Objective To investigate the probability and dosimetric risk factors of lung injury after sequential immune checkpoint inhibitors (ICIs) and thoracic radiotherapy. Methods A retrospective analysis was conducted on 139 patients who received sequential ICIs and thoracic radiotherapy in Xuzhou Cancer Hospital and Affiliated Hospital of Xuzhou Medical University between February 2020 and February 2024. The relationships of clinical factors and lung and heart volume dose parameters with grade ≥ 2 acute lung injury (ALI) in patients with thoracic tumors were studied using univariable (χ² test, t test, nonparametric test) and multivariable (binary logistic regression analysis) methods. The thresholds of dosimetric risk factors were determined using the receiver operating characteristic curves. Clinical factors included age, gender, smoking history, type of ICIs, cycle of ICI application, and the interval between ICI application and thoracic radiotherapy. Dose parameters included total radiotherapy dose, single dose, planning target volume, maximum dose of planning target volume, average dose of planning target volume, total lung volume, heart volume, and the V₅, V₁₀, V₁₅, V₂₀, V₂₅, V₃₀, V₃₅, and V₄₀ of lung and heart. Results The incidence of grade ≥ 2 ALI in the included cases was 36% (50/139). The χ² test did not find any statistically significant clinical factors. In the univariable and binary Logistic regression analysis, lung V₁₅ and V₂₀, heart V₁₅ and V₂₀, and lung volume were independent risk factors for the occurrence of grade ≥ 2 ALI in sequential ICIs and thoracic radiotherapy. The thresholds were 18.51% for lung V₁₅, 14.43% for lung V₂₀, 32.41% for heart V₁₅, and 17.74% for heart V₂₀. Conclusion For patients who are going to receive thoracic radiotherapy after ICIs, the thresholds of lung V₁₅ and V₂₀ and heart V₁₅ and V₂₀ in the radiotherapy plan are recommended to be less than 18.51%, 14.43%, 32.41%, and 17.74%, respectively, which can effectively reduce the occurrence of grade ≥ 2 ALI.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

OBJECTIVE: To observe the effects of electroacupuncture (EA) with different frequencies on spermatogenic function, testicular morphology and oxidative stress in oligoasthenospermia (OAT) rats, and to explore the mechanism and the optimal parameters of EA for OAT. METHODS: Sixty SPF-grade male SD rats were randomly divided into a solvent control group, a model group, a 2 Hz EA group, a 100 Hz EA group and a 2 Hz/100 Hz EA group, with 12 rats in each group. Except for the solvent control group, the other 4 groups were administered ornidazole suspension (800 mg·kg^-1·d^-1) by gavage for 28 d to establish the OAT model. Starting from the 1st of modeling, EA was applied at "Guanyuan" (CV4), "Qihai" (CV6) and bilateral "Sanyinjiao" (SP6) and "Zusanli" (ST36) in the 3 EA groups, continuous wave of 2 Hz, continuous wave of 100 Hz, and disperse-dense wave of 2 Hz/100 Hz were used in the 2 Hz EA group, the 100 Hz EA group, and the 2 Hz/100 Hz EA group, respectively, with current intensity of 1-3 mA, 30 min a time, once every other day, for 28 consecutive days. After intervention, the testicular index was calculated, epididymal sperm quality was assessed, and the fertility ability was observed; morphology of testicular tissue was observed by HE staining, and the Johnson score was calculated; the positive expression of reactive oxygen species (ROS) in testicular tissue was detected by immunofluorescence; the activity of superoxide dismutase (SOD) and catalase (CAT), as well as the level of malondialdehyde (MDA) in testicular tissue were measured by ELISA; the protein expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in testicular tissue was detected by Western blot. RESULTS: Compared with the solvent control group, in the model group, the testicular index, sperm concentration, sperm motility and the number of offspring were decreased (P<0.01), the seminiferous tubules atrophied and the Johnson score decreased (P<0.01); the activity of SOD and CAT, as well as the protein expression of Nrf2 and HO-1 in testicular tissue were decreased (P<0.01); the sperm deformity rate, the positive expression of ROS and the MDA level in testicular tissue were increased (P<0.01). Compared with the model group, in the 2 Hz EA group, the 100 Hz EA group and the 2 Hz/100 Hz EA group, the testicular index, sperm concentration, sperm motility and the number of offspring were increased (P<0.05, P<0.01), the pathological morphology of testicular tissue improved and the Johnson scores increased (P<0.01); the activity of SOD and CAT, as well as the protein expression of Nrf2 and HO-1 in testicular tissue were increased (P<0.05, P<0.01); the sperm deformity rate, the positive expression of ROS and the MDA level in testicular tissue were decreased (P<0.05, P<0.01). Compared with the 2 Hz EA group, in the 2 Hz/100 Hz EA group, the testicular index, sperm concentration, sperm motility, as well as the CAT activity and HO-1 protein expression in testicular tissue were increased (P<0.01, P<0.05); the positive expression of ROS was decreased (P<0.01). Compared with the 100 Hz EA group, in the 2 Hz/100 Hz EA group, the testicular index was increased (P<0.01), the positive expression of ROS in testicular tissue was decreased (P<0.01). CONCLUSION EA with 2 Hz continuous wave, 100 Hz continuous wave, and 2 Hz/100 Hz disperse-dense wave can all improve the spermatogenic arrest and reduce the level of oxidative stress in testicular tissue in OAT rats, the mechanism may be related to up-regulating the protein expression of Nrf2 and HO-1 and improving oxidative stress. EA with disperse-dense wave of 2 Hz/100 Hz shows the optimal effect.
Male ; Animals ; Electroacupuncture ; Oxidative Stress ; Rats ; Rats, Sprague-Dawley ; Spermatogenesis ; Oligospermia/genetics* ; Humans ; Testis/metabolism* ; Superoxide Dismutase/metabolism* ; Asthenozoospermia/genetics* ; Acupuncture Points ; Malondialdehyde/metabolism*

