OBJECTIVE: To investigate the clinical characteristics and prognosis of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). METHODS: Clinical data of 10 patients with PTCL-NOS in Gansu Provincial Hospital from May 2016 to June 2023 were collected. The treatment outcomes were evaluated, and the factors affecting prognosis were analyzed. RESULTS: The median age of onset for the 10 patients was 60.7 (47-75) years, with 7 males and 3 females. Nine cases received chemotherapy, while one case died suddenly after diagnosis, and the median course of chemotherapy was 6.9 (1-13) courses. Assessing the efficacy, 3 patients achieved complete remission (CR) while 7 patients showed progression. Age, sex, lactate dehydrogenase (LDH) level, Ki-67 and the presence of hemophagocytic lymphohistocytosis (HLH) were not statistically correlated with CR rate ( P >0.05). Patients with IPI score 3-5, and Ann Arbor stage III-IV had statistically lower CR rates (both P <0.05). Age, B symptoms, LDH level ,hemoglobin, Ki-67 index and PLR value were not statistically correlated with overall survival (OS) time ( P >0.05). Male, platelet <150×10⁹/L, IPI score 3-5, Ann Arbor stage III-IV, presence of HLH, NLR≥4.05, and LMR <2.81 were statistically correlated with shorter OS (all P <0.05). Among the 10 patients, 3 cases have survived and are still in CR status, while 7 cases have died, with a median survival time of 7.5 (1-85) months. CONCLUSIONS Patients with IPI score 3-5 and Ann Arbor stage III-IV have low CR rate and poor prognosis. The OS of patients who are male, with platelet <150×10⁹/L, IPI score 3-5, Ann Arbor stage III-IV, complication of HLH, NLR≥4.05, and LMR <2.81 is short, and prognosis is poor.
Humans ; Lymphoma, T-Cell, Peripheral/diagnosis* ; Male ; Prognosis ; Middle Aged ; Female ; Aged

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with hemophagocytic lymphohistiocytosis (HLH). METHODS: Clinical data of 78 patients with HLH admitted to Gansu Provincial People's Hospital from January 2014 to May 2023 were collected, and the correlation between relevant indicators and patient prognosis was analyzed. RESULTS: Among the 78 HLH patients, there were 48 males and 30 females, with a median age of onset of 48 (1-84) years old; 26 patients were treated with chemotherapy, 44 patients were treated with glucocorticoids, immunoglobulin or cyclosporine, 5 patients received symptomatic treatment, 1 patient received plasma exchange, and 2 patients refused treatment. By the end of the follow-up, there were 39 survivors, 35 deaths, and 4 patients lost to follow-up. There was no significant correlation between sex, ferritin, triglycerides, hemophagocytosis, bone marrow cellularity, Epstein-Barr virus (EBV) infection, SUV value of PET-CT, alanine aminotransferase (ALT), interleukin-6 (IL-6), platelet-to-lymphocyte ratio (PLR) and overall survival (OS) of the patients (P >0.05). Patients with age≥60 years, neutrophil-to-lymphocyte ratio (NLR) >0.59, red cell distribution width-to-platelet ratio (RPR) >0.30, lymphocyte-to-monocyte ratio (LMR)≤2.74, red blood cell distribution width (RDW)>16.45%, tumor-associated HLH, aspartate aminotransferase (AST)≥148 U/L, procalcitonin (PCT)≥0.66 ng/ml, neutrophils (NEU) <2×10⁹/L, fibrinogen (FIB)<1.85 g/L, lactate dehydrogenase (LDH)≥1 740 U/L, hemoglobin (Hb)<85 g/L, platelet (PLT)<57×10⁹/L had significantly shorter OS, with statistical significance (P < 0.05). Multivariate analysis showed that LMR≤2.74, RDW>16.45%, LDH≥1 740 U/L, and NEU<2×10⁹/L were independent risk factors affecting OS in HLH patients (P < 0.05). CONCLUSION Some blood-based inflammatory markers are significantly associated with OS in patients with HLH. NLR, RPR, LMR, RDW and PCT can be used to assess the prognosis of HLH patients, and RDW and LMR are independent factors affecting OS of HLH patients, which provide greater predictive value for prognosis. Hypercellular bone marrow in HLH patients may indicate a poor prognosis.
Humans ; Lymphohistiocytosis, Hemophagocytic/diagnosis* ; Prognosis ; Female ; Male ; Middle Aged ; Adult ; Aged ; Adolescent ; Child ; Child, Preschool ; Infant ; Young Adult ; Bone Marrow/pathology* ; Aged, 80 and over ; Inflammation

