregnancy and nonpregnancy groups (OR: 0.51 [95% CI: 0.14-1.87; I2: 59%]). Conclusion::In general, pregnancy appears to have a minimal association with the disease recurrence of DTC with initial treatment. Clinicians should pay more attention to progression of DTC among pregnant women with biochemical and/or structural persistence.Registration::PROSPERO, https://www.crd.york.ac.uk/PROSPERO/; No. CRD42022367896.

Objective To preliminarily analyze the efficacy of laparoscopic surgery versus open surgery in patients with intrahepatic cholangiocarcinoma(ICC).Methods A retrospective analysis was conducted on 84 patients with ICC who underwent surgical resection from September 2010 to March 2023,including 45 cases in the laparoscopic surgery group and 39 in the open surgery group.By using propensity score matching,34 matched pairs were successfully identified.The study compared intraoperative blood loss,proportion of achieving≥6 lymph nodes dissection,R0 resection rate,complication,postoperative hospital stay,survival,and recurrence between the two groups.Results In the laparoscopic group,intraoperative blood loss was significantly less than that in the open surgery group(median:250 ml vs.750 ml,Z=-3.406,P=0.001).The proportion of achieving≥6 lymph node dissection in the former was lower than that in the latter,but the difference was not statistically significant(5.9%vs.17.6%,χ2=1.275,P=0.259).There was no statistical difference in R0 resection rate between the laparoscopic group and the open surgery group[88.2%(30/34)vs.82.4%(28/34),χ2=0.469,P=0.493].The complication rate in the laparoscopic group was 17.6%(6/34),significantly lower than 47.1%(16/34)in the open surgery group(χ2=6.719,P=0.010);however,the rate of severe complication was the same in both groups at 2.9%(χ2=0.000,P=1.000).Laparoscopic surgery significantly shortened the postoperative hospital stay(median:7 d vs.10 d,Z=-3.021,P=0.003).The median overall survival in the laparoscopic group was 60.6 months,significantly longer than 15.9 months in the open surgery group(log-rank χ2=5.788,P=0.016).The median recurrence-free survival was 26.4 months in the laparoscopic group,significantly longer than 7.6 months in the open surgery group(log-rank χ2=4.532,P=0.033).Conclusions Compared to open surgery,laparoscopic surgery for ICC offers advantages such as less blood loss,lower complication rate,shorter postoperative hospital stay and longer survival.It achieves comparable R0 resection rate and adequate lymph node dissection.

Objective:To explore the expression of PD-L1 and B7-H3 in intrahepatic cholangiocarcinoma (ICC) and their relationship with the prognosis after surgery.Methods:Clinicopathological data of 63 ICC patients undergoing surgery at the Department of General Surgery, Peking University Third Hospital, from Sep 2016 to Mar 2023 were retrospectively analyzed.Results:PD-L1 and B7-H3 are highly expressed in 41.3% and 60.3% of ICC patients, respectively, and their expression levels were positively correlated with each other( P=0.005). High PD-L1 expression is significantly associated with poor tumor differentiation ( P=0.014), while high B7-H3 expression is significantly related to lymph node metastasis ( P=0.035). In patients with high co-expression of PD-L1 and B7-H3, the overall survival ( P=0.031) and recurrence-free survival ( P=0.031) were significantly decreased. High co-expression of PD-L1 and B7-H3 is an independent risk factor for recurrence in ICC ( HR=3.998, 95% CI: 1.211-13.198; P=0.023). Conclusions:ICC patients with high expression of both PD-L1 and B7-H3 have a poor prognosis. Using both as the combined biomarker significantly improves the prediction of long-term survival after surgery, compared to using either one alone.