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

OBJECTIVE: To determine the prevalence of lumbar spondylolysis (LS) and the proportion of spondylolytic spondylolisthesis (SS) in China, and to evaluate the musculoskeletal status of patients with LS and SS. METHODS: Spine Computed Tomography (CT) images were collected from community populations aged 40 and above in a nationwide multi-center project. LS was diagnosed, and SS was graded by an experienced radiologist. Bone mineral density (BMD) and paraspinal muscle parameters were quantified based on CT images. RESULTS: One hundred and seventeen patients of a total of 3,317 individuals were diagnosed with LS, corresponding to a prevalence rate of 3.53%. 63 of the 1,214 males (5.18%) and 54 of the 2,103 females (2.57%) were diagnosed with LS. SS occurred in 64/121 vertebrae (52.89%). BMD was not associated with LS ( P = 0.341). The L5 extensor paraspinal muscle density was higher in the LS group than in the non-LS group. In the LS group, patients with SS had a smaller L5 paraspinal extensor muscle cross-sectional area than those without SS ( P = 0.003). CONCLUSION The prevalence of LS in Chinese adults was 3.53%, with prevalence rates of 5.18% in males and 2.57% in females. Patients with LS have higher muscle density, whereas those with SS have smaller muscle cross-sectional areas at the L5 level.
Humans ; Male ; Female ; Middle Aged ; China/epidemiology* ; Prevalence ; Adult ; Lumbar Vertebrae/diagnostic imaging* ; Spondylolysis/diagnostic imaging* ; Aged ; Bone Density ; Tomography, X-Ray Computed ; Aged, 80 and over ; Spondylolisthesis/epidemiology* ; East Asian People

Chronic prostatitis is a common and frequently occurring disease in male clinics. Due to the diverse symptoms， complex etiology， unclear mechanisms， and recurrent episodes of chronic prostatitis， Western medicine often faces the challenge of limited treatment options and unsatisfactory outcomes. In order to fully leverage the unique advantages of traditional Chinese medicine （TCM） in the treatment of chronic prostatitis， the China Association of Chinese Medicine organized a discussion among experts from the fields of TCM urology， Western urology， and related pharmacy. The experts focused on the advancements in the understanding of chronic prostatitis in modern medicine， various theories on the etiology， pathogenesis， and treatment of chronic prostatitis in TCM， entry points from interdisciplinary fields， the role and advantages of TCM in the comprehensive management of chronic prostatitis， and research into mechanisms related to chronic prostatitis. After discussions， the experts concluded that chronic prostatitis is one of the diseases where TCM has a distinct advantage. TCM can effectively improve the clinical syndromes of chronic prostatitis， including urinary issues， social psychology， organ specificity， infection， nervous system problems， pain and discomfort， sexual dysfunction， etc.， and can enhance the quality of life. For patients with chronic prostatitis who cannot tolerate or may not accept the adverse effects of Western medicine， as well as for those with non-inflammatory chronic prostatitis/chronic pelvic pain syndrome （CP/CPPS）， those with pain as the primary symptom， those with urinary tract symptoms， those with coexisting anxiety and depression， and those with abnormal semen liquefaction， TCM-based treatment can be the main approach. Currently， the optimal diagnosis and treatment strategy for chronic prostatitis has not yet been established， and further research from perspectives such as clinical epidemiology， evidence-based medicine， and molecular biology is needed. Both TCM and Western medicine should integrate their respective strengths， clarify the role and advantages of TCM interventions based on mutual reference， and improve the diagnosis and treatment standards for chronic prostatitis in China.

