Vernal keratoconjunctivitis is an allergic ocular surface disease mostly present with recurrent chronic inflammation, which usually affects children and adolescents and possibly results in corneal complications such as keratoconus. Keratoconus is a corneal disease characterized by a local cone-like corneal deformation. Previous studies have respectively put forward pathological mechanisms of vernal keratoconjunctivitis and keratoconus and the progressive risk factors, among which we find there's mutual mechanisms as well as cytokines' expression, including type I and IV hypersensitivity, inflammatory reaction, enzymatic changes, oxidative stress and mechanical injury. This review aims at summarizing the possible intrinsic mechanisms and cytokines exacerbating vernal keratoconjunctivitis patients corneas to keratoconus, so as to provide reference for the prevention and management in keratoconus caused by vernal keratoconjunctivitis.

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.
Humans ; Middle Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Chemoradiotherapy ; Immune Checkpoint Inhibitors/therapeutic use* ; Neoadjuvant Therapy ; Prospective Studies ; Rectal Neoplasms/pathology* ; Thrombocytopenia/drug therapy* ; Treatment Outcome ; Adult ; Aged

Tenofovir disoproxil fumarate （TDF） is a first-line treatment for chronic hepatitis B. With increasing use worldwide， the adverse events of renal injury caused by this drug have also attracted industry attention. This article reports a 61- year-old patient with liver cancer complicated with hepatitis B virus （HBV） infection. The patient started using TDF in mid-March 2022 and developed kidney injury after 2 months of treatment， during which he received 2 courses of donafenib combined with sintilimab chemotherapy and irregular administration of diclofenac for pain relief. In this paper， Naranjo’s assessment scale was used to evaluate the drugs that may be associated with renal injury， including TDF and sintilimab， and the drugs that are suspected to be associated with renal injury are donafenib and diclofenac. The renal injury caused by TDF can be judged according to the changes in the patient’s condition， the incidence of drug-induced renal injury， clinical manifestations， occurrence time， occurrence mechanism， drug combination， and high-risk factors. The changes of serum creatinine in patients with liver cancer complicated with HBV infection after TDF should be dynamically monitored in the clinic， and the dose of antiviral drugs should be adjusted if necessary and other antiviral drugs with less impact on renal function can be selected， to provide individualized medication recommendations for tumor patients， reduce the incidence of TDF-related renal injury.

Objective: To analyze the value of 3-dimensional speckle tracking echocardiograghy (3D-STE) derived strain parameters on the detection of subclinical myocardial deformation alterations in patients with lymphoma treated with anthracycline agents. Methods: This study was a retrospective study. A total of 37 patients with newly diagnosed diffuse large B cell non-Hodgkin lymphoma between December 2012 and December 2014 in Cancer Center, Fudan university were included. 3D-STE strain measurements were performed at baseline (T0),after the completion of two therapy circles (T1) and at the end of anthracycline regimen chemotherapy (Te). Echocardiography images were analyzed on the TTA workstation, and the indexes included left atrial minimum volume (LAVmin), left atrial emptying index (LAEF), left atrial active emptying index (LAAEF), as well as the left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), left atrial global longitudinal strain (LAGLS). The overall left atrioventricular longitudinal strain (LAVGLS) was calculated, which was the sum of the absolute values of LVGLS and LAGLS. The changes of left ventricular strain indexes measured by 3D-STE at different time points of patients were evaluated. Results: Thirty-seven patients with DLBCL, aged (48.3±12.1)years, including 23 males (63.9%), were enrolled. Compared with baseline, LVGLS (T1: (-18.63±4.73)% vs. (-22.13±4.40)%, P=0.001; Te:(-18.26±4.64)% vs. (-22.13±4.40)%, P<0.001), LAGLS (T1: (20.41±5.56)% vs. (23.98±5.59)%, P=0.003; Te: (17.60±3.96)% vs. (23.98±5.59)%, P<0.001) and LAVGLS (T1: (39.05±7.60)% vs. (46.11±7.77)%, P<0.001; Te: (40.34±8.55)% vs. (46.11±7.77)%, P<0.001) were all deteriorated at the T1 and Te. While LVGCS ((-21.98±5.82)% vs. (-26.15±7.51)%, P=0.010), LAVmin ((23.93±7.29)ml vs. (20.33±7.03)ml, P=0.029), LAEF ((28.94±11.16)% vs. (35.79±11.12)%, P=0.002) and LAAEF ((11.93±10.00)% vs. (18.10±9.96)%, P=0.013) were decreased only until Te. Conclusions: 3D-STE strain measurements could detect early myocaridial function alteration in patients receiving anthracycline regimen chemotherapy, thus may provide a novel approach to monitor anthracycline caused myocardial toxicity.
Male ; Humans ; Anthracyclines/therapeutic use* ; Ventricular Function, Left ; Retrospective Studies ; Heart Ventricles ; Antibiotics, Antineoplastic/adverse effects* ; Polyketides/pharmacology* ; Lymphoma/drug therapy*