Objective:To explore the mechanism of herb-partitioned moxibustion in relieving rat intestinal inflammation by focusing on the neutrophil extracellular traps(NETs)in Crohn disease(CD)development. Methods:Rats were randomly divided into a normal group,a model group,a herb-partitioned moxibustion group,and a mesalazine group.The CD rat model was prepared with 2,4,6-trinitrobenzene sulfonic acid except for rats in the normal group.Rats in the normal group and model group did not receive any treatment but had the same fixation as the other groups.Rats in the herb-partitioned moxibustion group received herb-partitioned moxibustion at Qihai(CV6)and bilateral Tianshu(ST25).Rats in the mesalazine group received intragastric administration of mesalazine enteric-coated tablets.The general situation of rats in each group was recorded,and the histopathological changes in the colon were observed and scored by hematoxylin-eosin staining.The serum concentrations of NETs DNA(NETs-DNA),neutrophil elastase(NE)-DNA,and myeloperoxidase(MPO)-DNA were detected by ABC enzyme-linked immunosorbent assay,and the citrullinated histone 3(citH3),MPO,and NE protein and mRNA expression levels in rat colon tissue were observed by immunofluorescence and real-time quantitative polymerase chain reaction. Results:Compared with the normal group,the mucosal ulcer reached the muscularis,the epithelium was incomplete,the goblet cells decreased obviously with significant inflammatory cell infiltration in the colon;the colonic mucosa damage index(CMDI)score increased significantly(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations increased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue increased significantly in the model group(P<0.01 or P<0.05).Compared with the model group,the mucosal epithelium in the herb-partitioned moxibustion group and the mesalazine group was repaired and the goblet cells increased with a few infiltrating inflammatory cells in the colon;the CMDI score decreased(P<0.01);the serum NETs-DNA,NE-DNA,and MPO-DNA concentrations decreased(P<0.05);the NE,citH3,and MPO protein and mRNA expression in the colonic tissue was down-regulated(P<0.01 or P<0.05). Conclusion:Herb-partitioned moxibustion reduced the serum NETs complex and inhibited the protein and mRNA expression of NETs complex in the colon tissue,which may be one mechanism of herb-partitioned moxibustion in relieving colon mucosal inflammation in CD.

Objective:To analyze the diagnostic value of cell-free plasma metagenomic next-generation sequencing (mNGS) pathogen identification for severe aplastic anemia (SAA) bloodstream infection.Methods:From February 2021 to February 2022, mNGS and conventional detection methods (blood culture, etc.) were used to detect 33 samples from 29 consecutive AA patients admitted to the Anemia Diagnosis and Treatment Center of the Hematology Hospital of the Chinese Academy of Medical Sciences to assess the diagnostic consistency of mNGS and conventional detection, as well as the impact on clinical treatment benefits and clinical accuracy.Results:①Among the 33 samples evaluated by mNGS and conventional detection methods, 25 cases (75.76%) carried potential pathogenic microorganisms. A total of 72 pathogenic microorganisms were identified from all cases, of which 65 (90.28%) were detected only by mNGS. ②All 33 cases were evaluated for diagnostic consistency, of which 2 cases (6.06%) were Composite, 18 cases (54.55%) were mNGS only, 2 cases (6.06%) were Conventional method only, 1 case (3.03%) was both common compliances (mNGS/Conventional testing) , and 10 cases (30.3%) were completely non-conforming (None) . ③All 33 cases were evaluated for clinical treatment benefit. Among them, 8 cases (24.24%) received Initiation of targeted treatment, 1 case (3.03%) received Treatment de-escalation, 13 cases (39.39%) received Confirmation, and the remaining 11 cases (33.33%) received No clinical benefit. ④ The sensitivity of 80.77%, specificity of 70.00%, positive predictive value of 63.64%, negative predictive value of 84.85%, positive likelihood ratio of 2.692, and negative likelihood ratio of 0.275 distinguished mNGS from conventional detection methods (21/12 vs 5/28, P<0.001) . Conclusion:mNGS can not only contribute to accurately diagnosing bloodstream infection in patients with aplastic anemia, but can also help to guide accurate anti-infection treatment, and the clinical accuracy is high.

The incidence of pancreatic neuroendocrine neoplasm(pNEN) increased over the past two decades. Liver metastasis, the most common type of distal metastasis, is also one of the most important prognostic factors. Although several medical treatments, including biotherapy, chemotherapy, targeted therapy, peptide receptor radionuclide therapy and locoregional therapy, are available for pNEN with liver metastases, surgery is still the only possible treatment for cure. Currently, there are several controversies as regards surgical treatment for pNEN with liver metastases. These controversies include, but are not limited to, whether surgical resection is appropriate for pancreatic neuroendocrine tumor G3 with liver metastases, how to classify primary lesion and hepatic metastases comprehensively and accurately, what is the optimal surgical strategy for type Ⅱ liver metastases, who can benefit greatly from cytoreduction, and how to refine the Milan criteria for liver transplantation. This article aims to discuss those main controversies and provide prospects for future clinical trials.

The incidence of pancreatic neuroendocrine neoplasm(pNEN) increased over the past two decades. Liver metastasis, the most common type of distal metastasis, is also one of the most important prognostic factors. Although several medical treatments, including biotherapy, chemotherapy, targeted therapy, peptide receptor radionuclide therapy and locoregional therapy, are available for pNEN with liver metastases, surgery is still the only possible treatment for cure. Currently, there are several controversies as regards surgical treatment for pNEN with liver metastases. These controversies include, but are not limited to, whether surgical resection is appropriate for pancreatic neuroendocrine tumor G3 with liver metastases, how to classify primary lesion and hepatic metastases comprehensively and accurately, what is the optimal surgical strategy for type Ⅱ liver metastases, who can benefit greatly from cytoreduction, and how to refine the Milan criteria for liver transplantation. This article aims to discuss those main controversies and provide prospects for future clinical trials.