Secondary organizing pneumonia after infection is a pathological condition characterized by connective tissue filling and obstructing the alveoli and bronchioles, in which following an infection in the lung, the inflammatory response is not controlled in a timely and effective manner. The pathogenesis and treatment of this condition can be interpreted through the Sanjiao membranous tube theory and the concept of stagnation within the pulmonary micro-membrane. Sanjiao is conceptualized as a four-way membranous tube that internally connects with the zangfu organs and externally with the skin and muscles, enabling the circulation of energy and fluids throughout the body. It also maintains communication with the zangfu micro-membranes. Within the lungs, the pulmonary micro-membrane is distributed and connected to the upper jiao membranous tube, facilitating the movement of qi and fluids and supporting nutrient distribution. External pathogens may invade the Sanjiao membranous system through the external membranous tube, travel internally along this system, and transform into latent pathogens that settle within the pulmonary micro-membrane. These latent pathogens can subsequently transform into heat or dampness, leading to the depletion of lung qi and impairing the lung′s ability to regulate and transport body fluids. Consequently, fluids may seep into the pulmonary micro-membrane, where they are transformed into dampness, turbidity, and phlegm. The accumulation of damp-turbidity and phlegm obstructs the flow of qi and blood, resulting in blood stasis in the pulmonary collaterals. This stagnation occurring within both the pulmonary micro-membrane and its associated collaterals underlies the development of secondary organizing pneumonia after infection. In severe cases, this condition may progress to pulmonary interstitial fibrosis. The therapeutic approach emphasizes expelling latent pathogens, regulating and dredging the pulmonary micro-membrane, tonifying the healthy qi, and supporting health. Regulating and dredging the pulmonary micro-membrane is a crucial step, with a focus on promoting the flow of lung qi, resolving dampness and phlegm, and activating blood circulation to remove stasis.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Objective To systematically evaluate the efficacy and safety of single and bilateral lung transplantation in the treatment of end-stage chronic obstructive pulmonary disease (COPD). Methods Chinese and English databases were searched by computer, including PubMed, Web of Science, The Cochrane Library, EMbase, CNKI, Wanfang database, VIP database and CBM. Case-control studies on single lung transplantation or bilateral lung transplantation for COPD were collected from the inception to July 31, 2022. We evaluated the quality of the literature via Newcastle-Ottawa Scale (NOS). All results were analyzed using Review Manager V5.3 and STATA 17.0. Results A total of 8 studies were included covering 14076 patients, including 8326 patients in the single lung transplantation group and 5750 patients in the bilateral lung transplantation group. NOS scores were≥6 points. The results of meta-analysis showed that there was no statistical difference in the postoperative 1-year survival between the two groups (P=0.070). The 2-year survival rate (P=0.002), 3-year survival rate (P<0.001), 5-year survival rate (P<0.001), overall survival rate (P＜0.001), postoperative forced expiratory volume in one second/predicted value (P<0.001), postoperative forced vital capacity (P<0.001), and postoperative 6-minute walking distance (P=0.002) were lower or shorter than those in the bilateral lung transplantation group, the postoperative intubation time (P=0.030) was longer than that in the bilateral lung transplantation group. Bilateral lung transplantation group showed better surgical results. There was no statistical difference in the mortality, obliterative bronchiolitis, length of hospitalization, primary graft dysfunction, or postoperative adverse events (P>0.05). Conclusion Bilateral lung transplantation is associated with better long-term survival and postoperative lung function compared with single lung transplantation. In-hospital mortality and postoperative complications are similar between them.

AIM: To observe the changes of corneal densitometry(CD)in patients with keratoconus after corneal cross-linking(CXL).METHODS: Retrospective study. A total of 32 patients(43 eyes)with keratoconus in Ningxia Eye Hospital from April 2020 to April 2022 were selected. Pentacam analysis system divided the cornea into three layers: anterior 120 μm, middle layer and posterior 60 μm, and divides it into five regions with diameters of 0-2, 2-6, 6-10, 10-12 mm and full diameter according to the diameter, and measures the CD in different ranges. The changes of CD were compared before operation and at 1, 3 and 6 mo after operation.RESULTS: There were differences in uncorrected visual acuity, best corrected visual acuity and intraocular pressure before and 6 mo after operation(all P<0.05), and there was no difference in corneal endothelial cells(P=0.477). CD reached its peak at 1 mo after operation, and decreased at 3 mo and 6 mo after operation, but it was still higher than that before operation. There is a significant positive correlation between CD and Kmax in the anterior layer and the whole layer(r=0.164, P=0.016; r=0.152, P=0.023).CONCLUSION: The values of CD peaked at 1 mo after CXL, then it gradually decreased, tending to become stable at 6 mo postoperatively.