Objective: To investigate the current basic situation of the staff of ultrasound departments in Shanghai′s medical institutions, for providing references in making management policy of these professionals. Methods: Questionnaire surveys on human resource and service ability were made to all the ultrasound departments of medical institutions in Shanghai in December 2013 and November 2018 respectively. Data of the two surveys were compared and analyzed, and were descriptively analyzed by mean and percentage. Results: The number of ultrasound professionals per 10 000 people in Shanghai was 1.04 in 2018. Tertiary hospitals had advantages in the number of the professionals, and the proportion of professional qualification, age, education background and professional title of the professionals. Compared to those data in 2013, the number of ultrasound professionals had increased 31.8% in 2018. The proportion of medical practitioners with medical imaging specialty was 95.6%(2 063/2 158), and had increased by 4.7 percent. The medical services workload of ultrasound was 19.82 million person-time, and had increased 45.8%. Conclusions Development of ultrasound departments was rapid, but the development of professionals was unbalanced with the development of medical services. It is suggested to strengthen training of ultrasound professionals and improve the system of hierarchical medical system.

Liver cancer has high morbidity and mortality worldwide. Traditional morphological imaging can offer crucial anatomical information for the diagnosis and treatment of liver cancer, and when combined with the functional data shown by PET imaging, the diagnostic accuracy of tumors can be further improved and assisted in treatment selection. Fibroblast activation protein (FAP), a signature protein of cancer-associated fibroblasts, is highly expressed in a variety of malignant tumors of epithelial origin and is an important target for tumor diagnosis and treatment. Compared with routinely applied ¹⁸F-fluorodeoxyglucose (FDG) PET imaging, FAP inhibitor (FAPI) PET imaging has the advantages of high image contrast and independence from blood glucose. In recent years, a variety of radiopharmaceuticals targeting FAP have been continuously expanded in the diagnosis, staging and targeted therapy of different liver cancer types, and the progress of their related applications is reviewed in this paper.