Objective:To observe the emulsification of silicone oil in eyes with rhegmatogenous retinal detachment (RRD) after silicone oil filling surgery, and to preliminarily analyze the possible clinical factors related to it.Methods:A cross-sectional clinical study. From January 2019 to April 2022, 50 eyes of 50 patients with RRD who underwent pans plana vitrectomy (PPV) combined with silicone oil filling surgery in Eye and ENT Hospital of Fudan University were included in the study. Among them, there were 25 males with 25 eyes and 25 females with 25 eyes; the age was 54.86±11.79 years old. The retina was in place 3 months after surgery. Before silicone oil removal surgery, intraocular pressure >21 mm Hg (1 mm Hg=0.133 kPa) or treated with≥1 anti-glaucoma drug (high intraocular pressure) in 20 eyes; intraocular pressure ≤21 mm Hg and no anti-glaucoma drug treatment in 30 eyes (normal intraocular pressure). During follow-up after surgery, silicone oil emulsification was found and those who met the indications for silicone oil removal were subjected to silicone oil removal surgery. The first 2 ml of lavage fluid was collected immediately after removal of the silicone oil, and the particle diameter and number of emulsified silicone oil were measured using a Multisizer ? 3 particle/cell counter and particle size analyzer. The measuring range was 0.4-12.0 μm, and the diameter is accordingly divided into 0.4-<1.0, 1.0-<3.0, 3.0-<5.0, 5.0-<7.0, 7.0-12.0 μm. Each sample was measured 3 times and the average value was taken. Spearman correlation analysis and multiple linear regression analysis were used to analyze the correlation between the number of emulsified silicone oil particles and clinical factors. Results:The number of emulsified silicone oil particles was (1.74±2.94)×10 7/ml (0.96×10 7-14.11×10 7/ml), of which the diameter of 0.4-<1.0 μm emulsified silicone oil particle was (1.25±2.41)×10 7/ml, accounted for (64.26±12.70)% [(1.25±2.41)×10 7/(1.74±2.94)×10 7]. The results of correlation analysis showed that there was no correlation between the total particle number of emulsified silicone oil and various clinical factors ( P>0.05). The number of emulsified silicone oil particles with a diameter of 7.0-12.0 μm was negatively correlated with age ( r=-0.298, P=0.036), and positively correlated with axial length ( r=0.325, P=0.021). There was no correlation between the previous ocular trauma, choroidal detachment and different lens states and the number of emulsified silicone oil particles ( P>0.05). Multiple linear regression analysis showed that eye axis ( β=1 570.868, P=0.023) and age ( β=-316.128, P=0.039) were the risk predictors of silicone oil emulsification into large diameter particles (7-<12 μm). The number of emulsified silicone oil particles with a diameter of 7-12 μm in the patients with high intraocular pressure was significantly higher than that in the patients with normal intraocular pressure, and the difference was statistically significant ( U=195.00, P=0.037). Conclusions:Most of the emulsified silicone oil particles in the eyes of RRD patients after silicone oil filling surgery are small-diameter particles; the silicone oil emulsification is more serious in young patients and patients with long ocular axis, and young patients are more prone to high intraocular pressure.