Objective To explore the mechanism of the therapy of promoting blood circulation and nourishing yin(PBCNY)in improving spermatogenesis in rats with varicocele based on Bcl-2/Bax pathway.Methods Thirty 8-week-old male SD rats were randomly divided into six groups(five rats per group):sham,model,levocarnitine(1.0 g/kg),and PBCNY low-dose(5.2 g/kg),PBCNY medium-dose(10.4 g/kg),and PBCNY high-dose(20.8 g/kg)groups.Apart from the sham group,all the groups were built a varicocele model by the classical Turner method.After 4 weeks,the sham group and model group were gavaged with normal saline,and the remaining groups were given with levocarnitine or different doses of PBCNY decoction once a day for 4 weeks.At the end of gavage,the sperm quality of rats in each group was detected by a computer-assisted sperm analyzer,and HE staining was used to observe the testicular tissue morphology of rats in each group and performed with Johnsen score.TUNEL method was used to detect apoptosis,RT-qPCR was used to detect Bcl-2 and Bax mRNA expression,and immunohistochemical method was used to detect cytochrome C protein expression.Results Compared to the sham group,sperm total count,motility rate and percentage of sperm with grade(a+b)motility were lower in the model group of rats(P<0.05).HE staining showed disturbed arrangement of seminiferous tubules in the testicular tissue with significant changes and decreased Johnsen score(P<0.05).The result of TUNEL assay showed that the apoptosis rate was increased in the model group(P<0.05).Bax mRNA expression was increased in testicular tissue(P<0.05).The result of immunohistochemistry showed that the positive expression of cytochrome C was increased in the model group(P<0.05).Compared with the model group,the rat sperm total count in the PBCNY medium-dose group,motility rate in the PBCNY low-and medium-dose groups,and percentage of sperm with grade(a+b)motility in the PBCNY low-dose group increased(P<0.05);the pathological structure of rat testis had different degrees of improvement,and Johnsen score increased in the PBCNY medium-dose group(P<0.05);the apoptosis rate of testicular cells decreased in the levocarnitine group and all doses of PBCNY groups(P<0.05);the expression of Bcl-2 mRNA increased in the PBCNY low-dose and high-dose groups(P<0.05),and the expression of Bax mRNA decreased in the levocarnitine group and the PBCNY medium-dose group(P<0.05);the positive expression of cytochrome C decreased in the PBCNY medium-dose group(P<0.05).Conclusion The therapy of PBCNY can improve sperm quality,repair damaged testicular tissue structure and improve spermatogenic function in rats with varicocele,and its mechanism of action may be related to the activation of Bcl-2/Bax pathway and inhibition of cell apoptosis.

Objective To explore the mechanism of the therapy of promoting blood circulation and nourishing yin(PBCNY)in improving spermatogenesis in rats with varicocele based on Bcl-2/Bax pathway.Methods Thirty 8-week-old male SD rats were randomly divided into six groups(five rats per group):sham,model,levocarnitine(1.0 g/kg),and PBCNY low-dose(5.2 g/kg),PBCNY medium-dose(10.4 g/kg),and PBCNY high-dose(20.8 g/kg)groups.Apart from the sham group,all the groups were built a varicocele model by the classical Turner method.After 4 weeks,the sham group and model group were gavaged with normal saline,and the remaining groups were given with levocarnitine or different doses of PBCNY decoction once a day for 4 weeks.At the end of gavage,the sperm quality of rats in each group was detected by a computer-assisted sperm analyzer,and HE staining was used to observe the testicular tissue morphology of rats in each group and performed with Johnsen score.TUNEL method was used to detect apoptosis,RT-qPCR was used to detect Bcl-2 and Bax mRNA expression,and immunohistochemical method was used to detect cytochrome C protein expression.Results Compared to the sham group,sperm total count,motility rate and percentage of sperm with grade(a+b)motility were lower in the model group of rats(P<0.05).HE staining showed disturbed arrangement of seminiferous tubules in the testicular tissue with significant changes and decreased Johnsen score(P<0.05).The result of TUNEL assay showed that the apoptosis rate was increased in the model group(P<0.05).Bax mRNA expression was increased in testicular tissue(P<0.05).The result of immunohistochemistry showed that the positive expression of cytochrome C was increased in the model group(P<0.05).Compared with the model group,the rat sperm total count in the PBCNY medium-dose group,motility rate in the PBCNY low-and medium-dose groups,and percentage of sperm with grade(a+b)motility in the PBCNY low-dose group increased(P<0.05);the pathological structure of rat testis had different degrees of improvement,and Johnsen score increased in the PBCNY medium-dose group(P<0.05);the apoptosis rate of testicular cells decreased in the levocarnitine group and all doses of PBCNY groups(P<0.05);the expression of Bcl-2 mRNA increased in the PBCNY low-dose and high-dose groups(P<0.05),and the expression of Bax mRNA decreased in the levocarnitine group and the PBCNY medium-dose group(P<0.05);the positive expression of cytochrome C decreased in the PBCNY medium-dose group(P<0.05).Conclusion The therapy of PBCNY can improve sperm quality,repair damaged testicular tissue structure and improve spermatogenic function in rats with varicocele,and its mechanism of action may be related to the activation of Bcl-2/Bax pathway and inhibition of cell apoptosis.