Objective: To investigate the current basic situation of ultrasound machines of ultrasound departments in Shanghai medical institutions, and to provide the basis for making management policy in order to promote medical quality. Methods: Questionnaire surveys about ultrasound machines and service ability including producing countries of ultrasound machines, the number of ultrasound machines, using years of ultrasound machines, yearly workload and the yearly number of patients that each ultrasound machine accepted were made in 2013 and 2018, respectively. Statistical results were compared between the two surveys. Results: Compared with 2013, the share of imported ultrasound machines declined in 2018 (82% vs 91%). Compared with 2013, the number of ultrasound machines in Shanghai medical institutions had increased by 31% in 2018 (2 123 vs 1 617). The occupancy rate of ultrasound machines in tertiary hospitals was the highest (tertiary hospitals 40%, secondary hospitals 25%, primary grade hospitals 20%, and private hospitals 15%). Compared with 2013, the proportion of ultrasound machines that have been used for more than 10 years increased (9% vs 4%), the yearly workload of ultrasound examination had increased by 46% (19.82 million person-time vs 13.59 million person-time). Tertiary hospitals bored the highest proportion of the workload (tertiary hospitals 51%, secondary hospitals 35%, primary grade hospitals 4%, and private hospitals 10%). Currently, the number of ultrasound machines per 10, 000 people in Shanghai was 1.14. The yearly number of patients that each ultrasound machine accepted had increased by 11% (9300 person-time vs 8400 person-time in 2018). Conclusions The scale of ultrasound departments in Shanghai medical institutions has been developing. Brand localization of ultrasound machines is improving. However, the renewal ability of ultrasound machines still needs to be improved. The workload of ultrasound department is getting heavier. Hierarchical diagnosis and treatment is unbalanced.

Trace elements and vitamins are essential micronutrients for metabolism. Micronutrients deficiency results in adverse effects on human body, and brings huge challenge to clinical nutrition therapy. To normalize micronutrients application in clinical practice, European Society for Clinical Nutrition and Metabolism (ESPEN) published ESPEN practical short micronutrient guideline on January 2024. Based on previous version published in 2022, current guideline shortens the interpretation of biochemical and physical mechanisms, focuses on micronutrients deficiency and inflammation, recommends the methods of micronutrients assessment and supplementation in different statuses during clinical practices. This paper summarizes specific recommendations and comments for domestic peers to communicate, and provides reference for the management of micronutrient therapy in China.

ObjectiveTo observe the clinical efficacy and safety of Chinese medicinal mixture for dispelling stasis and resolving phlegm combined with western medicine in the treatment of epilepsy combined with cognitive impairment by randomized， double-blind， placebo-controlled， parallel-group trial. MethodA total of 123 inpatients and outpatients with epilepsy complicated with cognitive impairment admitted to the department of neurology at Longhua Hospital from October 2020 to October 2021 were randomly assigned into a control group （62 cases， carbamazepine + placebo） and a treatment group （61 cases， carbamazepine + Quyu Dingxian Zhengtong mixture） by random number table method. In the treatment group， 4 cases were exfoliated and eliminated. In the control group， 3 cases fell off. Finally， 57 cases in the treatment group and 59 cases in the control group were included. The total course of treatment for both groups was 12 weeks. The clinical efficacy， efficacy for traditional Chinese medicine （TCM） syndromes， and incidence of adverse reactions were compared between two groups. The changes of seizure frequency， abnormal rate of electroencephalogram （EEG）， cognitive function score， serum homocysteine （HCY）， folic acid， and vitamin B₁₂ （B₁₂） were measured and compared before and after treatment. ResultAfter 12 weeks of treatment， the treatment group had higher clinical efficacy ［92.98% （53/57） vs 79.66% （47/59）， χ²=4.327， P<0.05］ and efficacy for TCM syndromes ［96.49% （55/57） vs 84.75% （50/59）， χ²=4.660， P<0.05］ than the control group. The treatment group was superior to the control group in reducing the seizure frequency （Z=-3.938， P<0.01） and improving the Montreal cognitive assessment （MoCA） score （t=4.333， P<0.01） and mini-mental state examination （MMSE） score （t=9.531， P<0.01）. The variations in serum HCY， folic acid， and B₁₂ in the treatment group were less than those in the control group （t=-7.233， t=-7.972， t=-6.871， P<0.01）. After treatment， the abnormal rate of EEG in the treatment group was lower than that in the control group （χ²=4.437， P<0.05）. The incidence of adverse reactions in the treatment group （1.75%， 1/57） was lower than that （13.56%， 8/59） in the control group （corrected χ²=4.116， P<0.05）. ConclusionChinese medicinal mixture for dispelling stasis and resolving phlegm in combination with western medicine had better efficacy and safety than western medicine alone in the treatment of epilepsy complicated with cognitive impairment. Specifically， the combination outperformed western medicine alone in terms of clinical efficacy， efficacy for TCM syndromes， reduction in seizure frequency， abnormal rate of EEG， adverse reactions， improvement of cognitive function， and variations in serum folic acid， B₁₂， and HCY values. Chinese medicinal mixture for dispelling stasis and resolving phlegm may improve the clinical efficacy and safety by changing the metabolism of folic acid， B₁₂， and HCY in serum of the patients with epilepsy complicated with cognitive impairment.