Objective:To explore the mechanism of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the inflammatory response induced by Helicobacter pylori ( H. pylori) infection. Methods:From May 1, 2020 to January 31, 2021, 60 patients with gastritis (30 H. pylori positive and 30 H. pylori negative)and 30 healthy individuals, who initially visited the Department of Gastroenterology, Shiyan Taihe Hospital were collected, and their serum PCSK9 levels were detected. Normal gastric epithelial cell line GES-1 and macrophages induced from THP-1 cells, and GES-1 infected with H. pylori were selected to prepare different supernatant media. Phosphate buffer saline empty medium (negative control group), normal GES-1 cell supernatant medium ( H. pylori-uninfected GES-1 group), H. pylori infected GES-1 cell supernatant medium ( H. pylori infected GES-1 group), H. pylori infected GES-1 cell supernatant + PCSK9 neutralizing antibody medium (anti PCSK9 group), H. pylori infected GES-1 cell supernatant+ human immunoglobulin G medium (isotype control group) were established. The differences between H. pylori infected GES-1 group and H. pylori-uninfected GES-1 group, negative control group, anti PCSK9 group and isotype control group in number of migrated macrophages, relative expression level of CC chemokine receptor ( CCR2), the levels of released interleukin(IL)-6 and cell necrosis factor (TNF)- α, level of CD8 + T cell membrane phosphorylation, and the number of macrophage colonies were determined by Transwell assay, real time fluorescence quantitative polymerase chain reaction, plate colony assay, H. pylori and phagocytosis lysosome co-localization assay. The regulating mechanism of PCSK9 in H. pylori infection induced inflammation was analyzed. Independent sample t test was used for statistical analysis. Results:The serum level of PCSK9 of patients with H. pylori positive gastritis was higher than that of patients with H. pylori negative gastritis and healthy individuals ((384.00±57.57) g/L vs. (208.80±48.89) and (176.10±47.14) g/L), and the differences were statistically significant ( t=12.71 and 15.31; both P<0.001). Compared with negative control group, H. pylori standard strain and 4 isolated H. pylori strains could stimulate GES-1 to secrete PCSK9 ((1 267.00±287.50) g/L vs.(2 717.00±199.20), (4 858.00±302.40), (3 167.00±334.20), (6 075.00±597.30), (4 283.00±331.20) g/L), and the differences were statistically significant( t=10.15, 21.09, 10.56, 17.77, 16.85, all P<0.001). The number of migrated macrophages, CCR2 mRNA expression level in macrophage, expression levels of IL-6 and TNF-α, and the number of macrophage colonies of H. pylori-infected GES-1 group were all higher than those of H. pylori-uninfected GES-1 group and negative control group (132.20±5.67 vs.84.83±4.62, 39.83±4.12; 8.66±0.94 vs. 6.52±0.47 and 1.00±0.09, (281.00±8.56) ng/L vs. (115.00±7.72) and (64.00±5.44) ng/L, (619.80±18.47) ng/L vs.(373.30±12.85)and (225.70±6.44) ng/L, (357.00±16.31) colony forming unit (CFU) vs. (134.80±8.64) and (74.17±9.68) CFU), and the differences were statistically significant ( t=15.85, 32.27; 4.96, 19.79; 35.28, 52.43; 26.84, 49.37; 29.49, 36.53; all P<0.001). The percentage of co-localization of H. pylori and phagocytosis lysosome, and the expression of cell membrane CD3ζ Tyr142, granzyme B and perforin in CD8 + T cell of H. pylori-infected GES-1 group were lower than that of H. pylori-uninfected GES-1 group ((15.33±1.86)% vs. (34.50±3.72)% and (65.67±3.56)%, 464.20±120.80 vs. 1 924.00±262.10 and 2 390.00±484.10; (6.41±0.42)% vs.(17.37±0.73)% and (26.60±1.57)%; (6.84±1.37)% vs.(14.53±0.48)% and (26.22±1.21)%), and the differences were statistically significant( t=11.27 and 30.70, 12.39 and 9.45, 30.50 and 31.90, 25.96 and 13.00; all P<0.001). The number of migrated macrophages, the relative expression level of CCR2 mRNA, the expression levels of IL-6 and TNF-α, and the number of macrophage colonies of anti-PCSK9 group were all lower than those of isotype control group (72.50±4.97 vs. 128.30±6.74, 0.82±0.06 vs. 1.00±0.08, (85.50±4.37) ng/L vs. (277.70±8.98) ng/L, (291.80±13.69) ng/L vs. (615.30±12.65) ng/L, (111.50±10.21) CFU vs. (346.20±18.04) CFU), and the differences were statistically significant ( t=16.33, 4.40, 47.13, 42.50 and 27.73, all P<0.001). The percentage of co-localization of H. pylori and phagocytosis lysosome, the expression levels of CD3ζ Tyr142, granzyme B and perforin of anti-PCSK9 group were all higher than those of isotype control group ((51.05±3.03)% vs. (16.71±1.91)%, 2 948.00±384.00 vs. 1 156.00±178.60, (53.88±3.86)% vs. (5.88±0.93)%, (32.80±2.07)% vs. (6.83±0.54)%), and the differences were statistically significant ( t=23.49, 10.36, 29.60 and 29.76, all P<0.001). Conclusions:H. pylori can inhibit CD8 + T activation and cytotoxicity by inducing the release of PCSK9 from gastric epithelial cells, and can also recruit macrophages, activate nuclear factor-κB signal axis to up-regulate the level of released inflammatory factors from macrophages, inhibit the phagocytosis and killing effects of macrophages, so as to regulate the inflammatory response.