ObjectiveTo establish a rat model of moderate-to-severe knee osteoarthritis, laying the foundation for studying the pathogenesis of moderate-to-severe knee osteoarthritis and its prevention and treatment methods. MethodsThirty male SD rats were randomly divided into three groups: a sham surgery group, an 8-week model group, and a 20-week model group, with 10 rats in each group. Rats in the 8-week and 20-week model groups underwent surgery to cut the anterior and posterior cruciate ligaments and medial collateral ligament of the right knee joint, and remove the medial and lateral menisci. After surgery, the rats were allowed to move freely. The rats in the sham surgery group had only skin incisions to expose the joint without any surgical treatment. At 8 and 20 weeks post-surgery, Micro-CT scans were performed to analyze the femoral osteoporosis in the rats. After euthanizing the rats, gross observations of the knee joints were made, and the cartilage of the joint surface was scored using the Pelletier scoring system. The knee joints were collected for hematoxylin and eosin (HE) staining and safranin O-fast green staining to observe changes in cartilage morphology. The modified Mankin's scoring system was used to assess the tissue pathology of the joint surface. Immunohistochemical staining was used to detect the expression of type II collagen and matrix metalloproteinase 13 (MMP13), reflecting the anabolic and catabolic metabolism of the knee joint cartilage. ResultsThe knee joint cartilage in the 8-week and 20-week model groups was severely damaged, with Pelletier and modified Mankin's scores significantly higher than those in the sham surgery group (both P<0.01). The Pelletier and modified Mankin's scores in the 20-week model group were significantly higher than those in the 8-week model group (P<0.01). Micro-CT observations revealed irregular joint surfaces, osteophyte formation, and signs of osteoporosis in both the 8-week and 20-week model groups, with the 20-week model group showing more loose bodies around the knee joints. Immunohistochemical staining showed increased expression of MMP13 and decreased expression of type II collagen in the knee joint tissues of the model groups, indicating that the balance of anabolic and catabolic metabolism in the joint cartilage was disrupted. MMP13 increased while type II collagen decreased. ConclusionThe surgical method of cutting the anterior and posterior cruciate ligaments and medial collateral ligament and removing the medial and lateral menisci successfully creates a moderate-to-severe knee osteoarthritis model in rats. Imaging examinations reveal osteophytes, osteoporosis, and loose bodies in the knee joints, while pathological observations show a reduction or even disappearance of joint cartilage, with a disruption in the balance of cartilage anabolic and catabolic metabolism.

OBJECTIVE: To evaluate the positional relationship between protective channel and sural nerve while treating acute Achilles tendon rupture with channel assisted minimally invasive repair (CAMIR) technique based on anatomical observations of cadaver specimens. METHODS: Twelve adult cadaveric lower limb specimens (6 left, 6 right) were utilized. A CAMIR device was implanted at a distance of 4 cm from the proximal end of the specimen to the Achilles tendon insertion. The skin was incised along the tendon's medial side, the sural nerve was dissected, and the positional relationship with the protective channel was observed. The distance from the sural nerve-Achilles tendon intersection to the calcaneal insertion, the vertical distance between protective channel and the calcaneal insertion, and the horizontal distance between the sural nerve and protective channel were measured by using vernier caliper. RESULTS: Anatomical examination demonstrated a variable positional relationship between the sural nerve and protective channel, with the sural nerve positioned above (8 specimens) or below (4 specimens) the protective channel. The distance from the sural nerve-Achilles tendon intersection to the calcaneal insertion was (105.67±14.94) mm, the vertical distance between protective channel and the calcaneal insertion was (93.20±9.57) mm, and the horizontal distance between the sural nerve and protective channel was (0.31±0.14) mm. CONCLUSION The use of CAMIR technique for the treatment of acute Achilles tendon rupture can effectively avoid iatrogenic injury to the sural nerve.
Humans ; Achilles Tendon/injuries* ; Sural Nerve/anatomy & histology* ; Cadaver ; Minimally Invasive Surgical Procedures/methods* ; Tendon Injuries/surgery* ; Rupture/surgery* ; Adult ; Male ; Calcaneus/injuries* ; Female ; Plastic Surgery Procedures/methods*

Rosuvastatin(RVS)is an excellent drug with anti-inflammatory and lipid-lowering properties in the aca-demic and medical fields.However,this drug faces a series of challenges when used to treat atherosclerosis caused by hyperhomocysteinemia(HHcy),including high oral dosage,poor targeting,and long-term toxic side effects.In this study,we applied nanotechnology to construct a biomimetic nano-delivery system,macrophage membrane(M?m)-coated RVS-loaded Prussian blue(PB)nanoparticles(MPR NPs),for improving the bioavailability and targeting capacity of RVS,specifically to the plaque lesions associated with HHcy-induced atherosclerosis.In vitro assays demonstrated that MPR NPs effectively inhibited the Toll-like receptor 4(TLR4)/hypoxia-inducible factor-1α(HIF-1α)/nucleotide-binding and oligomerization domain(NOD)-like receptor thermal protein domain associated protein 3(NLRP3)signaling pathways,reducing pyroptosis and inflammatory response in macrophages.Additionally,MPR NPs reversed the abnormal distribution of adenosine triphosphate(ATP)-binding cassette transporter A1(ABCA1)/ATP binding cassette transporter G1(ABCA1)/ATP binding cassette transporter G1(ABCG1)caused by HIF-1α,promoting cholesterol efflux and reducing lipid deposition.In vivo studies using apolipoprotein E knockout(ApoE-/-)mice confirmed the strong efficacy of MPR NPs in treating atherosclerosis with favorable bio-security,and the mechanism behind this efficacy is believed to involve the regulation of serum metabolism and the remodeling of gut microbes.These findings suggest that the synthesis of MPR NPs provides a promising nanosystem for the targeted therapy of HHcy-induced atherosclerosis.