ObjectiveTo observe the effect of Feiyanning prescription （FYN） on cisplatin （DDP） resistance in non-small cell lung cancer （NSCLC） and explore the underlying mechanism. MethodCell counting kit-8 （CCK-8） assay was used to detect the proliferation of A549 and A549/DDP （DDP-resistant） cells treated by DDP （0， 2.0， 4.0， 6.0， 8.0， 10.0 mg⋅L^-1） and the proliferation of A549/DDP cells treated by FYN （0， 100， 200， 300， 400， 500， 600 mg⋅L^-1）. Based on immunofluorescence staining and Western blot （WB）， the expression of epithelial mesenchymal transition （EMT）-related proteins in A549 and A549/DDP groups was observed. A549/DDP cells were classified into control group， FYN group （200 mg⋅L^-1）， DDP group （6.0 mg⋅L^-1）， and combination group ［FYN （200 mg⋅L^-1） + DDP （6.0 mg⋅L^-1）］ and respectively treated with corresponding drugs. Then， invasion ability of each group was examined by transwell assay， and the expression of EMT-related proteins in each group by WB. Moreover， real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and immunofluorescence staining were separately applied to detect the mRNA and protein expression of drug resistance-related factors in each group， respectively. ResultCompared with A549 group， A549/DDP group showed high resistance to DDP （P<0.01）， low expression of E-cadherin， and high protein expression of Vimentin， N-cadherin， and Snail （P<0.05， P<0.01）. As compared with the control group， FYN inhibited the proliferation of A549/DDP cells in a concentration-dependent manner （P<0.01）， and the FYN group， DDP group， and combination group demonstrated low invasion ability （P<0.01）. In addition， the invasion ability in the combination group was particularly lower than that in the DDP group （P<0.01）. The expression of E-cadherin protein was higher and the protein expression of N-cadherin， Vimentin， and Snail was lower in the in FYN group than in the control group （P<0.01）. The protein expression of E-cadherin， N-cadherin， and Vimentin was lower and the expression of Snail was higher in the DDP group than in the control group （P<0.05，P<0.01）. The protein expression of E-cadherin， N-cadherin， Vimentin， and Snail in the combination group decreased as compared with that in the control group （P<0.01）. Compared with the DDP alone， the combination raised the expression of E-cadherin and lowered the protein expression of N-cadherin， Vimentin， and Snail （P<0.01）. The protein and mRNA expression of lung resistance-related protein （LRP） and multidrug resistance 1 （MDR1） was lower and the protein and mRNA expression of topoisomerase Ⅱα （TOPO Ⅱα） was higher in the FYN group than in the control group （P<0.01）. The protein and mRNA expression of LRP， MDR1， and TOPO Ⅱα was higher in the DDP group than in the control group （P<0.01）. The expression of LRP protein and mRNA showed no significant variation， but the protein and mRNA expression of MDR1 and TOPO Ⅱα increased in the combination group compared with those in the control group （P<0.01）. Compared with the DDP group， FYN group and combination group showed low protein and mRNA expression of LRP and MDR1 and high protein and mRNA expression of TOPO Ⅱα （P<0.01）. Compared with FYN， the combination elevated the protein and mRNA expression of LRP， MDR1， and TOPO Ⅱα （P<0.01）. ConclusionFYN prescription can reverse the DDP resistance of NSCLC by modulating EMT.